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Leptin Reset Easy Start Guide How to start the Leptin Reset and regain Leptin Sensitivity Step

One: Are You Leptin Resistant? The Leptin Rx FAQs Overweight, large appetite and craving carbs are signs you re Leptin Resistant. If you are fit and in decent shape, then your reverse T3 will be elevated, also indicating you re Leptin Resistant Step Two: Follow a strict Paleolithic diet For best results follow the diets outlined in The Paleo Solution: The Original H uman Diet by Robb Wolf or The Primal Blueprint by Mark Sisson Step Three: Eat within 30 minutes of rising Make sure breakfast is little to no carbs (less that 50 grams) LOTS of protein (50-75 grams) Overweight: limit carbs to 25 grams Fit: less than 30 carbs DO NOT count calories Step Four: How to eat/use your fuel (most important) NO SNACKING! Snacking destroys timing and circadian clocks that work in unison w ith Leptin Most will notice a change in cravings within 4-6 weeks Eat 3 meals a day initially (as your hunger and cravings fade you can adapt to 2 a day) Other DOs and DON Ts Do not work out before or after breakfast (if you must work out do it after 5pm) Do allow 4-5 hours between dinner and bedtime Trouble sleeping? Do 3-5 minutes of body weight exercises (i.e. pushups or squat s) Signs it s working: Change in your sweating pattern Energy levels will rise Hunger and cravings will become less and eventually disappear When you awaken you will feel refreshed and well rested Men: quicker weight loss Women: Mood changes (calmer/sleepy), then sleep will improve. Clothes will fit d ifferently and weight loss will occur if you continue the program *Note: When all signs are present, I recommend exercise with heavy weights Food Sources: For breakfast: Pastured/organic eggs; grass fed meat, poultry and fish; protein shakes (less ideal) Cooking oils when using carbs: (liberal amounts) butter, heavy cream, coconut oi l, or palm oil. Avoid nut or seed oils in initial stages. Cold Thermogenesis Easy Start Guide COLD THERMOGENESIS (CT) This should gradually be added to the Leptin Rx reset protocol (not everyone wil l need this). CT training should be done at sunrise or after dinner. CAUTION: If you have a serious health condition, please consult a medical doctor before beginning a CT regimen. Immediately stop treatment if you experience lig ht-headedness or a pale pink to white coloration of the skin. Cold Thermogenesis Benefits: Lower body fat Increase hormone levels

Reproductive fitness! Fertility Reverse diabetes Cut food cravings Kill fat permanently Strengthen adrenal function Fix thyroid disorder Super immune function Deep sleep Pain management Sense of well being and better attitude Cut visceral fat first Promote cessation of eating disorders BEFORE every CT session: Eat a high fat and/or protein meal Immediately drink 16-32oz of ice cold water. DO NOT drink more than 32oz. Face Dunking: What you need: skin thermometer, a timer, ice, and a bathroom sink or larger bow l. Remove make-up or facial products Get the water between 50-55 degrees Dunk your face into the ice water and hold as long as you can Record time and dunk again Continue for the next two weeks and work your way to using less breaths DO NOT let your skin temperature fall below 50-55 degrees Compression Shirt & Ice: Lay down flat on your back Place a 20-40 lbs block of ice on your torso (whilst wearing compression shirt) Try to extend your time 5 minutes a time until you get to 60 minutes You will notice your skin is pink to cherry read and numb in places If you can complete the 60 minutes- remove the compression shirt and place the bag of ice directly on the skin *Note: If you develop cold urticaria at this time, this is a sign you have high levels of tissue and serum omega six content. Stop the experiment and adjust you r diet until you have a blood omega six to three ratio that is below 10 to 1 usi ng a ketogenic paleolithic diet. When you can tolerate the skin being covered for one hour with pink to cherry re d skin you re now ready for the Cold Tub step! Full Body Immersion with Ice: Fill the bathtub with cold tap water Wear socks, gloves, and a knitted cap to keep the heat in your body Add 20 lbs of ice to chest and abdomen When your body is use to the ice you can remove the socks, gloves, and cap DO NOT let your skin temperature fall below 50-55 degrees Stay for 45 minutes Continue daily 2-5 times a week Full Body Immersion with NO Ice: Jump into a pool, lake, or hot tub from the neck down Stay for 10-20 minutes Pay attention to skin color

READERS SUMMARY: 1. How do I start?

2. What are the guidelines to remain mindful of? 3. The fuel is the food, but how you eat that fuel is more important 4. How does Leptin tie into the quilt survivability index? I have been asked by many to put a short post out about how I reverse Leptin res istance in my own clinic for my patients. After reading all of the comments lef t here, at MDA, and on Jimmy Moore s forum, I decided that it was a good idea. 1. First make sure you really are Leptin resistant (LR) to begin with. The easiest way to do this if you are heavy is to look in the mirror. If you re o verweight you definitely are Leptin resistant. If you still have a large appeti te and crave carbohydrates, especially at night, these are also signs that you a re likely Leptin resistant. If you are fit or in decent shape and not sure base d upon the above symptoms, I would tell you to go get a blood test and check you r reverse T3. It will be elevated. I also recommend simultaneously checking a salivary cortisol level. With LR, you will always see higher cortisol levels la ter in the day. 2. To regain Leptin Sensitivity (LS) follow a strict Paleolithic diet as outlin ed in The Paleo Solution by Robb Wolf or The Primal Blueprint by Mark Sisson. The type of fuel you eat is important in eliminating the foods that cause Leptin receptors to become nonfunctional. These two books clearly outline a solid ref erence point to achieve this. A. Try to eat as soon as possible upon rising in the morning, ideally within 30 minutes of waking. Make sure that breakfast has little to no carbs (less than 50 grams), and has a lot of protein and fat. I use as a general rule 50-75 gram s of protein with most patients. Some patients can use less and some need more. The key point of knowing how much is right for you is your hunger later in the day. If you remain ravenous throughout the day, you need to eat more protein i n the morning. If you can hold off eating until dinner you probably are at home ostasis for you. If you can skip both meals you likely are overdoing it at brea kfast. As for sources, I suggest pastured or organic eggs first, served with le ft over dinner scraps of grass fed meats, poultry, or fish. A third option, alth ough less ideal, would be whey protein or protein shakes. B. Try to limit carb intake to 25 grams if you are overweight by more than 30 lb s. If you are fit and have a small amount of weight to lose, (less than 30 lbs. ) you can titrate up your carb loads. Even then, I do not advocate potatoes or rice as some Paleo diets allow for. You will be able to eat them eventually, bu t try to avoid starches until you have mastered your cravings and hunger. Do no t count calories; it is not needed at this point. Any time I eat carbs I use li beral amounts of butter, heavy cream, coconut or palm oil. I do not recommend o ther oils initially such as olive oils or industrial seed oils. I would also av oid nut oils at the initial stages. My personal favorite is coconut oil because of the great metabolic effects of MCT, and how it helps heal the guts of LR fol ks. 3. How you eat your fuel is MORE IMPORTANT than any other factor, including the food itself. A. Never snack at all. This is meant initially and forever. Snacking complete ly stresses the liver s metabolism and is just not recommended. Your liver needs to re-learn how to use gluconeogenesis normally again when you are asleep and aw ake. Snacking just destroys the timing and circadian clocks that work in unison with Leptin. B. Try to eat three meals a day initially; but as your hunger and cravings fade you can adapt to two a day. C. Try to eat breakfast as early as possible from rising. D. Do not work out before or after breakfast. E. Try to allow 4-5 hours between dinners and sleep time.

F. If you decide to incorporate working out, do it after 5 PM. G. Within an hour of sunset try to make your surroundings as dark as possible. H. If you have trouble falling asleep I suggest 3-5 minutes of body weight exerc ises right before bed (pushups or air squats are fine, but avoid this if your ev ening cortisol is high). I. If you re inclined to, try becoming mindful when you first lay down. I use tr anscendental meditation techniques to help me clear my mind and concentrate on i mproving my thinking. (Optional; but this is awesome if your eveningcortisol is high). 4. Most people will notice a change in their cravings and hunger within 4-6 wee ks. Other changes I advise of my patients, is to supplement with prescription grade fish oils. The dose depends upon their HS CRP and salivary cortisol levels. 5. Signs that you are becoming Leptin Sensitive (LS) again A. Men will notice quick weight loss. B. Women will notice mood changes first (calmer/sleepy) and their sleep will imp rove. Their clothes will fit differently but weight may not change drastically initially because of effects on the pituitary. This will change too if they con tinue moving forward. C. You will notice a change in your sweating pattern. D. You will notice you have better recovery from exercise and your energy levels seem to have risen. E. Your hunger is gone and so are your cravings. F. When you awaken you will feel very refreshed like you slept well. Generally when the signs are all present, I then really push HIIT exercise with heavy weights. 6. (QUILT SURVIVABILITY) = (Total Energy Growth and immunity expense) X (RESOUR CES) X (efficiency) X (awareness of our environment). Stated in levee form where: Cell longevity = LS IGF-1 + immunity X Food Quality X leakiness of Mitochondria X environmental cues



The cold thermogenesis protocol should be added gradually to the Leptin Rx rest protocol. This blog post is additive to the Leptin Rx, and is an evolution exten sion of it for those who need it. I hope you all realize that not everyone will need it. Some will need it because they have special needs that they face. This blog is designed for those who have been previously left out of the reset protoc ol. Those people are gastric bypass patients, HCG users, those on exogenous ster oids, chronic pain patients, and those with T2D and metabolic syndrome, as a few examples.

Prolonged and controlled local peripheral skin cooling can induce selective damag e, and increased hypothalamic signaling by forcing adipocyte apoptosis and subseq uent loss of subcutaneous fat without damaging the overlying skin or the underly ing muscle layers. This means that acute cold cause rapid leptin sensitivity! I t means that fat is forced to liberate leptin from fat cells to slowly lower its serum levels as long as the cold stimulus is applied safely. This is new scien tific information that was first carried out in pigs in 2008, and subsequently t ested in humans and found to be quite effective for fat removal in certain selec ted areas of the body. Maintenance of a normal temperature and the normal variations of the circadian a nd lunar rhythms are achieved by changes in all physiological systems, one of th e most important of which is alteration in skin blood flow in humans. My versio n of cold thermogenesis for the Leptin Rx reset is the process where we generali ze these effects for the entire body s fat mass to force the brain to slowly rewir e in the hypothalamus to burn all excessive WAT by inducing the formation of BAT using cold alone. There is a way to force an epigenetic change to our DNA that opens a metabolic t rap door that humans rarely use these days. A cursory version was first popular ized by Ray Cronise in 2010, and by Tim Ferriss in 2011, but neither one of them took this process to its biological end point for permanent fat loss. I plan t o show this and a whole lot more. I have done an epic 18 month bio-hack on this very topic and plan to slowly release what I have found. I believe what I have found has profound and wide clinical applications for us all. Moreover, neither one of these men realized that the proper dietary forces might be used in combination with this process to dramatically produce different resu lts in humans when using cold. Cold is not just a fat loss tool. It has severa l other benefits to human physiology. I believe the reason for this is the hypo thalamic biology is not well appreciated by most scientists today. The permanent fat loss they both talked and wrote about is what I call the low ha nging fruit result of this process. When you sustain this process, steepen and e xpand the temperature gradient across a larger surface area, while specifically altering the macronutrient ratios, some other more amazing things become possibl e. None of these were covered well by Ferris or Cronise, but I call this proc ess Factor X. I will get into more of the biochemistry and where it can take us , later this year. For now, I want to share with you how cold thermogenesis can augment the Leptin Rx reset, and can make a huge difference to those with vagal nerve damage who do not get a large bang from my standard reset.

If you have a gastric bypass, T2D, chronic pain and are on narcotics, adrenal fa tigue, or poor sleep this addition will likely shock you at how well it helps yo u. NASA data from the 1970?s shows that fasted mammals cannot increase glucose turnover rate when cold adapted. They also cannot increase their muscle glucose uptake when exposed to cold environments. This is because the cold selects for an epigenetic program that enhances supplies of fatty acids and ketone bodies to active muscle contractions during exercise. I have tested this on myself for the last 18 months to look for all the pitfalls I could muster. I ended the epic bio hack on January 9th, 2012 with a very dra matic N-1 experiment designed to test some of the borders of this science that I have found has given my neurosurgical patients a huge metabolic advantage in ce rtain situations. Before you begin, you must make sure your cardiac risks are l ow and talk things over with your doctor and family. Most people will have no t rouble doing this at home.

Let us learn the best way to cold adapt for the Leptin Rx reset now


0. You first must choose what environment you want to cold adapt too. The physi cs of heat loss following cold water immersion dictate a more rapid drop in surf ace and core temperature than from exposure to a cold air environment. So, most people will choose to use water because it works a lot faster. Before you star t, always eat a high fat (MCT>saturated fats>MUFA s>PUFA s) and/or protein meal rig ht before you attempt to cold adapt. Also, drink 16-32 oz. of ice cold water immediately prior to the test no matter what stage you are at. Why you ask? Your body temperature is incredibly hot at approximately 98.6 degrees Fahrenheit, and ice water is approximately 40 degree s Fahrenheit. In order to maintain this homeostasis, your body has to bring that ice water up by about 60 degrees, and, by definition, it takes 1 calorie to rai se the temperature of 1 liter of water by approximately 2 degrees Fahrenheit. Th at means that to raise the temperature of 1 liter of ice water by 60 degrees Fah renheit, your body would burn about 30 calories. Two liters, which is about eigh t glasses of water, would burn 60 calories. Do not drink more than 32 oz of wat er before this test because cold adaptation also affects our thirst centers. Yo u should always consider drinking cold liquids as part of your dietary plan as i t can increase your metabolic rate by 30-40%. If you get a lot of brain freezes when you drink cold things this might signal you suffer with a high tissue omeg a six level. You need to proceed with caution while trying to apply cold thermo genesis. You will see why your omega 6 level matter soon.

I usually will do my training in the AM at sunrise or at night fall after dinner . I do not recommend trying this on an empty stomach. In the beginning of my a daptation, I also used Bitter Melon extract to cold adapt. The reason is that b itter melon appears to be quite effective at causing formation of BAT from WAT e specially in T2D or those with metabolic syndrome. No one knows why it really w orks. However, I believe it is has to do with the simultaneous loss of adiponect in and leptin from fat cells with the simultaneous induction of Irisin from the cold stimulus on the skin and subcutaneous fat.

1. Cold adaptation occurs fastest when you use a metal to help it along. It is a 100 times faster adaptation than it would be if air alone was the medium. Thi s is far too dangerous to use at home, so never try it. I have used it myself a nd on some volunteers but it needs to be very controlled in a clinical scenario. When you use water, it is 24 times more effective than using just cold air. T he easiest way to cold adapt is to place your face alone first in ice cold water as you monitor times. You must not use any makeup or facial products before yo u attempt this. You need a simple skin thermometer, ice, a bathroom sink and a watch with a timer. How does one cool the skin but not the core you ask?? Simpl y pay attention to your skin temperature as it goes from where it is at normally in your house and until it gets to 50-55 degrees while in your cold environment on your skin surface and maintain it there. Go no lower. How do I do this? Whe n you get there, watch your skin color when it begins to get to pale pink or whi te, it s going south of 50-55 degrees. End the session then. In the beginning your sessions will end faster than later because you re cold adapting. When I began this 18 months ago, I did a lot or reading on NASA astronauts, Spec ial Ops and Navy Seal training. I also looked to a lot of natural human experie nces with cold thermogenesis as well. The safest way to adapt to is to submerge

your face first into water in a sink where you add ice to with a cooking thermo meter. Wait until the water is between 50-55 degrees, and enter face first and see how long you can tolerate it using a time piece. Record the time. For the next two weeks work your way up until you need to take a breath for O2. The rat e of adaptation to this will vary for people. When you finish this proceed to n umber 2.

2. Buy a compression shirt that is quite tight and begin to place 20 or 40 lbs o f ice on your torso. Double bag the ice to stop leakage on clothing or furnitur e. Compression shirts collapse the surface capillaries and allow your skin temp eratures to fall faster than without wearing them. It sensitizes you quickly to cold. Initially, this will be tough to do, but you will adapt to it with time quickly. Try to extend your time 5 minutes a time until you get to 60 minutes. You will notice your skin is pink to cherry red and numb in places. When you g et to sixty minutes, then take the compression shirt off for further testing. P lace the direct plastic ice bags on your skin now, and repeat the skin cooling. If you develop cold urticaria at this time, this is a sign you have high levels of tissue and serum omega six content. Stop the experiment and adjust your die t until you have a blood omega six to three ratio that is below 10 to 1 using a ketogenic paleolithic diet. You can also test your serum for this as well if you choose. If you do not deve lop cold urticaria, proceed on to see how long you can tolerate the cold. Make sure you have no metal on your torso or ears or nose when you do this. Record y our times. Pay attention to your skin color. After ten minutes, you will notic e numbness and tingling present on these cold areas. As your times increase, yo u may notice numbness in areas adjacent to the ice develop, too. This usually o ccurs with longer exposures and with more surface area covered to your skin. Th e length of time you expose yourself should be matched to your BMI. The fatter you are, the longer your exposure should be. You want your skin to always remai n pink to cherry red when you are doing this. If it gets white you need to stop the test and take a warm shower. Do these things indoors initially where you c an control the air temperature during adaptation. Do not start this outside unt il you cold adapt for at least a month. When you can tolerate the skin being co vered for one hour with pink to cherry red skin, you re now ready for the Cold Tub step.

3. Once you complete Step 2, you can try cold showers to ready your body for imm ersion, but I did not use this much when I was training my brain to rewire. I w ent straight to the bath tub and filled it with cold tap water. With immersion, the major heat exchange in water occurs by means of conduction with the surroun ding water. The exceptions to this are the non immersed body parts, in most case s the head. The head can represent a significant site of heat loss to the enviro nment owing to its minimal insulation (small fat layers), and lack of vasoconstr iction in the scalp. I then proceed to add twenty pounds of ice to my chest and abdomen region while my body is in the tub. Initially, I kept my socks and gloves on my extremities , and I also wore a knitted cap to my head. This was all to combat the vasocons triction that normally will occur in extremities. The hat was to keep in heat f rom the veins of the scalp to allow for an adaptation to immersion. This step w ill take you some time to get used too. You lose 20-40% more heat from cerebral blood shunting when you cool adapt. After I was adapted to 20 lbs of ice (abou t 5-7 days), then I removed socks, gloves, and head cap. If you get lightheaded , this means you re not ready for the tub. Abort the tub and go back to dunking y our face in the cold water. If you can handle the 20 pounds of ice, you can inc

rease it ten pounds of ice at a time to cover more of your body with icy water. If you have access to skin thermometers (I did) that an anesthesiologist would normally use during a surgery, the key thing you are looking to do is get your s kin surface temp to 50-55 degrees. You can buy these online now too, I was told by a patient. I have no idea where he got them. We are trying to use the peri pheral nervous system s cold receptors in the skin to tell the brain something has radically changed in our current environment. After you can get past 45 minute s of this, you will notice your tolerance to cold dramatically changes in water, air, and in ice. You will be able to wear less clothing and go outside and not be cold. In fact, you may notice your temperature rises in anticipation of the cold tub. I do this now all the time. You will be able to drive on the highwa y with the windows down in the dead of the winter and feel amazing. Your signif icant other will notice you seem to radiate heat at rest when you lay down to sl eep. The longer you tolerate this situation, the better adaptations you will ge t. The extent of the training depends upon your goal. For this blog, we are co ncerned only about weight loss. So I will limit this discussion to this adaptat ion alone. However, there are many others.

4. At 45 minutes, you can choose to stop and then plan on doing this 2-5 times a week depending upon your starting weight, BF %, and what your goals are. You a lso need to be cognizant of where you want to lose the fat on your body. If you have it in your belly, butt, or legs, continue using the indoor tub or outdoor lake, or pool. Immersion is the best way to shred body fat and regain LS. Once you can accomplish this in your house for one month, you can than move to the o utdoors if you would like. If you have a pool, lake, or hot tub you can set its temp lower to replace the ice use. I tend to use the lake or my hot tub, but I use them differently. When I want a quick training to maintain my adaptation, I just jump into the lake for a 10-20 minutes from my neck down. I pay attentio n to my skin color as I do this. The hardest part is emerging from the lake and walking back to the house and not being in the water. It is easier now for me, but in the beginning it was tough. Most of the time presently, I use my hot tu b to train. I get in it and I cold adapt my upper body with ice bags on my tors o, while my bottom half is submerged in the water. I alter the water temperatur es to higher than my torso, because I have very little fat on this part of lower parts of my body today. So, often I will sit in warmer water while my upper ha lf is completely exposed to the elements with ice on my chest and abdomen. It i s very effective at lowering your surface temperatures to 50-55 degrees in 2-3 m inutes. This augments thermogenesis naturally using convection currents of diff erent temperatures. Here, I am using Fournier s Law. In heat transfer, conductio n (or heat conduction) is a mode of transfer of energy within and between bodies of matter, due to a temperature gradient between the hot tub my body, and the c old air and ice on my skin. I can do this for amazing lengths of time now, afte r 18 months of training. Do not try to bit off more than you can chew. Heat sp ontaneously tends to flows from a body at a higher temperature to a body at a lo wer temperature. A warmer lower body and a 50 degree skin temperature on the tor so create a dynamic that makes using cold thermogenesis really easy daily. Anyo ne who as soaked in a volcanic geothermal spring can tell you they hardly notice the cold on their exposed bodies unless they see the piloerection of the skin a nd hairs, their pink skin, or the sub clinical shivering of the underlying muscl es. This method is really effective at increasing thermogenesis in the exposed areas for fat loss. If you have a lot of belly fat, this is not your best metho d, but it will still work. If you have torso, back, facial, neck fat (sleep apn ea) this works like a charm quickly.

5. You burn a lot more calories when it s cold outside, so you MUST get outside in cold and try not to wear a ton of clothing as you adapt. In the beginning, most

wear a ton of clothing when they go outside in cold weather. That slows adapta tion to cold. According to Andrew J. Young, Ph.D., of the U.S. Army Research In stitute of Environmental Medicine in Natick, Mass., There are two factors that co uld cause energy expenditure to increase with falling outdoor temperature. First , if shivering is elicited by cold, then energy expenditure increases. However, different people have differing shivering-response sensitivity, and intensity of shivering will be influenced by magnitude of decrease in body (deep core and sk in) temperature, which in turn is influenced by body size and fat content that v ary widely among people, as well as clothing worn. So some folks don t shiver at a ll (too warmly dressed, excessive body fat, LR), and a man in the cold is not al ways a cold man. The more LR one is the more you should consider a steeper slope of adaptation to lose fat. The other reason energy expenditure might increase in cold weather is if you per form heavy physical labor like weight lifting (walking in deep snow). Additional ly, there is a likelihood that you could have a slight increase in calorie burn (about 3 to 7 percent) from your body re-warming itself from cold air touching y our skin and warming the cold air that goes into your lungs. This is also why w hen I emerge from my cold tub, lake or ice baths, I will remain outside in the b uff for several minutes to really heighten the cold stimulus. I immediately go inside to a warm terrycloth robe, which captures my thermal loss and actually in creases by caloric burn for about an hour after the cooling. This is a great ti me to work out as well. You will also notice your ability to lift and workout i ncreases by 5-10%. Recovery is simply stunning. You won t believe what a cold tu b does after a serious high intensity work out. Your recovery will amaze you, a nd you sleep will be shockingly solid. Nothing is better to induce sleep in my view than cold thermogenesis induction. The beauty of this adaptation is that is does not require any change to your cor e temps. When you begin to mess with your core temps you can get into trouble w ith frostbite and freezing injury. The higher your omega six content, the worse cold adapted you will be. The higher your omega three content is, the better y ou will adapt to cold. The higher protein/fat intake you have, the slower you w ill adapt to cold. The more carbs your have in diet (LR), the easier you will f ind it to adapt to cold. If you have a history of smoking, dipping, cigar use yo u will not cold adapt well. If you are dehydrated (booze/wine) you will not col d adapt fast either.

6. If you use just air to adapt to cold thermogenesis it will take a lot longer, but there is one thing I should mention to you. Try to slowly remove clothing as you proceed over time. As you remove clothing, there is a specific way you s hould pick the clothes to remove. You want to expose your face and head to cold as soon as possible. Remember when in number 1 we begin cold water adaptation with our face? This is because all mammals have a reflex called a dive reflex t hat is built in because we all were formed in a fluid filled placenta. When we e xpose ourselves to cold on our face first, we stimulate slowing of our heart rat e. This is soon followed by vasoconstriction of blood flow in our extremities. When we continue to dive deep (think about dive in the movie the Abyss) we force blood and water to pass through our organs and endothelium to fill our air fill ed cavities like our chest. This has been experimentally shown even in humans w ith deep water cold dives in adults. We actually drown in pulmonary fluids but we can still survive! As a physician, I see this problem clinically daily in ou r ICU s in patients with ARDS. Sadly, we do not treat them as I think we should, given what we know about the mammalian dive reflex but that is another blog. Do not worry, I do not plan to use this adaptation in my reset in the near future! I d love to try it but I hear it takes years to perfect from my research on it. When you first begin cold training with clothing on, when you re-enter a warm en

vironment the way you disrobe also matters for the adaptation to become more com fortable and less agonizing. So first expose your face, then your head to the w arm environment. Then expose your extremities to re establish the blood flow and lastly your torso and abdomen. If I am wearing clothing in liquid when I am in cold water, I do the same thing. This progression of re-exposure to the warm e nvironment from the cold will make it more bearable as time progresses. If you remove clothing in a different layered fashion, you can abruptly increase cortis ol release to cause a vascular instability. This instability is felt to be behi nd a thermal dump that underpins vascular reperfusion injuries seen in frostbite and hypothermia injuries. If you are not overheated by heavy clothing or your warming environment, the cold (when other symptoms are warm) will trigger non-sh ivering thermogenesis to be induced and you will continue to burn calories as fr ee heat for many hours after the cold exposure. This is why people who are in c old environments tend to be quite thin when they are eating a non Western diet. You will also notice a change in your hunger and appetite, because they will de cline. This addition is also quite beneficial to those with binge eating disord ers too.

The metabolic programs that underpin all these adaptations will blow your mind w hen I lay them all out this year. I believe that cold thermogenesis is an evolu tionary forerunner for all mammalian physiology before exercise was evolved or n aturally selected for in mammals. This is a controversial point, but I think bas ed upon what we know to be true today it s not a fringe theory. The available food sources also helped simultaneously sculpt evolutionary pressures that were natu rally selected for in a cold environment. I believe natural exercise was select ed for movements to warmer environments, longer light cycles, and more abundant carbohydrates in the environment. Mammals did not first evolve predominately in warm environments. Humans certainly might have evolved this way, but we are de scended from these eutherian mammals and their epigenetic programs remain burie d within us but are just not selected for these days. When we do induce the pro grams, what this may mean for us today is among the most exciting things in biol ogy I have come across in 30 years. It appears cold thermogenesis not only open s a novel metabolic pathway in modern mammals and humans, but it also activates our longevity genes epigenetically. Many of the things aging researchers and sc ientist currently hold to as core beliefs may in fact not be true. The ability to test these theories is now here because of how we are unfolding the story of our own biology using a piece by piece approach that the QUILT provides.

I think evolution sculpted all mammalian life using cold to naturally select for a specific diet that combined for longevity and certain behaviors for optimal l iving in our world. Today, those factors have been buried in modern mammals by the newer environmental changes that have preferentially selected for new epigen etic traits. Yet when the environment calls for this program,we can use it to o ur full advantage to do many special things.

Consider this a 26.2 mile marathon burns 2600 calories. My three hour training ses sion I did this AM burned 3800 calories. The cold effect on weight loss is grea t, but what has me more excited is which form of exercise do you think might har m me more long term? One thought might just alter your DNA!

A document that will evolve as science eliminates past dogma This document is a compilation of three decades of thought secretions on medicine as a science and an art form. Healing is not axiomatic, yet you would never know that if you opened a new textbook or current journal. Medicine today is all abo ut evidence-based findings. Evidence-based medicine is a great idea if the under lying dogma is based upon undeniably true facts . I think you will find that I d o not accept many of the foundations that evidence-based medicine now currently rests upon. For me, biochemistry or physiology are absolute certainties about ho w humans work. Practice standards are based upon prevailing opinion. For example , evidence-based medicine believes that everyone with total cholesterol over 200 should be treated with a statin medication. After many years of studying this, I realize that we may need to question that kind of advice. The science that is published and in the media today is not based upon truths like biochemistry or p hysiology are. Sadly, evidence-based medicine founded on data paid for by a corp oration or branch of government is subject to the influence of many biases. Seve ral years ago I read an article in The Atlantic titled Lies, Damned Lies, and Med ical Science that changed my thoughts on this. Shortly after, I read Good Calories and Bad Calories by Gary Taubes which confirmed much of what my intuition was te lling me. What I saw, and was doing as a surgeon, often felt incongruent to what the reality was for the patient. Many good doctors practice medicine today. I h onestly believe that they think they are doing good work. I know this because I was one of them. I thought everything I was taught was based upon solid scientif ic facts. I allowed my medical and dental educators the intellectual leeway of t rusting the facts they told me. Good intentions, however, are not congruent with longevity nor with health. Good doctors were a dime a dozen, I found out; howev er, great doctors were few and far between. I no longer wanted to be good; I wan ted to be great. To be great you have to reject being just good. That was my ini tial thought after reading the Atlantic article. Yet the current system rewards only good doctors. This document will help you, the reader, differentiate betwee n the great healers and the good ones. Your life actually depends upon it, so I strongly suggest you begin to think as you read. Today, medicine is dominated by doctrine and dogma that caused us some serious m issteps in thinking. These missteps have made us advocate for treatments, behavi ors, and thoughts that have become ingrained within our society. With science, t he truth always updates itself. Moreover, one must realize that every mile that puts us in the wrong direction will require us to walk two miles back just to re turn us to square one and a new beginning. This document is not about our species becoming successful in creating a new gen eration; it is about making current humans all they can become with respect to t he aging cell and where they are now. It is about increasing our life span while we simultaneously expand our health span. I suspect we are going to explore sub jects in the future that none of us are thinking about now, because that is the nature of science. Living long without intervention of conventional medicine is the goal. Pointing out the good and bad in medical care will also be helpful to the lay person and healer alike. We should begin to rely on our physicians to gu ide us to pathways that attain that goal. I believe that my profession will evol ve into taking care of healthy humans, and leave behind the old paradigm of tryi ng to repair people after they have already been damaged by disease. I believe this expertise will become the currency of the new paradigm, and I bel ieve the change will be an obstacle course for many. Patients already know that we do not know everything just ask them. But I believe we lose our credibility w hen we do not act congruently with the knowns of biochemistry and physiology. We cannot use treatment algorithms that promote data sets that are not factual or are incredibly flawed. We have all read what has been said by the medical and nu tritional gurus about the current beliefs on diet yet we have the world s worst wei

ght problem and a massive public health dilemma. Maybe we need to stop making ex cuses for what we believe to be true, and understand what really is true regardl ess of the implications it draws. Accepting the proposition that randomized control trial (RCT) is the golden goos e of research has given my profession a slow steady decline in reputation. It is not because a RCT is a bad thing. It is the best thing we have if it s based upon real facts. Therein lies our real problem. When the underlying science is fault y, the randomized trials become worthless. Do we need a RCT to tell us that a po tassium level of 4.0 is good? No we do not. Do we need a RCT to tell us that a p otassium level of 3.1 is bad and requires treatment? No we do not. The current t hinking in medicine is that we need a RCT for everything we do. This is not true if we practice using the biochemistry and physiology found in humans. We can no longer allow a drug company to tell us that a cholesterol level of 200 is bad w hen it is not. That is a great opinion when you are selling a statin, for sure. But if it was good for humans then why is heart disease still the number one kil ler in the US after 50 years of actively lowering LDL cholesterol? At some point you must ask this question if you are a patient or a doctor. We will not need to have the support of big pharma or medical implant companies to run trials because our focus will be on promoting health longevity and not tr eating disease. The transition of the healthcare economy is already occurring. I ndustry has a vested interest in treating sick people and not the healthy. Patie nts want to be healthy, but struggle to find physicians or insurance coverage wh o offer those services. Our government makes it easy for the current paradigm to exist, because they advocate for agriculture policy that makes us ill with diet s laden with omega 6 fats, fructose, and grains. It s because processed food stuff s can be stored and shipped to economically feed the world population. They are not doctors or researchers so they can t know unless we tell them. But they also a re now beginning to feel the pain of that decision which is continued currently by their incongruity in intellect. The current healthcare crisis is ground zero for this epic battle to be fought. Instead of focusing on what I cannot do, (i.e. change Washington, DC thinking), I will instead focus my attention on what I can achieve and teach the public on remaining healthy so they can cure themselves. So we need to start that trend to gether. This is what my blog is about. My primary weapon in this battle is thinking. The greatest of humans are deep th inkers. Show me a success and I will show you a thinker. A human is the only ani mal that can actually change its DNA just by thinking. Moreover, thinking is jus t a biologic secretion. No different than any hormone released by the pituitary gland. Thinking is a meme that hijacks our brains chemistry. Any thought can alte r our genetic and biologic purpose in life. Yes, thinking well or badly becomes a vector that changes us all in some fashion. This thought experiment occurs dai ly in our country on myriad mediums of media. In fact, I believe it is the one t hing that is speeding up the evolutionary pressures that we currently face. I th ink it is a real problem behind many health issues we will explore in the docume nt. The pathways I have identified over my thirty years in healthcare I call Longevit y Levees. Remember that a levee is a protective barrier from flooding and devasta tion. These levees are biologic protectors of our cellular machinery. My goal is to share it with the public and my colleagues. As new data emerges, blogs will be added to the quilt by me and I ll bet by you. This document should be a collabo rative effort. The longevity levees are as follows and in order of importance. Each one of these will be expanded upon in blog form. I will attempt to go throu gh each one until I begin assembling the quilt in other dimensions. The quilt wi ll link together in hypertext format to allow ease of navigation. I am open to c

omments and suggestion to make this platform to your liking but I will remove an d edit comments I think our counterproductive to the goal of the levee. I hope y ou enjoy and that we can stimulate some thinking. DETAILED LEVEE DISCUSSIONS Levee 1: Current cellular homeostasis determines cellular fates all of the time. This is the cornerstone of my theory of longevity. We must stop focusing in on disease s tates and instead think about what happens to the cell s environment that dictates its fate. The cellular terroir are what cause the disease states. This is my ce llular theory of relativity. My theory of aging is that the environment the cell finds itself in is directly proportional to outcomes the cell may face. In my mind, these levees will uncover a new paradigm that requires the patient and physician to forget about the disease states and think first about the normal c ell. This theory will require you, the reader, to embrace paradox and ambiguity at every turn. Levee 2: Leptin sensitivity and resistance determines all energy balance. This levee is all about energy. No life can sustain itself without controlling energy metaboli sm. A body without energy is called a cadaver! Leptin is a hormone secreted by f at that signals the hypothalamus as to what the 20 trillion cells in our body ne ed. Leptin is obtained through breast milk at birth. This immediately loads the hypothalamus with data, much like a disk drive with a PowerPoint presentation on it would do for your laptop. Leptin receptors are very specific in how they wor k, and they are found concentrated in the lateral hypothalamus. This hormone reg ulates all aspects of energy metabolism, hormonal status, fecundity, and eventua l cellular generation. Simply put, the leptin axis is akin to the relationship t he sun and plants have in energy generation. Plants use sunlight to convert carb on dioxide and water into sugar which supports their life via energy generation. Photosynthesis is effective for plant life but it may not have been an efficien t mechanism to support animal ascent in the evolutionary development to humans. To continue to allow complexity of life, evolution had to come up with a new mec hanism of energy metabolism and a way to control it. It incorporated the plant-l ike mitochondria into a cell and modified it to generate energy. It appears that quantum biology is critical to this step based upon recent scientific developme nts. The amount of energy generation was quite impressive and this gave life the power to eventually evolve into complex organisms like humans. Leptin controls all of this machinery of energy generation for humans. It is our photosynthesis. The sun still plays a huge role in oxidative phosphorylation. S leep plays an enormous role in here as well. Sunlight and leptin signals remain tied together by the hypocretin neurons in the lateral hypothalamus of the brain . Both hypocretin neurons and leptin neurons are small in number and found in fe w areas of the mammalian brain. Humans have only 50,000 hypocretin neurons in th eir brains. Mice have but 3,000. Moreover, these neuronal tracts appears very ne w in evolutionary times. And, because of that newness, they are subject to signali ng errors, receptor single nucleotide polymorphisms (SNP s) and errors, neuropepti de modification, and out of sequence firing due to signaling issues at many step s. So, in humans, it appears obesity has many causes and features that confuse r esearchers. This levee will have many blogs pointing out the various forms obesi ty can take due to problems in this system of control. To fully understand the g ravity of this hormone, consider this analogy: What would happen to life on eart h if, all at once, we eliminated all coal, oil, nuclear fuel, and all sunlight f rom our planet? I believe life would surely be changed dramatically and quickly. When leptin is not working correctly this is precisely the fate the cell has to

deal with and it can dramatically alter how the cell or organ system responds w hen fuel demands cannot pace needs. Levee 3: Cellular inflammation is critical. It is akin to the fire in a burning house. Th e more of it your cell possesses, the more chance bad outcomes will come to the cell. Cellular inflammation comes in many different forms. It tends to flow down in certain biochemical pathways and cause havoc. (link) It also now appears tha t inflammation is the base cause of obesity, diseases of aging, and the cause of cellular death. There are many pathways it uses to achieve this signaling and t his part of The Quilt will delve into matters more deeply and show how they tie concepts together that lead to problems we humans face as we live our lives. Levee 4: Dietary principles of longevity. We have already seen that energy metabolism is critical to life and why Leptin holds position two in The Quilt. This levee conc erns itself with the substrates that give us that energy. We will explore the di et we eat, the energy that comes from it, and nutrition optimization. Humans hav e adapted to many environments on Earth but this levee is not concerned about wh at we can do in adaptation; rather it is about how long we can live in our own c urrent dietary edicts. The key principles here will be eating to satisfy the tru e facts and not the opinions of the day. Our biochemistry and physiology have be en carved by millions of years of natural selection and have not failed us yet. It is now becoming clear that biologic systems have for many millions of years u sed quantum mechanics to do some of the amazing things animals can do. It appear s energy generation is one of them. We will explore quantum biology in this leve e many times over the next few years to open the discussion of this brand new fr ontier. The foundational cornerstones of this levee will be limitation of inflammation, low levels of omega 6 foodstuffs, limited fructose, limited carbohydrate intake, concentration of omega 3 laden protein sources, limited uses of foods known to cause nutrient depletion or nutrient loss in the gut. The balance of this levee will have many blogs tied to the nuances of paleolithic eating and whether micro or macro nutrient issues should dominate or not. The key points here will be ho w foods affect telomere lengths and what the research is pointing to, and how fo od may affect quantum biology. Levee 5: The Brain Gut axis is critical to organizational health. The major route into an d out of the human body is via the gut. The brain senses this axis before food e ven touches the palate via the five senses. When food touches any part of the to ngue, signals are immediately made on leptin receptors on the tongue to begin di gestion and assess the dietary values of what we are eating to see how it will a ffect our energy balance. Almost the entire gut is innervated by one cranial ner ve, called the vagus nerve, that provides this feedback. The vagus nerve is extr emely specialized and carries many special fibers to and from the brain and its targets. It originates in the floor of the fourth ventricle of the brainstem and covers every cell down to the transverse mesocolon of the large intestine to gi ve the brain constant feedback on the energy coming into the animal. The increti n system is monitored directly by this nerve. If this axis is disturbed in the t ime it takes for food to pass through, or in the integrity of its lining, it can have drastic effects upon energy utilization. In some cases it can open the blo od-brain barrier to direct assault and cause fatal brain damage quite quickly. T he immune system plays a monster role in regulation of this levee and the autono mic nervous system has over a billion cells in the wall of the gut to monitor pr ogress of how this axis continues to function as the human ages. If this axis fa

ils in some fashion, disease usually follows quickly thereafter. Major diseases like MS, ALS and autism are affected by this axis, as are the neurodegenerative disorders. Depression and Alzheimer s also are greatly affected by a defect in thi s axis. IBS and Crohn s disease are common diseases that cause massive leaky gut s cenarios. A disease I treat as a neurosurgeon also plays a role in this levee: c erebral aneursymal rupture and the development of vasospasm. To date, no theory in neurosurgery has been able to find the cause of this deadly phenomena. My the ories point to the leaky gut as the conduit to it rise. Levee 6: Immunity affects regulation. This levee is critical because it is the major prot ective arm of the body. It contains two major parts, cell mediated immunity and humoral immunity. We will delve into both of these systems to show you how they are imperative for protection of organ systems, integrating development of the o rganism as it grows from a fetus to an adult, and how the system adapts to patho gens it faces as it grows and ages. Moreover, this system has so much complexity that is can also be turned back upon itself and cause huge issues for the organ ism with autoimmune diseases. These can wreak havoc and cause early death and di sease if not kept in check. This system works in tight balance and is built with many redundancies to protect from malfunction but it does happen if the cell fa ces the wrong environments with a mismatch. Examples would be the effect of HIV on cell mediated immunity, the lack of a functioning brain-gut axis, graft versu s host disease, molecular mimicry, low vitamin D levels, or failures of the comp lement system in humoral immune response. Levee 7: ROS generation. ROS stands for Reactive Oxygen Species generation. We all know l ife is based upon energy production from the use of oxygen. This process is call ed oxidative phosphorylation. Examples of ROS include oxygen ions and peroxides. Oxygen species are highly reactive due to the presence of unpaired outer shell electrons. ROS forms as a natural byproduct of the normal metabolism of oxygen a nd has important roles in cell signaling and homeostasis. This process occurs in the mitochondria. When we generate energy packages, adenosine triphosphate (ATP ), from nutrients, we also generate free radicals of oxygen that leak from the c ytochromes of our mitochondria. Cytochromes are the furnaces in mitochondria whe re ATP is made. This leakiness is critical to life and to the death programs insid e our cell. The more leaky our mitochondria the more ROS we generate. Generally RO S is a bad omen for the cell but it can also signal the cell to lengthen its tel omeres at times or to recruit the formation of new mitochondria to make energy. ROS generation is a measure of cellular stress, and that stress can be so great that is can damage cellular structures so that they no longer work properly. Exa mples are UV exposure or radiation exposure. In general, lower ROS is better for longevity of the cell and for it to function optimally. A simple example of this fact is coenzyme Q10. Most people have hear d of this cofactor, and this protein is used up to a great degree when you are m aking energy or the cell is stressed. Statin drugs cause depletion of this prote in because of their mode of action on enzymes in blocking the building blocks of cholesterol, so they cause the cell to be more inefficient making energy as the CoEnQ10 is depleted. It is also used up when we are under stress due to long te rm insulin or cortisol secretion. Depletion of CoEq10 is why people can get cogn itive change and muscle cramping when they are on statins too long or the dose b ecomes too high. The cause is because the cells in that part of the body can t mak e the energy they require because of the side effect of the drug. Therefore many patients are told to add CoEnQ10 to their supplement list daily if they are on a statin. Levee 8:

ALE s. ALEs are short for advanced lipoxidation end-products. These are proteins t hat are modified in our body after we assimilate the nutrient and they become ha rmful to us. Most of us know about AGEs advanced glycation products from excessi ve sugar intake. Estimates have put the oxidative stress of ALE s at four to six t imes as great as AGEs. Clearly, both are bad and our levee will deal with how to limit the collateral damage of ALEs. These proteins are made from PUFAs (polyun saturated fats) and become malondialdehyde (MDA for short). MDA is a biomarker f or ALE stress in the cell. Malonaldehyde reacts with deoxyadenosine and deoxygua nosine in DNA, forming DNA adducts, the primary one being M1G, which is mutageni c. The guanidine group of arginine residues condense with MDA to give 2-aminopyr imidines. MDA plays a big role in the development of keratoconus in the eyes or osteoarthritis of the joints of the body. One clinical measure we use of ALE tox icity in the body is presence of skin tags in folds of the skin. This finding se ems to correlate with the omega 6/3 ratio in plasma. Generally we want a diet th at approaches a 1 to 1 balance of omega 6 (PUFA) to omega 3 fats but in the stan dard American diet (SAD) that ratio can be up to 40 to 1 with heavy intake of pr ocessed foods. This is the reason we have seen tremendous increases in orthopedi c joint replacement and degenerative spinal conditions in the American populatio n. I believe it is a great contributing factor to the tremendous increases we ha ve seen in osteoporosis and metabolic bone disease caused by hormonal disruption of bone metabolism. It leads to damage and early aging of all tissues. ALEs als o generate carboxymethyllysine (CML). These can be seen in foods with added asco rbate and PUFA enrichments, such as salad dressings and Similac. Many baked whea t products are particularly prone to CML formation. Since I am a clinician who t reats neurodegenerative diseases and complex spine conditions, this levee will c ontain many entries over the years. Moreover, it will be the levee that stimulat es me to write a book about my thoughts on spine disease in the modern world Levee 9: AGEs. AGEs stands for Advanced Glycation Products. This is the levee that concer ns itself with how high levels of sugars we intake cause disease. The disease pr ocess is mediated through a receptor system. Activation of the receptor for adva nced glycation end products (RAGE) by its specific ligand N(epsilon)-carboxymeth yllysine (CML) results in the activation of NF-kappaB (the 911 system for the ce ll) and the production of proinflammatory cytokines. This is the mechanism of ho w degenerative disease begins and progresses. Moreover, it is now clear that thi s process feeds forward if the stressor is present chronically, as it is in diab etes. For the lay person, a good way to understand what glycation by glucose, su crose, or fructose does to our organs and proteins over time is to think of this analogy: Imagine pouring maple syrup on your granite counter top and leaving it there for three months then trying to remove it on month four. It becomes rock hard and does not allow you to use the counter top like it was designed to. That is what an AGE does. Limiting AGE generation is a clear levee of protection and we will examine many areas here for study and prevention. Damage by AGEs is com mon in diabetic neuropathy, Alzheimer s, high blood pressure, stroke, atherosclero sis, osteopenia, and generation of epithelial cancers. Levee 10: Mitochondrial Signaling is Pleotrophic and adaptable. Pleotrophic means the pro cess can move in multiple directions both good and bad in this context depending o n the amount of cellular stress. We have already seen examples in cellular stres sors in the above levees. Mitochondria are the cells power plant to make energy. Cells use ATP (adenosine triphosphate) generated from multiple pathways of bioch emistry as their fuel. Mitochondrial signaling is a pathway of communication fro m mitochondria to the nucleus and cytoplasm of a cell that influences many cellu lar and organismal activities under both normal and pathophysiological condition s. In animal cells, retrograde signaling is linked to mTOR signaling, which dire

ctly affects the cells next biologic step in its life. In mammalian cells, mitoc hondrial dysfunction sets off signaling cascades through altered Calcium concent ration reactions, which activate factors such as NF?B, NFAT, and ATF. Retrograde signaling also induces invasive behavior in otherwise non-tumorigenic cells, im plying a role in tumor progression. Anterograde signaling appears to be signific ant in mitochondrial biogenesis and in activation of telomerase to lengthen the cell s telomeres to allow it to divide and the tissue to live longer. This levee h as many unknowns but is vitally important to understanding how we avoid disease and live longer. It should be clear to any reader that life, healthy or not, is all about energy generation and utilization. The mitochondria are the engine wit hin our Ferrari and we need to keep that engine working efficiently if we are to remain fit. Levee 11: mTOR pathway is life or death. We just mentioned mTOR in levee 10. I did not de scribe it because it is a levee by itself. mTOR stands for mammalian target of r apamycin pathway. This pathway is a giant factor for the cell. Signaling through mTOR is activated by amino acids, insulin, and growth factors, and impaired by nutrient or energy deficiency. mTOR plays key roles in cell physiology and disea se states. mTOR regulates numerous components involved in protein synthesis, inc luding initiation and elongation factors, and the biogenesis of ribosomes themse lves. Oncogenesis uses mTOR pathways to make parts for the immortal cell when mT OR is biochemically linked to phosphatidylinositide 3-kinase (PI3K)-AKT. Insulin and leptin play huge roles in PI3K as well. Strategies are being developed and used now involving horizontal and vertical blockade of the pathway, as well as t he use of biomarkers to select appropriate patients for certain treatments. More over, this pathway is being used to provide proof of target modulation. Curcumin , cacao chocolate, and ECCG have been found to give some of their clinical effec ts by interrupting this pathway. The mTOR pathway integrates signals from nutrients, energy status and growth fac tors to regulate many processes, including autophagy, ribosome biogenesis and me tabolism. The pathway has two major components call Rictor and Raptor. Rictor is involved in protein protein interactions and is not as well conserved in all anim als as is Raptor. Ironically, Rictor is also not blocked by Rapamycin either. Th e rapamycin-insensitive rictor mTOR pathway regulates Akt/PKB, PKCa, Rho/Rac to co ntrol cell survival, proliferation, metabolism and the cytoskeleton. Raptor comp lex of mTOR is highly conserved in animals and is blocked by Rapamyin. Raptor is a cellular kinase protein that has wide ranging effects. Long term research has shown that raptor mTOR positively regulates cell growth and that its inhibition causes a large decrease in cell size. The mitochondria signal through mTOR rapt or directly. This pathway is worked out fully and can be seen in most biochemist ry textbooks today. Most research has focused on Rictor and Raptor inhibitors bu t it s a pathway that has vexed scientists. Most recently, research in this pathwa y has focused on the dual nature of mTOR that is integrated by the mTOR complex 1 and complex 2. These two complexes are formed and regulated by different prote ins and are also driven by multiple different compensatory feedback loops making understanding them very complex. Levee 12: PPAR gamma is the confluent gate. PPAR (peroxisome proliferator-activated recep tor) gamma is regarded as the master regulator of the adipocyte and of lipid met abolism in the cell. It is under the direct control of leptin and its receptors. There are three total PPAR, alpha, delta and gamma. PPAR gamma are nuclear prot eins that function as transcription factors regulating gene expression from all aspects of dietary metabolism. PPAR gamma s role is essential in cellular prolifer ation, energy generation, cellular differentiation, and tumorogenesis. ? (gamma) although transcribed by the same gene, this PPAR through alternative s

plicing is expressed in three forms: ?1 expressed in virtually all tissues, including heart, muscle, colon, kidney, p ancreas, and spleen ?2 expressed mainly in adipose tissue (30 amino acids longer) ?3 expressed in macrophages, large intestine, and white adipose tissue. So why do I call this the confluent gate? Because all metabolism goes through t his path to directly affect DNA activity. This is precisely how epigenetics occu rs. Diet directly affects our DNA function. All PPARs heterodimerize with the retinoid X receptor (RXR) and bind to specific regions on the DNA of target genes. Lipids transformed into free fatty acids (F FA s) play a huge role in the physiologic function of PPAR gamma. Endogenous ligan ds for the PPARs include free fatty acids and eicosanoids. PPAR? is activated by PGJ2 (a prostaglandin). Levee 13: Defective signaling responses can wreck havoc. All cellular homeostasis is based upon this principle. If you have no control over the systems that govern how a cell works, then you have chaos. Cancer in my way of thinking is a complete los s of signaling. The most vital signal in a cell is that of energy homeostasis. T his is dominated by leptin sensitivity. If one is leptin resistant there is no w ay to control cellular biology and disease processes begin. This levee is acts m uch like a conductor does over an orchestra. If we look at the New York Symphony ensemble individually we all know they are expert musicians and can play extrao rdinarily well independently. But it is the conductor who brings these 300 music ians together and coordinates their activities so well that the music sounds mag ical. Now think about what the music would sound like if there were no direction . The trombones and flutes would no longer be synched to the drums or violins. I n essence we would have noise, not music. This is what a lack of signaling can d o to the cell. Bad signaling can cause cell death, cell senescence, diabetes, ne uro degenerations, autoimmunity, or cancer. Understanding how to maximize this l evee is a study in maintenance of your cellular machinery to make sure it functi ons long term. Levee 14: Epigenetic modifications is quick and dynamic. We saw in the PPAR gamma levee t hat dietary forces can force immediate gene transcription on the cell in questio n. Not only does diet induce immediate changes in DNA activation but so does the organism s hormonal status. Moreover, humans are the only animals that can induce DNA changes just by the way we think. We know that DNA activation occurs with t houghts from functional MRI data and PET scans on brain function. Many call this area the mind/body connection but I find this to be a misnomer. The mind is the sum total function of the central nervous system (CNS) and its endocrine secret ion is called a thought. That secretion can directly up regulate DNA and RNA act ivity with gene expression and protein formation. This happens within nanosecond s according to functional MRI data, and EEG strips. It s nothing short of amazing to think evolution can move that fast on a micro level but still not affect the phenotype of the organism in any great macro way. Another paradox of life revea led I guess. (link) We also know that epigenetic modifications usually involve activation of NF kapp a beta at some point in the pathway. Therefore we must, in this levee, consider inhibitors to NFkappa beta in future additions to The Quilt Levee 15: Autophagy. In cell biology, autophagy, or autophagocytosis, is a catabolic proc ess involving the degradation of a cell s own components through the lysosomal mac hinery. Why, you ask, is this so important? Well, the leading cause of death in humans is heart disease. Autophagy is the mechanism that cardiomyocytes die from

. Therefore, if we can understand this pathway in detail and how to protect ours elves from it we may finally do something to stop cardiac death. All of the card iologists in the world believe in the lipid hypothesis of heart disease. I think , however, that the data overwhelmingly shows that it is not the case; understan ding how autophagy occurs will help you understand why this levee may be extreme ly useful to us as humans. Autophagy was first described in the 1960s, but it to ok a back seat for the last twenty years to apoptosis, the new darling find in c ell biology. Autophagy is best described to the non-scientist as a mechanism the cell uses to auto digest cellular components. This is called microautophagy because it invol ves parts of the cell. Chaperone mediated autophagy (CMA) is a process of select ive autophagy. Entire cells can be engulfed and taken out. The tissue then has m ore stroma/scars and less cells. This is precisely what occurs in heart disease. A dying heart loses heart muscle cells and replaces them with scar stroma. The remaining cells have to hypertrophy to compensate but they never can get back to the baseline and so the heart s function slowly wanes with time. Autophagy is hea vily influenced by mTOR signaling; therefore, what activates mTOR affects cardia c death. One of the major players in mTOR is the polyphenols of cacao. If you Go ogle search the MARS Corporation and see what they are up to in the Amazon basin you might become very interested in slowing your own cardiac autophagy down. Th is topic will surely interest many people because it affects all of us with a he art. Levee 16: Oncogenesis. I bet most of you thought this one would have been higher on the li st? Most people really fear cancer. I think once we develop this part of the The Quilt it may move down in importance. Cancer incidence and prevalence has risen dramatically in the last 125 years in our country. I do not believe that someth ing magically has changed in the world to cause this. Instead, I think our focus on curing cancer is completely backwards. I think we need to prevent it and not worry about curing it. Once cancer occurs we have a cellular mutant that is mad e immortal by altering normal cellular pathways to make it resistant to normal c ellular death pathways. I doubt we ever get a chance to reverse it. I do however think once we know how cancer begins we can avoid it. If we control the cellula r environment and limit damage to it, the cell will never have to make the choic e to become immortal due to the chaos we are causing it. The factors causing can cer are all multifactorial and include: metabolic, dietary, environmental, genet ic, senescent. The key is to focus on the cell and not the cancer. If we do many things correctly over long periods of time we will not face cancer , and I believe the incidence and prevalence will fall. Let me give you this sce nario: In 1900 colon cancer was the 37th leading cause of death in the USA. Toda y, it is the second. So what exactly happened to us in this country in the last 112 years? There will be many theories after some read this. But my theory is si mple: To have a huge short-term shift in a disease prevalence and incidence in a n entire population ties it to a common source. That source is the introduction of cereal fibers and grains into our diet in massive forms. I think if you go ba ck and read about how grains came to dominate American politics and culture, you will see several trends that begin with Mr. Kellogg, a growing population that needed cheap food, a large plot of land that was underutilized for years (the br ead basket), and the political decisions that monetized the agriculture complex to cheaply feed the masses during a great economic downturn. Add that to the fal se hypothesis (See Ancel Keyes) made about animal products and proteins and fats as well as the promulgation of industrial seed oils loaded in omega 6 PUFAs (se e Eisenhower s cardiac issues) which was further expanded in the 1960s by the incr ease of soybean oil. In the 1970s we took Japan s worst idea ever, high fructose c orn syrup (HFCS), and tried to use it to replace all fats in everything that was

food. From the 1980s on, we have gotten fatter and sicker and suffered from inc reased cases of colon cancer. Simultaneously, our government pushed USDA foods b ecause they realized we could make lots of it cheaply and export it all over the world to make tons of money. The only part Senator McGovern did not foresee was the current healthcare nightmare that the US now faces. Our diet depletes the d istal colon of omega 3s from butyric acid (butter) and limited use of fermented carbs that convert to protective omega 3s. This leads to ROS chronically in the face of constant glycation and lipoxidation. Are you starting to see how colon c ancer went from 37th to 2nd in 112 years? Moreover, the explosion in the use of grains caused massive changes in our gut biology, breaking down our immunity to allow the guts toxins to see the gut-associated lymphatic tissue (GALT) and dire ctly affect oncogenesis production through loss of p53 gene control. P53 gene is the guardian gene of our entire genome. Once it goes south, chaos ensues at the cellular level and oncogenesis occurs with amazing regularity. If we change what we do to our cells, we avoid what we fear. It s that simple. Levee 17: Stem Cell depots. This one, I bet, will move up as I age. I think what we are l earning now is nothing short of amazing. As autophagy and apoptosis take out cel ls as they age, get infected with vectors, eliminated by ROS, ALEs, AGEs, and ma ny other things, they get replaced with new cells that are not differentiated as yet that are hiding in our stroma as soldiers in waiting. The real issue is we do not appear to have an unlimited supply of them. Scientists are now challengin g that assertion, and I hope they are right, because if they are, we all might s tart living a long time. The key to this levee is time and context. My theory holds that if you deplete y our depot too early in life, your lifespan is shortened tremendously. In fact, I will be less tactful: If you abuse your body from ages 0-40, I think it has gre ater effects than if you abuse your body from 40-80. The reason is simple: The l ess we need to replace early in life allows us to have many more as we age when the effects of time and cellular damage accumulate. This is why the major diseas es in humans all get more common as we age. We no longer have the reserves we on ce had. If science proves that we can go back and create pluripotential cells an d reengineer our stem cell depot then this risk certainly lessens. Right now thi s option does not exist. Damaging your depot includes poor dietary choices, trau ma, cellular and emotional stress, and endurance exercise. We need to protect ou r stem cells at every age but we tend to lose most of them when we are young bec ause we do not employ a levee strategy until we get to the back half of life. Levee: 18 Sirtuins as a black box. Sirtuins have been described as guardians of the cell. They hit the scene in the early 2000s with the discovery of resveratrol and its effect on lifespan. In people, for example, they seem to halt the normal cellula r cycle that ends with old cells committing suicide, and instead help rejuvenate them by beefing up their DNA repair processes and stimulating production of pro tective antioxidants. It appears that if a cell is at a point of deciding whethe r to live or to die, these sirtuins push toward the survival mode and allow the cell the option to survive longer to rejuvenate itself. Sirtuin, or Sir2 proteins, are a class of proteins that possess either histone d eacetylase or mono-ribosyltransferase activity and are found in organisms rangin g from bacteria to humans. Sirtuins work in calorie restricted states to improve cellular stress response and regulate transcription. However, their main effect is on energy generation by improving the NAD/NADH ratio to decrease mitochondri al leakiness at the first cytochrome. This generates less ROS than we would norm ally see. Resveratrol works with quercetin and is generally found in certain win es, grapes, and cacao chocolates. Quercetin is found in grapes and apples.

Sirtuins bring about the effects of calorie restriction in the brain s IGF axis, k nown as the somatotropic signaling axis, which controls growth and influences li fespan and lengthens telomeres. Levee 19: Apoptosis. Apoptosis is the preprogrammed cell death in animal cells. Apoptosis has certain biochemical features that characterize it. These changes include ble bbing, loss of cell membrane asymmetry and attachment, cell shrinkage, nuclear f ragmentation, chromatin condensation, and chromosomal DNA fragmentation. Excessi ve tissue apoptosis is seen in atrophy and insufficient amounts occur in cancer generation. Apoptosis is controlled by both intracellular and extracellular signals to affec t the cell. Some of those extracellular processes are toxins, growth factors, ni tric oxide, cytokines, and hormones. These signals can both positively or negati vely regulate cell suicide. Intracellular signals come from glucocorticoids, hea t, radiation, nutrient depletion, viral infection, and hypoxia. Before the actual process of cell death is precipitated by enzymes, apoptotic si gnals must cause regulatory proteins to initiate the apoptosis pathway. This ste p allows apoptotic signals to cause cell death, or the process to be stopped, sh ould the cell no longer need to die. Several proteins are involved, but two main methods of regulation have been identified: targeting mitochondria functionalit y, or directly transducing the signal via adaptor proteins to the apoptotic mech anisms. Another extrinsic pathway for initiation identified in several toxin stu dies is an increase in calcium concentration within a cell caused by drug activi ty, which also can cause apoptosis via a calcium binding protease, calpain. The process involves increasing mitochondrial permeability and induces swelling and eventual cell death. Levee 20: Supply side stability. Clearly, if an organism doesn t survive its early stages, t hen genes that promote survival in later life are meaningless. Supply side stabi lity is important in the later stages of life to increase lifespan. It is becomi ng clear that the guardian of the genome gene P53 executes this function. P53 s ma in function seems to be inducing cell cycle arrest in somatic cells, the cells t hat currently make up our organs. They do not include stem cells or the cells of reproduction. If the cell cycle is arrested, that cell cannot go on to form a c ancer because it cannot divide. Loss of P53 control, however, can and does lead to chaos many times. Ironically, it also appears that P53 controls the stem cell supply of many organs as well. This appears to be true in the mammalian brain b ased upon current research. It also appears that the cellular machinery used to go from stem cell to a somatic cell is present in human aging but the supply of stem cell is now the rate-limiting factor for longevity. This points to two area s of thinking: One, we must look to youth to keep the supply vibrant as we age, or two, we must figure out a way to reverse-engineer the somatic cells in our or gans today back to the pluripotential cells that we had as children to redivide and replenish our diminished stock of stem cells. Sounds idealistic, no? It appe ars it is possible based upon what we now know. This levee will explore this are a. Levee 21: Adaptogens. These are plant derivatives that can affect the neuroendocrine and i mmune systems to bring back a sense of balance to those systems when they are de regulated by cellular stressors. These plants have been used for thousands of ye ars in Chinese Medicine and Ayurveda medicine. Their longevity and safety is cle

arly documented by time, but western medicine often does not support their use b ecause they have not been subjected to RCTs. It is ironic that most of the chemo therapeutic drugs western medicine uses are also used without an RCT but we seem to overlook this fact easily. The interesting point about adaptogens is that th ey have really begun to be looked at by research scientists recently because mos t of the adaptogens used for thousands of years have been shown to contain heat shock proteins that are very important in the biologic system. Licorice is very common in candies yet most Americans do not know that this is an adaptogen. So a re Maca, Rhodiola, Resveratrol, Quercetin, Ginseng, Holy Basil, and astralagus. The interesting factor is that astralagus extracts are now commercially being de veloped by major biotech companies and being sold as telomere lengthening device s. TA-65 is one such example that was developed from Geron Corp. in the last 15 years. This is a levee that I think will grow in importance as we learn more abo ut how adaptogens effect the biologic system. Levee 22: Cellular Depletions. It appears that cellular damaging and aging can occur from depletion of certain co-factors. For example, the depletion of ATP in cells caus es them to lose their cytoskeleton architecture very quickly. The cell can no lo nger function and undergoes apoptosis rapidly. This is most commonly seen in lac k of oxygen or blockage of blood flow. (link) We have known in medicine for year s that dialysis leads to early heart disease. For many years it was not well est ablished why this occurred. We now know that dialysis membranes remove water-sol uble proteins, and the B-complex vitamins are water soluble. This is why we see very high homocysteine levels in renal patients on dialysis. And the depletion o f the B vitamins leads to early heart disease. Chronic Coumadin use depletes cel ls of vitamin K analogues. This leads to earlier osteoporosis and calcification in the blood vessels all over the body. High levels of glucose, and fructose in the diet, causes cells to use massive am ounts of B6 and Magnesium in the production of energy, leading to cellular deple tion over time. This is clearly seen in diabetics and is being looked at in the development of neuropathy and nephropathy by those patients. B6 and Magnesium ar e also co-factors in the production of serotonin from 5HTP. This might explain w hy depression is more common in diabetics than in those who are not diabetic. Be ta blockers and diuretics also deplete Magnesium and B6. Recently, the anesthesi a literature has begun questioning the higher complications seen in those treate d with beta blockers. See how depletion can hurt a cell or animal? Magnesium dep letion is very common these days due to the diet being loaded with fructose. Dru gs like Digoxin and Nexium are commonly used in older Americans and also deplete magnesium. These all cause restless leg syndrome in older people. This problem is endemic because of a wide variety of ways Magnesium is depleted in our diets. HIV cocktails contain several antiviral meds that all deplete zinc. Zinc is vita l for testosterone production and for wound healing. Certain legumes contain lec thins and phytic acid that block absorption of minerals from the gut, worsening the cellular environment. This levee will cover how cellular depletions can caus e disease and rapidly increase aging. Levee 23: Iatrogenic effects. This levee will concern itself with the negative outcomes we get from trying to heal or help the human live longer. Estimates have reported that close to 100,000 deaths a year are caused by medical errors a fact that cause d quite a stir when the study came out. I believe this number is actually too lo w because we do not realize how many things that we advocate for today are bad m edicine in disguise. For example, an iatrogenic effect may be the use of mammogr aphy (X-rays) to detect breast cancers from 1 mm to 1 cm in size. We know X-rays are oncogenic, and since it takes decades to develop cancer there clearly is an

iatrogenic risk here. We now have new technology, like thermography, being deve loped that can detect breast cancer much sooner. When I was in residency, thermo graphy was looked at as quackery, but this technology uses angiogenesis and heat to detect changes in cells that are quite small in breast tissue. This technolo gy was recently used to find and kill Osama Bin Laden in Pakistan and is current ly deployed in all our smart weapons in our missile systems. It likely will make a huge impact in medicine, and change the standard of care, once it is realized how much more sensitive this technology is compared to the mammograms of today. It can detect cancers much smaller than 1 mm in size when they can easily be er adicated by today s conventional treatments. This levee will cover numerous areas of iatrogenic errors in dentistry, medicine , alternative medicine, denial, drug interactions, and in failing to diagnosis o r treat issues. Many specialties will be discussed in this section as well as po tential problems that can arise from complications. Levee 24: DNA/RNA alterations. Over the last decade, the human genome project has allowed us to sequence our entire genome. This has allowed researchers to study genomic alterations and the mRNA they lead to. Those mRNAs tend to lead to genes that a lter the DNA to force certain cellular biochemical pathways to become operationa l or to shut down completely. Genome-wide studies are now routine for examining diseases using arrays based on hybridization techniques. These studies have show n us much about how certain diseases begin and propagate, and how the biochemica l pathways influence decision pathways in the cell. It allows us to identify gen es that are expressed by certain stimuli in cells to cause disease propagation q uite efficiently. This levee will explore the complexities in DNA and RNA function and how both ca n affect the human or animal in aging and disease. For example, we now realize t hat fat lipodystrophy that occurs in HIV-positive patients is caused by the effe cts of antiretroviral drugs on depletion of mitochondrial DNA and RNA, and it le ads to interactions that alter fat biology in these patients. This also explains why Growth Hormone treatment in HIV patients is quite effective in also restori ng their normal body composition. Levee 25: Hypoxia. Hypoxia is a cellular state that disrupts normal oxygen supply to the tissue, causing cellular dysfunction. Examples of this are altitude sickness at high elevations and clots in a blocked artery causing an organ to fail and die. Apoptosis and autophagy allow cells to adapt over their lifespan to many situati ons. Hypoxia is directly toxic to mitochondrial energy production. In humans, wh en oxygen is in short supply we can shift to anaerobic energy production, but it is not as efficient as mitochondrial energy production. Athletes with proper tr aining can perform well in anaerobic conditions but it does appear that they pay a steep price for this adaptation by depleting their stem cell supply. Hypoxia plays a role in aging because as one ages the amount of blood to organs declines as the heart fails to deliver the same amount of blood through a stiffe ned arterial tree throughout the body. This causes cellular oxygen levels to fal l and usually is a signal to mitochondrial biogenesis to offset the deficits. As one ages, this signaling system is not as accurate in sensing changes to the ox ygen level. Low oxygen tension is a signal to autophagic pathways that normally help repair cells. If this gets impaired, signaling autophagy become less effect ive as we age and results in more organ failure and diseases of aging. Hypoxia i s a critical signaling in the cell for repair processes. This is disordered in h eart disease and in sleep abnormalities such as sleep apnea. Levee 26:

Organizational failure of structure. This levee will deal with organs and tissue s, how they sustain failures as we age, and what we can do to prevent this. All organs have different rates of failure and some organs fail in typical patterns. We will look at ways to stop this from happening and at strategies designed to prevent it from occurring. A simple tissue failure to understand is that of a bone fracture. This is well u nderstood and rather straight forward to deal with. Osteoporosis is another type of failure of bone that is much more complex to deal with and is a result of th e failure of multiple systems acting upon the bone. Heart failure is very common and occurs under autophagic control. The causes vary but we understand how the heart fails. What we do not understand well yet is how to modify the process to facilitate health as one ages. For the brain, we now believe that most degeneration occurs by autophagic proces ses but it is clear that the interaction with other systems plays a huge role on its ability to stave off functional decline. We have already seen this in the b rain-gut axis but it is clear that the brain is impacted by most other organ sys tems in some fashion once they begin to decline. The brain must compensate to of fset that loss of efficiency. In this levee we will look at organ systems and see how they fail both acutely a nd chronically over time, and see how these failures can be impacted by strategi es to lessen their effects for increased longevity. Levee 27: Heat shock proteins (HSP). HSPs are proteins that are only expressed when the ce ll is faced with higher temperatures or other cellular stress. It appears that h eat shock proteins origins come from direct transcriptional processes once a stre ssor is encountered. Most heat shock proteins are named by their weight, but the more important ones have names. One such example is ubiquitin, which is a HSP t hat marks proteins for degradation. Most HSP can be thought of as cellular pathw ay chaperones that help the cell do the business of homeostasis more effectively . They are very active in infection, trauma, burns, inflammation, exercise, hypo xia, starvation, nitrogen depletion, alcohol use, UV radiation, and heavy metal poisoning. The interesting thing about these proteins is that they seem to affect tertiary and quaternary structural folding of proteins in our bodies. This effect seems t o be lost as we age so we see a defect in protein folding in aging related disea ses. They also are critical in transporting proteins across cell membranes in al l tissues. HSP are also vital in maintenance of steroid receptor function. Foldi ng issues are thought to play major roles in Mad Cow disease, Alzheimer s disease and Parkinson s disease. Levee 28: Sleep. Why we sleep is currently unknown. This sounds crazy considering we spen d one third of our life sleeping, but it is factual. There are, however, some pl ausible theories. It appears sleep is vital for auto repair processes to occur i n the body and brain. It also appears that sleep, and energy metabolism, are tig htly regulated in the hypothalamus. Cognitive decline is obvious with sleep depr ivation, and learning is impaired. Sleep apnea is a known killer in humans and g enerally appears in those with obesity, again linking energy metabolism to sleep . It appears that less than 5.5 hours or more than 9 hours of nightly sleep seem to predict a shorter longevity clearly, sleep is critical to longevity. This process is quite complicated but incredibly fascinating; we will explore ma ny facets of how sleep and obesity are likely close relatives, and we will intro

duce you to concepts that you may not have ever heard of. I think sleep will tur n out to be a top ten levee before too long, but there is so much we don t know ab out it at this time it is hard to make a claim to put it there now. With energy metabolism at position two and sleep clearly tied to it, I guess you could say t his is this documents quantum entanglement! Levee 29: Hormesis. Hormesis is the biologic process that allows for a favorable biologic response on a cellular level to a small or low-dose exposure of the hormetic age nt. A good example of hormesis is exercise. In the right amount, it confers long evity and lengthens our telomeres. In excess, it will hurt us by causing high co rtisol levels and generating ROS to deplete our stem cells and cause us to use a naerobic energy production which does not suit our biochemistry long term. When cells are faced with mild stressors, it seems to confer an increase in func tion and longevity. This occurs in all organs of the body that have been tested, but we do not know if this effect has a floor or a ceiling in some cases, thoug h in others it is obvious. Too much exercise or alcohol can kill a human. This i s true of stress and certain drugs as well. Cardiac hypoxia without cell death h as been shown to increase cardiac output and stroke volume and improve heart fun ction. Curcumin and Ginger are examples of spices with hormetic effects. Resveratrol an d Quercetin are plant polyphenols that have similar effects on humans. This leve e will discuss this biologic process and its role in aging. Levee 30: Geopathic stressors and Quantum biology. Geopathic stress is a natural phenomen on affecting certain places and can be damaging to our health. In some cases it may actually help us. Birds use geopathic stressors to map their flights during migrations. It relates to irregularities in the earth s magnetic field, which can be aggravated by a variety of features. One way humans may be affected by this i s from cell phones. The EMF signal appears to be a geopathic stressor. It also a ppears to be the root cause in the death of honey bees. Electric power grids, ea rth transitions in agriculture are well known geopathic stressors that can affec t cellular function. Signs of geopathic stress are areas in the earth prone to m old or lichen formation. Many animals will avoid these areas because they functi on sub-optimally. Many in conventional medicine do not believe this is a factor, but quantum biology may help answer why this occurs. Many new exciting researc h areas are pointing to no-locality factors in the earth that dramatically affec t the way biologic systems operate. This levee will examine this fascinating fro ntier of disease and see how it can affect our longevity.

READERS SUMMARY: 1. WHAT QUESTIONS DO YOU HAVE ABOUT THE LEPTIN RX? 2. WHAT QUESTIONS WOULD YOU LIKE TO SEE ADDED TO THE FAQs? 3. POST YOUR EXPERIENCE WITH THE LEPTIN RESET IN THE COMMENTS What should I do before I start the Leptin Reset? Before you start, take a pictu re of yourself from all angles. Don t be bashful or you ll be sorry in 18-24 months. Next, weigh yourself naked. Let your significant other or a family member take this picture. Go to the store and buy a piece of clothing that does not fit you now, but will when you have met your goal. Remember, calories are important when you re LR (leptin resistant) and mean nothing once you are LS (leptin sensitive). Macronutirents count when you re LR and mean nothing when you re LS.

How do I determine if I am leptin resistant? Remember, you can be LR (leptin res istant) if you re fat or skinny. If you re overweight by more than 30lbs, it is a lo ck you have some degree of LR. If you re underweight by 20 lbs, you are likely LR, too. If you had an eating disorder, you re likely suffering from a serious leptin issue. The easiest test is to look in the mirror. The mirror does not lie and it is rea lly cheap. For those people who still can t be sure after peeking in the mirror, y ou can order some blood tests. My favorite is the HS CRP (highly sensitive C-Rea ctive protein) and the reverse T3 tests (but there are others). They are accurat e in over 90% of cases. My next favorite test is the salivary cortisol test, along with at least two of the following: HDL level, serum ferritin, homocysteine, fasting triglycerides, f asting insulin, or post-prandial glucose readings done every 15 minutes for one hour after eating. (Read my Hormone 101 blog for details.) How do I restore leptin sensitivity? If you re overweight, eat a low carb version of the paleo or primal diet as outlined in The Paleo Solution by Robb Wolf or Pr imal Blueprint by Mark Sisson. If you re really obese, eat a ketogenic version of this diet. If you re underweight, you need to eat a regular paleo or primal diet u sing leptin reset principles found in the Leptin Rx. (see The Leptin Reset Proto col) How long does it take to restore leptin sensitivity? This step depends upon how badly damaged your metabolism is. It also depends upon how willing you are to ad apt your diet and your exercise routine. My standard answer is 6-8 weeks for mos t people. Most people refers to those within one standard deviation on either side of the mean, and that includes about 68% of people. How do I know when I am no longer leptin resistant? Changes in appearance: Your hair and nails will improve in color and presentatio n. Your pedicurist will notice you have less dead skin on your feet. Your face w ill look a lot better, with softer skin and better color, especially if you use olive oil or coconut oil on your skin. Changes in mood, personality, and thoughts: You will become more thoughtful, mor e mindful, and less explosive in explosive environments. If you decide to add mi ndfulness to your reset, (you should) you will notice tremendous changes in your thinking and your ability to learn and comprehend things. Your insight, intuiti on, and mental acuity will be sharper. Also, your sexual desires will change and your libido will awaken. Your spouse will begin to notice things and treat you differently. Changes in appetite: Your carbohydrate cravings will go away. You ll feel full and not really need to eat three meals a day. You ll notice your taste and smell chan ge. Changes in energy and sleep: Over 6-12 months, expect your energy to gradually i mprove. You will feel warmer and exude body heat, but your body temperature will actually be lower. It will continue to trend lower over the next 18-24 months w hile you thyroid settles into its new biologic groove. Dramatic improvements wil l be made in your sleep. Both migraines and muscle soreness from exercise will d ecrease. After leptin sensitivity is restored, what practices should I follow? Once you r ealize things have changed, you need to immediately begin HIIT (high intensity i nterval training) exercise. I am a huge believer in lifting heavy weights at low

reps. At this stage, I want most people lifting at 85-95% of their maximum weig ht, 2-3 times a week. The exercise rotation can be simple. A good resource is th e Body for Life workout found at the end of the book in the weight lifting secti on. You do not need anything but a good set of dumbbells. You should do this for about three weeks. Women especially need to regularly lift weights. Women never listen to me about this, but they should! Ladies, you will never get huge muscles doing this, I pro mise. The reason that weight lifting is so important for women is because their pregnenolone level declines fast after the age of 30. This causes steep declines in the sex steroids (known asperimenopause), in growth hormone secretion, and i n vitamin D status. The muscle strain from weight lifting is the best way to sti mulate the pituitary gland to say, We are not aging yet, and we need to continue to make these hormones. Leptin sensitivity controls that switch. And ladies, your body composition is directly tied to this action! If you lift, your curves will be maintained until you re ninety or greater. Both men and women need to consider their HS CRP levels. High levels indicate a person you have entered perimenopause or andropause at a much faster pace than o thers. This means your time to a total reset and optimization will take longer. It does not mean it is not possible! Do not compare yourself to others. Compare yourself to how bad your own labs were when you began. The worse your labs were, the longer it will take you to get to optimal. Do not forget this biologic fact , you can t run away from it! After three weeks of lifting, you should add two days of running sprints. The sp rints should be no longer than 40 yards and you should not exceed 20 sprints. If you can t do twenty, work up slowly and steadily. Walking in the beginning is fin e. Do not stress about this. If you do you, will raise your cortisol and the res t will take longer. Your thoughts will drive your cortisol. As for your diet, you can begin to increase or decrease macronutrients slowly to see if it affects your cravings, weight, and your moods. If your symptoms start to return, return to your original diet. Why should I avoid aerobic exercise during the reset? This will require some exp lanation. If you re LR, you are a sugar burner, not a fat burner. That means you c an not do glycolytic exercise until your muscles and lever become completely LS as well. Your brain being LS is not enough. If your muscles are still LR, they c an t properly use the glucose or the fat delivered to them. This is detailed in th e Why is Oprah still Fat post. Another to avoid aerobic exercise at this stage is because the AMPk pathways are not working well yet. (This will be the focus of an upcoming blog post.) AMPk i s stimulated by re-teaching your muscles and liver how to deplete glycogen and m etabolically respond to hypoxia and cellular stressors. Any time metabolism is s tressed, AMPk should respond in kind with big results. In LR, it does not work w ell at all. This is why body composition is trashed in LR states. If you do aero bic exercise when you are still leptin resistant, you send signals to the mitoch ondria that conditions are really bad. Instead of making new mitochondria to hel p out, you wind up killing your cells via apoptosis. New stems cells are recruit ed to replace the suicidal cells. Sounds good? The problem is those stem cells w ere going to help extend your life span, and, well, you just shortened it! This is why NFL players, bodybuilders, and marathoners don t live long as group, and wh y they get many disease early, such as heart attacks, Alzheimers, and cancer. No t good. Longevity always mandates we protect our stem cells. We only want to use them when we really need them. If you use them early in life, you re subtracting years from the end of your life. Why do you need to eat within 30 minutes of waking? When you re LR, your diurnal c

locks in the brain, the liver, and muscles are all disordered. This is how we wi ll reset those organs to once again act in unison, like an orchestra. If you bre ak this rule, you can still find success, but it will make your reset take longe r. What exercise can I do during the LR Protocol? My personal advice it to do none. If you must, swim, walk, or have a lot of sex right before bed. Yes, timing of sex is important, too, in the reset. Oxytocin is released at climax and it is th e best chemical a brain can have prior to sleep. It jump-starts the conversion o f serotonin to melatonin without the four hours of complete darkness it usually takes. This is why orgasm can make you sleepy, and why moms and babies fall asle ep in a rocking chair after breastfeeding. Does everybody need 50 grams of protein at breakfast during the LR Protocol, reg ardless of size or sex? My answer is yes, 50 grams is the minimum for success. I f you re bigger, you can go even past 70 grams. If you can t eat that much protein, add fat to make up the rest. If you are obese, add coconut oil to your coffee or tea, or eat a tablespoon of it. I use Nutiva brand and love it. If you re underweight, eat more hashbrowns coo ked in pastured butter. Eat breakfast until you re stuffed. If you don t get to 50 g rams of protein, don t sweat it I don t want the stress to raise your cortisol! Just make sure your hunger is killed. If you get hungry before, during, or after lun ch, you need to eat more protein or fat at breakfast. What are examples of a 50 gram protein breakfast? If you can t figure this out, yo u have bigger problems than the reset can fix. Use the internet or any primal or paleo website. Talk to Diane Sanfillippo or grassfedgirl they ll tell you to just eat a shit-load of bacon. They have my stamp of approval. Both of these girls r ock and they can help teach you to cook paleoliciously. (And they are both smart and cute!) Does breakfast need to be just protein, or can there be vegetables or fruit? Wha t about fat? If you are overweight, avoid fruit. Veggies are fine as long as the y are not nightshades and have a low glycemic index. If you are underweight, you can eat fruit, and I suggest blueberrries, blackberries, and grapes over all ot hers. Fat is great. The obese can use coconut oil as their number one diesel. Google Nuti va Coconut Manna and then send me a donation for that recommendation you will soo n be addicted! If you don t like coconut oil or Nutiva coconut manna, you can use heavy cream, but you won t lose weight as quickly. For the thinner LR crowd, I recommend pastured raw heavy cream. Get some saturat ed fat raw cheeses from France. If you must use pasteurized stuff, go ahead, but it s not my top choice. What if I can t eat a big breakfast? Don t complain about your leptin problems then. To get where you want to be, you must do things you have not done before. How strict is the 50 grams of carbohydrates per day limit? It is strict for the overweight and not strict for the underweight. How should they be spread out ove r the day? The most carbs should be eaten when cortisol is the highest, in the m orning. Dinner should be the meal with the least amount of carbs. Eat the most f ood in the morning, with decreasing amounts as the day goes on. As you progress, you will notice yourself naturally falling into this pattern. Can I use whey as a protein source during the LR Protocol? Can you? Sure, but yo u should have asked, Should I? The answer is no. It is too insulinogenic and raise s NPY. (If you are underweight, however, you can do so without any restriction.)

Can I have coffee or tea between meals, with cream? You can have them plain, wit hout cream. But again, should you? Nope. No snacks are allowed at all, just thre e meals a day. Drinks without calories don t count as a snack and don t even ask me about artificial sweeteners because the answer is no freaking way. (Stevia is allo wed as long as it doesn t have any fillers such as maltodextrin. Generally the liq uid forms are fine.) The really obese or metabolically broken (such as people wi th fibromyalgia) may need four meals a day, but most people who eat a BAB (Big A ss Breakfast) will do fine with three meals. Can I skip lunch during the LR Protocol if I m not hungry? Yes, it is good if you can make it until dinner without being hungry. Then, you can eat more at dinner if need be. Can you do IF (Intermittent Fasting) in conjunction with the LR Protocol? No way . I love IFing, but don t try it until you are leptin sensitive again. IFing requi res the AMPk pathways to be working optimally. What if we can t eat dinner before 7 p.m.? Drink water, have sex, and go to bed ea rly. Turn the lights off early, too. What if my family isn t participating in the reset? You re not here to save them yet . Focus on you. You are worthless to them and the world if you re not working opti mally. Trust me, when they see where you are going, they will all change. Just a sk my wife how that road goes. What should I do about meal timing if I work night shift? This one will piss you off. You will never be optimal until you quit your job and work normal hours. I have no answer for you here. Do your best, but you re screwed. You can t fight circ adian rhythm biology. If I fall off the wagon on the LR Protocol do I need to restart the clock? Yes and kick yourself in the ass. If you re not ready to change your life, keep doing wha t you ve been doing. During the initial reset period, there is a 10-14 day setback each time you fall off the wagon. Will the Leptin Reset fix insulin resistance? It is designed to eradicate it com pletely, if you do it correctly. Will the Leptin Reset fix thyroid problems? If you read the Hormone 101 blog, yo u d know this answer already. Shame on you! Anyone with a leptin problem has a thy roid problem by definition. So if you fix leptin, you can easily fix the thyroid . If you have an extreme case, you may need a doctor to help guide you back to o ptimal. Will the Leptin Reset fix adrenal problems? It depends on the severity of the co ndition, as most are tied to cortisol issues. High cortisol levels are harder to treat than low cortisol levels. If they are really bad, I treat both the same t ime. Most often though, with adaptogenic support and some good doctoring, you ca n fix most adrenal problems. How do you handle cravings and headaches from the initial carb withdrawal, or th e urge to snack? Magnesium is the answer, and lots of it, but avoid supplements with magnesium oxide. Start with doses of 400 mg and then increase the dose. Your cravings will go away in a few weeks, if you don t give in. If you read the L eptin Reset thread at the Mark s Daily Apple forum, you ll see that some people who gave in to their cravings had to start the process over. It takes two weeks to r egain what you lost from breaking the rules. (If it s a minor issue like only eati ng 49 grams of protein or eating 55 grams of carbs, you re fine.)

If you drink a twelve pack of beer or soda and eat Domino s, you re cooked. Family g atherings or Chinese dinners should just be handled with beef jerky and nuts in your pocket, and tell them you have a virus. If your spouse rolls their eyes no ha ppy ending for a week. And make sure you announce that the public embarrassment will alter their behavior going forward. Can I drink alcohol or wine on the reset? Norcal Margaritas? Can you? Sure. Woul d I? Nope, not even Malbec! Will this have any affect on my pee or poop? Yes it will. With time, your pee ma y smell like cat pee. If this occurs, increase your B complex vitamins to 2-4 a day, and your vitamin C intake to 2000 mg a day. Your poop should be followed us ing the Bristol stool chart. Yes, I even evaluate poop. What s Dr. Kruse s personal story? You can listen to my podcast on Jimmy Moore s site (episode 474) or read my story here. Here is an edited version of post #206 from the monster Leptin Reset thread from Mark s Daily Apple. I have had a lot of requests for my personal story and how I lost weight and imp roved my health. You need to understand that this was my game plan and it can t be used as a plug and play game plan. As I evolved, I adapted my eating and my exerc ise plan. I began as a fat ass at 6 feet 2 inches and 351 lbs. Most of you need to hear how bad I was I was B. A. D., bad. I was dying ever so slowly, but I could still lie to myself about my condition. As I stood in Orlando, FL, in a mall, I knew a ch ange was coming to me; no one around me did, however. As a neurosurgeon, I knew I was a bright guy, but I also realized I was not too bright to get this fat and ruin my health and my life. So I started to listen to people who had already overcome this health trap. I al so began to read about both basic science and the latest scientific discoveries. As I read, I found out that everything I had learned in medical school was base d upon faulty opinion-based science . I then took a leap of faith and did what the real science told me to do. I ate a high fat, high protein diet. I ate very few carbs and loaded up on saturated fats. A funny thing happened after three months my fat began to melt away! The more I lost, the more I experimented with this new diet, changing it as my blood test r esults changed. (I am a big tester. Sometimes I run labs every few weeks.) I beg an to take more supplements and do more exercise that was complementary to my ne w way of eating. I shunned aerobics for heavy weight lifting and running sprints . If I worked out too hard, my cortisol levels went up and fried my sleep and my weight loss. I began to monitor my blood levels for general biochemistry and li pids. I also began to include hormone levels. I checked vitamin D, HS CRP, rever se T3, and salivary cortisol levels. I fired my primary care doctor three times back then. I had a torn knee meniscus and I needed surgery, but none of the surgeons I saw really understood why my m eniscus had torn. None of them understood why I shunned what I had learned in me dical school in favor of what I had found by reading about my injury. I distinctly remember one orthopedic surgeon I saw in consultation. I told him t hat my plan was to eat a ton of saturated fat and protein, get my knee repaired, and never see another doctor for the rest of my life. He laughed, and I left hi m. I was dead serious and I still feel this way. Next, I went to see a guy who was an old acquaintance. He remarked about my earl y transformation and he never critiqued me. He listened, even though he was a sk

eptic. I was fine with that. He told me regardless of my new way of living, I ne eded surgery on my knee. As a surgeon myself, I knew he was correct. I decided t o let him do it because he was non-judgmental. I had my surgery in May 2009. I operated on my own patients the next day. I neve r filled the Rx I was given for Percocet. I never, to this day, even went back t o my surgeon for any follow up. I took my own sutures out and have never looked back. I optimized my labs and retooled my supplements and my meds based upon my N=1 and my own medical theories. I lost a total of 133 lbs during my surgical recovery. I discovered leptin resis tance and how to treat it. I discovered that the timing of when I eat is more im portant than what I eat . I found out that I can t get away with snacking. At the time, I ate a fairly low-carb diet, with most days below 50 or even 25 grams of carbs. These days, I can eat anything I want. After I became leptin sensitive again, I also began IF (intermittent fasting). When I had previously tried it, when I was still leptin resistant, it caused plateaus in my weight. I found that many things changed about me. The first change was my mind. Every m orning at wakefulness I jumped in the hot tub and thought about three things to make my life better that day. I posted the best thought to my Facebook wall. I s till do this, even today. (I also make it a personal task to view every sunrise and sunset.) I then got out of the tub and made a monster breakfast (BAB) with 5 0-70 grams of protein to start my day. Next, I did yoga or stretching, before he ading off to work. I usually was able to skip lunch (IF) or eat nothing but rabbit food at lunch. I came home and loaded protein and fat again, and I worked out with HIIT and spri nts. I did everything consistently and my family and wife kept commenting on my dedication. I went from a 48? waist to a 32? waist in 11 months. Everyone asked H ow? What? Why? and I remained silent. I would only say, I am not close to done yet . Talk to me when I get there. Later, I told people about the speedo bet. I told them about the Thanksgiving di nner speech to my family. I told them about buying new wardrobes when I was fat 6 different wardrobes. I told them what I told the salespeople when I shopped. F or example, I distinctly remember going into a Nordstrom Brioni store and buying a size 42 R ro elevation of cortisol as the main generator of the inflammation in diseased neu rons. This further fuels protein misfolding and overwhelms the detector and refo lding mechanisms in the brain. SUMMARY: It appears that the brains cholesterol stores are used up to make the cortisol t hat fuels the inflammation that drives this pathologic process. This inflammatio n becomes the currency that overwhelms the internal quality assurance system of neurons to make sure proper protein folding occurs. When the system is overwhelm ed the end result is the formation of neurofibrillary tangles from insoluble pro teins. These insoluble proteins then block the transport of vital ingredients in to the brain cells to offset the assault. One of those ingredients appears to be cholesterol itself. It appears that normal lipid metabolism repair mechanisms b ecome so unbalanced that it induces the nerve cells to undergo apoptosis! This t ies another levee to the AD and Parkinson s disease story. Many physicians and researchers are hoping that we can find a place in this chai n of events that can be attacked or blocked by a medication to prevent the infla mmation, production of ozone reactions, slow the conversion of cholesterol to co rtisol, and encourage the refolding apparatus that evolution provided us to make

a dent in this disease. Maybe then we can improve protein solubility and even b oost the plaque removal mechanism that we were born with? I have a better idea. Why don t we stop providing that the fuels that are known to provide the lit match to the dynamite? Maybe we should advocate a low carb paleolithic diet that decreases carbohydrate s that upregulate IGF 1 and 2 and lower omega six free fatty acids? We know that will help slow the progression of the disease since we now know what drives it. Some how I bet they d rather make a drug they could make money on then teach peop le what really might help now? After all, no food company makes money unless the y are selling the SAD do they. The choice is clearly yours to ponder.


It s time to begin packing for Jimmy Moore s low carb cruise so I wanted to launch a post on some of the books I have been reading and spot light two of them that I think are really good reads. I have shared them with my members and my patients and now I want to share my thoughts with my blog readers. How to make your I cans always succeed your I can ts

First up, is Dean Dwyer s first book called Make Shift Happen I met Dean for the fir st time at Paleo fx and we happened to be a on a panel together and his response s to audience questions really caught me be surprise. He was one of the most ama zing breathes of fresh air in Austin I met. We spoke and he told me he wrote a b ook and I told him I d love to read it and he sent me a copy that came to my offic e during a clinic day at 9 AM and finished it at 3 PM, while I was seeing patien ts in my neurosurgery clinic. I could not put it down because it was so thought provoking. This is the finest paleo book I have read, and I have bought and read them all. As a clinician, getting people to change is my toughest task. But in Dean s book I found the easy to read recipe for true transformational change. This is the sec ret sauce of personal success. The book is awesome for any one interested in tra nsformational change and this topic is sorely missing in Paleosphere and in mode rn life it is a book that I can now hand to my patients when they tell me they can t do something .I don t care about their thoughts of I can t .I just care about their I can book opens their mind to I can big time. Dean has raised the bar for Paleo lifest yle and for modern thinking. I have told many people on this blog that a single thought can change our DNA an d I believe this with every sinew in my body. But Dean s book tells the reader how to prepare the mindset to make this quantum leap in thinking. If there is one t hing I can say is that most people fail at change because they suffer from impov erished thinking and never make this quantum leap to success. I heard Allen Claxton, a minister, once utter, Today the treacherous, unexplored areas of the world are not in continents or the seas; they are in the minds and hearts of men. Truer words have rarely been said. Modern life is in constant flu x and is unyielding in demanding us to adapt to changes. As time proceeds on, ch anges are accelerating in our modern world and paralleling what is also happenin

g in evolutionary biology. These changes are forcing us to do more with less tim e to adapt to these mismatches. When you factor in just how much data the modern human gets each day about health and diet, it s little wonder that we adopt speci fic habits of thinking and framing data just to survive. According to IT researc h in 2010, the amount of digital data online doubles every 11 hours in our world now! At this pace it is impossible to keep up with the pace of change. In order to keep up with this mountain of data, the human brain is designed by evolution to create desktop shortcuts and templates for thinking, evaluating, and getting t o quick decisions. Dean even used other books to describe this brilliantly when he tapped Malcolm Gladwell s Blink as an example of this, in his own book. Dean give s us his top 20 short cuts to improve our thinking to improve our DNA. Dean s use of his 20 shifts are used to form a framework or a mindset for transforma tional change. A mindset is a mental inclination and a tendency to form a new ha bit. Being in control of your mindset and the manner in which you think makes th e person better able to navigate the changes we face in modern life. When we con trol our own mindset with these shift s we are allowing our brain to function by imp roving our response to modern environmental challenges so that we can win back o ur hearts and minds to accomplish transformation. Having the best tools, product s, or diet available to us serves us no good if we do not have the individual or ganizational thought patterns that allows us to synchronize those tools with our thoughts to create the chance for optimal performance in our lives. Clinicians like myself know that the worldview a person adopts will profoundly a ffect the outcome they are likely to get. Mankind has two mindsets, fixed and va riable. People who have fixed mindsets believe their capabilities are carved int o stone. this is further entrenched by our educational system in how it is appli ed. Many teachers still believe today that children s IQ scores dictate the whole story of what they will become. People with this mindset interpret most of life with an either/or decision process, win/loss view, or a fail/ and succeed mindse t. People with this mindset also have a passion for the status quo and they make up the majority of people in our world. They are also the ones who are most res istant to change. If a need for change surfaces in their life they look at it as a change event , and after it occurs they look to go back to their business as usu al approach. This is why so many passionate New Years resolutions become forgott en promises by January 8th. People with a variable growth and development mindset believe that their qualiti es can be cultivated and expanded through their personal efforts. They believe t hat anyone can grow and change via an application of life s experiences. These peo ple feel that their potential is infinite and can be developed with challenging learning. These are the people I seek out here in my blog. There is a reason thi ngs should not be made easy. It weeds out the thinkers who are rigid about thoug hts. Individuals who think from this worldview see the world through a win/win perspe ctive, a both and and decisions process. Challenges are actively pursued as oppo rtunities and risk is measured to a predefined level of tolerance. Dean s 20 Shift s are designed to habitually force you to think in a growth variable m anner without consciously forcing it down your throat. He does it in an engaging fun way and uses words than anyone can understand. My personal favorite shift i s to think in Beta mode and not be afraid of being directionally accurate in a wor ld that demands precision. When I read it, it just spoke to me because instead o f hitting WHAT and HOW in my brain ..he hit the WHY first. And getting to the why f irst requires variable inside out thinking it requires the reader to engage their o wn primal instinct or horse sense that is based upon this win/win mindset. I think this is a book everyone should own to obtain transformational change, an d it has very little to do with the Paleo template it is a book that will give you the WHY you need to change they way you think to get to the inner masterpiece that

lies within you. ASHLEY TUDOR S BOOK: SWEET POTATO POWER When Diet is correct, there is no need for medicine Ashley s book, Sweet Potato Power , has beautiful aesthetics and has a simple message . Food is our best medicine and our most important tool in maintaining health. W hen our diet is wrong, no amount of modern medicine can overcome it.She makes th is bold statement in a very quiet fashion through her book. We live during a tim e where modern life can totally destroy us by what we eat and how we apply moder n conveniences to our lives. She reminds us, that we still have the ability to p eer inside of our bodies and begin to retake control and power because we have m ore tools today to navigate us back to optimal health. Ashley gives you the tool s to bridge the gap between your diseases and problems and to your doctors. In this book she gives us a road map to 21st century healthcare delivery. It is clear to me one of her goals were to help the reader navigate the nightmare of m odern health system by keeping you from it by giving you the tools to use food a s your medicine. Her chapters on calories, food, hormones and low inflammation w here like listening to an orchestra play flawlessly. She made it simple and easy to understand for anyone to read. Her visuals in this book were outstanding. On e in particular using wood and convenience food really made an impact for me. I left the book in my waiting room for a week and asked patients what they thought of the book as I saw them in the clinic. All age groups thought Ashley did a gr eat job explaining the complexities of the biochemistry in a simpleton fashion. Her chapter on hormones was a big hit with my older female patients. Many of the m loved her description of the hormones more than my own! By far everyone s favori te chapter was Chapter 7. This was also true for me as well. Internet forums are littered with people who are told that the paleo diet is all one needs to impleme nt to get ultimate success, but yet it eludes them. This causes frustration, and they all know it is not true for many of us. Ashley actively embraces experimen tation to find out what brand of paleo is best suited to the reader. She fully e mbraces the quantified self platform of testing in this book. She tells the reader that they need to monitor and learn and apply what they learn about their diet and their lab results to slowly get to optimal health. This is a very important message lacking in many paleo books today. She went into great detail for the re ader of how to look for well care physicians to partner with. She clearly says that if your doctor only doctors you in sickness they won t be expe rts in how to keep you well. This message is vital to get out the herds of peopl e who do not understand that our current system is built to work best for those who are already sick. There is little place in our current system for those who want wellness care. She introduced me and the readers to Wellness Fx and laborat ory that is providing over 50 diagnostic tests to patients in a cost effective m anner. Their labs cost a fraction of what it would cost if you had to use a conv entional lab for testing. I spend a lot of money for testing yearly so this info rmation alone was worth the book s cost for sure. This really excited me, because as most of you know I am a huge believer in serial testing and frequent labs for me and my patients. It uncovers hidden issues and allows me time to reconstruct what is going on with the patient in real time. It allows me me time to fully a ssess dietary and lifestyle changes easily and allows me to make actionable chan ges to our treatment plans as we see fit with the lab data generates with the cl inical data the patient reports. This also allows me to show a patient how their new behavior has directly affected their biochemistry and epigenetics for both the good and the bad to help them make better decisions. This is a book every patient should consider owning of gifting to someone who ne eds help avoiding our healthcare system. I also think it has information in it t hat can make a patient a better consumer in the healthcare arena. It will allow

them to make better decisions about the healthcare advice they are getting from their providers. I have a copy of the book in my waiting room for my patients to use and ask me questions they might have. I ask them to bring the book in to th e clinic if they have any questions they are unsure of. It has seemed to be a va luable resource for them so I think that this is a great thing. The final point I d like to make is that the ending of the book has everything abo ut how to prepare a sweet potato one might imagine! My personal favorite is foun d on page 201. Ashley includes her recipe for sweet potato linguine which is now being used as the base for many of my summer time recipes that will show up in my e-cookbook soon! The recipe is awesome! Ashley has given us all a piece of her that can help each and every one of us to improve our former selves today. The road to optimal is no longer a mystery to us .Ashley makes it clear it is a choice. Sweet Potato Power is a smart decision wh ile traveling the road to optimal in my estimation.

READERS SUMMARY: 1. What to do when you get a new cancer diagnosis? 2. Is the main cancer battle field oncologic treatment or in your own body? 3. How does diet play a role? 4. How to deal with your new doc the oncologist? 5. Do not be afraid of exploring every possibility to win this battle. Learn abo ut a ketogenic diet!!! This post is for one of my very special dear friends who just contacted me and t old me his wife got diagnosed with cancer at a very young age this week. I could hear from the call and his post on Facebook this was killing him. I told him im mediately to go out and buy the book the Anti Cancer: A new Way of Life by David Servan Schreiber and give it to his bride. The good news is that many of the 6 million people being treated for cancer today will go on to live a full life. Th e numbers of those who do survive in my opinion are still far too low (about 4550%). Moreover, many of the close to 2000 cancers deaths that occur daily happen because their families were completely unaware of the depth of resources curren tly available to treat cancer conventionally and with alternatives such as compl ementary or integrative therapies. Once diagnosed with this disease you get shaken to your core. It is imperative t hat you know that this disease cannot only be fought but it can be prevented if you decide to immediately alter some of the things you do and lose some of the d ogma you have accumulated in your life. This is especially true if you are in th e healthcare field and have lived in dogma your whole adult life. This book is w ritten by a physician researcher who not only got hit with the cancer diagnosis but got hit with a brain cancer that is exceptionally deadly. He was able to dec onstruct his own beliefs as a physician with new science that was around to rese archers but not well known by his oncologists. This book is a must for anyone wi th cancer or who has risk factors present so you can beat it before it begins. T his is honestly one of the reasons I wrote my QUILT because I believe if you pro tect your cells you will never get this disease. Now that a friend has it here is a post directed at what you may consider doing right away after consulting with your oncologist. Consider consulting a major cancer center like MD Anderson for a second opinion. 1. Read the book Anticancer mentioned above. It s critical to you seeing this dise ase in a new light. 2. Immediately alter your diet to a paleolithic or mediterranean diet and away f

rom a SAD. 3. Begin a meditation scheme as soon as possible to control your cortisol and an xiety. (Choice is unimportant but doing it is life saving) 4. The patient should consult the protocols entitled Cancer Treatment: The criti cal Factors in Cancer: Should patients take dietary supplements for the type of cancer you have? 5. Consider beginning a supplement regime to include Curcumin, Reservatrol, Quer cetin, Omega three Fish oil (RX grade), Vitamin D3 with a target of being over 5 0 ng/dl, liberal use of CoEnZQ10 daily, R-alpha lipoic acid and a vitamin K supp lement daily. Consider use of N Acetyl Cysteine daily as well. Notice I did not put the dosages down because the doses required for anti cancer therapy are sign ificantly higher than one would use in a preventative state. This should be done with consultation of your oncologist. If your oncologist is not open minded abo ut these issues after reading the book in step one you might need to find a new on cologist. These are what I consider to be the core supplements to most cancers h umans get. 6. Within your diet always added turmeric, ginger, garlic, rosemary, and basil t o your foods as much as possible. You should drink 1 Liter of green tea per day. Green tea contains L -Theanine which decrease anxiety but is an adjunct to chem otherapeutic drugs by making them more effective . You can also use green tea ex tracts if you don t want to drink this much fluid or you cant because of your cond ition. 7. In 1955 Nobel Laureate Otto Warburg found that all cancers use glucose for en ergy substrate and high levels of insulin also allow the body to lose control of the immune system that will defend it. This means the patient has to limit anyt hing that stimulates insulin. A strict low carb Paleolithic diet does just this. A Good reference book is The Paleo Solution by Robb Wolf. 8. Your immune system is your best defense against your cancer. Optimize your vi tamin D levels and keep your insulin levels below two. Lowering your cortisol le vels optimizes leptin but most importantly upregualtes your Natural Killer cells (WBC s) that are part of your cell mediated immune system that actively fights ca ncer. You will read a ton about these cells in the book I recommended in step on e. 9. Veggies. Make cruciferous veggies a staple. All plants of the Brassica plants are your friends. Glucosinolates can inhibit, retard, and reverse experimental multistage oncogenesis. The reason are the release of isothiocyanantes like sulp horaphanes. Sulphoraphanes do two main things. They promote apoptosis (levee 19) and they induce phase two detoxification enzymes in the liver that strengthen t he p53 gene as the guardian of our genomes. Necrosis of cancer cells is commonly seen when they are exposed to sulphoraphanes consistently overtime. Broccoli al so includes a secondary metabolite called Indole 3 Carbinol that further breaks down to another anticancer chemical called DIM, diindolylmethane. You can t eat en ough of these veggies if you have cancer in my view. I3C also blocks 16 -hydroxy estrone and is quite helpful in preventing breast and ovarian cancers in women a nd prostate cancer in men. 10. Here is the counterintuitive one to the dogma you have had drummed into your head eat tons of cholesterol. Especially coconut oil. Many epidemiological studie s have shown that lower levels of serum cholesterol correlate with higher cancer rates. This is why eating a ketogenic paleolithic diet makes a ton of sense. Wh y a ketogenic diet? Because all cancers utilize glucose for substrate. You need to change the cellular fuel of choice. Go Google Otto Warburg for more details. Ketogenic diets should be loaded with MCT from coconut oils as they confer huge

advantages to normal cells over cancer cells. This leg up allows your immune sys tem to catch up to the cancerous cells and destroy them using your own biologic machinery. There are numerous cancer journal articles published that show the sa me links. Dedicated to Mary. Never submit and conquer it with your defenses. They are your best weapon in this fight no matter what any physician tells you. Optimize them and you will win this battle.

READERS SUMMARY: 1. AD revisited for those of you who think this is an elderly problem. Its not! 2. Why is the incidence and prevalence growing for AD? 3. What is a proteopathy doc? 4. Why is protein folding so critical to so many disease? 5. What kind of nutrition guidelines do I follow to avoid AD doc? Many of you had questions after my first Alzheimer s Disease post (AD) but few see m to want me to call the cause of it. The truth is no one is willing to make the leap of faith just yet, but the data that we have found over the last ten years has given us a pretty good idea of what causes it to occur. I am not going to b e so kind. AD is the major neolithic disease coming for People 0-40 years old to day. No neolithic disease we have seen be born in the last 125 years will have t he impact on our society that AD will have. Humans evolved from other hominids b ecause of their brain and how they rely on social learning. AD completely destro ys that beautiful adaptation. Many younger people think that AD is a disease of the elderly brain. I have some bad news for you. It is not. It is a neolithic di sease whose onset is tied some critical decisions about the fuel choice you make for your brain. My prediction is that the next fifty years we will see AD begin to afflict many thousands of people below the age of fifty and it won t be becaus e they have a problem with their APo E 4 allele. AD is a proteopathy. A proteopathy is a disease that at its core has misfolded p roteins in its etiology. It appears that AD is caused by several key factors tha t all seem to show up in unison together. One is an extreme lack of lipids in th e brain. The lipids missing tend to be omega 3 fat variety. But even more intere sting it appears the brain needs between 25-35% of omega 3 fats called DHA to fu nction optimally. There also needs to be comorbid neuronal intracellular inflamm ation present. And we also see up regulation of the IGF-1 pathways and dysregula tion of the protein signaling that leads to faulty protein folding in the AD bra in. We used to think the Tau protein that caused the neurofibrillary tangle were the result of the disease but it is becoming clear that the real issue is that these are remnants of faulty protein folding and non functional neurons result. The neurons with these misfolded proteins are toxic and need to be replaced so t hey undergo apoptosis and the brain s stem cell supply in the temporal, parietal a nd frontal lobes become exhausted. This begs a major question then? Why is prote in folding so important and what controls it? Well, this is where we have to hit some hard core biochemistry now so rub your h ead now! Protein kinases are enzymes that donate phosphate groups from energy so urces like ATP to other proteins. This process, called phosphorylation, is what controls protein folding. This process is called phosphorylation. This biologic step is reversible as well so it can go in either direction. It allows for flexi bility in the system. The interesting part of this process is that each addition or subtraction of a phosphate group causes a conformational change in the prote ins structure. This means its shape changes. When its shape changes it also alte rs its biologic function as well. This changes the way the protein interacts wit h other proteins or how signaling occurs in the cell. Most cellular receptors us

e phosphorylation in order to record the chemical signals. This occurs with all hormone receptors for example. We know in AD there is a big association with dia betes. Diabetes increases the risk of developing AD by 147 times according to a recent Science Daily post! Since you all know we have anywhere between 60-150 million A mericans with diabetes or pre-diabetes you can see the table is set for AD to comp letely explode in the next several generations. Some people refer to AD as type three diabetes. The reason is that in diabetes there are high levels of insulin present and increased levels of IGF-1 (insulin growth factor 1) and Epidermal gr owth factor (EGF) signaling that occurs. These two receptors also rely on phosph orylation ( for their own signal transduct ion as well. It appears in AD when insulin levels are high or IGF-1 levels are h igh so is HS-CRP. Remember this is an inflammatory marker made in the liver. Whe n these things occur in concert we begin to see the protein kinases of the neuro ns constantly kept in the on position. This means that they are constantly changin g the signal transduction of the receptor sites by inducing folding changes in t he IGF-1 and EGF receptors. This process is called hyperphosphorylation. This si gnal noise in concert with constant elevated inflammation, insulin levels, lepti n levels, and cortisol levels induce more kinase activation that eventually caus ed signaling changes that lead to the formation of tau proteins and tangles that characterizes AD development. Once these proteins are made in neurons they induce chemical changes within the neuron to activate apoptosis and the cell commits suicide reducing the neuronal pool and eventually effecting cognition when neuron numbers reach critical low l evels in our brains. Hyperphosphorylation of the tau protein can result in the s elf-assembly of tangles of paired helical filaments and straight filaments, whic h are likely involved in the pathogenesis of Alzheimer s disease and other tauopat hies. Some people believe that this is not a pathologic finding and represents t he neuron trying to heal itself and overcome the misfolding. When the neuron die s and leaves behind the misfolded insoluble Tau protein. Normal Tau proteins are very soluble and tends to be found only in neurons. Tau protein s normal job in t he brain is to stabilize microtubules. Microtubules are the foundational buildin g block for consciousness to have evolved in the human brain. In fact, it is now becoming clear that quantum biologic effects between microtubules in the brain are why we sleep, how we go are able to go asleep via anesthetic gases and how we dream. This process is governed by something called gamma coherence. I will blog about that in the future you can bet. Several neurodegenerative and other disea ses are believed to result from the accumulation of amyloid fibrils formed by mi sfolded proteins as well. Parkinson s disease, Huntington s disease, Mad Cow disease , Pick s disease is just a few you may have heard spoken of. I told you that protein kinases are the turn on switch that causes misfolding prot ein in AD brains but what turns off the switch ? The off button is performed by a p rotein phosphatase. PTEN is one of those phosphatases and has been shown to also have disordered signaling in AD. This data is from my last cite in the footnote s. Most pharma research has been focused on the kinase turn on switch and very lit tle has been done on the off switches . In vivo, most phosphatases also double as t umor suppressor genes as well which further interests me in exploring this area of biology in AD. The reason I have focused on PTEN, is because after P53 (the g uardian of our genome), it is the most mutated gene in human cancers. This means it is important and worthy of our attention in our Quilt. It also has been show n to directly protect P53 in many cancer research studies. We also know that low er cholesterol levels are correlated with cancer generation while also being see n in the developing brains of AD patients. That connection is not lost on me and I think there is maybe more that meets they eye to this story. I think the phosphoproteomic studies being done in genomic cancer research may g ive us some huge clues in the direct mechanism of how AD develops. These genomic

wide analysis are beginning to show huge interconnected system wide connections to changes in protein kinase activation and phosphatase deactivation. Many of o ur older theories on AD are being blown up by the new data coming out of academi c research. The lay public need to be kept informed of these new findings. I per sonally think AD may help us uncover many other scientific facts that hopefully will continue to destroy the lipid hypothesis and the heart lipid hypothesis. Th ese two theories have caused more morbidity and mortality than cures in my opini on. We need to maintain and open mind in neurodegenerative disease causation, but it is clear what correlate to this disease .. 1. Heavy dietary intake of carbohydrates. 2. Omega 6 Poly unsaturated fats. 3. Simultaneous deficiency of dietary Omega 3 fats. 4. Trauma that is repetitive that increases injury and cortisol levels 5. Constant pressures to switch on epigenetic programing to cause misfolding of our proteins. 6. Non functional proteins that uncouple mitochondria from metabolism and lead t o early apoptosis and this drains our neuronal stem cell pool over a lifetime to lead to a loss of neurons and loss of brain mass. This is why we see loss of neurons on CT s scans and MRI s in my clinic. AD is preventible and avoidable if you choose to avoid Deep Malnutrition laid ou t above and make coconut oil your number one fat in your diet!

READERS SUMMARY: 1. 2. 3. 4. 5. es How do we tie the squabble at AHS to Neolithic disease generation? How does a cell react to acute stress and what results? How does this stress get measured by labs and my doctor? What happens when this stress lasts too long? Why cholesterol is always good for us, but why the surrounding terroir dictat the disease we get?

Lets continue talking about cellular stress and depletions of things in a cell. We got on that topic because of the macronutrient squabble from AHS. But after f ollowing some twitter feeds (@DigiSurg if you want to follow me) about supplemen t regimes I thought I might try to tie some cellular mineral depletions together with how it causes the cell stress and causes it to affect its cellular terroir and our resultant hormone status. I think this story will help you understand j ust how important following the trial of biochemistry is. Any type of cellular stress lowers our stores of ATP and of Magnesium (Mg) becau se they are coupled together by our ATPase enzyme as we saw in this post. This i s classically seen in diabetes development as we mentioned there. Another intere sting thing also occurs to the cell, that we clinicians can follow on our patien ts regular labs like a Chem 7. Their carbon dioxide (CO2) levels also fall becau se mitochondria are actively transfer tons of electrons to O2 to make more ATP t o replace the deficit from the stress. This causes a simultaneous drop in CO2. T he normal cellular response to ANY cellular stress however is rather telling to review for most lay people and MD s because they may have forgot how that biochemi stry works. The simultaneous fall in ATP and Mg stimulates the cell to make LDL cholesterol! Yes, you read that correctly folks, the supposedly bad LDL stuff, L OL! It is obviously not bad if the cell is making it for some reason. Let us loo

k why the cell does this. You may want to reread this blog on cholesterol. The cell responds to all stress by increasing cholesterol production. If you go into an ICU with a patient with an acute infection and draw their lipids (not of ten done except by a tool like me) you will find sky high LDL cholesterol. And t hat is both LDL and HDL, but they LDL fraction is much higher. Higher LDL choles terol stabilizes the inner mitochondrial membrane function during heavy oxidativ e phosphylation (cellular energy production). And since the cell is trying to re cover from a stress it needs a good inner mitochondrial membrane in which to tra nsfer its electrons to make ATP. That is the reason why this occurs. You can rev iew this in this post. But here is why the cholesterol story tends to trip clinicians up. The cholester ol is needed by the cell for many uses. To be used properly, cholesterol is made to stabilize membranes and make all our hormones. To do this several co factors are also required. If the cells have a lot of toxins around or the use of the c holesterol is too slow it can oxidize and become the real bad stuff called the s dLDL that is oxidized easily (sdLDLox). This is the stuff that can hurt you. How does this happen? Well to make steroids we need an adequate amount of thyroid h ormone (T3) and vitamin A around to convert the cholesterol to pregnenolone and then to DHEA. Remember the blog post that spoke of pregnenolone steal syndrome? So if someone is hypothyroid and/or has low vitamin A levels they can accumulate higher sdLDLox and this lowers the HDL level. Remember from the VAP post that a lower HDL means less filtering ability (endocytosis clearing by the liver) in t he liver s portal circulation for endotoxins. That means that the liver is no long er as good a sieve to filter any toxins from our guts to keep the antioxidant bu rden in our general circulation low. Continuing on, the lowered HDL causes a leak ier gut too to proteins, toxins and unwanted bacterial toxins that can further ox idize the plasma and even the increased amount of cholesterol the body just made to combat the stress. This is precisely why patients with chronic hypothyroidis m tend to have higher levels of heart disease and other neolithic diseases like autoimmune conditions. They can t use their newly minted cholesterol fast enough to make steroids or new mitochondrial membranes because they don t have enough T3 and or Vitamin A. So the excess cholesterol oxidizes and is taken up by the arteries and deposited in ma crophages that will later become foam cells and eventually an atherosclerotic pl aque that could make your coronary artery blow up or clot and cause a heart atta ck. Any cellular stressor can do the same thing. Infection, high cortisol levels , obesity, even trauma, even sleep apnea. The other affect of hypothyroidism is that it causes decreased steroid synthesis due to pregnenolone steal syndrome. Remember steroids secretion are how the bra in maintains control over the twenty trillion cells in our bodies. If you cant m ake the chemicals the brain needs to maintain this control all hell can break lo ose from a control stand point. It also stands to follow that the lowered levels of these hormones are predictive of this process to the inquiring physician by lab testing. What I look for in cases like this is decreased hormone levels earl y in the steroid cascade from cholesterol to the steroids. After cholesterol com es pregnenolone , DHEA, and progesterone. Those three are very proximal to the c holesterol conversion. If they are lowered then we know we really have got a pro blem brewing. So this is why I use those hormone assays as clues to what is goin g on in the cell during stress. For example, in ICU patients who are sick and ca nt sleep well they suffer from very low levels of DHEA. Low DHEA levels correlat e with very high IL-6 levels and poor sleep. If this is allowed to go on long en ough patients may get an acute ICU psychosis called delirium. In brain trauma pa tients we see very low levels of progesterone and this correlates with poor neur ologic outcome because progesterone is a co factor in brain derived growth facto r to make new neurons.

This means that all the steroids formed from cholesterol will also be lower if t his chronically goes one. That means the sex steroid hormones also fall, and so does Vitamin D levels. This is why low estrogen, testosterone, progesterone and vitamin D levels are all associated with heart disease, many cancers, autoimmune diseases and a chronic leaky gut and lower HDL level! Its all simple cellular b iochemistry that many of us have forgotten. Now that we have covered an acute cellular stress response lets talk about a chr onic one we all will become familiar with ..aging. In aging, our metabolic rates d rop. This means that we will have a lower T3 level as we age. This is in fact wh at we see in aging. We just reviewed above what a low T3 can do in acute cellula r stress. What do you think happens with aging? Your catching on now. Its does t he same thing but the onset is more insidious. And as this happens slowly over t ime what occurs? Our hormone levels all decline slowly. For some this decline ha ppens to certain hormones quicker than others. But with testing we can predict w hat this means means to the aging person s cellular stress. In the acute cellular example I gave you I told you about needing more cholester ol for stabilizing the inner mitochondrial membrane to make more ATP (energy). I n aging, we need to raise cholesterol for another more dire reason. As we age ou r cell divides multiple times over the decades. As it does this over and over ag ain it shortens a part of chromosomes called a telomere. This is actually a biom arker for really how old our cell is. But here is the important part. As a cell divides it needs cholesterol to make a new cell and new chromosomes. Cholesterol is found in the nucleus in our chromosomes. It is even bound to our DNA and to the nuclear terroir surrounding our chromosomes. This cholesterol helps to contr ol how a cell s chromosomes divide. This is called a mitotic spindle. Cholesterol also is needed to activate our genes and their epigenetic switches that turn the m on and off. If that cholesterol is not present, chromosomes don t divide properl y and genes get turned on and off at the wrong times. This results in bad signal s and sometimes the wrong number of chromosomes. This is called cellular aneuplo idy. When this happens we generally see can cancer form in the the cell. This is why we see cancer in older people. It is also why people with lower levels of c holesterol have higher rates of cancer in multiple studies! Even the highly tout ed Framingham Heart study showed this to be true. Ironically, however we still t hink in medicine a lower cholesterol is somehow better? So as we age the cell s no rmal response is to make more cholesterol to make cell division perfectly safe a nd carefree. So the moral of this story that when you see something in the cell that is deple ted or unregulated normally in response to an acute or chronic stressor you woul d be wise to pay attention to the cellular biochemistry to dictate what you shou ld consider doing. Cellular signaling and depletions can lead to neolithic disea ses. With depletion of magnesium due to high insulin levels we saw how diabetes becomes a problem. With cholesterol depletion acutely and chronically we see how it can lead to heart disease, acute delirium, poor sleep, complete hormonal dis ruption and if allowed to go on chronically you may eventually get cancer. If yo u are thinking that incidences of all these diseases has gone up in the last 150 years you are correct. They all go up as we age. So if you choose to do things differently than how most people handle acute and chronic cellular stressors you may exert control over your cellular fates (Levee One). If you pay attention to the cellular levees and protect against them you may never face any of these ne olithic diseases. Ponder those thoughts for a while, it could save your life and likely change your DNA too.


1. WHY IS LEPTIN THE LYNCHPIN TO HEALTH? 2. HOW DOES THE BRAIN CONTROL 20 TRILLION CELLS ENERGY NEEDS? 3. WHO ARE DRS. MARTIN MYERS and LUIS DE LECEA AND WHAT DOES THEIR WORK SAY ON L EPTIN? 4. IS LEPTIN DYSREGULATION THE CAUSE OF OBESITY, NEOLITHIC DISEASE, AND AGING? Today we are going to cut deeper into the leptin story. Today we need to look at the leptin receptor because its biology will explain why studying macronutients at a dietary level just becomes a confusing mess with seemingly multiple parado xes. I recently commented on this in Paul Jaminet s blog on August 24th 2011. The comment was very detailed but not written well so I am going to lay out the reas oning in the next few blogs. As most of you know leptin is the lynchpin in my QU ILT and sits at position two. Many people might not realize how important it is for health, in sickness, and for optimal endocrine function. It is the dominant factor in obesity and this series is out to show you why this is the case based upon the data coming out of some labs who specialize in this neurobiology. Now w ould be a good time to reread my previous leptin posts to give you a 30,000 foot view of leptin (1) (2) (3) (4) (5). This series is going to be laser like bioch emistry on a 30 foot level. When we talk about this type of lab science it is ve ry easy to lose perspective of the larger story I am trying to unveil to you. I have previously called leptin the master hormone of the brain. Remember that t he brain has two ways to control things, one is direct neural wiring and the sec ond is the control over the hormonal secretions body wide. Given these two facto rs, I think I may have under called it, honestly. This hormone signals the entir e body s nutritional status, metabolic status, and endocrine status to the brain a t all times. The brain in turn uses leptin to regulate total glycemic control, e nergy balance, and all neuroendocrine function in all systems in humans. This me ans that energy regulation is centrally controlled by our neuroendocrine system. The brain uses this hormone as an afferent and efferent signaling hormone to kn ow precisely what is going on in our 20 trillion cells body wide. The brain does not have direct wiring to all 20 million cells because of space limitations of our cranium and our mother s vaginas. So it uses hormones and cytokines to extend its power and reach to send signals to those 20 trillion cells. Leptin is made from our fat cells but we are not born with leptin from our own f at. We initially get leptin from our mother s colostrum from breast feeding. This initial bolus of leptin then immediately goes to our hypothalamus to set the lepti n receptors and our epigenetic switches, neurologic wiring controlling appetite and feeding, neurotransmitters and peptides that all control energy balance. I v iew this like placing a USB drive into your new laptop with a new driver in it t o tell the computer how to use the new hardware you want installed. Serum leptin levels have been found not to be great clinical markers for a fat s et point. This has been shown in the recent Amgen trials. This really confused t he Amgen researchers and many others, it appears. And these confusing results, h ave limited leptin s use clinically in my opinion. I think this is going to change in the next decade based upon what we now are finding out about the leptin rece ptor. The reason for this issue is found in the biology of the leptin receptor. When Amgen s trials were ongoing they were completely unaware of any of the leptin receptor biology that was recently discovered. Most of leptin s biological direct ives are found in specific binding sites inside the leptin receptor. Some of wha t Amgen and Rockerfeller University researchers did find however, stimulated gre at research out of the lab of Dr. Luis De Lecea of Stanford University and of Dr . Martin Myers of University of Michigan. We know from Dr. Myers, that leptin ac ts via the long form of its receptor (LRb) to specifically regulate numerous dis tinct populations of neurons in the hypothalamus and elsewhere in the brain. Thi s means the leptin receptor has distinct parts that drive neural circuits that c ontrol energy balance and glucose utilization. The neurons that LRb work on are called the hypocretin neurons (also called orexins). These are the neurons you h ave heard me talk about a lot in the blogosphere. These neurons were discovered

initially by Dr. Lecea at Stanford, who is a sleep researcher. Damage to the hyp ocretin neurons causes the disease narcolepsy. This damage also confers the pers on the inability to become addicted to cocaine. Dr Lecea did the seminal experim ents in showing these effects while at Stanford. Research is now looking into if the same damage has the ability to effect obesity and or leaness as well. Understanding the biology of leptin s action is tough work. It is also very new re cent work. Most people are not aware of some of the things we now know about how leptin works. Each different set of LRb-expressing neurons in the hypocretin re gion serves a completely different biologic function, and the totality of leptin s biologic action requires the coordinated response of all LRb neurons in the hyp othalamus. This is not about total leptin receptor resistance many speak of. Tha t is far too simplistic and this is why the Amgen trial data was so confusing to decipher. It also was the reason why so many are confused by the leptin biology and current obesity data. Moreover, this central obesity story has very little to do with insulin as a controler. Insulin is merely one of the peripheral playe rs that the leptin receptor assesses at the hypothalamic level constantly and ma kes a specific coordinated response by its action on the hypocretin neuron outpu ts. Yes, you heard me definitely say this here now and in other places. Why so d ogmatic, doc? Before one becomes insulin resistant one has to first have a lepti n problem. Dr. Myers work over the last 15 years clearly shows this. They are ex tensive and detailed. Dr. Martin Myers worked first in the lab of Dr. Morris Whi te at Harvard who worked out all the insulin signaling pathways peripherally and in the brain. As a post doctoral candidate in the MD,PHd program, Dr. Myers dec iphered many of the insulin signaling pathways engaged by insulin receptor subst rate proteins in this lab. He has clearly stated in his writings that insulin si gnaling takes a back seat to leptin s action at the brain level. Again, you can re ad his publications to confirm this assertion. After he finished his PHd, Dr. My ers began his own independent work, at Harvard, by building a molecular framewor k for understanding the mechanisms of leptin signaling and how it coupled to ins ulin, including how individual phosphorylation sites on the leptin receptor recr uit distinct signaling molecules. At his recent June 2010 talk in Orlando, Dr. M yers made a very bold public comment that resonated with me. He said, it is not p ossible to understand the regulation of all metabolism and endocrine function wi thout understanding the neurophysiologic as well as molecular basis of leptin ac tion. That is his quote and not mine. But after reading much of this science I th ink you all know by now I agree fully with him. No where did I hear the word ins ulin in this statement. And this is a researcher who cut his teeth in the lab wh o found all the pathways for insulin signaling! I think his work is critical to understanding how dietary macronutrients are accounted for at the brain level. W hen I hear others talk about the dominant cause of obesity and not mention lepti n receptor biology, I just have to question it these days based upon this knowle dge we have. This included the recent Dr. Lustig starvation hormone talk from AHS 2011 and the recent reward theories out there in the blogosphere. I wrote in thi s blog that I enjoyed The Trouble with Fructose: a Darwinian Perspective try on Vimeo. by Robert Lustig, MD from Ances

>Dr. Lustig s talk immensely at AHS 2011 and the food reward blog series as well. M y initial comments on Dr. Lustig s talk can be found here. I was very happy both t heories finally included leptin in them, but I was not happy in how leptin was p ortrayed in either. Both theories have only parts of the obesity story correct i n my view, based upon what we do know today in 2011. These are incomplete storie s for obesity and the development of the metabolic syndrome in my opinion. I bel ieve this, because of what I learned from the work of Drs. Myers and De Lecea di scoveries in the last few years. Few of their findings are found in medical text books yet, because they are so young and cutting edge. But you can find their pu blished works in pubmed searches. They are extensive I can assure you. I include a small fraction of them in the cites below.

Next up we will cut into what Dr. Myers and others have found and why it is prof oundly important information to anyone who wants to remain healthy and stay opti mal as they age in my opinion.

READERS SUMMARY: 1. WHY ARE MEN AND WOMEN REALLY FROM MARS AND VENUS REGARDING LEPTIN? 2. WHY HAVING A BABY SUCCESSFULLY COMPLETELY IS DEPENDENT UPON LEPTIN? 3. HOW DOES LEPTIN CONTROL FERTILITY? 4. HOW DOES LEPTIN STATUS AFFECT EPIGENETIC SIGNALING? 5. WHY DR. LUSTIG s NEW HYPOTHESIS MIGHT BE LEAKING SOME FRUCTOSE? Continuing on in the Central leptin series we will resume in Orlando, Florida. I n Orlando Dr. Myers, went on to say, In addition to examining the molecular detai ls and importance of specific LRb signals, we are dissecting the regulation and function of individual populations of LRb-expressing neurons and examining the r ole of leptin in the development of neural circuits. By understanding the totali ty of leptin action in this way we hope to decipher the mechanisms by which lept in regulates the predisposition to diabetes and other aspects of the metabolic s yndrome. This statement carries huge implications. He has found that not only is leptin neurons somatotopically organized in the brain, but the leptin receptor a lso appears to be somatotopically organized into certain regions that wire and s elect certain neurons in the brain that modulate all parts of the obesity physio logic response. It also appears that this organization is different in men and w omen at the parvo-cellular nucleus in the hypothalamus. Certain parts of the rec eptor control total body glycemic control, others body weight and size, and othe rs power the para-mammillary neurons to directly control fecundity, placental gr owth and oocyte maturation. The receptor even codes for gender differences! Men and women really are from Mars and Venus when it comes to obesity and fat deposi tion, and this explains why the endocrine response is different in men and women . We have known men and women have different leptin levels as adults but did not know how or why this happens. Now we do. We now are beginning to understand why it is the case as well. It helps explain why we see can see PCOS and stubborn w eight gain together and why fat is distributed differently in both sexes. Leptin Receptor Biology: The real cause of obesity I mentioned to Dr. Lustig right before his talk at AHS 2011 that any discussion of obesity has to explain the apparent paradox of clinical leptin resistance in an orexia and the obese. These are two polar opposite phenotypes that have the same biologic basis and can be measured by high blood reverse T3 levels. This parado x is also seen in rodents. The scientific story began for rodents began in 1994, with the discovery of two independent mutant mouse strains at the Jackson Labor atory. The obese (ob/ob) and diabetic (db/db) strains suffer from an identical s et of problems: they are obese, they have type 2 diabetes, and a variety of thei r endocrine systems are disrupted in a pattern reminiscent of the response to st arvation (anorexia). Leptin was discovered in these experiments and named by Dr. Jeff Friedman at Rockerfeller University in 1994. Leptin is produced by fat cells. To a reasonable approximation, the more energy (fat) is stored in a fat cell, the more leptin the cell produces and secretes in to the circulation. Circulating leptin makes its way to the brain, where it bind s to the leptin receptor. Subsequent to the identification of leptin, the clonin g of the leptin receptor revealed that this gene was disrupted in db/db mice. Different parts of the brain mediate distinct functions, and only a few parts of the brain express the leptin receptor. It is found in high levels in the hypoth

alamus and very sparsely in the motor cortex. The motor cortex controls body mov ements. Leptin action via leptin receptors in the brain, suppresses appetite and hepatic glucose production (thereby modulating the amount of glucose in the blo od). Leptin also signals that the long-term energy stores in fat suffice to perm it the utilization of energy on energy-intensive endocrine functions including r eproduction. It also controls placental growth and maturation to foster the fetu s during pregnancy. The progesterone made by the placenta directly affects neuro n development and maturation and synaptic connections. This is done in concert w ith vitamin D levels in the brain all mediated by brain derived nerve growth fac tor (BDNF). This mechanism is felt to be disturbed in disease like autism spectr um disorders and in development of dyslexia and other neurologic causes of devel opmental delay. It is easy to see how leptin functioning can affect epigenetic s ignaling in this fashion and also the developing fetus synaptic neuronal connect ions. Leptin also controls oocyte selection and maturation in humans. If there i s a leptin problem in the mother it will directly affect her ability to mature a nd egg suitable for fertilization. This could jeopardize her ability to conceive any pregnancy because of poor egg maturation or poor placental growth to suppor t the fetus. Moreover, this egg is also susceptible to epigenetic signaling due to leptin s effects at this stage of development. It also appears that leptin may affect chromosomal fragility and the mitotic spindle critical for cell division in a growing fetus and may be the source of chromosomal abnormalities in pregnan cies that end in spontaneous abortion due to placental chromosomal abnormalities and in somatic mutations of the fetus. It appears energy metabolism is critical in these physiologic systems and leptin modulates them all. Falling leptin levels mediate the response to fasting. Fasting decreases the amo unt of energy stored as triglyceride in fat cells, thus decreasing the amount of circulating leptin. This reduction in leptin receptor signaling therefore incre ases the drive to eat, increases hepatic glucose production (helping to support blood glucose levels during fasting), and diminishes the permissive action of le ptin on endocrine functions. Genes that have mutations for leptin s receptor show dramatic response s in the anim al. In the absence of the leptin receptor signal in db/db mice, for instance, th e brain cannot sense the leptin signal at all. This leads to increased appetite. Simultaneously, it also allows the animal to respond by unleashing hepatic gluc ose formation and these two factors also stimulate feeding behavior that causes weight gain over time. The longer this persists, the animal develops and increas ed fat mass. The lack of leptin- mediated restraint on hepatic glucose productio n in db/db mice also predisposes to diabetes. (Hepatic leptin resistance) This e xcess glucose production leads to chronic surges in insulin and a simultaneous d rop of intracellular magnesium. To understand the role of mangnesium and insulin please read the link once again. Once enough time has elapsed, the leptin resis tance leads to insulin resistance and results in type 2 diabetes and eventually with more time, elevated cortisol levels. This is not Dr. Lustig s current vision. He presented his view for us at AHS 2011. The talk was great and it was dynamic . His view of how the system works is quite different from mine however.

Dr. Lustig, in his AHS 2011 talk said, insulin is an endogenous leptin antagonist @39:13 mark of the video made at AHS. He went on to hypothesize why this happens and says, because at puberty and/or pregnancy, becoming insulin resistant is ben eficial for growth and propagation of the species respectively. When he said this at AHS I was stunned ..Why? here is the rub .Leptin has been definitively shown to cont ol all aspects of fecundity, oocyte maturation, and placental growth in humans a nd insulin has not. If insulin resistance bolsters pregnancy for propagation of the species, and ins ulin is an endogenous antagonist of leptin why in God s world of evolutionary biol ogy would leptin control fecundity in humans? In his theory Insulin should contr ol fecundity and oocyte selection and placental growth. That is not what science

is telling us. Taking it one step further, using Dr. Lustig s own theory as a bas e, a diabetic could never have a child because as he says, insulin always blocks leptin. All diabetics have insulin resistance and high circulating levels and sin ce leptin controls fecundity in humans well, we have a big problem with this theory right here. Dr. Lustig s hypothesis has a major gaping hole that can t be easily ex plained biologically. There are some other issues I have with his theory at the brain level but the one I presented it a big problem for his theory. This is why I said in my post AHS blog I loved that his theory added leptin to the mix but I was not in love with the biology of his theory. The biology works a lot better when you understand that leptin controls the entire process not insulin at the hypothalamus. So how does leptin signaling work in the brain at a receptor level? First, we need to ask a few questions. One, what are the cellular mechanisms of leptin receptor signaling and how do specific leptin receptor signals control en ergy balance and glucose homeostasis? And two, on what set or sets of neurons in the brain does leptin act to control energy balance and glucose homeostasis? The leptin receptor operates as a preformed dimer that is integrated into the ce llular membrane of the hypocretin neurons. The remanding portion of the receptor sits in the extracellular space where hormones can bind to the receptor. Anothe r interesting finding of the leptin receptor is that it contains no enzymatic ac tivity at all. Most other receptors do. The leptin receptor relies on a tyrosine kinase (JaK2) for signaling when leptin binds to it. When leptin binds to it, i t activates JaK2 which then activates 3 different tyrosine residues on the insid e domain of the receptor. These domains have special amino acid patterns that us e special co factors at each position to activate and confer a biologic response . There are 4 inception points that confer a specific biologic response. Combine d, these four signals mediate all of leptin action on energy balance, glucose ho meostasis, and endocrine function. Each specific response was worked out by Dr. Myers lab using gene knock out experiments. They studied 6 types of knock outs. A normal wild type, and a complete knock of the four inception areas and confirm ed that the total knock out animals all gained a lot of weight. When the Jak2 kn ock out was completed it did not show a major weight effect, but did modestly ef fect blood glucose levels. This might represent the basis of liver leptin resist ance I wrote about here. When the next tyrosine residue (985) was knocked out, it affected two binding co factors (SOCS3 and SHP2). This showed the opposite clinical effect found in the complete knocked out mice. These mice lost weight no matter what they ate. It w as as if they were super leptin sensitive and were real lean. This modeled what we see in anorexia or cachexia. As these animals become exquisitely sensitive to leptin, they in effect decrease the receptor sensitivity to leptin to remain qu ite lean but they all had issues with sex steroid production. This caused major issues with fecundity and reproduction. This is also seen in the human condition of anorexia and starvation as well. Insulin plays no role in this issue. IR can cause PCOS in women and aromatizatio n in men, but humans with these conditions can reproduce with some difficulty. H umans with leptin problems are seeing fertility doctors because they can not get pregnant because their eggs and placentas can not mature for a successful pregn ancy. The last two tyrosine binding residues were then tested to see which one was the part of the receptor that controlled energy balance and glucose homeostasis. Th e first on was Tyr1107 and STAT5. It was found that STAT5 mutants showed modest increases in body fat and increases in feeding behaviors but no change in glucos e utilization. The Try1138 residue and STAT3 were then studied. This mutant show ed massive effects in body weight and in glucose utilization. It also appears th

at this effect is independent of insulin signaling. This point was further made crystal clear in Dr. Myers 2010 Orlando talk. This is in stark contrast to what Dr. Lustig presented in his AHS 2011 talk at UCLA. Based upon the leptin recepto r findings, it is clear that this was the part of the receptor that caused most (dominant) of the obesity effects seen in the animals for both body weight and % body fat (body composition). As they aged, the also showed marked glucose intoler ance. This part of the receptor seemed to fit the morbid obesity and diabetes ph enotype we see in humans. It was clear the receptor inception sites all had diff erent biological effects. It also appears that insulin signaling pathways and th e dopamine reward tracts are directly influenced by what happens at the leptin r eceptor level first in the hypocretin neurons. That is how I interpret the curre nt data on how this system is designed to work. Given this data we need to wonder how does the receptor control feeding behavior and glucose homeostasis? To answer this question we really need to look at how the peripheral tissues lik e fat, muscle, liver and brain differ as organs since the leptin receptor affect s these tissues dramatically. For example, the liver is a homogenous gut organ t hat is made up of hepatocytes. All of its cells are the same. The brain however is an organ whose cells are all specialized by wiring, connections, and even the neurotransmitters they use. Moreover, their functions can be completely flipped to give the opposite clinical effect with presynaptic of postsynaptic modificat ions or firing of adjacent neurons. It is clear that there is no way to understa nd the affect of leptin on the brain if one views the brain like one views the l iver, muscles or fat cells. The level of complexity at the hypothalamus changes the game substantially to explain leptin s vast and various affects on both sympat hetic and parasympathetic systems and on its endocrine functions controlling fec undity and oocyte maturation and placental growth. Next up we will begin to dissect the reward tracts and how they play a role in t his unraveling leptin saga.


So now that we examined Dr. Lustig s insulin theory of metabolic control we need t o take a look at the reward tracts that are located in the human brain. These tr acts have been well studied and their neurochemistry is well understood. What ap pears not to be as well known is how the hypocretin neurons and the leptin recep tor control and modulate their activity. The key point here is that the dopamine gic tracts eloquently spoken of Dr. Guyenet s reward series are the efferent only pa th that is part of the effector arm of the leptin receptor and the hypocretin ne urons. This means, in English, they are playing second fiddle to the leptin rece ptors and are not the dominant cause of obesity. They clearly play a major role in the neuro-circutry but they do not control obesity. They carry out the action but the orders were given by someone else. One of the reasons I had a major pro blem with the reward series, is because of my day job as a neurosurgeon. I have ha d the opportunity to operate on many brain tumors in the reward tracts and never have I ever seen either pre operatively or postoperatively one patient develop severe morbid obesity. If these tracts were truly dominant causes this would lea d neurosurgeon and neurologists to see many patients with this problem. Well, we

do not. That was a big issue for me with the theory. The second issue I had wit h it was that when we neurosurgeon s have patients with brain tumors involving the hypothalamus we see tremendous effects on feeding, obesity and on anorexia. Thi s is well documented and I have personally seen this in many cases. Dr. Lustig p ointed this out in his AHS 2011 talk when he showed some clinical cases of crani opharyngioma s and of hypothalamic trauma s that resulted in morbid obesity. Reward Story: We now have to go back to the science. The reward tracts are best understood if we read the work of Paul Kenny from the Scripp s clinic in Florida. His recent paper from 2010 is a phenomenal work in ne uroscience. His paper showed that the development of obesity was COUPLED(did not cause obesity) with the emergence of a progressively worsening brain reward def icit. He also referenced Dr. Lecea work on the hypocretin neurons and their affe cts on reward homeostasis on cocaine and on heroin addiction. The neurochemical change underlying obesity in the reward tracts showed striatal (part of the brai n) dopamine (D2) receptors were down regulated. This has been found in rodents a s well as humans. The lentivirus mediate knockout studies of the striatal D2R ra pidly allowed the development of reward deficits and caused addictive behaviors to develop to drugs and to food. So the neuro-biology of these tracts clearly sh ow that over-consumption of drugs or palatable food was able to trigger addictio n like neuroadaptive behaviors. No one disputes this. But here was the rub of the studies and where the dispute arises reward tracts neurochemistry to begin with? .What controls the

Here we head back to Dr. Myers lab and the answer, not surprisingly, is the hypoc retin neuron groups in the lateral hypothalamic area. These neurons project dire ctly to the dopamine receptors in the ventral segmental areas of the brain. This is the seat of the reward tracts in Dr. Kenny s studies and the ones referenced e xtensively in Dr. Guyenet s reward series. Dr. Myers work showed using various ade noviral and transgenic systems that the hypocretin neurons directly control the firing and the behavior of the entire reward tract. This means in simple terms t hat the reward tracts are the outflow of the hypocretin neuron system and they a re controlled totally by the leptin receptor. Given this work at the University of Michigan and at the Scripps Lab, I see no way one can say the reward tracts a re dominant in causing obesity. The reward tracts clearly do allow for the actio n of the hypocretin neurons and the leptin receptor. Dr. Myers works shows that the totality of biologic function of leptin and it receptor have to be the summa tion of its action on the hypocretin neurons. He has tediously worked these path ways out in numerous publications. No where in his works did I find any evidence for insulin to play any control in modulating the biology of the leptin recepto r or of the hypocretin neurons. In fact, there is a lot of evidence that leptin affects in the brain receptor modulate insulin effects directly. In simple terms , this means that the leptin receptor and leptin itself modulate control over in sulin and the reward tracts at the hypothalamic level of the brain. In fact, there is no neuro-biologic evidence that the reward tracts can feedback and modulate the hypocretin neurons outflow. This completely explains why I hav e never seen a brain tumor in the reward bundles cause obesity in a human. Moreo ver, there is no higher cerebral controls over the leptin receptor. This means t hat the cerebral cortex, the basal ganglia or thalamus play any role at all in m odulating energy balance in the humans system. The sum of my writing here means that control of all energy balance, feeding, appetite, anorexia and obesity are all controlled by leptin function. This tight control is also then linked to the reward systems to drive behavior and it is also linked to the Parvo-cellular nu cleus to control sex steroidogenesis and all endocrine function and fecundity to create a new generation of the species. Another point I d also like to make about these finding s of Dr. Myers. In Dr. Lusti

gs, AHS 2011 lecture he mentioned the Melanocyte concentrating hormone binding r eceptors (MCH4 to be exact) and their linkage to leptin and insulin in the brain . What he told us about those tracts was certainly true in 2009, but in 2010 Dr. Myers new data showed that MCH4 role has now changed. The new data showed that the leptin receptor neurons in the lateral hypothalamic areas are quite distinct from the adjacent leptin-regulated neurons in the melanin concentrating hormone cluster. These neurons are biologically different and perform different functio ns and do not appear to be involved in obesity pathways at all. In 2009, this wa s not worked out. This was another reason why I was not accepting of the theory as it was presented to the AHS group at UCLA. Dr. Lustig s theory and Dr. Guyenet s reward series have a lot in them that are corr ect and aid us all in understanding how obesity occurs. There is no doubt about this. But in science when we use the word always or never, or dominant, or non d ominant, you can bet that some researcher or clinician somewhere will challenge that assertion with a new hypothesis and experiment. The work of Dr. Myers on le ptin receptor biology and control put leptin as the King of the Hill with regards to obesity development. After studying this work for nearly 7 years as a neurosu rgeon I became fully ready to accept its dominant position about three years ago . I did not write my Quilt document until I had read Dr. Myers work in its entir ety. After doing so I put leptin at position two in my Quilt and I think I have laid out here in the last three blogs why I believe this to be true. I think obe sity and anorexia are the sum quotient of the outflow of the neurochemical signa ls from the hypocretin neurons which are controlled directly by the leptin recep tors biology. Any theory on the dominant control of obesity must explain the neurobiology find ings of these researchers work. What we learned here is the seat of control of e nergy metabolism is clearly delineated by these experiments. What the next step in researchers minds should be is how to clinically affect the leptin s action to help people and disease whose biology is coupled to energy metabolism at its cor e. Examples of such conditions are anorexia, bulimia, osteoporosis, obesity, dia betes and aging. Dr. Ron Rosedale is one of those early pioneer s and his work sho uld be looked at closely and dissected. I think his theories are quite solid for healthy living, but I have two minor areas where I do not fully accept his thes is for optimal longevity. His book has some negative connotations for saturated fats and for protein intake. He is particularly concerned about the mTOR pathway being unregulated with moderate to high protein diets. This theory really separ ates himself from the work of his former partners, Drs. Eades of Protein Power f ame. This protein issue has been linked to shortened lifespans in many articles in th e literature. The same is true of high carbohydrate diets that stimulate the IGF -1 pathways. Carbohydrates are broken down into two groups, high and low glycemi c. Both Dr. Rosedale and the power couple Eades are sour on them. Proteins are als o broken into two groups. Those that are insulinogenic are called the branch cha in amino acids proteins (BCCA) and the rest are made from unbranched amino acids (AA). Drs. Eades do not discriminate on proteins for his diet. Dr. Rosedale is not fan of protein at all in his diet. His diet is a high fat, low carb and low protein diet. The effect of neolithic diseases is directly proportional to aging . Neolithic disease increases as we age in all studies. So the diet we should ad vocate for humans is critical to us all. It also is clearly tied to this leptin story. An interesting aspect of the role of leptin in mTOR (levee 11) function i s that within mature human adipocytes leptin synthesis itself is dependent on mT OR activation. So that biologic fact alone tells me at the very least some prote in is very helpful. How much is optimal is unknown. This supports Drs. Eades and the paleolithic diet for health and longevity. Dr. Rosedale s concerns are valid no doubt but not yet proven beyond a doubt. My mind on this issue remains very o pen. On this I am not being dogmatic. I think telomere biologic studies and calo rie restriction studies will prove who s theories are correct or not in the future

. One thing that we already do know from telomere biology that supports the use of protein in diets for longevity is that telomere lengths are increased when th e diet is high in carnosine. The paleolithic diet has the highest level of carno sine in it. Carnosine is found in red meat that is grass fed. On the flip side o f this issue is the calorie restriction data and the data found in lower animals to yeast. This strongly points to limiting protein and calories to extend lifes pan. Given these contradictions, I cannot in 2011, indict all proteins based upo n what we know about leptin and mTor as it stands today. I personally believe th at the best paleolithic diet for aging may eliminate the part of the macronutrie nts of carbs, proteins and fats that all decrease our telomere lengths. Right no w this is completely unknown but the diet I eat uses this principle today. I thi nk BCCA maybe the bad side of protein for neolithic disease development. But I don t think the remaining AA that make the rest of proteins up are all bad. I think, like carbs, protein have the good and bad qualities. The same is true for fats. Sally Fallon and Dr. Mary Enig have shown this in their work. These are many yea rs away from completion but they are being done now on humans and primates. Thes e minor disagreements today may have huge implications for human aging and longe vity recommendations for patients in the future, but I don t believe any dogmatic statements can be made today based upon what we know now. My quest is for a long healthy lifespan free of the neolithic diseases of aging. The reason should be obvious I m aging as I type, as we all are. If there are things we can do with dietary alterations as we age to extend lifespan and simultaneou sly limit disease we should consider these options. But one thing should be clea r to you now. I believe leptin is king of the hill.

Readers Summary 1. 2. 3. 4. 5. in Why is leptin the Master Hormone? What labs tell you about your leptin status Leptin s connection to the brain Leptin s relationship to organs energy requirements Obesity is an inflammatory condition caused by leptin dysregulation not insul

Ok so you have heard me talk a lot about leptin. Why is it so important? It is a hormone that controls all of energy metabolism in the body. Not only that it co ntrols all the other hormones in the body as well. So if it is not working well you can bet that the rest of your hormones are going to show clinical problems a s well. I can t tell you how many people think they have thyroid issues when all t he time they have been leptin resistant. One becomes leptin resistant when the b rain no longer recognizes the leptin signal sent from our fat cells. Testing lep tin is easy to do but rarely done in medicine today. The easiest way is to look in the mirror. If you re way too fat or way too thin guess what? You are leptin re sistant, most likely. Biochemically we can also assess it with a test called a r everse T3 level. This is rarely ordered because many docs don t know about the tes t and because it is not covered by insurance. Reverse T3 is a competitive inhibi tor to T3 and T4. Those are your thyroid hormones. So yes, leptin resistance com pletely turns off your thyroid gland! That does not allow you to burn fat in you r muscles because it down regulates your basal metabolic rate. Now you know what controls your metabolism too! That process is called peripheral (muscle) leptin resistance. That is why some fat people can not burn fat with exercise. That is

why your thyroid test are close to worthless clinically in leptin resistance. I bet many of you just had an epiphany! The brain has to get information on the energy status on 20 trillion cells in yo ur body at all times. Due to constraints of space ( your skull size ) it does no t monitor every single cell in the body with a nerve cell connection to complete that task. It uses the endocrine system to do that. That is the system that hor mones come from. Leptin is made from your white fat cells in your body. But you first get leptin from your mother when she first breast feeds you. So if you wer e not breast fed you may have started life off on the wrong foot from an energy metabolism stand point. In fact the latest research is showing that not getting leptin from your mothers colostrum has huge implications right away for your DNA . It effects a chemical process that alters your DNA called methylation. That in formation is transmitted directly to your DNA and causes a change that leads to epigenetic signals. This is one way we know obesity can be transmitted across ge nerations. There are others. Leptin enters the brain through some complex signaling that occurs at the hypoth alamus. Once it enters the brain it begins to set off a group of neurons that wi ll modulate your energy status for the remainder of your life. This part of your brain is about the size of pea and it sits right over your nerves that go to yo ur eyes. Imagine a hole drilled between your eyes straight back about 5 inches. That is where all the action happens. The hypothalamus links the brain to all yo ur endocrine system in the body. The endocrine system includes every hormone you have heard of. The hypothalamus also modulates many of the most important cente rs in the brain. Without energy no animal could live or carry out any complex ta sks. Think about your car for a minute. How far could you go if you never knew h ow much gas you had? The only way to go anywhere and feel safe is if you just fi lled up and went. But then again you d never know when it was time to fill up agai n either would you? That is precisely what happens to a human when they are lept in resistant. The brain can t tell what the energy status is in the body. The ener gy status is your fat cells. Leptin is that connection from fat to the brain. It controls everything to do with energy. Without energy everything fails. Some of the organ systems in the body that rely on energy the most are also tied to leptin status. Once such tissue is bone. Bone is incredibly active as it con stantly remodels to stresses it is placed under. To allow a system that wide ran ge of change it requires massive energy sources. That is why leptin is important in bone physiology. Leptin resistance always pre-dates the development of osteo porosis. Leptin also controls the ability of women to get pregnant. That is call ed fecundity. If a women is leptin resistant she will have a lot of difficulty g etting pregnant. We see this in PCOS (polycystic ovarian syndrome), in anorexia, or over training. Having a baby requires a lot of energy for growth. Leptin is the key for that process to occur smoothly. Leptin also controls and modulates the immune system in the brain too. It is che mically very similar to an inflammatory chemical called IL-6 (interleukin 6) and in people with high leptin levels (fat people) we see high levels of white bloo d cells. It also modulates all the inflammatory cytokines associated with viscer al fat. Generally when someone is leptin resistant they also have low vitamin D levels. I also use this as a proxy to assess leptin status in working up patient s. Visceral fat is the fat below your six pack muscle in your abdominal cavity. Th is is one of the worse places to get fat because it is highly inflammatory. That is also the fat seen in type two diabetics that fills their liver cells. That i s called metabolic syndrome or non alcoholic fatty liver disease. Elevated lepti n is also the first sign seen before high blood pressure shows up and causes a c ascade of further physiologic problems. The reason for this is that high levels of leptin will destroy another protein secreted in your beta cells of your pancr eas called amylin. The beta cells in the pancreas make insulin. So you now know why high levels of leptin (fat) cause type 2 diabetes. The high leptin fries the

amylin in the beta cells and causes them to stop making insulin eventually. If it takes a long time it can cause type two diabetes. If that process happens fast, for example, because of an auto immune response su rrounding a pregnancy or a leaky gut then you can get an autoimmune diabetes oft en called type 1.5 diabetes. The only difference between type 2 and type 1.5 is the time is shorter and the immune response much greater. Again, all mediated by leptin resistance. The chronic leptin elevation leads to eventual leptin resist ance and usually occurs 5-7 years before someone becomes insulin resistant! (Typ e 2 DM) Today s medicine focuses in on insulin to treat diabetes. In my view this is completely off target. It makes no sense to treat insulin resistance after it has occurred. It makes more sense to target leptin resistance because it occurs 5-7 years before insulin resistance occurs!!! It is now clear that obesity is a disease of inflammation. But we know obesity has several causes. Obesity is not a disease of excess calories. Why? Because the body has several built in ways o f dealing with calorie excess without you ever getting fat if leptin is working properly in your liver and your muscles. I promise I will get to that story too soon in a future blog. Obesity is a disease of inflammation and hormonal disruption of hormone signalin g. That is why you want your physician to remain vigilant and concerned with mea suring your ultra sensitive or cardiac CRP with regularity. Now you know why I d o this test in all my spine patients. Leptin problems tell me degenerative disc disease and osteoporosis are going to occur in this patient unless I solve their leptin problems eventually. In my opinion it is a test that needs to be monitor ed more than any other in medicine. It can tell us a ton about your current cell ular terrain. Remember levee one in The Quilt. What ever happens to your cells d etermines what will happen to you eventually. If your inflammation is elevated b ad things are in your future as you will see as the quilt expands. Here is the key point to take home. Leptin resistance always precedes the develo pment of insulin resistance .(minus traumatic pancreatic loss) once both occurring long enough it leads to adrenal resistance. And adrenal resistance means you hav e a problem with CORTISOL. Don t forget this point s that important. WHEN INSULIN AND CORTISOL are raised simultaneously and chronically this is how cancer and c hronic diseases humans occur by effecting the p53 gene (oncogenesis levee). They all start with leptin problems not insulin.


Whatever you hold in your mind will tend to occur in your life. If you continue to believe as you have always believed, you will continue to act as you have alw ays acted. If you continue to act as you have always acted, you will continue to get what you have always gotten. If you want different results in your life or your work, all you have to do is change your mind. We do not need an intelligent

mind that speaks, but a patient heart that listens. Make your choices and you c reate your life. It has been often said that the best lifestyle is the one based upon moderation. Do you really believe that? How do you define moderation? I think each person h as their own idea of what moderation really means. I do not agree with this clic he at all. Why? Too many people use moderation as an excuse not to do their best for others. Why? Because it is safe for them to do so. Conventional medical adv ice often advocates the mantra, everything in moderation as its safety net. Even a s a kid that cliche bothered me deeply inside. Should a 350 pound man that eatin g 4 dozen chocolates at night believe this is moderately better than eating 6 doze n a night? Is OK for a drug addict to be pleased when they only take 5 oxycontin instead of the usual dozen? Is it OK for the person with mental illness to only take their medications 5 days a week over 7 days a week? Is it OK for an alcoho lic to drink five shots on a Friday night instead of the usual ten? I think the standards we need to have need to be a lot higher than moderation or just OK. I don t think an optimal energized life is possible when we settle for small achieve ments. I realized at an early age that life is not based upon average assumption s of moderation either. As I walked around the Museum of Natural History and saw examples throughout history and biology where moderation just got you mediocre results and often times extinguished things permanently. Many times people will have a rough day at work and wish that that day would be over. I do not think like that. Each day counts. That point recently was made fo r me in real life when a member of my OR team decided to take her own life at wo rk. Each day is a valuable day and I value each and every one I have. When someo ne asks me what is the best experience of my life, my answer is always the same. The best time in my life is the one I am about to have next. That is precisely how evolution rolls as well. She always plays for the next action, the next chal lenge that she has to face. She never settles and she does not like moderation m uch either. The lesson I learned from the rounds I made at the Museum of Natural History is that in life and in biology, it is never too late to revitalize your life if you follow Mother Nature s lead. What separates the best from the rest is how they manage the gift of their time. If you settle for moderation you settle mediocre. Too many people live the same year 80 times over, and call it a life. One of my friends is a medical school professor, and he said it best, If you acce pt mediocre, you have no room to complain when the consequences of the decision become apparent. He told me that those who espouse for things in moderation are oft en the beneficiaries of this action in some major way. If you are the consumer o r patient of this service, accepting something less than ideal. You re making a tr ade whether you know it or not. He went on in his history lecture for me, to use e xamples in life and in biology of how life always accepts major challenges and m akes sense from the chaos it was dealt. He used evolution as his main example. H e said Mother Nature never accepts moderation in its response to life. Evolution is life s crucible. No crucible is set to medium low! She always appears to reach for the ultimate survival mechanism to get to the ne xt generation and to ensure reproductive fitness. He gave examples like how the Mount St. Helens gophers reseeded the entire destroyed face of the volcano in le ss than three years to sustain new plant life. He used the the examples of the v olcanoes on Hawaii that have created numerous lava flows all over the Big Island of Hawaii becoming able to support moss and small vegetation within a few years of cooling. He talked about how how life bounced back from that oil spills and atomic blasts in the Pacific. He also used other ancient examples of how life ov er came devastation.

The Permian Triassic event was the most devastating event ever, to life on earth t hat we know about today. 57% of all families and 83% of all genera (53%) of mari ne families, (84%) of marine genera, about (96%) of all marine species and an es timated (70%) of land species including insects were wiped free because of a rai sed CO2 level. The evidence of plants is less clear, but new taxa became dominan t after the event because CO2 is the fuel they use to grow. The Great Dying event had enormous evolutionary significance. On land, it ended the primacy of mammallike reptiles. The recovery of vertebrates took 30 million years, but the vacant niches created the opportunity for archosaurs to become ascendant. In the earth s seas, the percentage of animals that were sessile dropped from 67% to 50%. Life wobbled but sustained itself. Life did not choose moderation when faced with tota l anihilation; it choose ultimate survival based upon the fossil data we have to day from China. It navigated the massive increase of CO2 by using plant photosyn thesis to take full advantage of the CO2. It did not settle for a low O2 existen ce. It took the long run and used what the environment dealt out. Moderation los t, yet again. At some point between 195,000 and 123,000 years ago, the population size of Homo sapiens plummeted, thanks to cold, dry climate conditions that left much of our ancestors African homeland uninhabitable. So what did our ancient ancestors do? They went back to the sea to save themselves. Life just finds a way when it is c hallenged. But it is clear that surviving life forms do not settle for moderatio n in these decisions. This raises the point what should a modern human consider to survive the modern world? In my view we need to default to the same decision making process. It requires the same decision trees to survive the emergency sit uations today we face. When a mountain climber was stuck in a crevice and knew he was going to die if h e did not act soon, what did he do? He cut off his own arm and he lived? Moderat ion or extreme? What was the result? 70,000 years ago there was massive volcanic eruption that changed most of life exposed to its effects. Yet, we are here tod ay as proof that Mother Nature found a way around chaos again. She never chooses safety over survival. To gain survival requires the first decision be your best . All survival classes teach this principle today. It also appears evolution use s the same plan. Her decisions always lead to survivorship as well. If that was not true life would not be here today. It does appear that decision is fluid and based upon what environment dishes out to her. About 10,000 years ago, modern man made what many consider was a great decision to move from a Hunter Gatherer lifestyle of life to a modern agricultural one. I told you in my Paleo Summit talk, that I felt this decision was the single grea test error that modern man has made because it created a species of mediocre mod ern neolithic hominids. We went in to some detail about how that ripple decision 10,000 years ago is hitting our children health like a Tsunami in today s modern world due to the affect of a sped up epigenetics. It is why ten year olds are dy ing of heart attacks and why I recently saw a 9 year old with 80% carotid artery occlusion. This is not supposed to happen according to the books in the medical school library, but they are happening today. Moreover, this is becoming very c ommon. A moderate approach would just say they are outliers, the result, due to their personal bad genetics. This is where modern medicine stands right now toda y. How many of these cases do we have to see before we begin to ask some more fo undational questions? One of my forum members made this astute statement recently, That wheat civilizati on got us to the Moon but it cost us humanity in the process. We are like evoluti onary terrorists surviving in the grain strangled MAD world today. I do not think I have heard a better statement regarding modern agricultural practices in the last 40 years of my life. The paleosphere seems to get that sense intuitively, but still applauds some amo

ng us, who choose moderation in their practices, over practices that are best fo r the survival of their own patients. I think all our decisions should be tied t o ultimate survival and optimal health, just as evolution chooses for life, when she is tested. We must be congruent with her message, and not in our neolithic beliefs or practices, dedicated to advocating for everything in moderation . We mig ht be making a great trade off that we may regret at some point later in our liv es. When we do it, we might even know why we don t know it. Evolution does not shoot for moderation it appears to shoot for an A when it is possi ble. If you want to feed your kids cake, do it. But you must realize the consequ ences of it as well. Some people will tell you that cheats are OK (moderation). They are OK, if you think they are OK. I don t think this way because evolution ta ught me to question that belief. After all, we did not have treats until recently. We are socialized to believe cheats are OK. This is a modern neolithic thought, I can do without now. Just because we can eat a banana in winter, does not mean it is without a biolog ic toll. We must begin to question those who advocate for everything in moderati on. Most humans today assume it is a risk free decision, because they don t feel a ny worse for it when they do it. This is a decision, you have to make as a moder n human today, based upon what we now know about epigenetic signaling and circad ian signaling in the brain. You can t let someone else think for you using CW dogm a they learned via a broken system. I can t legislate that decision for you, nor, would I want to. I just want you to hear it, so you can think about it now, and decide for yourself. I can show you what I know today to be true. I can tell you what I do, because of what I know t oday, but you have to decide what works for you presently. When things do go awr y, do not ask why they went awry, until you correct for these errors in thinking first. Most humans think these cheats are OK in moderation. We heard this mantra often on the stage in Austin, Tx. Yet, I have seen no proof of that moderation i s the standards used anywhere in evolutionary biology. Telomere biology and mito chondrial signaling changed my mind on this 5 years ago. Evolutionary history is pretty clear that moderation is a recipe for disaster. I think our diet directl y affects our epigenetic switches faster than any other thing we can do to ourse lves today. I think it is paramount to get it right all the time and not moderately correct as some espouse. Maybe we need to consider that the mantra of everything in moderation is really a serious danger to us? WHY EXTREME IS THE CURRENCY OF BIOLOGY: The irony of modern society is that we are now the best informed society that ha s ever walked this planet, but yet we also carry greatest risk of dying from our own ignorance. At its core, I think moderation eventually leads to extinction in biology. At Paleo fx a friend added this truth to that statement, And the mantra of this neolithic ignorance is Everything in Moderation attitude of the modern hea lthcare Rx to treat. I think when you hear the word moderation from a politician, a lawyer, an engineer, an architect, or a modern physician they might have just u ttered the most dangerous thing to your existence and to your health. They just told you that it is better for you to settle for the safety of middle ground, because they are likely to benefit in some way. Covering your ass (CYA) is pretty popular these days in medicine, and in all businesses today. But this be ing good for business practice for today, does not imply it is good for our opti mal health, longer term. On this blog, I strive to use an evolutionary lens to l ook at life and health. When I hear a physician call for moderation in the paleosphere it smacks of incong ruity to me. When we decide to go Paleo , is it not an anti-moderation position tod ay? Paleo is far from mainstream and it is looked at as extreme by the masses. P

aleo is an outlier today. Nothing about this lifestyle is about moderation when you think about it, and yet, we all embrace it. I think the decision to become p aleo personally, must spill into our professional life as well, if we are to mak e a real difference. We can t settle for less in anything we do in my opinion. It may not be comfortable at first to do this, but leadership is all about getting comfortable with the uncomfortable. Movements often begin and go against the grain before an inflection point is rea ched that facilitates real change. Choosing a paleolithic template give modern m an the best chance at health in our modern world. So, why would we then want to advocate for moderation then? This is a very serious question for this community . Paleo is an aggressive lifestyle, compared to modern SAD lifestyle that garner s mediocre results. The lifestyle allows us to obtain, and maintain, personal he althcare dominance in this sea of mediocrity. Paleo strives for excess health in c ontrol. It is mandated by evolutionary biology. So tell me, why do some still ad vocate moderation? I think we need to ask physicians who advocate for paleo to e mbrace their discomfort for sake of their own comfort? Modern healthcare and physi cians try to be all things to all people, and the result winds up being nothing to anyone. That is where the road to moderation leads today, in my view. I belie ve we need to stand up for something. I believe we need to play ferociously for our patients, to get them to world class, or don t play at all. Evolution is a bru tal teacher, and not one who uses moderation to guide her. We need to advocate f or aggressiveness in control. I think modern humans need to realize that mediocre is at the core of moderate ap proach or as a Rx for health. After all, if moderation was good why did the Saber tooth tiger and Megaladon go away? They were both apex predators that enjoyed a position of strength for a long time, before the environment changed, and made their common middle ground existence untenable. Adaptation does not use moderation . Epigenetic modifications requires quick aggressive adaptation for survival. Mo deration failed to lead to ultimate survival for either species. In fact, I can t find any example where moderation is good for survival. It certainly did not app ear in these personal decisions in I, caveman. The decisions made in Robb Wolf s l ife, those few days seemed awfully important, as we all watched it unfold on TV. We saw recently in this link that a polar bear swam 426 miles over nine days and lost 22% of her body fat and her cub during the ordeal. If she took a moderate approach to her food predicament, it would have lead to her death too. Evolution tells life to extend to its limits when faced with surviva l. Her survival instinct was to move and swim to look for the things to further her longevity. She could always have another cub if she could just extend her ow n life. We also recently saw this in a modern human. In Argentina, a child thoug ht to be still born due to a premature birth was pronounced dead by five modern physicians, recently. LINK Read again what the doctor said in this article. Dr. Greenburg said, Presumably, the whole physiology is tough to understand. There is nothing about description of the baby s existence that can explain survival, based on current understanding of cellular physiology. Then this: Another commenter Coriolana Magna disagreed.

It s not a miracle at all it is science . and the doctors incredible incompetence, wrote. She s a lucky child [that] she wasn t buried alive by these so-called healers! Moderation or Extreme? Life seems to find a way oderation response. ..when we get out of the way with a m


Her body was put into a freezer without any food. All humans are born into the w orld in ketosis, thankfully. Infants are better able to handle cold environments because they are born with a lot of brown fat to stabilize their temperatures w ith thermogenesis by burning their fat stores. They are not born with muscles lo aded with glucose to do what adults can do and shiver. Do you ever wonder why Mother Nature does this by design in infants? Ironically, putting the infant in the freezer likely saved this child s life. This is counter-intuitive to us today, but yet, the correct choice made by evolution . Her mother coming back to want to see the child was the real serendipity in th is case in my view. They found the child alive after 10 hours, and no worse for wear either. That should have made the doctors and scientists think how could th is biologically happen? Instead, they focus on suspending the doctors and fixing the breakdowns that allowed this to happen in the first place. VIDEO They chose to see the common and not the uncommon in the situation, while life j ust finds a way to survive. Everyone seemed to miss the part where Mother Nature reached into her bag of extremes and preserved a human life in ketosis and the co ld, yet again. That ability was built into her by Mother Nature, and is in each one of us. This is laid at in CT -6. Evolution does not settle for moderation, e ver! Most life on this planet lives at at extremes because evolution shoots for optimal, when life is at stake. It appears to me that modern healthcare, however , does settle for moderation because it is the short term SAFE choice. Safe does not yield optimal in evolutionary biology. In my view, if it was not good enough for Mother Nature, why is good for you now ? Why is eating a banana in the dead of winter OK or you today when Mother Natur e says it should not happen? Is it because you feel OK doing it? Does that OK feeli ng make it the correct choice, in evolutionary biology? A vote for moderation say s, sure it won t hurt you, or will it? Consider that when you hear doctors talk to you from this point forward in person, on the internet, or in a video presentat ion or from their blog. Really look at what they are asking you to do and make a deal for, when they tell you, everything in moderation is best for you. I complet ely reject the notion of moderation, as the most dangerous thing we can accept i n medicine. Why is that? Take a look at this clinical example from my clinic. ANOTHER EXAMPLE OF REJECTING MODERATION USING CT IN MY PRACTICE:

Why should we question settling for moderation in modern medicine? What if I tol d you I could take a 4 cm tumor out of the infra-clavicular brachial plexus of a women s armpit without any pain meds? Just so the ladies can clue the gentlemen i n to the pain involved, tell them how it feels when you nick or cut your armpit when you are shaving your armpit. Now think about having an incision made in you r armpit to remove a 4 centimeter tumor, off a major nerve, that controls your b iceps muscle? Got the picture now in your mind? What if I told you I could ice a n armpit for 3 weeks pre operatively to allow me to remove this tumor without an y local anesthesia or post operative pain medication, with the exception of extr a strength tylenol, would you believe me? A moderation approach to medicine woul d call that notion moronic or idiotic today. After all, it is not in any textboo k in the best medical schools, or the Ivory Towers of medicine, is it? And, beca use it is not in there, we should call it nonsense, right? Well, take a look at this video.

A patient with an armpit incision is one of the more painful incisions we make i n humans. Any general surgeon or plastic surgeon can back me up in this statemen t of surgical fact. When it is localized on a major nerve of the brachial plexus it can be a very painful procedure for the patient. Generally, I would have to keep these patients on narcotics every four hours for 4-6 weeks. Here I did not need any pain medications at all. I believed in Cold Thermogenesis before January 9, 2012. It told me that we migh t be capable to accomplish some even more amazing things for humanity, if we lea rn how to harness it. January 9th s bio-hack proved me correct in my own assessmen t of how this works on pain. Here is another example of a believer in the CT who benefited from my bio hack. No, you wont find that answer in your biochemistry text in Ivory Tower s library, but it occurred right here. Why is that? Maybe you are not aware of just how much you really don t know? Life has a habit of making us forget why we became physicians. We fall into a ro utine. We take things for granted. We stop taking risks because it is not safe f or our lives. We forgot why we became healers. It was to help people. We stop ai ming for the stars, for them because some in society says it may not be safe enou gh . We stop speaking the truth. We play small with the gifts of our life, that ma y actually help our patients lives. They deserve better than mediocre or a plan for moderation. Ordinary people can do extraordinary things by recalling who the y truly are and living that way. That is what being paleo is to me. It is an all in proposition and not one born on the middle of the road position. If this sen sibility is different than yours than I suggest you just stop reading this blog and mock me as the paleo elitists have. I am standing up to be counted. I like e mbracing the discomfort of my position.. I do things my way, and I do them this way because I think I can do better for my patients today than I did in the last 15 years. Moreover, I am going to show you there is a better way to do things, than moderation calls for today. To me, this is very congruent to the paleo lifest yle and goes against the grain of what is espoused in those Ivory Towers. Ivy To wers educate out the good ideas from our minds. Do not believe it? Watch this video. Cultivate your brilliant ideas and limit your bad education Never let someone who gave up on their dreams talk you out of going after your o wn. Sometimes in life a time comes when it s time to rethink everything That time is upon humanity today in my view. I reject moderation in medicine now. I want optimal for me, and all of my patien ts now. I leave moderate choices for those in the Ivory Towers. Leadership require s us to act fearlessly. Choose very wisely, people, because what you choose migh t just save or end your life early. Understand what the Rx for moderation brings y ou over time. There are big decisions for us all ahead when it comes to optimal health. If you want to live 80 ordinary years relying on an everything in moderation approac h, eat that banana on Dec 31, in the dead of winter, and don t worry about it at a ll. Everything in moderation might have you well covered based upon the old books in the Ivory Towers, after all, no? Next up .more Optimization and a lot less moderation.

READERS SUMMARY: 1. WHAT HAPPENS WHEN A PALEO FX LEADER DECIDES TO TEST HIS DOGMA AND INTUITION? 2. CAN MAGNESIUM HELP YOU OPTIMIZE HEALTH AND A CT REGIMEN? 3. IS IT POSSIBLE TO REVERSE INFLAMMATION/DISEASE WITHIN 30-45 DAYS? Today I want to introduce you to someone who is a true Paleo leader by stepping up to the the challenge I put to our community at PaleoFx conference recently held in Austin, Tx. Kevin Cottrell is one of the co founders of Paleo Fx. The leader s of Paleo fx have to be commended because the conference they were able to put on in 150 days of prep time was nothing short of remarkable. The conference exce eded all my expectations and the reviews of many attendees have been stellar. Th e future of this community is tied to clinical application of what the science c ontinues to show in the literature. For assimilation of the Ancestral Lifestyle to become mainstream we need to have more clinical conferences like Paleo fx, an d we need to take them globally. Today, I am breaking new ground and presenting to you my first guest blog written by Mr. Kevin Cottrell, who has agreed to shar e his personal story and personal medical history with all of you so that he may help you in some way. I think what he has agreed to do here is the most noble a nd worthy things to do to help our community and mankind. I am indebted to him f or this chance to publish his story for you to consider. The following post is w ritten by Kevin, in his words, to share with you and yours, to help open your ey es and challenge your own dogma and current intuition to help you reach for optima l health. Question everything, learn something, but answer nothing. Introduction: My journey to optimal health started with a major speed bump. The day was June 2, 2006 and it was a major wake up call. My wife and I were driving a UHaul Tru ck along I-75 passing through Atlanta GA when my cell phone rang. I picked it up and it was the dermatologist office in Miami with my results from the biopsy of a mole removed several days earlier. Exactly what we discussed I can t recall I actually can t recall even navigating the truck through traffic for the next 10 minutes I was on the phone with the office discussing options as I wasn t able to comply with their request of being in the office Monday to schedule surgery. I recall being very careful about my words and my questions I was asking so as to not pique the interest of my passenger (my wife) in the truck. This was a call you never expect to receive a diagnosis of cancer Melanoma to be specific one of the deadliest forms of cancer. After I hung up the phone, I wa s so in denial that I completely misled my wife about the content of the call st ating simply that I needed to go in for a follow up in St Louis when we get settl ed from our move. What an understatement that was, for the next 7 hours as I d rove the remainder of the way to St Louis, my mind raced with questions: How could I have cancer, I exercise 4-5 times per week? How could I have cancer, I eat reasonably healthy, don t do drugs, drink heavily, a nd have never smoked? How could I have skin cancer? I don t use tanning beds and certainly wouldn t be con sidered someone who s always baked or tanned? There really isn t a history of cancer in my family so, how did this happen to me? [n ote: we'll come back to this one later] Step one in my journey required me to have major surgery and treatment for cance r in the summer of 2006 leaving my body free of the melanoma with the only memen

to being a large scar on my left neck that looks like I was in a bar fight or ba d accident. What was interesting about this initial step in my journey was my complete misun derstanding of what had happened and the biologic mismatches that were leading m e down the path to being unhealthy and possible early demise. I was under the i mpression (based on conventional wisdom and treatment) that I had become victim of cancer due to things like sunburns, tanning beds and bad luck genetically. S ome sort of bad luck lottery result. Never once was lifestyle choices and diet/nu trition mentioned by my surgeon or any of the practitioners treating me. I neve r recall being tested for systemic inflammation or even counseled on risk factor s other than being constantly reminded to cover up and use sunscreen. Between 2006 and 2010, I went advice and continued working I would sleep for less than 6 airly healthy diet of low fat on about my life, heeding the conventional medical out (lots of chronic cardio), working long hours ( hours typically) and eating what I thought was a f and heart healthy whole grains.

The next major wake up call in my journey was my wife s ailments. She developed c hronic issues with her gall bladder and in the summer of 2010 had her gall bladd er removed in a surgical procedure. Again, we followed conventional wisdom and diet recommendations and thought we were on track for a healthy lifestyle. Afte r surgery, when her digestive issues didn t resolve, I queried the medical practit ioners several times about diet recommendations and received limited to no help. I happened upon a Podcast by Robb Wolff in the fall of 2010 covering recommend ations for someone without a gall bladder. I picked up a copy of the Paleo Diet b ook and read it cover to cover in one day. I was floored and shocked. It was s uch an eye opener for me about being off track from a nutritional standpoint for both myself and my wife. We began to clean up our diet in the fall of 2010. Again the phone rang this time it wasn t a wake up call for me. It was my mother ta lking about the fact that my father had been diagnosed with bladder cancer and w as going to have it surgically removed. He had also been struggling with high b lood pressure, his weight and Type II diabetes for years. My mother had been st ruggling with Ulcerative Colitis and had developed colon cancer and had her colo n removed in surgery. This was not something that had previously been disclosed t o the kids in the name of keeping us from worrying. I asked about other incide nts of cancer in the the family. Turned out my mother had cancerous growths rem oved from her throat when I was young and her mother and father both died from c ancer. So much for my thoughts about not having cancer in the family. My mind began to re-think/reconsider the neolithic thoughts from 2006. What if my entire framework for what I was doing in the name of being healthy was wrong? What if I was on the same track as my parents? Certainly after reading the Pa leo Diet, I knew that my family was typical and our diet/nutritional needs growing up as kids were way off track. What I was struggling with was whether this was just biologic bad luck and something that I was stuck being at risk for based on my family s history. My wife and I relocated from St Louis to Austin in February of 2011 and I schedu led a follow up visit with a medical practitioner with full blood work scheduled . The results shocked me again. I was told that unless I made some significant changes I was on track to becoming a Type II diabetic. My fasting blood glucose and hA1C (90 day average) levels were way too high. I might have looked reason ably good on the outside (I wasn t significantly overweight) however, my blood wor ked showed a different picture. This was the news I needed to go heads down with a Paleo/Primal lifestyle change . Beginning in January, my wife and I cleaned up our diet and followed a fairly strict diet based on ancestral principals. The results visually were dramatic

. My wife lost 3 dress sizes and the digestive issues began to resolve. My we ight didn t change significantly, however, my body fat % declined significantly fr om almost 30% to 17%. Progress From a vanity standpoint I was the image of Ancestr al Wellness/Paleo living and success six pack abs and all! The picture on the left was taken in the late fall of 2010 in St Louis prior to moving to Austin and starting the Paleo Diet. Pictures on right were taken in A ugust of 2011.

The final aha moment was in May 2011. The phone rang again while I was on a bus iness trip out of state. The family was told that we needed to rush to the Bay Area as my father had only a couple of days to live as he had cancer again this time in his kidneys. Being there at the hospital at Stanford University and ob serving what had happened to my father was shocking. He was merely a shell of w hat he had been and deteriorated dramatically since I saw him in the fall. Here s a picture of my father and myself at exactly the same age 47 years old. ifestyle choices and not genetics is the determining factor. He was on blood pr essure and glucose medicine at this age. L

What was even more shocking was observing the condition of my family vs. me and my wife. My mother was in poor shape and the picture of unhealthy. My younger brother and sister were both limping from chronic pain/injuries and certainly di dn t look healthy. I thought to myself, there s something missing here? Am I doin g enough to ensure longevity? I knew I needed to learn more about cancer as the prospect of going through what I had just witnessed scared the heck of our me. I was bound and determined to take every step to avoid that at all costs. More on my background and story can be found in a blog post on Being Primal and a Podcast interview I did with Abel James. A Biologic Fork in the Road lness! with huge implications for longevity and long term wel

My quest to understand the mechanisms for cancer led me to several major ahas. The first was that inflammation was a significant factor in not only all cancer but also cardiovascular disease. Especially chronic long term inflammation. T here are many factors that trigger inflammation. These factors are found in both our internal and external environments. Factors that trigger increased inflamm ation include excessive levels of the hormone insulin (insulin resistance), emot ional stress, environmental toxins (heavy metals), free-radical damage, lack of sleep, obesity, over-consumption of hydrogenated oils, and smoking. Problems wit h insulin metabolism are a major contributor to cardiovascular disease. Inflammation causes endothelial dysfunction and activated endothelium facilitate s adhesion and migration of cancer cells. Chronically inflamed tissues continue to generate signals that attract leukocytes from the bloodstream. When leukocytes migrate from the bloodstream into the tissue they amplify the inflammatory response. Then the aha moment when the inflammation research tied into my challenges well beyond the risks for cancer and brought the discussion full circle back to my me tabolic challenges with insulin regulation [remember my discussion that floored

me with my Austin doctor about being 'pre-diabetic' in Feb 2011]: Scientists at the Joslin Diabetes Center in Boston, have bred a strain of mice w hose fat cells are supercharged inflammation factories. We can reproduce the whol e syndrome (diabetes) just by inciting inflammation, Dr. Steve Shoelson says. Thi s suggests that a well-timed intervention in the inflammatory process might reve rse some if not all the effects of diabetes. Some of the drugs that are already used to treat the disorder, like metformin, may work because they also dampen th e inflammation response. In addition, preliminary research suggests that high CR P levels may indicate a greater risk of diabetes. Whatever makes us become less efficient at using insulin is going to aid in the development of diabetes. Treatments for diabetes work by replacing insulin, boosting its production or helping the body make more efficient use of the hormone. And a final aha moment, much more recently, was discovered as I researched some additional ways to reduce chronic inflammation: Inflammation not only further damages the artery walls, leaving them stiffer and more prone to plaque buildup, but it also makes any plaque that s already there more fragile and more likely to burst. A 2006 issue of the Journal of the American College of Nutrition an article show ing that as consumption of magnesium fell, the levels of C-reactive protein went up. C-reactive protein, or CRP, is produced in the liver and has emerged as a s trong predictor of clinical events of cardiovascular diseases, such as heart att acks and stroke, even in cases where cholesterol levels may be normal. For this reason, CRP assays may become a routine part of blood tests for determining CVD risk. CRP levels in the blood are normally undetectable or very low; high leve ls are strongly associated with inflammation. There are literally hundreds of physiological reasons to proclaim magnesium the ultimate heart medicine; its involvement in hundreds of enzyme reactions is just a start. Its use as an anti inflammatory makes magnesium absolutely indispensab le to not only heart patients but also to diabetics, neurological and cancer pat ients as well. The treatment of chronic inflammation has been problematic for me dical science because most of their treatments create more inflammation. Magnesi um chloride does not do this. Virtually all the components of the Metabolic Syndrome of diabetes, high blood pressure, obesity and lipid disorders are associated with low magnesium. Dr. Michael R. Eades Circadian Man on Fire Unresolved Systemic Inflammation! Why worry about this?

Greater than half of all sudden death from cardiac causes have no history of card iovascular disease. In fact, over 40% of all heart attack victim autopsies show clear coronary vessels. Clearly, there is much more going on than the simple chol esterol kills hypothesis. It is interesting to note that the first and most commo n sign of cardiovascular disease in post-menopausal women is death. Yes, death. In other words, there are no signs or symptoms. Doctor Michael Lam MD I read this quote as part of my research and it simply blew me away. I know man y of the readers of Dr. Kruse blog are women so you ll want to also view this TED talk about why this is such a huge issue for you. Okay, now I was getting somewhere. Biologically mismatched Paleo folks (especial ly the Crossfit set) are running around thinking they are healthy showing no sig

ns/symptoms and dropping dead as the first sign of any issue. This is not isola ted today Livorno soccer player Piermario Morosini died in April with no prior w arning. This was the second incident in a month. Dr. Kruse referred to a pati ent who looked like adonis and was a regional Crossfit competitor who presented wi th respiratory distress that was the first sign of cardio ejection failure. Cle arly something is amiss with these biologic mismatches. Inflammation was clearly at the center of what needed to be addressed in my ques t to avoid cancer, cardiovascular diseases and Type II diabetes. This was clear ly at the center of what needed to be addressed.

I had identified a biomarker to measure and track systemic inflammation. C Reac tive Protein (Highly Sensitive) was a great way for me to assess my progress in my quest for longevity and optimal living. Now, I also discovered a new player Magnesium the warranted some further research as a factor to remove chronic infl ammation as well. (Dr. K says, note to blog readers I talked about the Magnesium link in disease mo nths ago after controversy developed at AHS 2011 here between Taubes and Guyenet ) Well .the good news was I knew exactly what needed to be addressed (chronic system ic inflammation) and how to measure it (hs CRP). The bad news, despite my inten se focus on following the principals of ancestral wellness (Paleo Diet) and exer cising, my CRP test results revealed a chronic level of inflammation over time. HS CRP Test Results 8/2008 2/2011 8/2011 10/2011 3/2012 Pre Paleo Diet (look at my before picture) 1.0 Start of Paleo Diet ( pre-diabetic discussion) 2.3 Bodyfat down to 16.9% After Photo above taken 5.3 Bodyfat down to 10.9% 5.6 Prior to PaleoFX event 5.4

If I showed up in your office as a Cardiologist with this trend line, you re going to be highly concerned about systemic inflammation and my risk for a cardiovasc ular incident. Conventional wisdom would put me on the fast track for some sort of pharmacological intervention. My concern was the long term risk for cancer or a cardiovascular incident, let alone metabolic syndrome and challenges. Someth ing was still off track with my level of inflammation. Just Eat Real Food (JERF) like our Ancestors and all will be well, Correct? Wha t the Ancestral Wellness as a concept doesn t address about modern biologic mismat ches. Here s the bad news in Paleo/Primal living. Despite delivering fantastic results f rom a vanity standpoint for many (weight loss and lean good looking in shape folks ), there are still unresolved issues with inflammation for many. If you attended PaleoFX in March of 2012 and were present for the discussions ab out longevity vs. performance or several other masterminds, you heard first hand of Crossfitters and other in shape athletes presenting with catastrophic failures despite looking great. Lots of hand waiving from trainers and others from Phy sical Culture to just listen to your body and from my perspective almost all of th em were in complete denial of the issues of biologic mismatches. At one point, I stopped the discussion and asked the question if the first time you have any f eedback from your body you re either dead or in such dire straights, you ve permanen tly damaged your heart, is just listen to your body a realistic approach? The resp onse a collective gasp from the audience as they got the implications. Silence fr

om the Physical Culturists on the Mastermind panel. Back to Biologic mismatches and how Ancestral Wellness and the Paleo Diet is not the be all solution for everyone. What is amiss? My n=1 observation is its a function of biologic mismatches. As neolithic humans, we think if a little is okay, then more is better. From my story above, you ll see several references to this: * Chronic over-training My early training focused on chronic cardio and I was s till over-training until mid-2011. * Sleep Issues I used to pride myself on getting by on 5-6 hours of sleep and b eing a morning person. * Technologic and lighting mis-matches We think we can simply ignore Circadian Biologic cycles * Magnesium and other mineral deficiencies [I - like most in Paleoland - had no idea about Magnesuim and mineral deficiencies until recently] * Environmental toxins (metals, bpa, etc) In August of 2011, I began to address each of these areas (save the recent focus on Magnesium and environmental toxins). I made a comment at PaleoFX that most attendees simply missed the implications of. From the end of July to the end of October 2011, the only major change I made in my lifestyle was adding in signif icantly more sleep. That single change resulted in a drop in my body fat from 1 6.9 to 10.9% in less than 90 days. From there, I focused on dramatically reducing the technology and lighting misma tches. This is the typical lighting (unless using a fireplace in the winter) af ter dark at the house. 100% of the computers have a program called F.lux instal led. My wife and I use goggles that block inappropriate lighting after dark. W e follow a very purposeful ritual at sunset and after dark to wind down and get ready for healthy sleep. Poor sleep is a chronic problem today that results in insulin resistance and chronic inflammation. Some might scoff and make fun of th ese steps as being excessive and silly. That very well may be true if you re focu s is on mediocre. When seeking optimal, intense focus on all the required steps is necessary.

Still not convinced that biologic mismatches are going to get you off track? A recent study about shift work discovered some very interesting results when they subjected test subjects to biologic mismatches based on lighting and circadian timing: The study found that otherwise-healthy adults who were both sleep deprived and sl eeping on schedules that put them at odds with their biological clocks common pr oblems for millions of people who work at night made 32% less insulin, the hormo ne that controls blood sugar, than they do when they are well rested. As a result, their blood sugar rose significantly. In some cases, those increase s reached pre-diabetic levels. Despite all the aggressive steps, my systemic inflammation (based on my measured hsCRP) had not resolved as of March 2012. Something systemically was still pro ducing chronic inflammation. Rather than trying to further tinker with my envir onment or going on a continue search for specific sourcing of the issue (environ mental toxins, etc), I made a decision, that I was going to undertake an aggress ive Cold Thermogenesis bio hack under the direction of Dr. Jack Kruse. The purp ose of the biohack was to combine CT with my current lifestyle and the addition of aggressive Magnesium supplementation to put the fire out for good in myself.

Why Biologically aligned living combined with CT and Magnesium are your best fri ends for an optimal life and longevity Super Charge Your Ancient Pathway! So, I was ready to put the fire out and fix my chronic inflammation for good. S omething was nagging at me to look into Magnesium further. After a close frien d suffered a seizure a week after PaleoFX and almost died in a car crash with hi s wife and the resulting causative factor was severe Magnesium deficiency, I was strongly motivated to dig in and learn as much as possible. This person was al so a very fit Paleoite with a body fat below 10% as well.

Here s my top 10 ahas about magnesium and how it super charges Cold Thermogensis a nd the activation of the Ancient Pathway. There is a strong feedback loop when you look at the research I ve linked to in this post and below, in that most cold adapted subjects have high (above normal) levels of magnesium and are exposed (d ietarily and environmentally) to sources of magnesium. The challenge today is o ur food sources (even from a Paleo/Primal diet) is not sufficient to provide opt imal levels of magnesium due to soil depletion, lifestyle choices, . Magnesium in turn through its varied essential processes in your body ensures you get the optimal benefits of CT and your circadian biology. Magnesium has been linked to optimized thermoregulation Magnesium levels are tied to BAT functionality and BAT levels Magnesium is needed than ATP and optimized cell membrane function Magnesium is needed in order to properly metabolize EPA/DHA from Omega 3 oils optimized O6/O3 level is critical for successful CT and cold adaption 5) Magnesium is involved in more than 300 key transactional biologic functions y ou can t be optimal with sub-optimal levels of Mg 6) Magnesium is highly anti-inflammatory 7) Magnesium is needed for optimized Hypothalmus & Pineal Gland function Mg is e ssential for optimized circadian regulation Magnesium optimization results in more optimized sleep 9) Magnesium optimization has been linked to resolving leaky gut & auto-immune i ssues 10) Magnesium optimization is not available by simply following a diet based on Ancestral Wellness (Paleo/Primal Diet) and requires supplementation to be optimi zed Bottom Line: Optimized Magnesium levels critical to experience superior Cold T hermogensis results. Further, the biologic benefits of testing and optimizing y our Magnesium levels are too critical to overlook. Its the difference between b eing mediocre and optimal. Why settle for an B or a C when an A is available. My CT Protocol 4 Weeks Post PaleoFX 1) 2) 3) 4)

As part of Cold Thermogenesis Bio Hack, I followed the Cold Thermogenesis Protoc ol designed by Dr. Jack Kruse with the following modifications: 1) Caveat one and this is a big one Cold Adaption is a very specific process to each individual. I have a background in cold water search and rescue from the Pacific Ocean. During a 10 year period, I spent almost every weekend and many n ights immersed in the cold Pacific ocean in a mild hypothermic state. My mind/b ody have been exposed to CT before and as such I was able to skip ahead so to sp eak. 2) Based on #1 above, I started with 50 degree water for immersions @ 2 x day f or the first week 60 minutes per session. I didn t wear any socks or a hat and wo uld immerse my hands/arms for the last 15-20 minutes of my sessions. I wore a c ompression shirt and compression shorts and placed a 20# bag of ice over my abdo men during the entire session. The ice pads see picture below were placed on my

back mid-shoulder and remained there during the entire CT session (I used two pa ds and had my wife bring in the fresh one at 30 mins into the CT session). I di d this for seven days straight. 3) Beginning in week #2, I shifted back to 1 X per day @ 60 minutes most due to scheduling. Week 2 was another 7 days straight. 4) Weeks 3 & 4 continued daily sessions for 60 minutes increased the CT gradient /intensity by decreasing the water temperature down to 45-46 degrees as a startin g point by pre-cooling the water for 60-75 minutes with 40#s of ice (see picture below). 5) I would always eat a high protein meal prior to CT and drink a glass of ice water as well. 6) Beginning in week 1, I began an aggressive Mg supplementation program as fol lows: a) Daily am Mg Threonate @ 200mg orally / Mg Chloride Daily pm 60 minutes foot soaks w 2 oz / ZMA Supplement w 450mg Mg & 400mg Mg Glycinate. b) I also have added Grass Fed Beef Liver (offal) and other sources of dietary Mg into my diet. 7) After Week 4, I moved into a maintenance CT mode @ 2-3 times per week at 60 minutes each session. 8) Additional supplementation of Krill Oil @ 750mg daily, Curcumin @ 750mg and Resveratrol @ 1000mg


My HS-CRP Test Results and Summary

I found that I cold adapted fairly quickly my supposition is that this was based on my strong familiarity with being cold/mildly hypo thermic previously. That said, I had (and still have) very strong bouts of muscle shivering. The initial week, these would last as long as 60-75 minutes as my body would re-heat/defend my core temperature and fire up my furnace. The muscle shivering returned aga in stronger and with longer duration as I increased the intensity of CT with col der water. The results per the HS-CRP test are dramatic to say the least. After a 9 month h ighly elevated trend, the HS-CRP is down by more than 90% and a level lower than the first time it was ever tested! 3/2012 4/2012 PaleoFX event 5.4 Post CT/Magnesium 0.44

Note: I will be completing further testing for magnesium deficiency via hair ana lysis in May along with an RBC test for key minerals and ratios. Look for a fut ure blog post/discussion on the results of that.

READERS SUMMARY: WHAT ARE THE TOP 25 QUESTIONS ON CT FROM MY FORUM? The readers of my forum asked for a FAQ s on CT and I decided it would be a good i dea to make a short blog about this .They picked their top 25 questions and I decid ed to answer them for this blog. If you have any others just ask in the comments se ction. I answer them all when I have time. 1. What in the Heck is Factor X? [LisaAPB] Because of the last extinction event on our planet the weather was changed in se conds to a cold earth and all life forums that survived that event had to navigate that environment and this survival was wired into the animals who survived and a ll their descendants epigenetically. Survival occurred by speeding up the reacti on time to the environment. 67 million years ago this was an advantage .today this is killing humans. 2. How should diet and CT be adjusted to adapt to seasonal changes? At one extre me, I understand winter should be dark, COLD, and hardcore keto. What about summ er and diet, icy tubbing, etc? Can/should we ease up on the keto and cold? THANK S [Meyoolia] +1 If you re healthy and fit without disease or issue eat a seasonal ancestral diet. If your sick, obese, or not feeling well use CT and a ketogeneic template to rev erse your chemical clocks until your hormone panel approaches normal. Than get t o a seasonal ancestral diet. 3. Does being cold adapted make one more intolerant of a hot climate in summer? [healthnut] +1 How will the sunny weather effect me biologically now that I m cold adapted? +1 In my experience being cold adapted makes you more tolerant to heat of the summe r. This has been the experience of the patients who have implemented this in my practice as well. 4. Please talk about how to maximize CT . is there something to a compression garm ent or not? would we have to be moving, like in Vasper, to get this lactic acid/ HGH benefit? of-hgh/6246488 At NASA Ames Research Park, scientist Peter Wasowski has developed an alternativ e exercise machine called Vasper. The user wears compression cuffs on the arms a nd legs and core-cooling panels on the chest and head. During exercise, the mach ine traps large amounts of lactic acid in the body, stimulating the pituitary gl and and producing more HGH or human growth hormone. [Lexi] +1 Vasper is a great tool but it cost some serious cash. I love it and it has been tested in deep space and the data behind it show the result is not just pure hor mesis. My CT protocol is designed for the common man to do in their home to get results. A compression vest and ice water work too it will just take more time than Vasper. If you can get access to Vasper you d be a fool not to do it. 5. After some point does the law of diminishing returns set in? How much CT woul d one need a week to maintain what they got if they are happy with it? Will I ha ve to do CT daily for the rest of my life to maintain the pathway? Or once I m ada pted is there a different protocol?[Kpcst/Lexi] +1 CT & Age

Truthfully, I do not know the answer to this one .I have gone 4 months without CT a nd jumped back in and got immediate results. I will say that the younger one is the better the results of CT are because the younger one is the more BAT they have to activate CT. 6. How does CT reduce/reverse inflammation? [Shijin13] +1 It does this by demolishing the inflammatory cytokine array or storm from diseas e or from obesity. This is why it is not just a hormetic effect because it has d irect and long lasting effects on IL-6 and leptin. 7. Are saunas, hot tubs and sunbathing unhealthy? +1 Sauna are fine, Hot tubs wi thout halides are great, and sunbathing for some people is fine depending upon thei r diet, inflammation, Vitamin D levels and Vitamin D binding protein status. 8. How does CT reverse telomeres that are shortened? {Shijin13] +1 No one knows for sure as yet but based upon Dr. Elizabeth s Blackburn s cutting edge work (Nobel Prize in 2009) we believe that anything that decreases ROS at the mitochondrial level also improves telomere length and is better for health and longevity in ce lls and organs with a normal cellular terroir. 9. Why is it important to take Bitter Melon before CT and what is the recommende d dose? [Marsha] +1 It helps stimulate BAT from WAT. 10. What are good methods of speeding detox? [Glamorama} +1 I went over this in my first webinar on the site but the best way is observe you r reactions and your skin for estrogen dumping......and as soon as you see it us e foods first that help lower estrogens and then use supplements that I have out lined on the forum for you all. Most are listed on the Jack Recommend's tab of t he Website. 11. The big HCG connection.. I feel like 3 of us get it and the rest are trapped by their fear of fat plus HCG... If CT plus HCG will light the world on fire -A nd CT needs fat -Wouldn't HCG + CT require fat in the absence of the "protocol a pples"(ChimpChick) Not necessarily true. We do not know what CT and HCG will do long term because it has not been studied......but several people are in the pro cess of testing it and we will see what they all report back. I personally have zero experience with this. 12. What are the ranges you look for in the basic lab tests? (Please include dif ferences for gender/age/menopause differences.) If we are tracking progress what other metrics would be useful? [Nonchalant/Garfield] +1 I am assuming here you are talking about hormones .the answer is simple. I want mos t people in the top quartile of their reference range. 13.Dr. Kruse. Related to this, you have mentioned in your blogs that additional benefits acrue from steepening the gradient. could you describe some of these ben efits along with the specifics of what you mean by steepening ? Longer? Colder? Mor e often? Your CT protocol mentioned that it was focused mainly on weight loss. W hat are the other protocols for other benefits (please describe them)? Thanks! [ randychaps] Randy I can and have talked about it at length on the Webinar on Dee p CT but I can not talk about it on the website because some of those things are on the edge they are things that one needs to be very careful with to get cutting edge results. What is posted about the CT protocol on 2/11/2012 is safe for peop le to try at home Deep CT is another animal completely and requires a spotter and a ccess to a healthcare professional for guidance in real time.

14. How you should modify exercise while doing CT (donkjellberg). Depending upon your issues and goals you might not have to alter anything if your severely limite d by disease or illness CT can often replace exercise until you become more heal thy. Checking with your doctor serially is a great idea here if you are not heal thy and wondering when exercise can begin and what exercise is best. 15. Immediate perceived side effects of CT for both men and women (donkjellberg) . The first one most report is better sleep and better recovery from exercise. 16. Should Vit D supplementation level track the CT season.(localad) Great quest ion .I think it should. I take no Vitamin D supplements during March 15-Sept 15 and I rely on the sun to get mine. I came up with these dates based upon by locatio n on the planet and serial testing. It wont be accurate for everyone. In winter I use supplements. 17. Isn t CT mainly about activating, recruiting, and using brown adipose tissue ( BAT)? No, but it is a large part of it. CT also depletes glycogen like exercise does and this stimulates our IGF 1 and sex steroids to improve endotoxin clearan ce in the portal circulation, lowers FBG, lowers glycation and lipid perioxidati on, and destroys elevated inflammatory cytokine arrays 18. How do we know if we have adequate BAT to properly use CT? Adequate BAT is n ot needed to begin it. CT will force your sympathetic system to induce BAT from WAT. 19. How important is calorie restriction in CT? Long term .it happens naturally .short term it is not important but as you go and use CT CRON becomes natural. It is t he easiest form of IFing I know of and requires no training. It happens naturall y to most people. 20. Is CT enhanced if done at temperatures that DON T result in shivering? ie. Non -shivering Thermogenesis. It can be depending upon the persons initial condition . Those who are obese usually dont shiver but those with low BF % shiver quickly and deplete their glycogen stores pretty quick. 21. What are the signs/indications of hypothermia? If someone pushes themselves too far on the protocol, would mild hypothermia have any effect on the progress of cold adaptation? CT should never induce hypothermia as the protocol is writte n .it is designed to only use the surface cold receptors at 50-55 degrees and does not utilize the deep cold receptors. This is why the protocol is safe. If one ch ooses to embark on Deep CT all bets are off and you need a spotter and a doctor to help you implement it. That is just not a safe choice for a beginner. 22. Where does the 50-55degree skin temp specification come from? Is this a spec ific trigger that has been shown or is it a rule of thumb? Is the energy through put more important or the skin temperature. It would seem that the body would r espond to the energy demand of the pathway as well. If 50-55 degrees is a trigge r then we should trigger it many times a day, but possibly would not need to be for the 45-60 minute durations of the ice baths, which could provide a strong en ergy demand of the pathway at lesser temperatures. Please expand It is quite simp le this is the temperature that the PNS cold receptors begin firing based upon func tional MRI data and from direct recordings. This is set by mother nature in euth erian mammals. For humans the range is 50-55 degrees. 23. Did you use your protocol to lose your weight or did you do more with CT? I began with my protocol and as it worked I steepened the curve and monitored my r esponses .the steeper you go the more danger you incur. 24. Are their any dietary changes that everyone should make while using CT? Yes,

avoid all alcohol at all times and eat 3-5 meals with seafood as you apply it. 25. Since leptin is sexually dimorphic hormone in humans is cold adaptation diff erent for men and women? Yes, Women take longer to cold adapt than men because t heir generally have higher leptin levels than men. They can however offset this by increasing the amount of seafood they eat doing CT. I would not suggest cheat ing with fish oils ..and the closer your 06/3 ratio is to 4:1 the better your respo nse will be to the cold.

READERS SUMMARY: 1. HOW DO WE PERCEIVE ENVIRONMENTAL CHANGE? 2. DOES EVOLUTION USE CLIMATE AS THE CURRENCY FOR EPIGENETICS? 3. DOES THE FUNCTIONAL ORGANIZATION OF THE BRAIN TIE QUANTUM MECHANIC THEORY TO BIOLOGY? 4. HOW MIGHT ASTROPHYSICS GIVE US INSIGHT WE DO NOT CURRENTLY CONSIDER? 5. IF THE BRAIN UNDERGOES NEUROPLASTIC CHANGE DOES IT FOLLOW THAT BIOCHEMISTRY U SES THERMOPLASTIC CHANGE? Today, we are going to bend your mind a bit by explaining to you many of the thi ngs you might be believe as biologic truths published in biochemistry books toda y are in fact truths, when certain environmental truths are held within a consta nt range. Yet they change tremendously when certain factors are altered. Often the biophysical changes do not even have to affect the thermal coefficients of t he biochemistry in the hypothalamus. Just the perception of the environmental ch ange from the brain is enough to alter the chemistry as is the enzyme and protei ns existed on the top of Mount Everest or on the ocean floor in the coldest envi ronments on earth. When biochemistry was observed in living cells and described , the scientists rarely considered these effects on our biochemistry and how it may alter the cellular terroir. Our hypothalamus rewires too many stimuli, and it appears that temperature is a major factor in the rewiring protocol of our br ain. Evolution has clearly needed to use this in the past for some reason. Our job as enquiring primal bio-hackers, is to figure out why and how this might ha ve happened. In essence, they looked at the complex biologic machinery from a standard Newton ian platform. Most scientists know that Newtonian physics explain much of what we observe in the physical sciences here on earth, and that quantum mechanics be st describes the physics of subatomic matter of matter in space on a universal s cale. When QM theory is adapted to many biologic systems, some puzzling things e merge that are hard to explain. Complicating matters, we have few ways to measu re the quantum effects within biologic systems to test how they may affect livin g cells. This does not imply in any way that quantum mechanics does not apply t o biologic systems, because it clearly does. It is often buried in the biochemi stry equations that biochemists use to describe how living cells make order from the complete chaos that rules matter. This implies the effects might be diffic ult to discern or measure with current techniques we have, and this is why we ha ve yet to uncover them in biologic systems. The brain clearly uses quantum mech anics to operate. This is not a controversial point at all in the scientific wo rld.

When biochemistry laws and equations were laid down in human history, it occurre d in a time where our understanding of the nervous system was rudimentary and fe lt to be static and unchanging. The current laws of biochemistry have never abl e to explain how the human brain functions totally on a biochemical level or a f unctional level. Moreover, we have yet to hear a complete thesis on how it is a ble to perform all the things it is capable of even today. We still have no ide a how sleep occurs, why anesthesia works, or how the brain wakes us up every day . We understand many parts of it, but we do not understand the biochemical proc esses of the micro machinery in our cells, and how the make order of the chaos o f the matter in our cells. The belief that the brain was static remained medica l and scientific dogma until the last 15 to 20 years of modern science. When br ain researchers began to unlock new mechanisms of neuroplasticity and brain circ uitry, everything changed for us in the neural sciences. When it dawned on us that the brain could rewire and it was proven in humans to occur, we had no biochemistry to tell us how it all worked. In fact, we still d o not. Here is where some very smart biochemistists and physicists began to col laborate together and share ideas of how biology may be impacted by quantum mech anics to explain queer reactions in biologic systems where modern biochemistry the ory just stops. The organisms that sparked these theoretical experiments were e xtremophile organisms that live deep in the sea in the coldest darkest environme nts possible, and thermophiles that also live near boiling vents or deep in ceno tes in scalding hot sulfuric acid. How can life exist in these wildly diverse e nvironments is no longer just a biologic question, it is a question for physics too these days. It has brought many bio-astrophysicist to the same table to sol ve the mystery. Today, most of these bio-astrophysicists think that the best ch ance for extraterrestrial life may lie on the moon of Titan. Titan is a moon of Saturn and is a giant frozen ocean that has volcanic jet streams erupting from its surface in radiant displays of light that have been seen by the Hubble teles cope and by the Cassini spacecraft ( Thes e enigmas may be solved when we first relook at how the human brain rewires to e nvironmental pressures that climatic change brings to bear upon it. Neuroscienc e has taught us over the last 25 years the neuroplasticity in the nervous system is ubiquitous. Explaining the functioning of the human brain comes in to play b ecause it remains the one human organ whose function continually stumps modern s cience but readily adapts its own biochemistry. What are the links that here th at we might consider important? How might we experiments reconcile these issues?

The key to understanding these perplexing questions and paradoxical reactions re quires us to rule out the impossible first. This implication is not meant to me an that the laws of biochemistry or organic chemistry are wrong. Quite the cont rary, it means that humans today remain in the dark of how biochemistry reacts w hen extremes occur because we have not faced them and we rarely study them in cu rrent human studies. With extremes, what we believe to be true today in printed textbooks may just be mere folly, because all of the pathways were studied in mo dern day climates. The research on evolutionary biochemistry today is in its in fancy. With that all being said, iff the brain is capable of rewiring, this implies tha t the cells it is made from, the micro-machines within those cells, the proteins and enzymes they are made from, the space-time windows they exist in, and the a tomic and subatomic particles they are all made from must also have the inherit capabilities to be plastic as well. Einstein hypothesized this early in the 20th century and so far to date, no theory that has been mathematically proven by qua ntum mechanics has been experimentally proven to be false. This implies the the

ory is pretty solid. Assuming Einstein was correct, we must conceptualize what it may mean for biologic micro-machines in our cells. It appears biology is beginning to find out why these new founded ideas and real ities may hold for us a new world of possibilities and realities with regard to the biochemistry of life in general.

1. Radical new truth number one If our brain can rewire, then Einstein s theories pr edict our biochemistry might be able to as well.

Mind you, when I use the word rewire I am not saying this in the literal sense. I am saying it is thermoplastic. I am telling you that the laws of chemistry ex hibit some unusual properties at extremes, and that the laws of evolution seem t o have used this in our past for adaptation for and natural selection to allow a ll life a chance to thrive in the natural extreme conditions on earth. We have a model for this today in our own solar system that has transfixed modern bio-as trophysicists for the last few years because of the possibilities it holds for u s and for the universe. 2. Radical new truth number two: Considering that 90% of the earth s current biome lives in extreme conditions on our own planet still, we might need to consider that what we think is our normal environment is not so normal for most of life on our planet or our evolutionary history. Life on Earth evolved in an environment much like we see on Titan today; in a deep ocean frozen solid at its surface wi th the capability of life buried deep within it. The only escape was due to eje ctants of water vapor from super heated water from underwater volcanos. All the se things are present today on Earth s crust too. There is one major difference n ow between the two. We are warmer today than life began. There are others, but when one looks at Titan, we see a frozen giant moon with a monstrous ocean bene ath it. All life on our planet came from the oceans first. And because of this, maybe w e should consider studying extremophile forms of life here on earth. This might explain the complexities of how biochemistry allows for life to exist at all in a thermoplastic environment. Based upon what is in our textbooks today, underst anding how life lives in 25,000 feet of freezing water is unknown. Moreover, on those geothermal vents we have bacteria that live in 750 degree water that cann ot boil because of the pressure and cold of the water, causing us to wonder how life manages this perplexing set of circumstances. What the bio-astrophysics fo und on Titan with the Cassini Solstice mission, ( x.cfm) may be a huge clue that life first adapted to extreme environments, and t hen was naturally selected and adapted to a cyclic warming trend on our planets crust over time. Our hominid species may have adapted during this warming trend, but the DNA we i nherited came from animals that were cold adapted. Evolution uses epigenetics t o determine adaptation to environments. We have discarded the strict definition of genetic determinism. We know today that the power of epigenetics dictates a lot more about newer generation s adaptations than we even knew ten years ago. T he implications of this information now has to make us look at some of our own l ong standing assumptions about how living cells work in cold and warm environmen ts to see how our cells react to a thermoplastic environment. It may be that Titan represents today where the Earth was 3-4 billion years ago, and offers us an opportunity to gain some insights on how life starts in extrem e environments and how it slowly changes as the environment changes. Evolutiona

ry pressures are selected for by the environments of our ancestors were exposed to, and not for what we face today. We remain unsure what the power of those ep igenetic pressures can exert on our genome. They may not have even made a big im pact when hominids evolved 2.5 million years ago because by all geologic account s, it was still warm. But it remains possible that the impact could be a lot la rger than we expect as well. We may not fathom this possibility, but it is clea rly in the realm of possibility. The modern science of epigenetics shows that w ho we came from, and what they faced has a direct biologic effect upon subsequen t generations DNA and phenotypes. It is crystal clear today, but the biologic i mplications remain unexplored in all modern day literature. What is happening o n Titan maybe like opening up a black hole back to a reality that used to be our own. The ability to see Earth at life s evolutionary beginning.

Sounds pretty radical doesn t it? As Dr. Spock said in Star Trek movie, When you h ave eliminated the impossible, whatever remains, however improbable, must be the truth, correct? This is where the story of Factor X begins



I first became aware of this seeming paradox as a neurosurgical resident in my f irst year of training. We were doing a real gnarly brain surgery case. It was a young mother who had a massive basilar tip aneurysm. Back in the mid 90?s before endovascular coiling procedures we use today, this was the most risky operation that existed in all of medicine. I spent a month prepping for this case. We h ad to enlist the cardiovascular surgeons to come in and surgically open the pati ents chest wide open to stop her heart on purpose temporarily and place her on c omplete cardiopulmonary bypass to stop all the blood flow to her brain. We had less than 20 minutes to then place a clip across the aneurysm to save her life. To complete this herculean surgical task, we had to fill her entire chest cavit y with ice to preserve her heart muscle and cool her core temperature so that we

could have 20 minutes to complete the brain surgery. Simultaneously, we would open her skull and split the Sylvian fissure in the brain and approach her basil ar artery in the geographic center of her head and attempt to put a clip on it w ithout disturbing any of her surrounding anatomy. The best mental image I can g ive you for this is the ultimate game of Operation you used to play as a kid. You must avoid hitting the sides or the nose lights up!!!! One problem in this case, in this game there was live bullets. This maneuver was deadly if not performed correctly the first time. This is one of the most delicate surgeries one can do on a human. Moreover, even if we were successful with the clip obliteration of t he aneurysm, we had to restart her frozen heart, get her off cardio pulmonary by pass without an air embolus and awake. In this case everything went well until the last part ..and this taught me a lesson I would never forget. She died after t he operation was a complete success. Her head was already closed up surgically and dressed, the intraoperative angiogram looked awesome, and we restarted her h eart and got her off cardio pulmonary bypass without any evidence of a stroke ..and then she died suddenly. She received two units of cooled banked blood because our surgical team felt she lost some ability to carry oxygen in her blood because several of the monitors showed she had a low oxygen carrying capacity of her hemoglobin. This concerned us because we were worried about her risk of having a stroke because of low oxy genation due to her loss of blood flow for 20 minutes when she was on full bypas s. So we did what any surgeon would do .we gave her blood to restore her oxygen carryi ng capacity and the oxygen monitors showed her oxygenation had totally returned to normal. We were all happy until I noticed her pupils were fixed and dilated when I was putting on her dressings. She also had blue fingers. And then all o f a sudden she got a fatal heart rhythm, and she died right there in my arms. I was devastated. I will never forget talking to her family later that day. What I found out 2 weeks later about why this happened was more shocking. She d ied because of the combination of her cooled blood with her cooled heart allowed for a biologic change in how oxygen was released in her capillaries. In cold e nvironments, oxygen is not released in the same fashion as it is normally in a w armed surgical environment. In capillary beds that feed cells for respiration, the oxygen is tightly bound and it is returned to the heart still oxygenated. T his highly oxygenated blood was sensed as normal by our oxygen monitors giving u s the false belief that everything was fine. Her blood was fully oxygenated but the cold provided us with a major issue we were unaware of. If a anesthetized patients core temp is too cold red blood cells do not release the oxygen at the right time or in the right place in a capillary bed to allow for respiration. I t does not matter if your blood is well oxygenated at all. She basically suffoc ated because the cold starved her tissues of oxygen. The cold cause increases t he binding affinity of oxygen. It also causes protein transformations of the Hem oglobin molecule. In fact, cold environments can have some rather shocking effec ts on human biochemistry, I learned after this case. One factor can change ever ything you think is true. I never forgot this lesson. If we had used slightly warmer blood, as we warmed up her core temperature she likely would have never died after this epic operative feat. We did all the crazy hard surgical things correctly but the physical and chemical effects of cold on the oxygen disassoci ation curve took our surgical victory to utter defeat in the matter of 5 minutes .

The moral of this story is that biochemistry acts differently at extremes. Most things published in a biochemistry book are about normothermic reactions. Do n ot forget this because everything you hear from a scientists mouth is based upon those conventions. Modern humans have two pathays they can operate on metaboli

cally. One is just OK (mesophilic), and the other on is Optimal (Psychrophilic) 99% of the world does not know about the Ancient psychrophilic (cold) pathway in mammals. That is changing rapidly today. We are going to discuss this over the next few blogs as I slowly break down the biochemistry for you to digest.

THE BIOCHEMISTRY OF COLD: OK . BE PREPARED ITS GOING TO HURT YOUR HEAD NON SCIENTIST: Cold adapted mammals can do things warm adapted ones can t because at extremes chemistry, physics, and biology change when the temperature is colde r.

GEEK ALERT: Our anthropocentric point of view has resulted in the classification of cold-adapted organisms as extremophiles, even though environments of permane ntly cold temperatures (around 0C) abound on Earth, especially when one considers that these include not only the polar and alpine regions but also deep-sea wate rs. 90% of life on this planet is cold adapated as we speak. Psychrophiles, bo th prokaryotic and eukaryotic, have successfully colonized these cold environmen ts and are able to grow efficiently at sub-zero temperatures. This adaptation re quires a vast array of structural and physiological adjustments in order to coun teract the reduction in chemical reaction rates due to the low temperature of th e habitat. Most scientists study human physiology in mesophilic environmental co nditions. This is a big problem. The reason is that humans have completely diffe rent abilities in cold and the resultant physiologic changes are often 180 degre es opposite that one would expect. This fact has blinded many scientists and phy sicians to some deep realities about human biology. Temperature is one of the most important environmental factors for life as it in fluences most biochemical reactions. Low temperatures slow down and strongly inh ibit chemical reaction rates catalyzed by enzymes, the work- horses of cell metabo lism. The effect of temperature on chemical reactions is basically described by the Arrhenius equation: k = Ae -Ea/RT , where k is the rate constant, A is Ea is the so-called activation energy, R is the gas constant (8.31 kJ mol ~1) and T is the temperature in kelvins. Accordingly, any decrease in temperature wi ll induce an exponential decrease of the reaction rate, the extent of which depe nds on the value of the activation energy. The thermodependence of the activity can be approximately expressed by the Q10 value that is normally close to 2- 3. This is the main factor preventing the growth, at low temperatures, of non-adapt ed organisms. So biochemistry of cold says we should have slow growth patterns based upon the biochemistry. I told you earlier that evolution has sped up treme ndously as time has gone on. So the question remains is, how did evolution overc ome slower growth? Since the cell cycle was slowed by cold it sped up epigenetic s to compensate for the slower growth. That is the basis of FACTOR X. It is th e most important part of my theory because it is why the human brain was natural ly selected for in a mismatched environment.

THE LOW TEMPERATURE CHALLENGE TO LIFE: For the non scientists: the take home enzymes adapt at extremes to allow for ideal function and ideal signaling to improve metabolic efficiency For the geeks: Biochemistry at extremes reveals three basic features: (1) psychr ophiles synthesize enzymes with higher specific activity (kcat) at low and moder

ate temperatures; (2) the apparent maximal activity for cold-active enzymes is s hifted towards low temperatures, reflecting their weak thermostability. (3) the adaptation is not apparently complete, as the specific activity displayed by ps ychrophilic enzymes around 0C, although high, remains generally lower than that o f the mesophilic enzymes at their own environmental temperature.

KINETIC OPTIMIZATION OF ENZYMES: Biochemistry is thermoplastic too! For the non scientists: the take home: If evolution faced this problem before it has a plan to adapt already built in. Cold makes proteins and enzymes bend in d ifferent ways than oocurs in warm states. Skip ahead to next one to make your h ead feel better.

GEEK VIEW: A possible strategy to counteract the negative effect of cold on the activity of an enzyme could be to synthesize more enzyme, but it should be easil y understood that this would be energetically expensive move. Energy sources in cold are scarce because food is not abundant therefore evolution had to come up with a plan B. Therefore, the common strategy used to maintain sustainable acti vity at a permanently low temperature is to produce a cold-adapted enzyme with e nhanced catalytic efficiency kcat/Km (Feller & Gerday 1997). A compilation of a vailable data (Smalas et al. 2000) indicates that cold-adapted enzymes optimize their catalytic efficiency by increasing kcat, decreasing Km or by changes in bo th parameters simultaneously. Mother Nature is a master of biochemistry at extr emes. Too bad our species is not. She uses quantum effects to make this work. As also expected in cold, all psychrophilic enzymes studied so far display much lower delta H# values, with the consequence that the temperature dependence of k cat is buffered and thus the deleterious effect of low temperatures on enzyme re action rates is moderate in nature. This feature leads to an antagonistic effect of the activation entropy so he activation energy is not as low as would be expected from the decrease ivation enthalpy. It follows that the decrease of the activation enthalpy eaction catalyzed by a psychrophilic enzyme can be considered as the main ve character to low temperatures. that t in act of a r adapti

These interactions initially contribute to the stability of the protein folded c onformation and, as a corollary, their alteration presumably gives rise to an in crease in the flexibility of the structural domain of the enzyme involved in cat alysis. As a consequence of active-site flexibility, the ground-state ES complex occupies a broader distribution of conformational states translated into an inc reased entropy of this state when compared with that of the mesophilic homologue s, leading to a negative value of delta (delta S #)p-m3. ACTIVITY-STABILITY-FLEXIBILITY RELATIONSHIPS OF THE BIOCHEMISTRY: For the non scientist: cold shrink proteins and alters their function to meet ne w demands. Cold requires that we add PUFA s to our cell membranes and alteration of protein folding to accomplish biochemical reactions.

GEEK VIEW:Low temperatures tend to improve the compactness of a proteins by limi ting the breathing of the structure corresponding to micro-unfolding processes. Th erefore, at low temperatures, a mesophilic protein will lose the mobility requir

ed for its catalytic activity. What this means is that as it get colder we need to make the molecules more flexible to work in the cold. This means at extremes, physic laws (QM) do some strange things to our biochemistry. The current accept ed hypothesis (Gerday et al. 1997; Zavodszky et al. 1998) suggests that psychrop hilic enzymes have to increase their plasticity in order to perform catalysis at low temperatures. The enhanced plasticity being generated by the generally low stability of the protein structure. This balance between flexibility and stabili ty represents one of the crucial points in the adaptation of a protein to enviro nmental temperature swings. We now know in 2012 that cell membrane signaling is the single most important feature of cold adaptation. The colder it is the more omega 3?s are need for cell membrane signaling. The warmer it is the less omega three we need in cells to signal. This implies that in warm adapted mammals omeg a 3?s might have deleterious effects. They do. It has been shown that the psychrophilic alpha-amylase from Pseudoalteromonas ha loplanktis has reached the lowest possible stability of its native state (Feller et al. 1999). This has been notably demonstrated by DSC, which is a powerful to ol to investigate the thermal unfolding of proteins. Differential Scanning Calor imetry (DSC) is unsurpassed for understanding the stability of biological system s. DSC directly measures heat changes that occur in biomolecules during control led increase or decrease in temperature, making it possible to study materials i n their native state. I also saw this some remnant effects in my example that o pened this blog. Not only was oxygen binding tighter than normal but there had t o be changes in the hemoglobin molecules to make this physical chemistry happen. It appears that there are some unusual effects in the chemical bonds and in ato ms on a sub atomic level that allow biochemistry to adapt. These adaptations are also present in humans when they are cold adapted. I mentioned earlier in the C T series that mammals have a unique way of altering their own cell membrane stru ctures in anticipation of cold. My theory had predicted that because of the phys ics of the chemistry at cold I am describing to you here. It is clear PUFA addit ions make the cell membranes more fluid in cold so their signaling can work well . This has bigger implications for the optimal fuel for mammals in cold. The mor e extreme the environment the more flexibility the cell membrane needs. This is why omega three fats would be favored over omega six fats in mammals who are liv e in the coldest environments. The reason is that omega three fats have more uns aturated bonds that allow for more fluidity in the cell membranes for ideal sign aling. Take a guess where the omega three sources come from? The deep ocean. It appears evolution is using form for function ideally, once again. The best natu ral source is Krill and other fish that support huge ecosystems in our polar sea s for these mammals. Krill oil use makes a lot more sense for warm adapted mamma ls than fish oil does because of its stability in warm temperatures. This is a m ajor down side to Fish oils.

NON SCIENTIST AND GEEK UNITE: The best food source then for a cold adapted mamma ls biochemistry would be a ketogenic paleolithic diet that has a high omega 3 co ntent.

For the non scientists: This is similar to all the paleo 1.0 books we have in print today. They have com e to the same conclusion however from a different route than I have. I did not c ome to this life template via paleo 1.0/2.0, as I mentioned in my podcast with J immy Moore in May 2011. I came to it by following evolutionary medicine and wher e it took me. We did, however, meet here. This is no coincidence either. This is precisely why I believe the optimal diet for all eutherian mammals is a ketogen ic seafood laden paleolithic diet when they are cold adapted.

I think some will say here , Doc are you totally forgeting that we have had to ti me to adapt to a different diet and do well ? I have not forgotten at all. I think this is precisely what the evolution of the leptin receptor has allowed for ove r time in land based mammals and especially in modern primates and hominids. RADICAL RULE NUMBER 8: The leptin receptor is primordially a cold based electron counter. I think it evolved the ability to function in warm environments as mam mals evolved onto land and took the planet over. They began in the cold seas. My point is that while we can tolerate other diets and thrive on them, they are not optimal because they are not using the leptin-melanocortin pathway for optim al living. That is the distinction I am making here. I think the modern paleo te mplate is great in comparison to a SAD but the best design for all mammals is to use this fuel source while one is in this pathway for optimal functioning. Non scientists pay attention here: Let us use A new Ferrari as an analogy to exp lain this. If you spend 250,000 dollars on this car, would you put cheap gas in it to drive around or will you put super octane in it? Most car enthusiasts woul d not think twice about those options After all if you can afford this type of c ar what is the point of saving 20 cents a gallon on gas? If you buy a new laptop , do you put bad software in it? If you do, what do you get? You get bad perform ance. For tangible things we get this point implicitly. Where our neolithic thou ghts trip us up is in our own Ferrari engines from evolutionary design. Modern hum ans are facing the same choice. What are they putting in their engines? They are choosing cheap gas constantly, and not the best gas at the correct time of the season. And what do they get? Mediocrity as a species is that answer. More bioch emistry coming .Geek alert. Non Scientist take home: there is a lot of life (90%) that is cold adapted on ea rth. There is plenty of proof that biochemistry at extremes is common and exists . GEEK ALERT: Do we have proof of this from real life on our planet now? Yes, in c old adapted Antarctic fishes. The molecular flexibility I mentioned above, shou ld possibly be accompanied by a weaker substrate binding strength and consequent ly by an evolutionary pressure on Km in order to maximize the overall reaction rat e. Psychrophilic enzymes, however, display identical substrate binding site and active site architecture when compared with their mesophilic homologues, as illu strated in the case of A4-LDHs (lactate dehydrogenase) from South American and A ntarctic notothenoid fishes (Holland et al. 1997; Fields & Somero 1998) and chlo ride-dependent alpha amylases from Antarctic bacteria and pig pancreas (Qian et al. 1994; Aghajari et al. 1998a; D Amico et al. 2000). An experimental demon- st ration of the relationship between kcat and Km was recently provided using coldadapted and mesophilic alpha-amylases (D Amico et al. 2001). Stabilizing weak inte ractions found in the porcine alpha-amylase, but absent in the cold-active alpha -amylase, were reintroduced by site-directed mutagenesis in the psychrophilic en zyme. NORMAL MAMMALIAN BIOCHEMISTRY: NON SCIENTIST and GEEKS UNITE: Mammals have special cold adaptors on their skin that wire to the gut and to the central nervous system. This system is not well studied but it is clear that they are involved in readying the animal for cold a daptation quickly and eventually hibernation. Mammals add PUFA s from their tissue stores directly to their cell membranes by a process that we know exists becaus e chemistry says it has to for life to live at the ocean floor. I discussed the m in Cold Thermogenesis two blog. We do not know the precise molecular mechanism s yet, but we do know that it is not DIETARY dependent. This is how mammalian bi ology is designed to work normally. It is actually initially signaled for by exc

essive dietary carbohydrate loads in the diet during summer and fall that occur prior to hibernation. Since This is why diabetes, AD, and most other neolithic d iseases of aging seem to be associated with high omega 6 tissue content. When hu mans never face a winter to rid themselves of the omega 6 levels in their tissue s they concentrate slowly over time. When this occurs we see higher tissue omega six levels and our 06/3 ratios become unfavorable for health. Diabetics have th e highest levels. People with chronic neuropathy and chronic pain have higher le vels. The work of Chris Ramsden has been very helpful to me as a neurosurgeon in treating these people. It is not that the omega six content itself is pathologic, because we need to us e them for life daily. Where it becomes a problem is when we do not rid our cell membranes of excessive PUFA content once winter ends. The reason is because we never face winters any longer because of our brain has created warm clothing and housing for us to use. This is a mismatch. this allows us to concentrate omega sixes slowly over time. We see this in excessive 06/3 ratios in younger people a nd it eventually increases their HS CRP. It will further cause other hormonal de cay with time. I am no longer surprised that I rarely see normal hormone panels in my patients. Modern human behavior is built upon these mismatches because our neolithic thoughts are not congruent to any circadian cycle. Normal mammalian b iochemistry is based upon timing from circadian cycles and food signals. As I sa id in the Leptin Rx and the FAQ s blog timing is as important to us as what we eat . This is why. to regain control you first have to know how fast your chemical c locks are running in you. This gives you insight to how much your modern life is hurting your cellular biology. When dietary carbs show up in our diet normally, we begin to normally upload our PUFA s to our cell membranes because our cell membrane need to be more flexible i n the cold of winter. For modern humans winter never comes because we cover our bodies in modern life. The other mismatch is our diet. We eat a 24/7 diet of carbohydrates and PUFA s while winter never comes. We eat this because we feel bette r doing this. That feeling might be slowly killing you. Wild mammals might have fe elings but they can not act upon them because their are no supermarkets in the m iddle of Yellowstone park catering to their needs and wants year round. Our brai n created all of modern life. This creates huge problems for our cells. Our cell s get over run with omega 6?s and become pro inflammatory over time as our cells are recycled in sleep with autophagy. This is where the cytokine storms and le ptin resistance comes from that shorten our telomeres and age us faster. These cytokines are the fuels that speed our chemical clocks up and shorten our telome res. We remain unaware of this when we are young and have a large supply of ste m cells to replace the ones we are destroying but it catches up to us eventually . It is clear that there is a mechanism to replenish stem cells but it appears i t does not work optimally when our chemical clocks are working too fast. We depl ete more than we make. It is also clear that organ have their own individual che mical clocks so we see differential aging in organs because of this. The only known way to reverse this process is cold thermogenesis while eating a diet that optimizes our Ferrari engines given to us by Mother Nature. What else do we do to keep ourselves in the dark about mismatches? Humans protect themse lves from the cold by clothing and heating. We no longer hibernate because our b rain extinguished that need. We do not have a lot of surface hair either to warm ourselves because we no longer needed it when we evolved into a warm environmen t and began able to control it with clothing. Mammals became able to compensate for a slowed growth rate in cold, by speeding up epigenetic expression of our ge nome to eventually create our species whose brain power far outstrips its somati c genes. We are still prisoners to many parts of our mammalian biochemistry and we seem blind to this as well. The brain is so advanced that it puts our genes c onstantly at risk, while we remain blind to it as we deplete our life force with in us slowly. We, as a species have not realized this until we found out about telomere biology and what it means.

We can now see if this theory is correct for ourselves by checking our cellular age against our real age. So far, not one person I have checked has a lower bio logic age then a chronologic age on telomere assays. This implies that much of modern life is a mismatch. It also implies we need to question every aspect of our behavior to understand the mismatch and how it might harms us. This is how an optimal human thinks. This is also how thoughts can change our DNA. This is w hy I gave you the banana analogy in the Paleo Summit talk. It is an easy way to show you how blind you really are to this situation. Most people found it fasc inating because they never thought about it before I said it. I can not stop th inking about this since I realized it was true for our species 6.5 years ago. Wh en I saw my own mismatch for the first time it was sobering. Much like the video I showed you in the Holy Trinity blog. I have been studying human mismatches, a nd the inflammation cascades they cause for the last 6.5 years. I spend many day s and nights thinking about ways to use this evolutionary medicine to help treat and often reversing disease in my family and in my patients. It is critical to a healthy lifespan. Mammalian life uses this evolutionary blueprint. We are mammals. Mammalian bioc hemistry is thermoplastic in vivo. NASA andAthletes have found it first. Their a pplication and the applications by NASA have opened my eyes. We need to apply th is information to modern healthcare. Sleep and longevity researchers are waking up to this new reality today. Sadly, the human researchers do not understand that all their current studies are not controlling for this mammalian ability. This throws many of their results up in the air. That is a tough reality to swallow. I had to eat my own dogma 6.5 years ago and adapt my own practice. It was diffic ult. I sat down with a some friends who are biochemist in academia in Nashville and this news was sobering to them too. This reality has made them think differe ntly as well about many aspects of science.


Studies done on the Sherpa s and NASA astronauts clearly show a major metabolic be nefit that has not been well explored by modern science and medicine. These an cient programs can allow humans to not only survive on low calorie diets but the y can actually make us superhuman in some respects. Sherpa s and astronauts can s ustain themselves well on a lowered caloric intake yet with superior ability to handle their climates when they are cold adapted. The same has been found true of the native Inuit on their native diet as well. This ability is no longer foun d in the modern Inuit because most now eat a Western diet. We also found out si nce the Cold War ended that the Russians have also stumbled onto this science in their research. Their athletes and cosmonauts have been using this data for ye ars to dominate at alpine sports in Olympic games. It appears the U.S. Olympic swim team and Lance Armstrong got the message too before any of their competitio n here in the US or in Europe. It completely explains why they were able to do things some humans previously could not accomplish. It maybe why people still a ccuse them of cheating. We all heard about Michael Phelps eating escapades by b eing able to eat larger amounts of calories daily routinely in his training for the Olympics! Most scientists at the time said the NBC report of Phelps feat wa s not possible. Ray Cronise was one of those scientists. Well, by conventional calorimetry studies it is impossible. This is why many scientists were lost. They forgot to look under the right rock for the reason it might be true. I can assure you Phelps and Lance Armstrong learned what I learned about leptin and a bout cold. They used this knowledge to become world class athletes, and I used it to reverse my obesity.

The reason modern science believe this to be impossible is because their studies fail to account for the thermal coefficient of the environments that they train ed in. Phelps works out in a pool at 50 to 60 degrees for an extended amount in a day. His training regimen is closely guarded. His competitors have publicly commented that they know what is published in his books are smoke screens becau se he wont even train with his own teammates. Armstrong still has never said pr ecisely what he did but there are many leaks that he worked out in freezers inst alled in his house with stationary bikes built in to them. He also guards his t raining regimen. This regimen shredded their body fat to the small single digit s, and it allowed them to gorge on calories that they became able to just burn o ff as free heat, while increasing their ability to perform work at superhuman le vels. This was possible because they found out that in cold, the leptin recepto r allows for unbelievable adaptability in resting RER. In Phelps and Armstrong s c ase, they were both able to expand their native VO2 max ranges north of 70 acco rding to their former trainers! This is truly super human ability territory and explains their fabulous athletic feats. There are other humans who can induce this biochemistry too. The Sherpa s have the ability naturally because of where they live. In the cold a nd high altitude of the Himalaya s. They cold adapt in a few days when they take a climber to the summit of Everest. They lose an unreal amount of weight when they climb, so they eat pure butter and lard the last 2000 ft of the ascent. N ASA studied them closely and used this information to help maintain the weight o f the astronauts who also lost tremendous weight during space walks in the 1960? s and 1970?s. Many believe that humans are best adapted to use carbohydrates to burn for fuel using endurance exercise. Take a look at the following link from 1994 about the use of fat burning on its effects on VO2 max testing that is of prime importan ce in any high performance athletes. The Buffalo Bills of the NFL are the first team to institute this change because they were made aware of this study done i n 1994 in runners. It is one of the few studies that give a glimpse of what a col d adapted runners can do eating fat. Ironically, these runners were all from Bu ffalo, NY where it happens to be cold. This is the only reason this VO2 max exp ansion was found. When the NASA data came out over the last ten years the NFL t ook notice finally when it was brought to their attention by a the agent of a ho ckey player. The Bills have been the NFL team most ready to adapt because of wh at happened to Kevin Everett their TE in 2007. That story is for a later blog on Factor X.

Conventional wisdom and Paleo dogma state that you can increase your carb load a s you exercise. When you use carbs to fuel your Vo2 max flattens. When you are f at adapted your V02max expands. No one seems to correlate it with their performa nce VO2 max to see how dietary fat helps or hurts their exercise in a thermoplas tic environment. We have all seen and heard that those thoughts all over many b logs about how performance suffers on ketosis. The real problem is they have no idea that it soars when your biochemistry is cold adapted. Well this article s hows that assumption may not be true at all. In fact, the opposite might be tru e. Both used cold training techniques to raise their level of performance. Can fat loading be a better choice than carb loading for performance? Could this be true? Why might be this be the case? Question everything is my response.

TRAINING FICTION: Ketosis is most efficient mammalian fuel in the cold not carb loading.

Modern hominids think this is reversed because all the research is done on warm adapted humans eating the wrong diet. The elite athletes are now finding out th at is not true thanks to NASA.

Burning fat (FFA) actually increases our VO2max when the ancient pathway is indu ced. I test VO2 max routinely in some of my patients, and I will tell you those people who are interested in long term performance and longevity use a ketogeni c version of the paleolithic diet show huge gains in their VO2 max over 24-36 mo nths of adaptation. Being adapted to fat is better for performance too. It inc reases strength and power because the cold increases the steroid receptor affini ty for steroid binding. This means your Growth Hormone and testosterone levels s urge as you cold adapt over 2-3 years. No one studies it that long but it does o ccur. Modern elite athletes are now using it routinely. It just does not happen as quick as most athletes want in modern training, therefore they mistakenly bel ieve that carbs are better for their performance in the short term. The reason is that they only measure their performance over a few months at most. Few cold adapt. The elite athletes are all beginning to cold adapt these days. The NAS A data and Russian data is no longer a secret. Believing that carbs are better for performance might be also be a big mistake that might subjugate your paleoli thic genes. When humans are warm adapted carb provide great fuel but they also increase our ROS as we do this and we deplete our stem cells. Ironically, this methodology s hows no measurable loss in performance to the person in the short term, it actua lly improves it in the short run. This falsely gives the person a false sense o f security that they are improving their body. The look at their facade as proo f. The real problem presents but it does when the get past their 45th birthday. These athletes are depleting their stem cells. It can be measured in their te lomere lengths. Why does this happen? Carb training increases ROS at the first cytochrome of mitochondria when we make ATP from glucose. So what happens to athletes who are cold adapted who use fat to train? Why is k etogenic diet more energy efficient at a Krebs cycle level? The reason is that mammals generate very little ROS comparatively to the warm adapted carb burners mammals at their mitochondria. Why? NON SCIENTIST READ HERE: when you eat fat your mitochondria are less leaky so yo u age slower. When you eat carbs you leak more and shorten your telomeres. GEEK ALERT: During oxidative phosphorylation, almost all of the reducing equival ents produced by glucose metabolism in the Krebs cycle are in the form of NADH ( cytochrome 1/where carbs enter) with the exception of the succinate dehydrogenas e step, which takes place in mitochondrial complex II and makes FADH2. Metabolis m of one molecule of glucose produces an NADH:FADH2 ratio of 5:1 whereas fatty a cid metabolism in beta oxidation and the Krebs cycle will produce a ratio of a 3:1 depending on the length of the fatty acid. This implies that fat burning is red ucing to the interior of the cell compared to glucose burning. Carbohydrates cr eate more oxidation inside the cell. If you do this over a life time you are ju st throwing gasoline on your stem cell population as you age. The toll is seen in your telomere length. This effect is more pronounced in organs that use tremendous energy like the bra in. Over a life time this can results in serious disease of aging that occur so oner than expected. This is what we see in our modern world. Our species is me diocre because this has remained in our blind spot. This is commonly seen in re

tired NFL football players who have substantially reduced life spans. The NFL i s the best example of my theory in practice today. They train hard and carb loa d while building amazing bodies that just wither away quickly as they hit their 5th decades. If you train and eat like this, you burn out fast instead of fadin g away slowly. When you look at the NFL data on longevity it is eye opening. I n modern humans, aging is a biologic novelty. NADH is oxidized only in mitochondrial complex I whereas FADH2 is oxidized only in complex II. Complex I produces more reactive oxygen species than complex II. This means that carbohydrate metabolism increases mitochondrial leakiness compare d to fat burning does. The more leakiness a cell metabolism exhibits the short er are its telomere lengths. Short telomere lengths correlate with disease and shortened lifespan. Fats metabolism by contrast is a less leaky process. Moreo ver, oxidation of fats reduces mitochondrial leakiness and decreases intracellul ar oxidation that depletes stem cells and shortens our telomeres over a life tim e. This is why telomere lengths are a great way to see what your lifestyle choi ce are doing to you as a gross measure of effectiveness. The production of a specific number of ATP molecules from glucose/carbs has the potential to generate more reactive oxygen species compared to the generation of the same number of ATP molecules from fatty acids. THE TRAINER BLIND SPOT? They key question then should be why are these benefits not perceived by athlete s or trainers today? The reason is quite simple. Modern life is fast and we wa nt results yesterday. This is another example of how our neolithic beliefs subj ugate our paleolithic genes. Once again, time is relative for most performance athletes and trainers. This fact is axiomatic in physics, chemistry and biology . This is a neolithic thought that can hurt you over a lifetime without you rea lizing it if you do not look for the evidence in your cells. None of them have realized that the thermal coefficient of their environment makes this biochemist ry work against their telomere lengths in this fashion. It is all relative to th e time of the adaptation. If they changed the environment to cold and used the same diet things would be dramatically different because ROS would be low and th e stem cells protected. If the diet was adapted to a ketogenic version over 2436 months they would see amazing expansion of performance. At extremes, biochem istry changes in nature for our benefit. Evolution has a plan for this because it tapped it many times before. REALIZE THAT modern trainers are oblivious to th is therefore they regurgitate what is best from the literature that is based upo n mammals who are warm adapted eating a warm adapted diet! Can you say major mis match!

Can you prove me wrong or right on this training assertion? Yes you can. We ca n follow this with VO2 max progression in training or with a quantified self pla tform of testing. You could also check your telomere lengths over a fat burning and carb burning training periods. Many professional teams are realizing just how bad warm adapted training on a carb loaded diet is. Since VASPER was studie d in space in the 1980?s and 90?s, the world of training has been inverted over night. It promises 2 hours of exercise in 20 minutes using cold technology lice nsed from NASA. You will not find this reflected in the modern day literature ye t because its been in exercise physiology s blind spot. It takes 15-25 years for bench top research to hit the clinical shores. You will find that when you fat burn 100% of the time your VO2 max goes higher than at any time when you are tra ining using carbohydrates. You can do this yourself in your own gym without any Rx. It is the ultimate challenge to our community. You owe it to yourself to question your own dogma and find out what I already know to be true. The ketoge nic version of the paleo diet is what mammals are best adapted to because it inc

reases our VO2max, REE and RER. This is how all mammals are designed to functio n best. We seem to forget we are mammals too. NFL teams are now introducing thi s type of training over the last few years because of NASA technology and findin gs. Moreover, they are trying desperately to make their game safer for the play ers. This was recently licensed to a company called VASPER in California. It ap pears humans are awakening that their might be a new way to train to live that t hey have never pondered before.

Individual difference in humans who cold adapt.

Special forces training has been at the fore front of this type of information. I have a few friends who are former Seals and Rangers. I spent a lot of time t alking to them picking their brains about their training. Most of what they wer e taught and trained for is not published for obvious reasons. Here is what I f ound. Cold tolerance is increased by large body size (small surface area body m ass ratio), abundant subcutaneous fat, good physical fitness (good ability for h eat production, good circulation), male gender (predominantly due to larger body size), young age (via muscle mass and circulation), cold adaptation and good he alth. Recently it has been shown that also personality affects thermal responses , especially the levels of extrovertion and neuroticism. Increased level of neur oticism dampens or slows the autonomic thermoregulatory responses whereas increa sed extrovertion has an opposite effect.


Why has this escaped your awareness? Your brain is far advanced in design than your genes are because of epigenetics. This is a mismatch you remain blind too for your whole life. This was the basis of my paleo Summit talk. I am going to continue to make you aware of how many modern humans face. They are vast becaus e of our amazing brain. Each mismatch that does not favor our genes shortens yo ur telomeres right under our nose s. That is a reality you better get very comfor table with because it is why our species is now mediocre. It is why old age hap pens in the 50?s now and why neolithic disease is accelerating in younger genera tions. It is why children now have heart and carotid disease below ten years ol d. It is why heart failure is the number one reason for admission and death in a ll humans. It is why Alzheimers is now common when 100 years ago no one knew wh at it was. It is why colon cancer went from 37th to 2nd in death from cancer. It is why ADD and ADHD are common today and were not in decades past. It is why the NHANES curves for obesity have shifted. Yes, fructose is playing a role, b ut it is not the major cause. There is not a disease we face that is not accele rating as time marches on. It is because our modern world is speeding up our bi ological chemical clocks because our brain is expert at creating biologic mismat ches for our genome. There is a reason these things are happening. These diseases did not just show up out of the blue. These mismatches speed up our chemical clocks. It means th e young become older faster so the diseases of aging will show up in us as young people. This has happened in just 8 generations from the Industrial revolution. It is a situation where a progeria-like state has become our modern day primordi al condition.

The cold and a ketogenic diet can slow and often reverse that process. Thermal adaptation, either natural acclimatization or artificially produced acclimation, to cold takes 2 weeks. After the development of adaptation, the physiological r esponses to cold are usually attenuated and cold environment is subjectively con sidered less stressful than before adaptation. Cold adaptation of hands diminish es the local vasoconstriction which allows higher circulation and skin temperatu res in hands (fisherman s hands). The classical forms of physiological cold acclim atization are insulative (increased skin vasoconstriction or subcutaneous fat), hypothermic (decreased core temperature), insulative hypothermic (most common ty pe of cold acclimatization) and metabolic (increased energy consumption).


Behavioral adaptation is most important for the survival of human species. It in cludes e.g., well heated houses, good thermal insulation of clothing, warm vehic les and short exposures to cold. In fact, behavioural adaptation can work so wel l, that no physiological adaptation is developed in winter, as shown in young ur ban residents. These neolithic creations are why we do not see the metabolic ben efits of this pathway in modern humans often. When modern humans become aware of them and their benefits they may consider building a small part of their curren t environment for cold thermogenesis. Modern humans may find that when they col d adapt it will help treat diseases due to mismatches in circadian biology.

Warm clothes and buildings are neolithic creations that t the ancient pathways benefits. Wild mammals can t do oo. Mismatches are not just not good for humans in our nstantly seems like it is summer time due to artificial carbohydrates.

kept us in the dark abou what our brain allows us t modern world where it co light and 24/7 access to

Neolithic disease of aging is total chaos .health is perfect order, in between is m ediocrity. We are searching for optimal. Next up the biochemistry in the brain begins.




The best way to describe this pathway to the lay public is to explain this is ho w evolution allows for ideal form to meet function in a tough environment. This environment is likely the primordial environment for life on our planet. This ma kes astrophysicists excited, because life might also be evolving in places like Titan. The pathway uses very little and gives a whole lot to the organism who us es it. But it requires cold to be present. In the pathway, the less effort you g ive, the faster and more powerful you will be when this pathway is active. Peopl e who live in this pathway can run a marathon with no training. They can lift un real amounts of weight with little training. Their reserve and recovery are just incredible. You have to see it to believe it. Many will cold thermogenesis a ho rmetic process. Those people dont know this because they do not live in this pat hway for the majority of their life and no studies have been done to say otherwi se. For those of us who live in it, (2 in the world I know of) .well, no one believ es it. Everything about this pathway in the human brain is about optimal mammali an functioning. It is as good, as good gets. My entire life now consists about living within the confines of this pathway. Not everyone will choose too but when t hey do get a taste of it, they are just bowled over. The more we induce it the m ore beneficial it will be to our health and to our longevity. Welcome to the leptin-melanocortin pathway of eutherian mammals. Modern life all ows us to live outside your biology and this pathway ..and this pathway brings you inside your optimal self. It is that simple. Optimal is for everyone who wants it. From today on, optimal is now a choice and not a mystery to humans.

I know this sounds to good to be true. You might be wondering how this all occur s biochemically in our brain? NON SCIENTISTS and GEEKS UNITE: Step 1. The metabolic trap door to the ancient pathway is found in our eye. The first step in the process is the normal high dietary carbohydrate intakes in sum mer months when the SCN is entrained to high light levels. During this time many mammals will mate and begin the process of getting ready for winter. So carbohy drates are very good for us in season with high light cycles. This is when they are quite safe. When they do hurt us? The fact that eNOS ENTRAINS THE SCN to react to COLD and not light cycles has ma jor implications for autophagy which occurs in sleep in humans, The major functi on of the leptin receptor in humans is to couple sleep and metabolism, When they are not coupled, due to mismatches it has major implications for human biology. This is where safe starch theory dies slowly on the vine. eNOS directly inac tivates the function of hypothalamic NPY! NPY is stimulated by carbohydrates in the hypothalamus and it drives carbohydrates cravings and food seeking behavior s. Why would mammals and humans have this hardwired into their DNA and in their brains? Evolution says it is biologically impossible to find carbohydrates in chronic freezing cold, is the short answer. There are massive benefits to cell membrane signaling when carbs are excluded in a cold environment. Cell membranes have to exclude carbohydrates in cold to function well. This is why diabetics g ets neuropathy and many other illnesses from glycation. My job as a physician is to point the facts out to you. I ll let you be the judge of who is correct about the science of what is safe of not. For the skeptics who

said I had no proof blog.

.more is coming to demolish the safe carb starch dogma in this

Evolutionary thinking is always the king of the mountain. The literature, in my view, takes a back seat to Mother Nature in the new paradigm of healthcare. In my view, Mother Nature always is right, no matter what the modern research sa ys. Most of the research never took this pathway into consideration. The textboo ks were written in the 1950?s and the cold adapted pathways of mammals are still not studied even today. Since modern scientists do not know mammals have two ma jor biochemical pathways in which they seasonally operate their data is at best incomplete. Moreover, the research is useless when it is based upon a flawed ass umption. (see the cholesterol data as a great example) What is the major flaw in the modern literature? No one realizes mammals have tw o metabolic pathways that they live within normally on our planet by evolutionar y design. In fact, this is how all mammals evolved. One pathway dominates spring and summer, and the other dominates fall and winter. It is the mammalian versio n of Yin and Yang. Moreover, both function in unison on a continuum to make bioc hemistry work for us over a wide variation of environments we are adapted to. Th e metabolic pathways governing cold are the bastard child of the modern world, a nd it has lead to major health care issues for modern man. If you fight Mother Nature s rules for mammals by eating outside normal circadian biology she will bite you in the ass every time. There is always a biologic toll t o pay for this behavior. You need to be very aware of this biologic fact at all times. My point is clear ..modern man is not aware of this, and in fact, his though ts, feelings, and beliefs have kept these facts, in his blind spot since the agr icultural revolution. I think the American Indians were the last group of modern hominids who really understood these natural laws best. Let us look to the Arct ic now for a prime example of how carbs can destroy a cold adapted group by crea ting a mismatch. Let us examine the modern Inuits experience in how that experiment has worked ou t over the last 50 years for their culture. I happen to have a modern Inuit cit izen in Nashville, who is quite famous, so I get his insights all the time. The modern Inuit drive warm cars, eat carbs 24/7, have warm houses, and do not have to battle the cold to live any longer in the Arctic. They have conquered their e nvironment. The results of this are seen in their health today. Modern humans ar e the only mammals that can create their own environment to subjugate their pale olithic genes to get mismatch because they can alter their diet and environment because of their thoughts and their feelings of well being or sickness. An arcti c fox, seal, or polar bear can not do this. For humans, this can work well if yo ur thoughts and feelings are congruent with how our mammalian biochemistry works . There is one big problem; few people and most of the published science have no clue how it does really work to begin with. This blind spot creates major healt h issues that we see today in modern civilization. This is why we perceive diabe tes and cancer as diseases today when they may represent mismatches in modern hu man biochemistry. We must become mindful that those mismatches, may well, kill you. If you eat ca rbs in a warm adapted world, as modern man does today, you create a huge biologi c mismatch. This, in essence, becomes a reverse leptin Rx experiment . The same is true of using lights after the sun set in ipad, iphones, and LED TV s. These misma tches speed up our circadian clocks in a pro-growth mode constantly, while we ar e young. You do many things that are pro-growth, that for a time seem to help yo u, until things falter. Longer term, you pay dearly for this in disease and tra shed hormone panels, and terrible energy and a lack of well being. When you are blinded to all this, your feelings of short term gratification keeps these biolo gic dangers out of your sight and present reality. To you, they just do not exis

t. We essentially become blind to these inherent risks. These results present as a neolithic diseases of aging while you simultaneously lose your stem cells pop ulation. This enables you to look like a rock star on the outside while your lab s crash and burn (assuming you are smart enough to look) and your slowly die wit hin. This is modern Paleo man s ultimate paradox. Check the health records on the native Inuit to see if I am right about this. Th ey are living proof of this mismatch. What has happened to them, is happening co nstantly to us in the western world now. This is why modern man is mediocre. Tho ughts and feelings of a lack of well being on a low carb template today, allows us to falsely believe that carbohydrates maybe safe starches. because we examine t hat data in warm adapted hominids ONLY! It appears on the surface, that this might improve our feelings of well being. In the short term it does make a modern warm adapted hominid feel better, but th e biologic toll is that it speeds up your chemical clocks and it depletes your o f your stems cells as you feel better. We can grossly measure this today with th e rudimentary telomere tests. In the Arctic, when these carbs were provided to Inuit by modern transportation, out of the normal circadian cycle of their environment, they were devastated by disease in two generations. You must live congruent to your biology at all time s for optimal health. Since 1940 the Inuit have been decimated by neolithic dise ase. They are very mediocre group today. Albert Schweitzer s papers on them from 1 913, paint a far different view of their culture and phenotypes of what they wer e like when they ate they way Mother Nature intended them too. There is a huge l esson here for us all. Step 2. NS AND GEEK ALERT: MAJOR NEURAL CIRCUITRY APPROACHING: Mammals send the ir tissue omega 6 to their cell membranes during late summer and all through the fall when the temperature begins to fall and light levels drop. Amazingly, the amount of so-called n-6? polyunsaturated fatty acids (those with the final double bond at the sixth position) in the membranes was found to increase dramatically before the start of hibernation in marmots recently, apparently to prepare the body, and particularly the heart, for operation at very low temperatures. Consis tent with this idea, the transition to a higher content of n-6 fatty acids in me mbranes takes place extremely rapidly just before the animals enter their hibern ation chambers. The changes are reversed, again over a short time, around the te rmination of hibernation in spring, when the animals return to a life at high bo dy temperatures. As the temperature falls further as winter solstice comes, the mammal will then have constructed their cell membranes to further increase flexi bility (more omega 3) as the cold increases as the winter deepens. Cell membrane s loaded with AGE s do not work well in the cold. This is a biologic fact. So evol ution makes sure we do not use carbs in the winter. I think some of my cell memb rane biology friends at Johns Hopkins University might drop their two cents here in the comments, soon enough. Dr. Patricia Kane s life long work confirms what I am saying here. In fact, there is a neural pathway that shuts off all carbohydra te cravings to bolster this evolutionary dictum. Moreover, Mother Nature has sel ected for a special taste receptor to fluorish in cold called CD36. In cold, we need fat not carbs. In fact, we saw in CT five that it requires a more fluid mem brane to get proper signaling to work. When signaling is broken disruptions cont inue further in the chemical clocks of organs. This is why diabetics have so man y unusual organ diseases (eye, nerve, kidney, brain) tied to their diagnosis as the process worsens. This process is controlled by surface skin cold receptors and wiring from the uth, gut, Peripheral Nervous System and to the Central Nervous System via the inal cord and then to the brain. The brain gets inputs of this tract from the gus nerve, and from a CD 36 receptor in the mouth which relays sensory inputs the spinal cord and from the surface cold receptors. mo sp va to

What does CD 36 do for mammals? CD36 is an oral receptor in the lingual papillae of taste buds that mediated perception of long-chain fatty acids. It involves t he gustatory neural pathways in cranial nerve 9 and 10 (glossophayrngeal nerve a nd the vagus nerve). These inputs head to the floor of the fourth ventricle (are a postrema) of the hind brain to synapse in the nucleus of the solitary tract. H ere they interact with the somatic sensory cold receptor system of the face and of the body. The mere presence of the CD36 receptor in all mammals suggests that mammals are built by evolutionary design to have a taste for fatty foods in cold. the fact tha t the SCN also wires to the hypothalamus to turn off NPY is another big clue why we should not eat carbs in the winter. This evolutionary designed system consti tutes a physiological advantage under conditions of food scarcity (in winter s col d environments) by leading the mammal to select and absorb fatty foods when cold is the predominate sensory afferent delivered to the area postrema. This sensor y neural processing is far more efficient in water based mammals because water t ransmits cold afferents more effectively. These mammals, also have a huge dietar y source of omega three s in the deep polar seas to allow for them to do this. La nd based mammals use more omega 6?s in their tissues to increase flexibility and fluidity for signal transduction because the thermal barriers they face are not as steep as water based mammals. This is why I cautioned people early on, that 0mega 6 fats are not always bad for humans here. Mammalian neural circuitry is t he key to understanding where optimal really lies. If you do not understand the essence of what we are, you remain blinded to what may harm us too. HCG DIETING ALERT: Eating MCT, in winter is probably not the best choice for a c old adapted mammal, because they do not help fluidity of cell membranes. This is why we see so many problems in the literature with saturated fats in humans. Th e results did not make sense and researchers attributed them to disease generati on. They did not make sense because they were studying animals at different stag es of their mammalian biochemistry. These fats also can make a cold adapted mamm al gain weight when eaten off season because of this mismatch. This is a revers e analogy to the one I used in the Paleo Summit with the banana in Canada. If yo u want to see proof of this fat reversal ask any person who uses the HCG diet ho w coconut oil or palm oil work for them on protocol. In short it sucks. Why? tho se oils protect warm adapted mammals eating tons of carbs. This is why CO and Pa lm oil are tropical oils and not found in our polar regions. When you ask a human who uses HCG for dieting, you will find they do not do well with MCT s during their HCG protocol use for this reason. In winter, mammals pref er animal fats like ghee, tallow, lard, bacon grease, and pastured butter as the best choices. This is wired into our brain by the CD 36 receptor and the floor of the fourth ventricle in humans too. Seafood is always a good choice no matter what season we are in. Pastured meats and offal are ideal too. Evolution is dic tating what we should eat not Dr. Kruse. I am merely pointing out what many in o ur community are blind too today. I hope to change your reality tonight with thi s knowledge. HUMAN Obesity Caveat: MCT however, will help the obese human however to reverse weight loss in winter because they are a far better choice than any carbohydrate at this time. It was my number one diesel fuel I used for my own weight loss. I t will also make the obese person radiate heat if they use it in fall and winter which is a good sign that they are fat burning and not sugar burning. Coconut o il and palm oil are the ideal fats for spring and summer uses for humans. This w orks only for reversal of a disease and not for optimal living. I have a plan fo r optimal living once you reverse your disease here. Step 3. The suprachiasmatic nucleus (SCN) is the circadian pacemaker that monit ors this dance between darkness and light and the seasonal cold and hot temperat

ures in our environment. Cold temperatures reverses all the normal biology that is used when the SCN is entrained to light. This metabolic trap door is huge fo r mammalian biochemistry. This is the only way to naturally way to enter this br ain pathway now that we know of. When temperature becomes the dominant environme ntal trigger and not light cycles, the leptin receptor induces endothelial nitri c oxide synthetase (eNOS) formation. EDIT 5/12/2012: it appears science has alre ady beginning to find out what I knew was true 6 years ago: Read this link. This really should a dagger to any safe starch belief you still hold. Mother Nature is telling you this, and not me. Are we clear on that? NS: There is no safe starches in winter period because Mother Nature said so, no t Dr. Kruse. GEEK ALERT: Expression of VEGF is high in proliferating and mature brown adipoc ytes and the VEGF receptors, FLK-1 and FLK-4, are expressed in BAT. Irisin is st imulated by cold from muscle as well. The expression of VEGF in BAT may promote and maintain the high level of vascularization in this tissue so that the it ca n counter balance the development of frostbite. Chronic norepinephrine stimulati on and cold stress both result in increased levels of VEGF expression in BAT. Bo th of these pathways cause expression of inducible nitric oxide synthase (iNOS) and eNOS which then shuts down the photic effects of VIP on the SCN. Leptin forc es the SCN to be blinded to light to yoke circadian cycles and use temperature! Remember, endothelial NOS (eNOS) are expressed in BAT. Remember, step one, act ivation of eNOS by cold actually blocks the SCN from reacting to photic stimuli to entrain our circadian rhythms! So the cold turns off control of all circadian rhythms to light and uses temperature instead! This is another shocking surpri se of cold thermogenesis! Can you say bye bye to safe starches now? If you are s cientist, yes you can, and you will say no if you are a paleo dogmatist that enj oys your feelings, more than your health. The activation of eNOS seems to be tie d to the cold environment and replace light as the entrainment molecule for biol ogical rhythms in cold. STEP 4: When cold is perceived by skin cold receptors over two weeks leptin is l iberated from fat cells in massive quantities. Cold empties fats stores like lik e a fire empties a movie theater. It can occur even faster if the method of adap tation is controlled with metal. The modern Zeltiq procedure does this in 45 min utes in a medical office. The cold liberates leptin directly from white adipose tissue (WAT). Cold environments induce a long buried epigenetic program in all mammals that allows for WAT to convert to brown adipose tissues (BAT) to burn ca lories as free heat and not generate ATP or to increase ROS simultaneously. Thi s allows us to age more slowly, while increasing our metabolism and ability to w ork on less calories all while burning fat to make heat to stay warm. We also l ower our body fat while improving our body composition too! The cold temperatur es also raises IGF-1 mRNA to increase Growth Hormone release tremendously. This increases autophagic efficiency and improves muscular and cardiac function quick ly. It does this all without exercise! The cold also increases GnRH and selects for reproductive fitness too. This is important in cold, because most mammals ar e pregnant during winter months. This is where the HCG link comes in for mammals . They use HCG as a turbo boost to burn fat stores from the summer months as the y fattened on carbohydrates. This is where Gary Taubes was partially correct, bu t he failed miserably on how we are designed to get rid of the fat because he di d not know anything about leptin. Ditto for Dr. Lustig. They both came late to t he leptin party. This fat fuel feeds their growing fetus. Leptin controls all oo cyte and placental function in all mammals. The lower leptin levels are, the mor e safe and sound the pregnancy will be. ANOREXIC/ED/OBESE PEOPLE CAVEATS: The corollary here is that the more LR a mamma ls is the more problems they have getting pregnant or staying pregnant. In cold, leptin is at its lowest levels and the mammals is leptin sensitive because of i ncreased receptor binding affinity. This sounds counter intuitive until you see

why evolution would select for this epigenetically when we discuss factor X late r this year. Infertile modern humans take note: So this means that cold environments may also improve fecundity, because cold lowers leptin in number while its receptor beco me supra sensitive. It is too bad conventional wisdom of modern medicine does no t use this to help LR couples who are infertile. I in 7 couples in this country can not have kids because of a leptin receptor problem. The main reasons are cy tokine elevations that inhibit leptin function of oocyte maturation and placenta l development and function. Progesterone is a major foot soldier of leptin here to support a pregnancy. The older the mammal mom, the more critical the leptin s tatus becomes. This is why older mothers have higher risk pregnancies. Their pro gesterone levels suck. And this puts the baby at higher risk for epigenetic fail ures. Epigenetic failures are failures of cell membrane signaling. If you are gl ycated you epigenetic switches do not work well. This is how transgenerational e pigenetics functions. This is where the environment meets the cell. This is why modern children are born with a disadvantages because modern life has pushed pre gnancy back in a womans life cycle. Cold thermogenesis can help your fertility i n a big way. So how does the Leptin receptor flip its function in cold doc? Since cold acutel y raises the serum leptin levels as it is liberated from fat, it confirmationall y alters the leptin receptor to become more sensitive to the hormone level as it is liberate from the WAT. This process is a function of physics, (quantum) as all steroid receptors have higher affinities for their receptor molecule. This i mplies that even if a person has low hormone levels in a warm adapted state once they become cold adapted it does not matter! NON SCIENTIST ALERT: COLD IS YOUR OPTIMAL HORMONE MAKER AND YOU DONT NEED A DOCT OR TO DO IT! COLD THERMOGENESIS CAN BE DONE IN YOUR HOME! Your inner masterpiece is literally inside of you right now, if you learn how to tap it. This was my M ichelangelo moment. (my future book reference) STEP 5: As leptin rises in the serum, It gains much easier access to the brain b ecause Triglyceride levels are low when its cold and you re not supposed to eating carbs!!!! Wild mammals have no problems with this rule but mammals who can cont rol their environment always seem to. This mismatch cause inflamamtion at our gu t lining and raises IL-6 , TNF alpha, and NF kappa beta. All three BLOCK LEPTIN FROM GETTING IN TO THE BRAIN!!!! So if it can t get in, it does not matter if the leptin receptor is set to hold on to the leptin hormone tightly in a love lock. Here is another reason starches are not safe in winter period. This is also why di abetics why are told to eat carbs year round never get better! Diabetics need wi nter and cold more than they know. Diabetes is not a disease. It is normal physi ology missing winter. Cold is what reverses their metabolic syndrome completely. Eating carbs in autumn or winter can alter leptin entering the brain at the hyp othalamus to derail the ancient pathway before it ever has a chance to work. NS moment of clarity: This is why diabetics die early. The ACCORD Trial data jus t showed this. No matter the treatment diabetics get they die 6 years earlier. C hange the channel in your head now. If you live within the cold of winter the an cient pathway reverses you metabolic derangement and it confers health and longe vity. This is 180 degrees opposite, what a diabetic faces. If you want an optima l life you must live with in the confines of this pathway at all times. This pro cess is a life saver for a diabetic. REUNITE: When Leptin enters the brain it binds to the leptin receptor tightly. I t hugs that receptor like a baby latches to a boob when hungry. It this shuts of f all hunger signals rather abruptly in the brain. I am talking like lighting fa st. People in cold have no hunger cravings.

STEP 6: Simultaneously, The cold also raises IGF-1 (Growth Hormone) levels. Whe n IGF-1 is raised by cold it allows us another shocking benefit. It blocks the action of TNF alpha apoptosis of brown fat. Leptin, is also now indicted as a co murder too. (it cause fat apoptosis) See below. NON SCIENTIST ALERT: Leptin and IGF-1 are the mafia hit men of your fat cells in cold. They just melt your fat cells from your body, by killing them PERMANENTLY ! GEEKS ARE UP: The cold decreases our WAT but it also favors formation of BAT. P aracrine factors synthesized by BAT include nerve growth factor (NGF), vascular endothelial cell growth factor (VEGF), angiotensinogen, and NO. The secretion of NGF occurs primarily from proliferating brown pre-adipocytes and in this capaci ty is believed to promote sympathetic innervation of the tissue which in turn pe rmits increased norepinephrine stimulation of the cells in BAT to allow the mamm al to liberate calories as free heat and not ATP to generate energy. Irisin fro m muscle, stimulates the formation of BAT from pre adipocytes in WAT, in the face of extreme low leptin levels with low cortisol levels. The leptin levels g et rid of the extra adipocytes via cell suicide. Told ya leptin was the Quilt s bad ass hormone. There is no need to store fat when you need free heat to survive. This is precisely why Sherpa s exhibit unreal REE, RER and VO2 max measurements compared to the climbers they help reach Everest s summit. Their metabolisms are so fast that they have to eat pure butter and lard for the last 2000 feet of the climb to Everest s peak to maintain weight! WIM HOF ALERT: This is why you are a rockstar, Wim it is not the Tummo!. Do not let anyone else tell you otherwise. You remain the best example of the Ancient p athway on this planet today. PALEO 1.0 and 2.0 dogmatists: Warm adapted mammals wrongly believe that you must increase muscle burning to get rid of fat. That biochemistry is only operationa l in warm light entrained metabolisms. It does not work that way in cold adapte d mammals! GEEKS AND NON SCIENTISTS UNITE: Do we have more proof of this in humans. Yes, I do. It comes the frost bite data on young children. When they get frostbite on t heir faces plastic surgeons realized that they could never repair the fat losses because the fat cells just vanished permanently. This was reported in the liter ature in 2008. Guess where? MGH at Harvard is the correct answer. Right under th e noses of Paleo dogmatists too. Guess what those plastic surgeons did with that observation. They made a company called Zeltiq and became millionaires on the b acks of fat humans. You can now go to any plastic surgeon and ask for cool sculp ting or Zeltiq and have your fat frozen away in 45 minutes with a metal plate. I t cause apoptosis (for the GEEKS) and is called permanent fat loss for NON SCIEN TISTS. For the dogmatists, it s called a biologic reality check. IMMUNITY TOO, LOVES ITS ALPHA MSH FROM POMC: EVOLUTION S LEAKY GUT RX IS RIGHT HE RE FOLKS NS: Say good bye to adrenal fatigue and adrenal issues. How? Remember POMC proteins we talked about earlier? REUNITE: POMC cleaves into alpha MSH and ACTH! Both rise huge! Clarity moment fo r all you afraid of the cold! Your brain is wired to raise ACTH and optimize cor tisol in cold. Can I hear a Hallelujah from the followers! The activation of these programs in BAT has another more clever evolutionary rol e. It allows for activation and repair of the immune system to protect us maxim ally when we are facing a chronic caloric deficits to survive chronic seasonal c

old temperatures. Cold thermogenesis actually strengthens adrenal function by i ncreasing alpha MSH levels across the entire genome and really is the key to the biochemical pathway. These are the ancient leptin- melancortical pathways. No rmally low dietary calorie densities lead to a failing immune system in new born mammals. In cold we do not see this. Polar bear cubs are born in the dead of the winter and live 3-4 months before they emerge from the Den the first time an d rarely die from immunity. They die because of starvation once they are out in the environment. Momma is their main food source, not the polar arctic s food cha in. THYROID TOO? ALL REUNITE (MORE GEEKY THOUGH): THE WARM ADAPTED STORY of metabolism and bioche mistry YOU HEAR REGURGITATED EVERYWHERE ON THE NET: Once leptin enters and binds to its receptors, it effects the lateral hypothalam ic tracts to immediately send a second messenger signal to the thyroid to signal it to up-regulate thyroid function and efficiency. See whne we are warm adapted it require help to partially access this pathway from T3 hormone. If you are LR you never can access this pathway. This specifically is how we can raise our ba sal metabolic rate when we are leptin sensitive. These coupled events, matched w ith leptin s actions peripherally in muscles, occur at the UCP3 sites to burn fat as we sleep at a higher basal metabolic rate. This means electron chain transport d oes not make ATP as usual. When leptin allows this uncoupling to occur we make h eat and not energy from normal metabolism. This means we will burn off our exces s calories as pure heat. This is one reason why calories in and calories out arg ument makes no biologic sense once you understand how leptin works. Humans are b uilt to burn fat at night as we sleep to loose excess weight we don t need. This i s our modern day equivalent of hibernation. Out big fat amazing human brain got rid of winter sleep and took over a two hour window during sleep to replace it. CT-7 covers the gorgeous symphony of human circadian biology. Since it shrunk o ur risk of mismatches has risen exponentially. This is how your brain or feeling s, can undercut you, when you are unaware of what a sped up epigenetics meant to human mammalian biochemistry. SKEPTICS: You wanted data, and now I am killing y ou with it. THE COLD ADAPTED HUMAN THYROID FXN: does not bother with T3 at all. Why? When yo u are supremely LS by cold you go straight the the source, the hypothalamus and make TRH from the brain. The brain controls all thyroid function in cold .forget th e Moose thyroid. SKEPTIC BOMB: You bypass all hormones and TSH too. TRH drives the whole show. Th e brain is completely in control and it up regualtes fat burning everywhere. Thi s is how the Ancient Pathway lights your pilot light. The warm adapted human alw ays complains about the cold and always feels cold the cold adapted on is always pi nk to cherry in cold radiating heat like a furnace. You can thank TRH for this. This is does not even require a thyroid gland either. Is not life grand in the c old, folks? SLEEP IS BETTER TOO, DOC? During sleep however when our temperatures are lowest, their is autophagic repai r constantly ongoing to help repair the immune system. This phenomena is not se en in mammals in warmer environments. Our metabolic and immune functions actual ly increase because of better autophagy due to calorie restriction and heightene d DHEA levels from the cold. Better autophagy also favors deep sleep because it severely lower IL-6 levels. Remember IL-6 is a structural relative to leptin to o. This is why it is easy for mammals to sleep deeply in winter months under gro und. In the warm adapted mammals the biochemistry books say the opposite is tru e. They report those mammals have high levels of inflammatory cytokines increase

temperature to allow macrophages work better for immune surveillance. That is t rue in warm adapted but not in cold adapted ones. Sutherland Simpson has shown that during deep anesthesia a warm-blooded animal t ends to take the same temperature as that of its environment. He demonstrated th at when a monkey is kept deeply anesthetized with ether and is placed in a cold chamber, its temperature gradually falls, and that when it has reached a suffici ently low point (about 25C in the monkey), the employment of an anesthetic is no longer necessary to maintain anesthesia. Pretty nifty trick for a surgeon to kno w. The animal becomes insensible to pain and incapable of being roused by any fo rm of stimulus; it is, in fact, narcotized by cold, and is in a state of what ma y be called artificial hibernation. Once again this is explained by the fact that the heat-regulating mechanism has been interfered with. Similar results have bee n obtained from experiments on cats. I believe the same is true in humans as we ll because I tested this on me. NS: Isn t temperature just amazing? Flip it on, and we become superman. Who knew? Who would have thought this? Still thinking all that published research is reall y worth something to ya now?

IMPLICATIONS OF THE ANCIENT PATHWAY: NON SCIENTISTS (NS): No, you do not need exercise to induce fat loss. Major myth propagated by warm adapted modern hominids. They really buy it because they don t walk on the wild side of our biochemistry. Wil Hof does and so do I. In the co ld adapted, the rules of engagement change. In fact, you can lose weight with n o exercise at all! Yes, I went there. Remember mammals don t do WOD while they are hibernating!!!! GEEKS: This means that a cold environment (skin temps 50-55 degrees) selects for heat production no matter what the light cycles or the thyroid status says it i s on any hormone panel. Anyone who thinks you need carbs to up regulate your th yroid to get you to burn fat just does not understand how we are designed to wor k in a cold environment. It appears long light cycles and warm temperatures all ow for apoptosis for BAT and the growth of WAT in all mammals. This is why we d o not see much BAT in animals that live in the tropics or in humans as they grow into a warm adapted habitat. This includes modern day hominids.This is why man y modern day doctors and consultants believe that carbs are needed for thyroid f unction. Not true if you know about the cold .they don t and now you do. NS: Cold eliminates appetite and hunger period. This makes calorie restriction a n easy thing to complete. This means we live longer. Really Doc? Yes, and here is why .Anytime we increase REE in mammals in cold it calls for reduced calorie die t; because of this we generate less ROS at the inner mitochondrial membrane. T his means that cold thermogenesis will likely extend survival because it selects for longer telomere lengths! To me this information is the most shocking revel ation of the evolutionary biology of the leptin receptor. Are you now starting to see why you feel so good since you trusted me and jumped in the cold water and did not listen to the elitist Paleo 1.0 or 2.0 bloggers? See, I am on your team, and I have been looking out for you because I know somet hing very few do. Now you do too. And I am cashing the check I promised you all, right here and now. Considering the great adaptations this pathway holds, it am azes me why the rest of us are not using it routinely, or why the unhealthy skep tic would not at least try it, as Robb Wolf might say, for 30 days. GEEKS: When leptin is liberated by any biochemical method is generally reduces a ppetite and all feeding behaviors. Cold environments not only liberate leptin b

ut they also liberate adiponectin while creating an increased production of alp ha MSH and ACTH from the POMC protein made in the hypothalamus. Ok, time to hur t your head with some brain biochemistry. Sorry in advance. The first key was the SCN modulation switch that killed the theory of safe starc hes, the second shocker is what happens in the hypothalamus with cold because of leptin. The cold receptors of the skin signal the brain two ways. One is through the bra in gut axis (in the mouth, CD36) and the second is via the spinal cord directly from the cold receptors. The chronic stimulation of the cold receptor turns on t he production of alpha MSH and ACTH. When ACTH acutely rises your sense of well being rockets northward. We are not talking a small amount either, we are talkin g a large amount. Real large. If you have been an estrogen collector as a warm a dapted hominid (most are too) you will notice some bumps as you adapt. Fear not. It soon shall pass. Just up your B12, B6, and your betaine HCL acid as you indu ce CT protocols. So large the increase of alpha MSH and ACTH, that cold adapted mammals tend to have darker skins and the best attitudes even under constant as sault. (Think Inuit, Sherpa s or Monk dark) The Hypothalamic Cold switch of the Ancient Pathway: NS AND GEEKS UNITE RUB YOUR HEAD: This large surge in ?MSH acts as a switch for o ur neural biochemistry; it triggers immediate oxytocin release centrally. The high oxytocin levels stimulate the endocannabinoid production from the PVN as w ell. When both of these hormones are raised simultaneously, it inhibits the rel ease of oxytocin peripherally in tissues. It was recently showed that central i njections of ?melanocyte-stimulating hormone (?MSH) also inhibits oxytocin cells , and reduces peripheral release of oxytocin, but induces oxytocin release from dendrites. Dendritic oxytocin release can be triggered by agents that mobilize i ntracellular calcium. Mammals all have cold receptor systems that use calcium ga ted receptors. This is why Cold thermogenesis only requires the skin temperature modualtion to gain entrance to the pathway. It also makes evolutionary sense be cause the skin and gut are far more exposed to the elements than the core cold r eceptors are so it makes the system far more sensitive to the environment as it slowly changes. The mammalian skin s cold receptors are calcium gated the TRMP8 cold receptors. O nce this receptor is activated it increases mRNA increases in MSH neurons and in creases mRNA of UCP 1 and 3 within 4 hours of exposure in the brain and in our m uscles. This is a very fast adapting system. When UCP 1 and 3 are raised this si gnal is transduced over our fluid filled cell membranes (high 06 and 03 content) to increase the numbers of our mitochondria in our FAT. White fat becomes brown fat and the first fat out is VISCERAL FAT!!!! Say goodbye to diabetes. NS: this means we just invited a fat burning specialist where our big fat stores are so we can get skinny real fast and live longer too. REUNITE: In a warm adapted mammals to be able to do this we would need to be LS and have adequate T3 hormone. We don t need any T3 in cold. Mitochondrial biogenes is is increased dramamtically and WAT turns immediately to BAT and fat is oblite rated. This is how evolution cures diabetes. If your a diabetic you better start embracing the cold and loving the winter. It is the key for reversing most of y our big issues. No CARBS while doing it either! Modern medicine has this ass bac kwards and it is the reason no one is cured . More implications of the Ancient pathway is designed for optimal human longevi ty yep, I went there too. This data implies all that we currently believe about mod ern neolithic aging may have to be re tested in cold environments. I am pretty confident I am correct. For the last 18 months I have been running two simultan

eous N-1 evolutionary directed experiments to disprove this pathway exists. Neit her failed. The currency that drives this pathway is FACTOR X. So you may be ask ing now, how in the hell is this possible from the biochemistry angle? Here is a nother sharp turn in the road. The ability to extend life is due to a cold confirmational change in the leptin receptor! If researchers just alter their testing environments they could use th e natural power of leptin to shut hunger off completely and allow humans to make life long calorie restriction an easy task. But what that really means is more important. All neolithic disease of aging can effectively reversed, if we work within this pathway constantly, and not outside it constantly as modern life has dictated. What is clear is that this ancient pathway is hardwired into all of o ur DNA and our brains and has not been extinguished. I think I know why too. Tha t is also tied to Factor X. I believe that cold is a game changer for longevity and the reversal of many neolithic diseases of aging too. I think if we just ch ange the environmental factor when we study longevity we can activate this ancie nt mammalian program for improved survival. It also means that humans might be best adapted for longevity to a certain environment for survival as well. These insights floored me when I was studying leptin and how I might use it to revers e my own obesity. 1.0 and 2.0 skeptics here: This theory is backed up by these findings in 2006. In November 2006, a team of scientists from the Scripps Research Institute repor ted that transgenic mice which had body temperature 0.3-0.5 C lower than normal mice (due to overexpressing the uncoupling protein 2 in hypocretin neurons (Hcrt -UCP2), which elevated hypothalamic temperature, thus forcing the hypothalamus t o lower body temperature) indeed lived longer than normal mice. The lifespan was 12% longer for males and 20% longer for females. Mice were allowed to eat as mu ch as they wanted. The effects of such a genetic change in body temperature on l ongevity is harder to study in humans, but now in the age of telomere biology I think this is soon to change too. The UCP2 genetic alleles seen in humans so far are associated with obesity so I think this link is biological plausible and ve ry likely too. Having fun yet? NS: The ancient pathway confers optimal living but also longevity for humans. Th e leptin receptor becomes super sensitive and turns on Alpha MSH and ACTH produc tion in every neural circuit in our brain to allow us to have total metabolic ef ficiency. It basically lights our pilot lights of our internal furnaces. Isn t fat burning grand in cold!

1.0 and 2.0 skeptics here: Why temperature is a bigger deal for longevity than m ost think: QUANTUM BIOLOGY/Kitavins link H.M. Vernon has done work on the death temperature and paralysis temperature (te mperature of heat rigor) of various animals. He found that species of the same c lass showed very similar temperature values, those from the Amphibia examined be ing 38.5C, Fish 39C, Reptilia 45C, and various Molluscs 46C. Also, in the case of P elagic animals, he showed a relation between death temperature and the quantity of solid constituents of the body. In higher animals, however, his experiments t end to show that there is greater variation in both the chemical and physical ch aracteristics of the protoplasm, and hence greater variation in the extreme temp erature compatible with life. This means that clinicians who base their beliefs on longevity data on lower animals might be making a big error in judgement abo ut the effects of cold on mTOR and IGF-1 pathways. Until the effects of thermal coefficient of the environment is studied with calorie restriction in humans an d primates we may never have this answer. Understanding the evolutionary reason s for how the system evolved how might give us better insight what really is bes t for longevity.

Moreover, we do have some very serious data from biology and physics that show us that in polar animals their enzymes and proteins work very differently in col d then they do in warm environmental animals who have the same proteins. This i mplies that quantum biology is at play. We have known this data since the mid 9 0?s but the two fields of science do not mingle often. Psychrophilic organisms are capable of growth and reproduction in cold temperatures, ranging from ~15C to +10C. Temperatures as low as ~15C are found in pockets of very salty water surro unded by sea ice in our polar seas. Psychrophilic organisms have successfully c olonized polar and alpine regions and are able to grow efficiently at sub-zero t emperatures. At the enzymatic level, such organisms have to cope with the reduct ion of chemical reaction rates induced by low temperatures in order to maintain adequate metabolic fluxes for biochemical reactions. Thermal compensation in col d-adapted enzymes is reached through improved turnover number and catalytic effi ciency of their biochemical reactions. The environments they inhabit are ubiquitous on Earth, as a large fraction of ou r planetary surface experiences temperatures lower than 15C. They are present in alpine and arctic soils, high-latitude and deep ocean waters, polar ice, glacier s, and snowfields. They are of particular interest to astrobiology, the field de dicated to the formulation of theory about the possibility of extraterrestrial l ife, and to geomicrobiology, the study of microbes active in geochemical process es. In experimental work at University of Alaska Fairbanks, a 1000 liter biogas dige ster using psychrophiles harvested from mud from a frozen lake in Alaska has produ ced 200-300 liters of methane gas per day, about 20-30 % of the output from dige sters in warmer climates. This implies that the same organisms in different par ts of our planet with one environmental change can produce more work and energy than those in others? Sound familiar? HCG diet? Calorie restriction? Michael Phelps? Lance Armstrong? Anyone? ALL UNITE: The point is if life can do this people! Become aware of it now!!! I am fine with you not believing this, but honestly, science does not care if you believe it or not. It remains true, despite your dogma. The reality I am giving you here is a new world order for biology .it means evolution has had to face this in our past. It also means that our biochemistry changes drastically when the e nvironment changes. What happens to Kitavans and Masai do not equal Inuits, She rpa s or Emperor penguins. It means comparing these groups are like comparing appl es to oranges, but we see many in the blogosphere make that error all the time. This is why the macronutrient arguments are a pure waste of time. The environm ent is what controls epigenetics and epigenetics controls how biochemistry works . And biochemistry principles have to follow laws of quantum mechanics. Biology is not immune from them. Quantum mechanics is built in to all organic chemistr y and biochemistry equations .but we remain unaware of how the effects of quantum b iology alters proteins, their bonds and their atoms when extreme situations exis t. So what happens in biochemistry at extremes at a sub-cellular levels to prot eins, enzymes and leptin you ask? WHAT DOES COLD DO TO SUBATOMIC BIOCHEMISTRY? GEEKS and SKEPTICS: Here comes the organic biochemistry answer that will hurt yo ur head. As a biologic rule, all cold-active enzymes display a very high cataly tic efficiency, associated simultaneously however, with a very low thermal stabi lity. This means that as the environment cools the physical properties with pro teins and their bonds radically change even though their chemical formula does n ot. This is due to the quantum effects inherit in their stored energies. In mo st cases in biology, the adaptation to cold is achieved through a reduction in t he activation energy that possibly originates from an increased flexibility of e ither a selected area or of the overall protein structure. So with a thermal pha

se change proteins can rewire just as an organ can. This is an ancient evolution ary fractal design plan, where the biology of the organism at a macro organ leve l, parallels the plasticity in the biochemistry at a subatomic level. This als o implies that all organic biochemical levels in between where most biochemical reactions occur have to follow the laws of quantum mechanics as well. The impli cations here are pretty large because this means that life and enzymes and hormo nes (leptin) can change their function and chemistry dramatically when faced wit h just one single variable change ..the thermal coefficient of the environment they are in. It is true for many variables found on earth but human lineage has not been affected by some of these through evolution it appears. This enhanced plas ticity seems in turn to be induced by the weak thermal stability of psychrophili c enzymes in cells. These evolutionary adaptation strategies are beginning to be understood today by recent advances in the elucidation of the molecular charact eristics of cold- adapted enzymes derived from X-ray crystallography, protein en gineering and biophysical study methods. So how long does it take to get into this pathway? Thought you d never ask ..

It requires 2 weeks of cold to get full adaption in humans. Cold is the most po tent stimulator of alpha MSH and ACTH production. Oxytocin, like ?MSH, mobilize s intracellular calcium stores in oxytocin cells and triggers presynaptic inhibi tion of afferent inputs that is mediated by endocannabinoids.

MORE GEEKY BUT LET S REUNITE FOR LEARNING: Normally hunger would be stimulated by this because it raises agouti levels. But since Agouti uses calcium to be activ ated, and since calcium is driven down in cold as I mentioned earlier, you have no hunger even though you have low calories and low leptin levels. All of these things should be which should be highly stimulative to hunger, IF IT WAS WARM. T hat is what the biochemistry books say. This is where the Holy Trinity comes in. It takes the best of CRON and the BEST of HCG and allows us to eat hardly any f ood at all and not be hungry while our body is burn all our fat to make us this and it increases our body composition because our growth hormone and sex steroid hormones are tightly bound to our receptors firing on all cylinders. To prevent the natural decline in fat mobilization with a calorie restricted die t, cold thermogenesis is the only permanent alternative way to stimulate leptin release to decrease muscular malonyl-CoA. There is another non permanent way to do to it with the fat burning hormone called HCG. The problem with HCG it s effe cts on this system do not invoke the epigenetic programing changes in the liver or brain because the hormone is only active in human pregnancy. It is not desig ned by evolution to work full time, just for nine months in the placenta to libe rate fats for fuel. It appears to also work on the muscles and on the endogenou s opioid system to gain some of its effects. This is why it works clinically, and it has little to do with the restricted caloric diet. Anyone who is warm ad apted and employs a calorie restricted diet of 500 calories immediately raises t heir cortisol which turns off their thyroid by turning all T3 and T4 to rev T3. This is basic warm adapted biochemistry 101. This does not happen on the HCG die t. But its effects are short lived for the reasons previously mentioned and tha t is why people have to remain on protocol for it to work. Not a good long term strategy, if you ask me. But it does work, so I hope all the bloggers and paleo hackers out there can stop name calling the HCGers. Moving to Fairbanks and beg inning to swim in the Arctic Circle , maybe be a better long term move for a cou ple of years until the fat is gone! Wil Hof supports this message. LOL Cold thermogenesis allows for a constant supply of fatty acids to continuously e nter the mitochondria where fat is turned to free heat to allow the mammal to to lerate the cold and where the brain is rewired to allow the liver, heart and ske letal muscle to survive on a ketogenic diet indefinitely for long term survival.

This evolutionary adaptation provides substantial fuel for the body while not depleting blood glucose. This is how mammals naturally adapted over time and why they were naturally selected for by evolution in their environments. This adap tation optimized fat utilization to prevent the need for the body to use lean ti ssue reserves during extreme caloric deficits. This is why mammals were ideally adapted for hibernation too, until they got too smart for their own genes sake. NS: this means we get big ass muscles, lose our fat, and our ability to perform tasks rises beyond belief, while we do no exercise! Got it! This is the road to Optimal we all want that no one thinks exists. It does. I found it, and live in it a lot these days. REUNITE: GAME CHANGER MOMENT! Our biochemistry changes when temperature changes at the hypothalamic level. This implies that biochemistry also rewires as the org an rewires. Cold is very thermoplastic in all mammals. Thank god, our ancestors were all mammals, huh! I know you re all saying it cant be true doc, can it? If it were, wouldnt everyone would be doing it? CLARITY MOMENT: Yes, if they knew about it. They do not. It has been in the huma n blind spot for millions of years because we do not live in these areas of cold and we evolved in the middle of Africa just 2.5 million years ago. the other pr oblem is that since no one knew it existed the smart humans (Paleo 1.0 and 2.0 f olks and their researchers buds and all those trainers.nutritionists and dietici ans) never studied it. NASA found it in the 1960?s and then tested the Sherpas. Albert Schweitzer and Weston Price saw it in the Inuits in the 1900-30?s before they were polluted with the SAD. Then their biochemistry vanished. Most modern b iochemistry books were done in the 1950?s until today. That is why they do not k now. And because they do not know even today, it has become a NEOLITHIC thought that has subjugated your paleolithic genes. It is time you are aware of this fac t. It is the biggest game changer for modern humans. Now you know it too. I am proud to finally bring it to your attention for you to discuss and try. I tested the pathway out on my entire family and hundreds of patients. I know the truth. It s now your turn to find out if I am nuts or perceptive. Its your choice what to do with it. If you want to eat safe starches year round and slowly deple te your stem cells and shorten your telomeres as you do your WOD, be my guest. I think I would rather roll with Mother Nature, on path to Optimal health. I have for a long time now, so have my patients. RADICAL RULE NUMBER 9: BIOCHEMISTRY IS DICTATED BY THIS ANCIENT PATHWAY: WARM AD APTED BIOCHEMISTRY DOES NOT APPLY TO A COLD ADAPTED BRAINS: SKEPTIC ALERT: If y ou still doubt this you will pay a huge biologic toll. All biochemical reactions are thermoplastic in life. This means that many of ou r assumption are based upon what we know to be true in our current environment a nd not the ideal environment that sculpted out genome. These are all unexpected results when you consider the content of any modern day conventional biochemist ry textbook you read. Why is that? Its coming at the end of this monster series , I promise. I can t give it all away.

NEGLECTED GEEKS: So let s review this again from another biochemical perspective. Simulation of cold in studies studies have shown administration of a fatty acid synthase (FAS) inhibitor (leptin) to the central nervous system in obese mice, dramatically reduces feeding behavior, with the increase in hypothalamic malonyl -CoA concentrations. These findings show that during very low-calorie diets (th ink HCG use in humans), a stimulant of a FAS inhibitor like leptin or alpha MSH, would raise malonyl-CoA levels, and decrease the expression of NPY and AgRP to destroy hunger to allow you to actually exist on 500 calories. The reason so ma

ny Paleo s pound HCGer s is because they are clueless about how cold thermogenesis p athways work. Clinically this would sustain satiation for longer periods of time with less foo d. So what could fully induce this program? Cold environments with low light l evels is the evolutionary medicine response I give now. This is where the Holy T rinity meets Optimal. I am inclined to believe this is precisely how the inject able form of HCG allows people to subsist on 500 calories with out hunger. I th ink the reason the injectable HCGers find they need to continue with the protoco l to maintain their weight loss is that they are not controlling for the thermal coefficient of their environment while on HCG. Ironically, most of those patie nts do report feeling cold, too, on the HCG protocol. This is no mystery. It has to do with the activation of the cold receptors in the CNS/spinal cord by the H CG itself. The pathway does not activate fully because of the lack of action on the cold receptors of the skin. The brain is expecting the signal so it appears as a sensation to the women who use HCG from the unopposed spinal cord receptor s in the CNS. HCG, in my opinion, is a partial agonist to this ancient pathway. My bet is if HCG was tested in a colder climates, in human adult, s it would b e might be beneficial for weight loss because it would use leptin and alpha MSH as its tailwind hormones to induce more permanent fat burning while increasing T RH in the brain. In my opinion, using CT is a far better option, period.



NS: All these proteins and hormones allow for some amazing adaptations and behav iors in humans because of the cold.

REUNITE: These signals should dramatically reduce feeding behavior in cold. They all do. The peripheral cold receptors also send signals to the brain s higher co rtex signaling that something has dramatically changed in the peripheral environ ment. The cold releases large amounts of leptin from all stores. This increase in serum leptin is very steep and sustained over weeks to months, and is simult aneously registered in the human hypothalamus by forcing NPY and AgRP (agouti) t o very low levels. When NPY is low the dietary needs for carbohydrates diminish and should be eliminated. IE: biology does not expect to see a banana in your mouth in the winter at any point and if you see it there you will pay. (NS:bye b ye safe starch theory) NPY is also known bu neuroscientists to drive carbohydrat e cravings in all humans. NPY is high in high light levels and low in cold envi ronments. This makes sense because carbohydrates do not grow in low light or co ld environments, so evolution is acting in a congruent fashion with the normal e xpected biology correlates. Evolutionary biology has no built in answer for carb s in winter period. So, if you eat them you will pay a huge biologic price. NS: Fig 1 is modern man of this axiom. See our modern mediocre diabetic species loaded with neolithic disease and lots of little fat humans to follow for genera tions because of our sped up epigenetics. Still with me, non scientists (NS)?

GEEK FEST: The fall in agouti related peptide completely destroys our appetite. This also makes evolutionary sense if you think about it. If one was in a wint er polar hell hole, it would be wise to control hunger since food is quite spars e in a short growth season. This would allow the animal to exist on a low to no calorie diet for an extended period time to survive. This is precisely how pre

sent day eutherian mammals survive the polar winters. Since we are descended fr om them this program is built into to our DNA too, even though we rarely use it. But guess what .its there and I found it in my neurosurgery books. this pathway c ompletely explains the modern Sherpa s ability, it explains Wil Hof, Phelps, Armst rong, NASA s astronauts and Schweitzer s 1913 reports on the Inuit. REUNITE: In the summer, polar mammals become IR eating many seasonal fruits and tubers and they develop IR which signals their hypothalamus that it is time to d en and hibernate. The carbohydrate gut signal causes sped up circadian clocks o f the gut ATPase. Carbs are very stimulatory to the chemical clocks in our cells . This acute large dietary load of carbs then causes an inefficiency at the Mg/A TPase. This means that Magnesium levels drop and we do not make ATP well. We bec ome metabolically inefficient. Our DHEA levels fall and we get the sense of lost energy. We also lose autophagy efficency of sleep. This is all seen in modern d iabetics world wide. See, diabetes is not a disease. It is how mammals signal fo r the coming winter. It how evolution told us we are too account for seasonal ti me. We just created a perennial summer with 24/7 access to carbs and negated win ter entirely with warm clothes, warming seats in Escalades, LED TV s and iPhones, and heating systems in our houses. See evolution has no plan for that either. If you avoid winter you pay in disease. Our brains rapid development caused this m ajor mismatch. Its time to pull your head from your hind quarters and realize it too. You control all the cards here. Just in the last three years, were learned that all mammals have the ability to alter their cell membrane fatty acid content to improve fluidity in cold tempera tures. This signal is then sent to the stromal cells where omega 6?s levels are higher and there is a rapid replacement of omega 6?s fats into cell membranes p rior to hibernation. Amazingly, recent studies showed, the amount of so-called n -6? polyunsaturated fatty acids (those with the final double bond at the sixth p osition) in the membranes was found to increase dramatically before the start of hibernation, apparently to prepare the body, and particularly the heart, for op eration at very low temperatures. Consistent with this idea, the transition to a higher content of n-6 fatty acids in membranes takes place extremely rapidly j ust before the animals enter their hibernation chambers. The changes are reverse d, again over a short time, around the termination of hibernation in spring, whe n the animals return to a life at high body temperatures and circadian biology i s entrained to photic signals and they gut as carbohydrates reappear in longer l ight cycles. This carbohydrate presence increases NPY in the brain and the lept in melanocortin pathway is closed until it is induced by cold in cyclic fashion. These adaptations allow mammals huge advantages at the polar regions. These ani mals are then able to go 4-6 months in a deep sleep without eating or drinking a nd survive with no problem at all. They are also resistant to the pain of cold too. This is why diabetics also have chronic pain so often and neuropathy. It is reversible too. Why do I know that? I have done it and I ran some interesting e xperiments to prove it. That will be in the book. Why can mammals who are cold adapted resist pain? Chronic cold, lowers IL-6 and leptin levels, which signal the brain through the skin, mouth, and gut. This sig nal results in elevated hypothalamic alpha MSH and ACTH secretion by the POMC ne urons POMC is a hypothalamic protein. Elevations of POMC also explain why the native Inuit and Sherpa s have tinted skin. Tinted skin also is protective agains t the cold. I love when a story comes together don t you?

REUNITE AND HOLD HANDS WERE GOING ON THE ROLLER eath alpha MSH and ACTH cleavage from POMC is es is called for by the environmental triggers. aises DHEA levels while reducing IL-6 levels so

COASTER ONE MORE TIME: Take a br activated when this set of circumstanc High levels of alpha MSH also r that sleep is naturally selected

for as well with this epigenetic program. When DHEA raises it increases efficie ncy of autophagy. This makes low caloric density possible because the requireme nts for nutrients drop as the mammals become more metabolically efficient. The reason this system exists is because mammalian evolution called for it at one ti me because all life depended upon it. Was it life s origin, who knows, but it work s this way 100% of the time. 90% of all life on this planet still lives in these climates in our ocean depths and in the polar seas. This is also true in the alpine and deep tundra regions of our planet today. It used to be the normal program of all mammalian life on our planet, but in modern times that has changed radically. Today we make up p art of the 10% who have naturally adapted away from this program. But we think s omehow we are so special. (Neolithic thought cutting your knees out from under y ou) But be very aware that this program is hardwired into our DNA in every mamma l on this planet, including us. If you eat outside its cycle you pay a huge pric e. I know because I take care of those prices in surgeries and disease statistics and you all see what Disney and Walmart visits have become in modern times. Both places littered with obese humans who use motorized carts to get around. The pr oof is everywhere you look when plug in what I am sharing with you. RADICAL RULE #9: It appears modern humans have found that partial activation of this system is possible with injectable HCG, CRON, metaformin, turmeric, resvera trol, the modern paleo diet, and low leptin levels. None of these work well ind ividually unless they are all coupled together simultaneously. The Ancient path way shows its power when all are present together. Today s beliefs about the pale o diet are just partial truths. They are true, but the benefits are greater when you marry the optimal diet with the Ancient Pathway. The modern paleo diet is j ust a part of this gorgeous pathway in our human brain. It will not work unless all conditions are met in unison. This implies anyone who use a part of the path way is only tapping a small part of optimal living. Add them all up, and well yo u probably wont believe some of the things you might be able to do from this nig ht forward. I know I still cant fathom it all, after 6.5 years.


GEEK ALERT: In the normal thermic environment most humans are in today we see dr amatic increase s in skeletal muscle leptin sensitivity while simultaneously decre asing muscle malonyl-CoA needs. When this process occurs it triggers a metaboli c pathway that determines whether or not fat is used for energy by the mammal or not. Muscle malonyl-CoA is a potent allosteric inhibitor of muscle enzyme call ed carnitine palmitoyltransferase (CPT-1). CPT-1 opens a door on the inner mitocho ndrial membrane. It allows for the entrance of fatty acids to enter the mitocho ndria and be converted into energy. When CPT-1 is deactivated by muscle malonyl -CoA, entry of fatty acids into mitochondria for I?-oxidation is inhibited. Thi s means no fat burning is possible. AMPK is deactivated and it activates the enzyme Acetyl-CoA carboxylase (ACC). ACC creates malonyl-CoA, which inhibits CPT-1, and thus reduces fatty acid oxida tion. It allows human to adapt by burning other sources of fuels in the muscles layers and saving the fat for longer term survival. After eating, when blood g lucose and blood leptin levels increase, the activation of AMPK deactivates ACC, which decreases muscular malonyl-CoA. As muscle malonyl-CoA declines, CPT-1 ac tivates and opens access for fat into the mitochondria, where energy can be supp lied through I?-oxidation. This explains how eating food, that is not yet in a f orm that can be captured as energy, can stimulate the use of stored fuel for imm ediate use.

NS: When you eat a warm adapted safe starch diet you can follow the research in todays books and all the conventional wisdom of modern man. You can also find th ese proofs in most paleo 1.0 and 2.0 books. You will likely die earlier than nor mal, and you will get diseases you don t want either. The more you work out to avo id a bad body, the faster your life force depletes. But you will have a good loo king body for a time .before it falls apart too. Think Arnold Schwarzenegger or Gre te Waitz. If you chose to limit your carbs, and not work out like a nut at a WOD , you wont die early, but some bloggers will make fun of your skinny fat and oth er body parts. Both groups will have lots of fertility problems too. Think hypot halamic amenorrhea, eating disorders, hypogonadal failures, the need for in vitr o fertilization and expensive doctoring etc get the picture. It is called the wo rld you live in today.


GEEK FEST: Cold has more effects on cardiac and skeletal muscle. Cold thermogen esis activates a program in the brain that stimulates the skeletal muscle to in creases fatty acid oxidation (fat burning) and this chronic exposure increases resting energy expenditure (RER). RER controls precisely how many calories are required for us to eat in a given day. If you look at most calculators of REE o r RER they never include the most important variable, Temperature, pure and sim ple. They are assuming you are 98.6 F. Cold exposure reduces the need for calo ries tremendously in this equation but allows us to increase our metabolic funct ion (increases VO2 max) to thrive and improve survival. Stop for a minute and t hink what this means. It means you can eat less and survive while increasing yo u metabolic rate as you do it! This set of circumstances seems impossible. But it is not. In fact the Russian federation used it to kill us in the winter oly mpic games for close to 100 years. The ante was raised in 1957 when Russia beat us to space. NASA was formed and they found out about cold thermogenesis in th e most improbable of places where it was cold, high and closer to space. They m et the Sherpa s of Mount Everest. NASA astronauts were sent to train with Sherpa s and Sherpa s were studied by our scientists to see what magic powers they had that o ur astronauts needed for spacewalks in its extreme cold. They learned quickly th at cold is a game changer for human physiology. It created a super human physiol ogy. A pathway, who does not require the human to eat or drink often and yet cou ld sleep like a baby. One who had super human immunity and super fecundity. It also showed that a Sherpa had super strength and an incredible metabolic rate. Some times it was 400-500% above the people they were leading up the mountain. There is a guy right now in the Arctic named Wil Hof, who does all this stuff no w, but has no clue why he can do it. Ray Cronise is working with him too now. He believes his mind is special, and confers to him these amazing abilities. I am here to tell you he is no different than you or I. That ability is built into e ach and every human who wants to access it. Optimal is no longer a mystery to hu mans, it has now become a choice for you today. I have been living in and out of it for 6.5 years. I have done something things that would blow your mind. I exp ect to share some of them at Paleo fx and the remainder of this year before my b ook comes out. The Ancient pathway existence is why they can do this stuff, folks. It is confe rs to us amazing abilities that few of us ever tap, let alone think of. It is in modern man s blind spot, but it has been partially seen in many aspects of human history. Most biochemistry books that smart organic chemists read have been publ

ished from 1950. None of them have used the Sherpa s or any cold adapted mammal to test this. this is why we dont know about it. It is hard to study something you remain blind too. My 2012 goal was to allow sunshine to hit this pathway for the entire world to s ee. It was how I how brought myself back to health. I used it on my family as so on as it worked on me and then my patients asked for help soon thereafter too. I n my encore podcast with Jimmy Moore, I told you I was onto something big ..well, h ere it is. NASA found that Sherpa s had to eat pure lard and butter to maintain their weight when they left base camp for the climb to the top and yet they still shredded we ight! In the years after these discoveries new discoveries added more drama to the story. In 1994 leptin was found, and completely explained why their metabol ic rates were so amazing. It appears as the cold continues chronically, leptin leeches out from human fat rapidly and WAT undergoes apoptosis while BAT is nat urally selected for. Simultaneously, the leptin receptor becomes ultra-sensitiv e to any level of leptin by quickly lowering cortisol levels while dramatically increasing alpha MSH and ACTH. It is like the brain gets jolted into a new real m and immediately rewires, its abilities. Cold temperatures also sensitize musc les to leptin function and there is a quick adaptation by the hypothalamus and w e see a dramatic fall in reverse T3 levels in those who are LR. The increase in muscular performance is the most dramatic in human biology. It can create a su per athletes if it used properly overtime during adaptation. Moreover, it appears the Sherpa s are great athletes for climbing Everest because they are naturally adapted to cold and pressure. They remain the last humans wh o live most of their lives in this environment, but their current diet is not op timal to use this ancient pathway because the mountains block them from the sea. This means there is more performance available to us if we optimize the diet of the ancient pathway. Its close but its not optimal because they have no access to the sea like the Inuits do. Modern Inuits have been ruined by modern man s diet and warm conveniences, just as we have been. Our biology is built to need winte r to offset the damages done in summer. This is why our species is mediocre toda y. It appears evolution used it before for other reasons and that is why we keep it in our brains tightly locked away for a rainy day. The Sherpa s performance, even on a suboptimal diet, still exceeds most warm adapted humans to a great deg ree. This should make every crossfitter stop and think. This tells you that the Cold is big factor in all exercise platforms. Anothe rthing a crossfitter should consider as they kill themselves at a WOD, is how come polar bears and sherpa s c an kill their performance when they do not eat carbs all day and do WOD in the w inter months? In fact polar bears become elite athletes by sleeping and being co ld. I remember distinctly hearing Robb Wolf s podcasts saying how important sleep really is but we dont know why. Well, I do. When I learned about the SCN ability to change biochemical teams, about how lept in controls the metabolic gate of the Ancient pathway s function, and how all ster oid receptors increase their binding affinities in cold, it was on like Donkey K ong. I stopped settling for a D or a C, when I realized an A was available to m e. This amazing performance ability is what makes Sherpa s excellent guides to lea d climbers to the Himalaya s summits with no problem. It also makles polar bears a pex predators in the Arctic.

NS: Just get cold adapated using my protocol and eat a ketogenic paleo diet and watch your entire life change in a year like mine did.

New science has shown that this epigenetic program is hardwired in us and can be instantly implemented by anyone who understands how the system is designed to w

ork. It can be used to counter balance the symptoms of starvation whilst improv ing metabolic rates to help body composition and increase muscular strength and output while eating 40-60% less than non adapted humans. When leptin signaling i s supra-sensitized in the brain, muscle and liver levels by cold thermogenesis a lone, some truly counterintuitive things occur. Biochemistry at extremes, works by different rules. These rules are NEVER used in modern research on human phy siology. This implies, caveat emptor on every bit of CW, or new paleo dogma, yo u are hearing these days.


GEEKS: In cold environments in earths evolutionary history (ice ages), food sca rcity explains the adaptations to thirst, appetite, and increased immunity. The y also exhibit a rapid increase in the expression of skeletal muscle peroxisome proliferator-activated receptor-I (PPARI). This is a transcriptional activator of fatty acid oxidizing enzymes which mobilize fat for immediate use. PPAR I also up regulates uncoupling protein 3 (UPC3) we spoke about here. UCP 3 requires T3 and leptin (or heightened receptor sensitivity) to be working optimally for full functioning in normal environments. In cold environments, it appears the need for optimal T3 levels are provided by the immediate transformation of reversing reverse T3 back to T3 and T4 to stimulate thermogenesis peripherally. Once this is exhausted, TRH from the brain takes over and drives our body to NIRVANA. Lept in levels no longer drives reverse T3 higher as it does in normal physiologic co nditions we see today in humans. UCP3 allows skeletal muscle to turn ATP into p ure heat by uncoupling oxidation phosphorylation in the mitochondria. This mean s per unit calorie burned, less ROS occurs at the inner mitochondrial membrane at cytochrome one (NADH). This implies that our mitochondria are less leaky and m ore efficient burners of energy. The most efficient fuel for this pathway is a ketogenic paleolithic diet. This is covered in my early mitochondrial series an d earlier in this blog. The colder a mammal goes the more 03 it needs for optima l cell membrane signaling. It uses 06?s first in fall as temperatures gradually fall. See, 06?s are not always bad. You need context. Your ideal 06/03 ratio for optimal life needs to be around the 4:1 level for optimal functioning in this p athway. It also implies that the any mammal can raise its own RER and VO2 max easily in cold, increasing their ability to work effectively using less energy! This caug ht NASA attention in the late 1960?s and they went to the Himalaya s to check the Sherpa s abilities. The results of this research were recently just licensed to a company in California called VASPER. One of my colleagues is an investor in th is company. The data on VASPER is all NASA generated in space. This is the bes t cold adapted human data on this planet because it was not done on this planet. I t was done on the space shuttle and on the International Space Station. NASA ha s measured this in its astronauts and Sherpa s and found this all to be true. The Russian s have known about this way before we have. They have used this technolo gy to destroy other countries athletes at the Olympic games since the 1940?s whe n their scientists first found it. This information is why NASA was able to red uce food and water payloads in subsequent space expeditions on the shuttle to sa ve fuel and reduce risks of explosion. They also shared this information with t he US Olympic committee. I suspect this is how Phelps and Armstrong found this out as well and it likely has much to do with their accomplishments. This is th e best of all worlds to the athlete and to the mammal who needs to perform and o r live optimally. (Hey Don L are you listening?) If evolution faced the dilemma in our past, it has a plan for life to survive. I believe all life began in a frozen world at the bottom of our ocean. Cold is

the primordial condition everywhere in the universe, not just here on earth. I t hink it is amazing to me that we have not realized this before now. It appears o ur current reality of life on land is generalized to all other places. This is a nother neolithic thought that keeps the Ancient pathway in your blind spot. I ho pe I just put some windex on your glass eyes tonight. Evolution s modus operundi makes order from chaos. We need to learn how to embrac e the biochemistry of chaos in order to understand what we are ideally adapted t o and what we are ideally adapted to eat. There are some deep biologic implicat ions in these lessons for humans. Biology, chemistry, and physics all exhibit u nusual processes at extremes. Modern life is not lived at these extremes any lo nger but our metabolic engines are designed to live there. This is a biologic m ismatch of evolutionary design caused by FACTOR X.



1. Considering that 90% of the earth s current biome lives in extreme conditions on our own planet today still, we might need to consider that what we think is o ur normal environment is not so normal for most of life on our planet or our evol utionary history. 2. Human cold receptors: (GEEKS) Cold adaptation takes 2 weeks in humans. It i s mediated by surface skin receptors and not the deeper core cold receptors. Th is is the cold sensory afferent loop The cold receptor is called TMRP8 (transien t receptor potential melastatin-8 channel) and is a menthol receptor that is a c alcium/sodium voltage gated channel. These cold receptors wire directly to the dorsal root ganglion in the spinal roots and go to the thalamus and to the spina l cord. This organization is unusual and suggest that humans have a reason for this adaptation and an endogenous cold neurotransmitter system built in to their CNS. TRPM8 activated by cold exhibits steep temperature dependence [temperature coeff icient (Q(10)) of a??40], and the channel openings are accompanied by large chan ges in entropy and enthalpy, suggesting a substantial conformation change. Rela tively little is known about the processing of information from the skin or muco us membrane cold receptors within the central nervous system. But we do know fro m Dr. Jiango Gu (Univ. Of Florida) research that there are cold receptors in the human spinal cord. There are numerous nerve cells in the thalamus as well that respond only to cooling. Responses to cooling the tongue have been recorded fro m a single nerve cell of the brain s thalamus in monkeys and cats (Auen et al., 19 80; Lende and Poulos, 1970). Recently researchers have found how to induce cold in mammals without being expo sed to cold temperatures. The research, led by Andrej Romanovsky, MD, PhD, Dire ctor of the Fever Lab at St. Joseph s Hospital in Arizona have recently found a an tagonist of TMRP8 to induce hypothermia in humans who are awake. Take a guess w ho is a co-collaborator in this research? None other than Amgen! Remember who buried the synthetic leptin trials? This link to me is very suspicious. This i s being studied at Barrow Neurologic Institute (top neurosurgery program in USA) . Neurosurgery tends to use hypothermia more than any other specialty in medici ne because of the protective effects of cold on neurons. I have my eye on this research constantly. I think Amgen knows that cold is the key to many diseases and they want to corner the market on it.

3. Metabolic Trap Door: What most people do not know is how leptin plays a mass ive role in regulating the entrance to the pathway. Research has revealed that leptin can induce expression of a neuropeptide gene called vasoactive intestinal peptide (VIP) through the VIP cytokine response element. VIP actually is what sets the circadian pacemaker to light. Leptin yokes metabolism and and sleep to the light and dark cycle. When temperature becomes the dominant environmental trigger and not light cycles, leptin induces endothelial nitric oxide synthetase (eNOS) that shuts down the photic effects of VIP on the SCN. THIS MEANS LEPTIN IS THE ULTIMATE GATE KEEPER OF THE ANCIENT PATHWAY! It also means that leptin forces yoke our circadian cycles! This n mammals. Eating carbohydrates iring to hypothalamic NPY. This are no safe starches in humans. the SCN not to be able use light any longer to is what opens the leptin melanocortin pathway i seems to close the gate because of the neural w is the main evolutionary biologic reason there

4. Cold liberates leptin from WAT: If the cold is applied chronically, leptin i s natural released from our WAT and this provides our body with an ample serum l evel to drive hunger and appetite to the ground. This is why cold will stop man y eating disorder behaviors and it is also why those on HCG appear to get the sa me effect on a 500 calorie diet. It is no surprise to me any longer why HCG wor ks partially in warm adapted humans at all. It is a placental hormone that burn s fat in pregnancy in mammals. It is part of this ancient pathway. It is just not sustainable as a long term weight loss diet without the cold environment. T his makes the HCG diet limited in its use for 99% of us, but ideal for the cold adapted. It is like the seed in a nutrient depleted soil grows but not all th e way because of missing elements. That is the magic recipe of the Ancient Pathw ay. It needs all players to be present to show its power. 5. The gut control of the sensation of circadian biology is shut down by cold w ith increased receptor affinity binding becoming dominant body wide: The chronic exposure to cold daily increases the number of mitochondria in white and red s keletal muscle by mitochondrial biogenesis. It also causes the hypothalamus to r ewire naturally the lower leptin levels by making the leptin receptor quite sens itive to leptin. This is due to the level dropping but also to the quantum effe cts that occur to the receptor as the cold becomes chronic because of the periph eral skin receptors. It appears the leptin receptor is no longer acting in concert with the vagus ner ve (as it does normally) but it is driven by the cold receptors in the skin s surf ace which are far more accurate as sensing the environment. So this shuts VIP a nd the gut down gut down as a sensory entrainment organ for circadian biology in mammals. This coupled with the cold and negative leptin levels make us exquisi tely sensitive to leptin effects in our hypothalamus. 6. Extreme lowered leptin levels: This immediately drops our appetite while allo wing us to eat very few calories. The cold has another surprise for us. It dec reases CRH and adrenal cortisol production too while sensitizing its receptor to its function. This means cold can reverse adrenal fatigue by strengthening the receptor without raising the cortisol level! It is in fact the best way to imp rove your stress hormone response by ASI testing. What else can cold do? It in creases our endogenous immunity too by sensitizing our receptor to Vitamin D act ion body wide for survival!

Observed Clinical effects of Cold: This explains why NASA studies consistently show increases in metabolisms (RER) tested through indirect calorimeters and increased VO2 max testing. This exapans

ion occurs slowly over 36 months. Most modern athletes wont wait five minutes fo r result. Hence why the modern trainers and Exercise physiologist never see it. It also completely explains how a world class athlete can eat tremendous amounts of calories while not gaining any excess weight while increasing performance. They become adapted to burning fuels as free heat. This is precisely how Lance Armstrong and Michael Phelps were able to increase their VO2 max, REE, and RER s while increasing their muscles ability to efficiently to move loads. After a rec ent CT training session I was able to increase my bench press by 150 pounds with no training! In a recent personal conversation, I found out Wil Hof ran a marat hon of 26.2 miles with no training. He also climbed to Mount Everest s base camp f rom ground zero with shorts, a T shirt and a light jacket with no water or suppl emental O2. I want to see any warm adapted hominid duplicate this feat. It sound s crazy until you understand the power of this Ancient Pathway. The athlete athletes of modern times have finally discovered the benefit of cold training. The Russians have been using the same techniques for close to 100 ye ars now. We now know why all the Russian Hockey leagues are located in freezing cold areas. Might this be the Canadians advantage in ice hockey as well compar ed to US players? Physical exercise, in cold water, such as swimming causes th e body to lose heat at a much faster rate than remaining still in the water. Co ld water robs the body s heat 32 times faster than cold air. Swimming or treading water will greatly increase heat loss by more than 50%. This is good for cold adaptation for sports training, but a bad deal if you fall into the Bearing Se a with out training. The leptin melanocortin pathway uses surface skin receptor s to work and it does not use the deeper core receptors. This means we can indu ce this pathway form skin temps between 50-55 degrees safely. If you cool too fast, or drop your core temperatures you can die quickly. Evolut ion is about survival of the fittest. Not vice versa. Why would one die? Blood i s pumped to the extremities and quickly cooled there. Few people can swim a mil e in fifty degree water because they are not properly cold adapted. Should you find yourself in cold water and are not able to get out, you will be faced with a critical choice; to adopt a defensive posture in the water to conserve heat a nd wait for rescue, or attempt to swim to safety. Swimming to safety decreases survival time by 50% due to heat loss. The loss of heat increases so fast that it induces core hypothermia faster than the brain can rewire to adapt. Studies on Sherpa s show it takes them 5 days to cold adapt in the cold air of base camp a t Everest. In the people they help climb to the Summit, it take them 2-3 weeks to cold adapt at base camp. Elevation and decreased pressures also cause lept in sensitivity too. It appears that deep pressures also have the same effect. I now believe that life has another circadian cycle that it accounts for in barome tric pressures. I am now looking for that metabolic trap door. I know it causes an entrance to this pathway too. There is a clear pressure effect on the leptin re ceptor as well for a reason. Cold adaptation occurs faster in water. In cold adaptation this can also be tur ned into an advantage when one swims because it causes massive calorie burn to f ree heat allowing the person to eat enormous calories to offset the heat losses. NASA and high performance athletes use cold water or ice training to complete unreal feats that most cold adapted humans think are impossible. They are imposs ible to imagine, when you do not know how to access them.

OK HIT ME AGAIN WITH THE BIOCHEMISTRY .. This material is dense, so let s review it again from a new angle. Becoming chron ically leptin sensitive by cold, results in a higher caloric-burning capacity be cause you become able to increase mitochondria biogenesis dramtically. It also sensitizes the leptin receptor affinity to bind leptin tightly. This increased

affinity allows for leptin to induce apoptosis of WAT while Irisin rises and end othelial NOS increase the formation of brown fat to burn more fat as free heat. This is an inducible program that activate just from the chronic cold exposure and has ZERO to do with food or calories. Surprise .calories do not matter in this pathway. In fact, they are accounted for completely differently in the cold th en they are on the Savana using the exact same pathways! Are you beginning to s ee a trend here folks? Being cold adapted confers huge advantages to mammals. You can live perfectly fine and be very healthy at the equator but no one can do what a cold adapted humans can do in cold. So living at the equator while eati ng tight to your circadian biology can give you a B+, but it will never give you and A+. Modern humans routinely think this B+ is an A. Sorry to break the news to you modern humans. It is not even close. Remember the name of my website. It is Optimize Life. I don t settle for anythin g less than what is out there for me. 6.5 years ago I found what optimal really was about. It is now time you discover it for yourselves. RADICAL RULE #9: It should be crystal clear to you now why thinking affects your DNA directly? Thinking errors are the currency of telomere biology. They create the circadian mismatches I have mentioned here and everywhere I talk. The more of these, you make the shorter they become. The toll for bad thinking is paid te lomere length and not in money. Telomere length is time. Nothing is more valuab le in time. If you do not believe that, than you must die by your dogma. Modern hominids do not use these cold adaptations because our brains rapid evolu tion has extinguished the need for hibernation from our own mammalian physiology . This keeps it in our blind spot. When one is not using cold to prime supreme Leptin sensitivity, we expect to see patients who use the same food restriction to see a slowed loss in fat. They a lso undergo an increased loss of lean tissue reserves, and a resulting decline i n resting energy expenditure. This occurs because the cold environment is the s ignal that leptin and T3 use to determines which program is epigenetically expr essed. When people try caloric restriction in normal environments the results a re dramatically different than they are in cold. This single issue has hamstrung longevity researchers for quite sometime. They have found it extremely difficult to maintain primates and humans on these diets because the subjects are driven to eat more due to increased hunger. It appear s longevity research will be changed and their results dramatically altered, jus t by adding chronic cold exposure to their environments. This means what aging researchers believe today will be demolished by newer studies that employ this e volutionary magic. The results of cold thermogenesis predicts that aging will b e radically different when it happens in a normal warm adapted environment and a warm adapted diet. The reason is simple. Less ROS from the inner membrane of the mitochondria at cytochrome 1 means longevity is no longer limited by mTOR or IGF-1 as most research today shows in warm adapted animals or in worms who do n ot use leptin as we do.

NS: IF you want to live and live well become cold adapted ASAP, and stop listening t o CW, Paleo Dogma, or anyone from cross fit. What they believe is not true in a a cold adapted humans. I hope this gives you, your family, and your friends muc h to think about. I think I might take a break for awhile before Paleo fx and le t you all stew in these tomatoes for a while. The implications are huge for our sp ecies. This post has transfixed my being for 6.5 years, but took me forty years to put together in one place. It changed my life, and the life of those I love,

and I hope it changes yours now, too. GEEKS: Thanks for hanging with me through this all. SKEPTICS: Dogmatism and skepticism are both, in a sense, absolute philosophies; one is certain of knowing, the other of not knowing. What philosophy should diss ipate is certainty, whether of knowledge or ignorance. Bertrand Russell I hope you enjoyed this. This was foundational work for my entire Quilt. In fa ct, this is my entire life s work into one massive blog post. It maybe the most im portant blog I will ever write. I suggest you tattoo it, to the inside of your e yelids and remember it when you need it most. Time is our most valuable asset. A s you age that reality will set in to each and everyone of you. That, I can prom ise. I released the e-cookbook on my site today. I hope you like that too my wife was th e brains behind it. I just ate all the meat and protein and let her add the rest of the stuff. LOL That is garnish but she says it tasted real good. Now let s all begin to Chase Change together! Next up CT 7 .the Circadian Biology of Humans you need to pay attention too on the road to Optimal

READER SUMMARY: 1. WHAT SHAPES US, GENES OR ENVIRONMENT? 2. WHAT IS THE NORMAL CIRCADIAN BIOLOGY IN A 24 HOUR DAY? CT-7 is about how we are shaped by our environment by the evolutionary erosion o f time that our ancestors faced. All life on this planet is shaped by two major variables in our environment: the sun and the seasonal changes. No matter the pl ace present on earth, there are always alterations in these two factors that are cyclic, and always accounted for by all living organisms at some fashion. In so me mammals, like man, it is accounted for centrally in the brain and peripherall y in our organ ultradian clocks. This is why we have different patterns of aging in certain organs. From an evolutionary perspective, this makes a tremendous am ount of sense because life is using the knowns of its environment to construct a r eality that will ensure its survival. This is the basis of epigenetic signaling that we now know to be the major genetic modifier of the genome of all animals. The major signal transducer in Epigenetics is found in the cellular signaling in our cell membranes that interact with the environment and our inner hormones th at signal our epigenetic switches sitting on our genes inside the nucleus. Since it is clear that our cold adapted pathways use sensory afferents to signal to o pen the Ancient Pathway, I think it is time we just have a blog in the CT series that discusses what a normal 24 hour day is like in a human circadian biology. We will start our day at 6 AM for the sake of the blog. Non Scientists just read only your parts of this blog the first time. We have lots of GEEKS reading this stuff now so I need to hurt their brains so they get the significance of what I am saying from an evolutionary perspective. Neurosurgery geeks have their own s eparate area because this post has lots of neuroanatomy in it. This should be a review for them and may make them fall asleep though sleep is a very good thing fo r those geeks and, more generally, all of us.

HOW DOES OUR DAY BEGIN AND HOW DOES IT EVOLVE? Non Scientists: This is the modern warm adapted human circadian cycle: 1. Our brain wakes up with a morning surge of cortisol. That is what turns our b rain on at 6AM. VIP helps do this in long light cycles. VIP is highest at 6 AM a nd lowest at 6 PM. Ghrelin is also highest in the morning. Ghrelin is an increti n hormone made in the stomach that has a half life of one hour. NPY and Agouti s timulate the production of ghrelin. Ghrelin sends a signal directly to our pitui tary gland and it influences our metabolism. This is why the circadian cycle in the stomach in the morning is critical to optimal health. I laid that out here i n this blog and it is important part of the Leptin Rx reset protocol. Circadian cycles for the obese are dramatically altered compared to non-obese individuals in the morning. In the normal person, Ghrelin is high when cortisol is highest i n the early morning. In them, ghrelin drops fast when food is eaten too. In the obese, ghrelin is much lower in the morning than expected. Moreover, when food i s eaten, ghrelin stays elevated for an extended amount of time. This happens bec ause of the inflammation associated with the higher leptin levels in the morning in the obese. Melatonin is known to acutely decrease ghrelin and sometimes in t ough cases I will use supplemental melatonin to demolish the morning ghrelin spi kes in people with huge appetites. This is most common in the obese, eating diso rders, and in those with severe leaky gut who crave dairy and carbohydrates. Ghr elin spikes and stimulates NPY in the hypothalamus increasing our desire and abi lity to eat a lot more. Leptin makes NPY decline normally, but if one is leptin resistant this does not occur and appetite is out of control at the brain level. This is why obesity is an inflammatory brain disorder causing hormonal imbalanc e. It is not a disease of stress or emotion. Moreover, this should explain why t he SAD breakfast is so problematic for modern humans. It is a carbohydrate fest. It is also why the Leptin Rx recommendation for protein and fat are so high in the morning. It solves this problem fast. I use protein over fat in the Leptin R x because high fat levels with low protein in the morning cause a spike in gastr ic inhibitory peptide that can induce insulin resistance by itself. Many people do not know this. This is why so many people do not buy Gary Taubes theory of wh y we get fat. Gary has only part of the story correct in my view. When you under stand circadian biology, you get a much more complete picture of how the system works on a 24 hour basis. I became a student of circadian biology when I saw the entire view from a 30,000 foot level. 2. At 6:45 AM we will expect to see the sharpest rise in blood pressure in the e ntire day. This is due to many activated systems in the body getting us ready to fully supply blood to all vital areas to get us motivated to begin our day and search for food. This period of rapid BP rise is why we see so many cardiac deat hs occur in early morning sleep or early wakefulness. This happens when cortisol is highest. 3. At daybreak, when the sun hits the retina, the photic stimulus begins to shut off the secretion of melatonin from the pineal gland in the brain. 4. At 7:30 AM usually after an hour of light melatonin is completely shut off in the brain. 5. At 8:30 the gut has been awakened and peristalsis becomes more vigorous and b owel movements getting rid of yesterday s food stuffs are very likely. This is sti mulated if food is eaten around this time as well. This is called the gastrocoli c reflex. Cortisol, aldosterone and ghrelin are all raised at this time to drive activity, increase our blood pressure and stimulate feeding. 6. Around 9-10 AM we have the highest secretions of the sex steroid hormones in humans and these pulsatile crescendos lead to our highest alertness at around 10 AM in our day to allow us to explore our environment.

7. Our ideal muscle coordination occurs at 2:30 PM and this adapts us best to hu nt for dinner at this time. An hour later we see our fastest reaction times deve lop from our motor systems in our CNS. 8. At 5 PM humans exhibit there greatest cardiovascular efficiency allowing for maximal exercising or hunting. This also occurs during a period of time when we have our best rates of protein synthesis in our body. This is why exercise shoul d be optimally done in this window. 9. As the sun falls at 6PM we begin to see a major changes in the cardiovascular system about a half hour later. 10. At 6:30 PM we see our highest blood pressures due to changes in atrial natri etic factor and antidiuretic hormone (ANF, ADH) in the renin aldosterone axis. 11. Once this occurs over the next 30 minutes (7PM) we begin see a gradual rise in our body temperature as leptin (and IL-6) is released from our fat stores, wi th agouti s help, slowly after dinner is eaten to signal the brain about our fat m ass and inflammatory status. 12. For the next two to three hours leptin levels slowly rise as insulin levels fall. Adiponectin levels also fall during this time frame. These fat hormone sig nals are what activate adenosine system in our bodies. Adenosine is created over the course of the day; high levels of adenosine lead to sleepiness. 13. This peaks at 10PM and then the circadian clock allows for melatonin secreti on after 3-4 hours of total darkness. Serum leptin is rising quickly now (with a gouti s help) as it is released from the fat cells to enter the brain. Agouti is h ighest at this time of the day, even in a normal person. 14. As these trends continue the GI tract is slowly shut down by the circadian c locks and around 11:30 PM and bowel movements are shut down for the night. This means that the vagus nerve is quiet. 15. At midnight leptin begins to enter the hypothalamus to bind to its receptor in the hypothalamus to signal energy reserves while also yoking energy metabolis m to sleep via the hypocretin neurons that control all the sleep cycles. In diur nal animals, sleepiness occurs as the circadian element causes the release of th e hormone melatonin and a gradual decrease in core body temperature. This timing is affected by one s chronotype. 16. It is the circadian rhythm that determines the ideal timing of a correctly s tructured and restorative sleep episode. Melatonin, the hormone from the pineal gland, called the darkness hormone is of great importance in the functioning of t he SCN. The most important target of melatonin in humans appears to be the SCN, as the SCN contains the highest density for melatonin receptors. A double effect of melatonin in the SCN, namely, an immediate effect and long term effect, has encouraged its worldwide use against the ill effects of jet lag. As an immediate effect, melatonin is found to suppress neuronal SCN activity towards night time levels. In terms of long term effect, melatonin can phase shift and amplify cir cadian rhythmicity of the SCN. Melatonin application has been found to be useful in synchronizing the endogenous circadian rhythms not only in people who suffer from jet lag, but also in blind individuals, patients with dementia, and in shi ft workers. With seasonal changes in night duration, there are parallel changes in the duration of melatonin secretion, and this leads to more secretion in wint er than as compared to summer. In the cold environments of fall and winter, mela tonin couples to eNOS and not to light levels. In warm adapted humans in the tro pics light remains the focus of SCN entrainment year round.

17. After the 4 hours of darkness, melatonin secretion increases and this allows plasma leptin to enter the hypothalamus if we are sensitive to its receptor. If we are leptin resistant, this process can no longer occur. 18. Once leptin enters and binds to its receptors, it affects the lateral hypoth alamic tracts to immediately send a second messenger signal to the thyroid to si gnal it to up-regulate thyroid function and efficiency. This is how we can raise our basal metabolic rate when we are leptin sensitive. These coupled events, ma tched with leptin s actions peripherally in muscles, occur at the UCP3 sites to bu rn fat as we sleep at a higher basal metabolic rate. This means electron chain t ransport does not make ATP as usual. When leptin allows this uncoupling to occur , we make heat and not energy from normal metabolism. This means we will burn of f our excess calories as pure heat. This is one reason why calories in and calor ies out argument makes no biologic sense once you understand how leptin works. H umans are built to burn fat at night as we sleep to loose excess weight we don t n eed. 19. The timing of the leptin action is also critical. It usually occurs between 12-3 AM and is tied to when you last ate and how much darkness your retina (SCN) have seen. This generally occurs soon after our hypothalamus releases another h ormone called prolactin from our pituitary gland in the brain. 20. The surge of Prolactin is normally quite large in normal darkness but is sig nificantly diminished in artificially lit environments after sunset. This was sh own in the CT 2 video. This has big implications for modern humans. The reason i s that prolactin release is coordinated with sleep cycles where autophagy is at its highest efficiency and where Growth Hormone is released. If this is diminish ed we generally see lower DHEA levels clinically and higher IL-6 levels on cytok ine arrays. This is a measure of uncoupling of sleep from normal metabolism. I b ase every bio hack I do on this step in circadian biology because it is the most important. 21. The normal large circadian prolactin surge we should see at around midnight, after leptin enters the brain, does not happen if the patient has leptin resist ance, sleep apnea, or has eaten food too close (within 3-4 hours) to bedtime. Th is blocks leptins ability to enter the brain because insulin spikes. As mentione d above, this step is usually impaired if you are a post menopausal female as we ll. This is often why older women sleep badly and gain weight they can not seem to lose in the gym even with a good paleo template and good habits. This is anot her reason I am a big advocate for bio identical hormone optimization in women. This need is greatest in women who are warm adapted. The need is lowest in the c old adapted females because their leptin levels are already low due to the cold. Post menopausal women who are cold adapted tend to do amazingly well clinically in most disease parameters in my clinical experience. The main problem they fac e is that their vanity and dogma keep them from using the cold pathways to becom e rockstars as they age. Exercise training tends to frustrate post menopausal wo men because if their hormone response is altered they have a lot of trouble as t hey age. Men on the other hand do not lose their GH levels until 50-55 years old usually. They are also protected by their testosterone levels which persist thr oughout life provided that they are not suffering from inflammation which direct ly lowers their free and total testosterone levels. GH and testosterone keep a m ans heart and muscles in tip top shape. If inflammation destroys these levels ea rlier in life, it can show up even in younger people. I am finding this clinical result is an epidemic in my own practice. WHAT HAPPENS WHEN STEP 20 IS BROKEN IN MODERN HUMANS? This commonly happens in diabetics, but it is now becoming a very common finding in modern humans because of the excessive use of technology after sunset. These artificial lights also tend to be quite bright and completely un-yoke the norma

l circadian signals from the hormone response. Light after sunset reduces the pr olactin surge we normally see in humans. When we see chronic lowered prolactin s urges we also see lower growth hormone secretion during the anabolic phases of s leep. Lowered chronic GH secretion directly affects cardiac and skeletal muscle function because the process of autophagy is made less efficient as our life con tinues. Lowered GH and the sex steroid hormones at sleep lead to loss of cardiac function. This is why heart failure is strongly associated with low IGF-1 and s ex steroid hormone levels. When growth hormone is not released in normal amounts , it also decreases our lean muscle mass and increases our fat percentage in all our organs and in our body. This leads to slowly declining organ dysfunction an d poor body composition. We can measure this process clinically by looking for f alling DHEA and GH levels levels as we age. WHAT HAPPENS IN NORMAL AGING IN STEP 21? Aging is among the most common features found in studies on modern humans when D HEA and GH craters on hormone panels. The loss of the prolactin surge is especia lly prominent in post menopausal women. Most women begin to suffer from falling DHEA and GH levels around age 35-40 while they are still in peri-menopause. The higher their HS-CRP levels, the faster they enter peri-menopause and the quicker they enter menopause. They also age faster on a cellular level because their ci rcadian chemical clocks are sped up. As a consequence, their telomeres shorten f aster as well. Women have higher levels of leptin for child bearing, so they are more prone to leptin resistant issues then men. Leptin is sexually dimorphic ho rmone. This helps explain why older women struggle with cognitive haze, loss of body composition, poor sleep, and increased levels of heart disease after menopa use. Many physicians think the losses they suffer are due to the loss of estroge n from ovarian failure, but the loss of growth hormone and progesterone producti on are far more significant on their physiology. Progesterone is the off switch to anything that is pro-growth. Modern women are usually estrogen dominant even after menopause because of mismatches in circadian biology. Cognitive loss is es pecially common in post-menopausal women. They also lose on average 1% of their bone mineral density per year from menopause in large part due to the loss of pr ogesterone, not estrogen. Loss of progesterone also corresponds to poor sleep in these women too. Replacing progesterone in women has a major affect on their sl eep and bone stock. It also dramatically improves their memories and cognitive f unction as well. SNACKING AFTER DINNER: EFFECT ON CIRCADIAN CYCLES: If you choose to eat within 4 hours of sleep you will never see the prolactin su rge you need, because any spike in insulin turns off this critical sleep time re lease that corresponds to the cellular maximums of the autophagic process for hu mans. Agouti, the incretin gut hormone also rises in the blood to higher than no rmal levels to block leptin from entering the brain. Diurnal cycles for agouti a re coupled to NPY and have major affects on leptin. Agouti is a gene product tha t normally increases the release of leptin from fat cells at night to signal the brain of what the energy status is of the body. This is great when it is workin g well. When it is elevated due to heavy carbohydrate use in our diet it creates a massive problem. This is why late night carbohydrate snacking is a bad thing to do. It appears 12-3 AM are the critical hours at night are where the remnants of mam malian hibernation lies for our species. These are the anabolic times for sleep when we are rebuilding our proteins and recycling our cellular contents. They ar e three of the most important hours in all human biology. If you miss them, you can bet you have several neolithic diseases for sure. Why you ask? If these thre e hours are not reached enough during our sleep cycle, autophagy is never optimi zed and cellular repair does not occur for our cells. This means we are using ol d broken down parts in our cells as the next day arrives at 6AM and cortisol ris

es again to wake us up. We can measure this efficiency of this process by checking DHEA and IL-6 levels. I also like to measure hormone panels to see if the inflammation has destroyed any other hormone cascades in aging men or women. This is vital in taking care o f older people and treating their longevity. IL-6 levels correspond to Leptin re sistant states as well. This makes sleep and metabolic coupling tightly controll ed by circadian biology at all times of our life. It is magnified because sleep gets worse as we age and our DHEA, HDL, and HS CRP rise. This is where, during a bio-hack, we can see why circadian mismatches can cause neolithic diseases in h umans. Often times we can find the same issues develop much earlier in a young p aleo person who has a lot of mismatches in their circadian biology. I test them the same way I would an older person. PROLACTIN, DOC? You must be asking, why is this prolactin hormone so important in a warm adapted human? Prolactin is not just a hormone that secretes human milk. That is the be st known action of prolactin, but not the most important. Immediately after prol actin is released during sleep, another signal is sent to the anterior pituitary to release the largest amount of Growth Hormone as we sleep (GH). GH is stimula ted only during autophagic sleep cycles in stage 3 and 4 to increase protein syn thesis for muscle growth while you re dissipating heat via the uncoupling proteins . This is where the major release of GH occurs in humans post puberty when they are warm adapted. 99.9% reading this blog are warm adapted. If you chose to beco me cold adapted the GH story radically changes, as laid out in CT-6. The implications here are huge for the warm adapted human if this prolactin surg e is not adequate to allow us to enter the anabolic stages of sleep. Prolactin s urge is diminished by both artificial light at night and by foods that stimulate NPY, (namely carbs and protein) when they are eaten in fall and winter when bio logy says they should not be available. If you are leptin resistant for any reason, have sleep apnea, you will always ha ve an altered body composition because of a low GH level and an altered sex ster oid profiles on testing. The reason is because DHEA is the immediate precursor f or those hormones and is always low in people with bad sleep efficiency. Most VL Cers who are warm adapted face this very problem today. VLC diet is best used in the cold adapted mammal and not the modern warm adapted lifestyle. In essence, this diet is a mismatch for our modern lifestyle. This is why so many bloggers t hink ketosis is a dirty word for performance and body composition. This all implies that as you age you will have higher body fat %, lower muscle m ass %, if autophagy is not optimized by great sleep. This is precisely what we s ee today in most modern humans as they age. Invariably, their sleep cycles and s leep durations are poor and decreased from their childhood levels. As they age, there is a chronic insidious erosion of circadian biology by decisions made by m odern humans over and over again. WHAT ABOUT TEMPERATURE VARIATIONS IN WARM ADAPTED HUMANS? Where does temperature enter the picture? In warm-blooded animals, homeotherms, such as humans, can change their metabolism in order to keep their heat producti on equal to the heat loss. Such animals have a temperature control system and th ereby maintain a rather constant core temperature. Warm-blooded animals live wit h the advantage of an unchanged cell activity and temperature in their core. How ever, the human core temperature falls during the estrogen phase of the menstrua l cycle (pro-growth) and during sleep (circadian rhythm by melatonin). The lowest temperature of the day for modern humans is usually between 2 AM and 6 AM. The temperature cycle is part of the normal circadian periodicity. Our bio logical clock seems to be synchronized with the rotation of the globe daily. Mea l composition and timing, light cycles and temperature plays a role in altering normal cycles and autophagic optimization.

Ovulation releases a sharp rise in morning temperature with its estrogen surge. Progesterone effects seem to explain the higher temperature in the last phase of the menstrual cycle where it calms the the pro growth effects of estrogen. In p ost-menopausal women, this balance is usually not ideal, and it leads to many me nopausal complaints these women face today. The reduced temperature induced by melatonin in sleep is needed for Central Nerv ous System autophagic repair, for another, less well known reason. The lowered t emperature sets the stage for the biologic quantum effects to be optimal on our neurons microtubules that facilitate learning and neuronal spouting that occurs brain-wide. This is why if you don t sleep well you feel badly the next morning and your menta l performance suffers the next few days on cognitive tasks. Research also shows your learning is severely impaired because of lowered BDNF and changes in diurna l cortisol due to the sleep deficit. This is why we monitor truck drivers and air line pilots sleep and wake cycles by law! Moreover, in hospitalized ICU patients or the elderly when this occurs, it sets the stage for the appearance of acute onset delirium. This is exacerbated when t hey also have a simultaneous cytokine storm from sepsis or obesity. We see this often in hospitalized patients who cannot sleep well in ICUs. Acute delirium sta tes very much look the same as chronic sleep deprivation patients we see clinica lly as well. Inducing cold, using progesterone and using hypnotics helps manage these conditions. I mentioned this in my hour long PaleoFX talk last week. Read this link in 3/11/2012 NYT: -the-claim-your-body-clock-can-determine-when-you-get-sick/ OK, NON SCIENTISTS TAKE A BREATHER. GEEKS ARE UP: So today we are going to look more closely about how circadian bio logy sculpts our species. We will assume the sun rises for us today at 6 AM. Abo ut two hours before the sunrise we are at our lowest body temperature and this s ignal is sent to our hypothalamus to the hypocretin neurons that link metabolism (leptin receptor) to the sleep cycle clocks. This temperature dip signals that sleep is coming to an end and that the brain needs to raise its cortisol levels to wake up the cerebral cortex not connected to the autonomic portions of the br ain in the brainstem. This is called the reticular activating system. When the r eticular activating system is damaged, humans remain in a sleep like state calle d coma. Neurosurgeons call this a chronic vegetative state. The release of corti sol is a neuro-chemical signal from the hypothalamus that allows the reticular a ctivating system to wake up the cerebral cortex in the AM. Now we have to think about what season we are in? Is a long light cycle (summer) or is a short one that is cold (winter)? VIP regulates the circadian rhythm in humans and most mammals. VIP is a gut horm one and is found in our taste receptors too! So if we taste sweetness from carbs in our diet when it s warm and they are growing in the environment, our brain is expecting us to be in a warm season rather than a cold one. So sweet means warm to the brain, not cold. If you mismatch that and eat carbs at the wrong seasonal time, you create inflammation in the brain and it throws off our chemical clock s in our cells and ages us faster. That means our telomeres get shorter. This is not good. EVEN GEEKIER: Taste perception and its relationship to glucose homeostasis begin s with stimulation of taste cells located in tongue taste buds. There are five b asic taste modalities: bitter, sweet, umami, salty, and sour. Taste cells are cl ustered into taste buds in the tongue epithelium. Mammals have four different ty pes of taste cells (types I, II, III, and IV), exhibiting different molecular ph enotypes and functional roles. Type I cells are glial-like cells that maintain t aste bud structure. Type II taste cells transduce sweet, bitter, or umami stimul

i and communicate information through G-protein coupled transduction cascades. T ype III cells synapse directly with afferent nerve fibers from three cranial ner ves, and most release serotonin upon depolarization. Type IV basal cells are rap idly dividing progenitor cells that differentiate into type I, II, and III cells . Along with biogenic amine neurotransmitters, it is becoming evident that multi ple peptide hormones including glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), and neuropeptide Y (NPY) as well as VIP are located in taste cells, poten tially acting as signaling modulators of multiple gustatory stimuli. The circadian clock not only can generate its own rhythms but can also be entrai ned by the environmental light-dark (LD) cycle. Multiple single cell circadian o scillators that are present in the clock can, when synchronized, generate coordi nated circadian outputs which ultimately regulate the overt rhythms. VIP is a gut polypeptide, has been identified as one of the main neurotransmitte rs of SCN neurons, and participates in SCN function. These SCN neurons are retin o-recipient and are found in the core of the SCN. They are activated by light, a nd exogenous application of VIP can reset the circadian clock in a manner simila r to that of light application, both in vitro and in vivo. It is estimated that 9%-24 % of SCN neurons express VIP. Leptin was originally described as an adipocyte-derived cytokine that signals to the hypothalamus to regulate food intake and energy expenditure. Leptin signals through its receptor, which is closely related to the gp130 cytokine receptor. Leptin can induce expression of the neuropeptide gene vasoactive intestinal pept ide (VIP) through the VIP cytokine response element, the same element that media tes the response to the gp130 cytokines. Leptin acts synergistically with TGF-be ta to activate transcription through this element. One of the main chemical constituents of SCN neurons is vasoactive intestinal po lypeptide (VIP). Such neurons are retino-recipient and activated by light. Exoge nous application of VIP resets the SCN circadian clock in a light-like manner bo th in vivo and in vitro. These resetting actions appear to be mediated through t he VPAC2 receptor (a type of receptor for VIP). Unexpectedly, genetically ablati ng expression of the VPAC2 receptor renders the circadian clock arrhythmic at th e molecular, neurophysiological and behavioral levels. These findings indicate t hat this intrinsic neuropeptide acting through the VPAC2 receptor participates i n both resetting to light and maintenance of ongoing rhythmicity of the SCN. NEUROSURGERY GEEKS ONLY: In mammals, the part of the nervous system responsible for most circadian behavior can be localized to the suprachiasmatic nucleus (SCN ). Although previous studies suggest that each SCN neuron may be an independent oscillator, these pacemaker cells must be synchronized to each other as well as to the environment to function adaptively. Therefore, answers to questions about cell-to-cell communication within the SCN lie at the core of understanding how his timing system operates. The daily cycle of light and dark is the dominant en vironmental cue responsible for synchronizing this biological timing system to t he environment. The SCN neurons receive photic information directly from the ret inal hypothalamic tract (RHT). Many of the SCN neurons that receive retinal inpu t from these cells are located in the ventrolateral (or core) region of the SCN and express GABA and, in many cases, vasoactive intestinal peptide (VIP) and the Peptide Histidine Isoleucine. These retino-recipient cells then convey this env ironmental information to the rest of the SCN. In brain slice preparations, appl ication of VIP alters the firing rate of SCN neurons through a VPAC2 receptor-de pendent mechanism and induces expression of mPer1 and mPer2 genes. These two gen es are how the circadian cycles yoke directly to the cell cycle and are related to tumor suppressor genes and oncogenesis when mismatches occur chronically in m odern man. Functionally, the administration of VIP, and to a lesser extent PHI, can cause p hase shifts of the circadian rhythms in vivo and in vitro in man. The role of AVP (arginine/vasopressin) in circadian time keeping has also been w ell established in the neurosurgery literature. Its role in the control of circa dian rhythm of food and water intake has been reported and well documented. Anot

her intrinsic neuropeptide, VIP, acting through VPAC2 receptor (a type of recept or for VIP), participates in both resetting to light and maintenance of ongoing rhythmicity of the SCN. NPY and GABA seem to be the neurotransmitters in the pro jection from the intergeniculate leaflet to the SCN adjacent to CN II. Raphe nuc lei projections to the SCN contain serotonin as a NT. AVP and prokineticin 2 are seen in the outputs from the SCN as efferents. NPY, which is an established neurotransmitter of the geniculohypothalamic tract (GHT), was found to regulate SCN neuronal activity and to produce long-lasting s uppression of firing rate of SCN neurons. When co-applied with NPY, NT (neuroten sin) was found to dampen the profound inhibitory effect of NPY. So when NPY is h igh, which would be in equatorial or high light conditions, NPY basically makes the SCN less efficient and allows animals to perform outside their normal circad ian boundaries. They stay awake longer for eating and for reproduction in high l ight times during summer. ALL GEEKS REUNITE: VIP (along with GRP and AVP) show circadian variations in the level of mRNA in constant contact with environmental conditions from our tongue and our gut. When light becomes long lasting in summer, NPY dominates the SCN i n mammals when light becomes low and temperature falls to 50-55 degrees constant ly at our surface cold receptors, and eNOS rises and blocks all photic input to SCN and circadian rhythms are maintained by a new program. Alpha MSH induces and potentiates that seasonal change within the hypothalamus as laid out in CT-6 bl og. THE MORAL: So the brain is wired for foods when they grow naturally, not when we feel or think we can/should eat them regardless of their availability in modern times. Leptin sensitivity directly regulates VIP production. VIP regulates the circadia n rhythm and entrains the SCN to light. When it is cold, leptin is released from fat cells in large amounts, and we begin to use eNOS to entrain our SCN to cold cycles and we should avoid carbs like the plague then. Remember from CT-6, cold empties fat cells like screaming fire would empty a crowded cinema. In cold, th e pituitary-hypothalamic portal is involved in the production of lots of alpha M SH and ACTH. When MSH rises, you are allowing the brain to control everything to get you to optimal. This should make it abundantly clear that cold and warm ada pted mammals are not sharing the same circadian biology. Cold selects for suprem e LS and superior hormone optimization as laid out in the CT 6 blog. In long-light summer cycles, when VIP is controlling the SCN again, androgens no rmalize if the mammal is leptin sensitive. VIP usually fixes our Vitamin D level to optimal too. VIP is a master controller of all inflammation for circadian cy cles, but leptin is the hormone that produces VIP in the correct amounts even in light cycles. So if we are leptin resistant for any reason in long-light cycles , we have no control over our circadian cycles and this leads to neolithic disea ses. Normally, VIP lowers our cytokines as the light cycle lessens as the day progres ses. At night time the cell is more reduced and not as oxidized. Reduced means b etter cellular health and oxidized means more cellular inflammation. The act of cellular reduction happens in autophagy during sleep with repair processes. Reme mber VIP is highest in the morning and this helps it elevate cortisol to wake us up. This is also why cortisol levels are highest when we start our days and low est in the night when we sleep. VIP down regulates most inflammatory cytokines and TGF-B1. It also raises activa tion of T-Regulator cells of our immune system. All of the sickest patients have very low VIP levels and they also have changes in immune toll receptor proteins . Recently, researchers found that circadian rhythms influenced levels of an imm une protein called Toll-like receptor 9, or TLR9, causing a daily peak and nadir . When mice were exposed to bacteria at different times of day, those who were i nfected at the low point of TLR9 activity developed severe sepsis and died much

sooner than those exposed when TLR9 was high. In another phase of the study, mice vaccinated near the daily TLR9 peak had stro nger immune responses than those vaccinated at the circadian low point. This implies those humans with sepsis, leptin resistance, and obesity all have p oor circadian cycle control. It should be no mystery any longer why all of these groups suffer from collateral damage from other neolithic diseases. The risk of neolithic disease goes up in all those conditions. This is how mismatches can c ause inflammation and shorten our telomeres in our cells. Remember circadian cyc les are yoked to the cell cycle as I mentioned earlier in the CT series. This im plies that any source of inflammation will shorten our telomeres and speed up ou r circadian clocks and result in neolithic disease and earlier death. In the late night (4AM) when temperature levels are lowest, cortisol begins to r ise in the blood while leptin levels in the blood are falling. Leptin levels pee k in the blood at midnight to 2 AM. They are lowest in the morning when cortisol is rising. When leptin enters the brain and binds, this is the signal that caus es the surge of prolactin that allows us to enter the two most important hours o f human life when autophagy happens. Leptin is a direct fatty acid synthase (FAS) inhibitor. Fatty acid synthase is a multi-enzyme protein that catalyzes fatty acid synthesis in humans. Its main fu nction is to catalyze the synthesis of palmitate from acetyl-CoA and malonyl-CoA , in the presence of NADPH, into long-chain saturated fatty acids. Fatty Acid Sy nthase expression is stimulated by insulin, a hormone produced when blood glucos e is high. Fatty Acid Synthase is inhibited by leptin, a hormone that has a role in regulating food intake and fat metabolism. Leptin is produced by fat cells i n response to excess fat storage. Leptin regulates body weight by decreasing foo d intake, increasing energy expenditure, and inhibiting fatty acid synthesis. INCRETIN GUT HORMONES GEEK LINK: Leptin is an endogenous hormone released from f at cells and it is an appetite suppressant and stops hunger. Hunger is stimulate d by the incretin gut hormone called ghrelin that is released from the stomach w hen light levels are rising and cortisol levels are rising. Recent evidence sugg ests that food deprivation, and the associated decrease in hypothalamic malonylCoA, increases the expression of neuropeptide Y (NPY) and agouti-related protein (AgRP), which stimulates gherlin release in the stomach to produce the sensatio n of hunger. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Leptin activates the anorexigenic axis (appetite suppre ssion) in the arcuate nucleus (ARC) of the hypothalamus by increasing the freque ncy of action potentials in the hypothalamic POMC neurons by depolarization thro ugh a nonspecific cation channel and by reduced inhibition by local orexigenic n europeptide-Y (NPY) neurons. THE COLD LINK: WHY CT SIMPLY ROCKS Cold temperatures sensitize us to leptin by causing it to be released from fat c ells over time leading to a lower level in the blood chronically. Low temperatur es also cause us to increase our RER, while eating a low calorie diet and still maintaining our lean skeletal muscle mass. These findings show that during very low-calorie diets, and low temperatures , a stimulant of a FAS inhibitor, like l eptin, and would raise malonyl-CoA levels, while decreasing the expression of NP Y and AgRP. Clinically, this results in sustained satiation for longer periods o f time with less food. Remember that NPY is also the neuropeptide that is high i n the SCN during high light levels when carbohydrates are highest. This peptide is directly regulated by leptin function. So if one is leptin resistant it appea rs to the SCN that winter has become summer. This is a circadian mismatch and a source of inflammation in the brain. When cold comes and light drops eNOS is ind uced and shuts the SCN off to photic entrainment of the circadian clock. The rea son for this is not only annual seasonality, but for periodic ice ages mammals h

ave faced on earth, and appears to be our primordial situation for life. This is clearly a survival mechanism that is hardwired into all mammals by evolu tion, but the ancient pathway has another more important role that we have faile d to uncover yet. (FACTOR X) The environment required for the cold pathway expression is under cold, low ligh t, and low calorie conditions. All must all be met at once. This is precisely wh at all cold adapted eutherian mammals are ideally adapted to. These are modern h uman ancestors, and their biochemistry is foundational to our current paleolithi c Ferrari engines. Many believe this pathway represents a starvation response (n ot), but its real biologic value is of even more interesting. We will talk about this later this year. This temperature gradient gradually reduces all hunger, pain, thirst, and facili tate sleep in humans and all mammals. These functions were all selected for by e volution via natural selection pressures faced by eutherian mammalian evolution. Moreover, these effects of leptin cause specific epigenetic modification effect s on the other hypothalamic hormones or peptides derived from POMC protein cleav age. Those changes are linked via the biology of the POMC neurons in the arcuate nucleus. Leptin and its receptor is especially sensitive to changes in temperat ure and to the light cycles that humans and all mammals face. Leptin is intimate ly tied to hunger, it is linked to thyroid function and directly tied to fat met abolism in all mammals. Fatty acid synthesis, from acetyl-CoA and malonyl-CoA, o ccurs by a series of reactions that are in mammals catalyzed by individual domai ns of a very large polypeptide that includes an acyl carrier protein domain. Evo lution of the mammalian Fatty Acid Synthase enzyme apparently has involved gene fusion? in our evolutionary history. NADPH serves as electron donor in the two r eactions involving substrate reduction. The NADPH is produced mainly by the Pent ose Phosphate Pathway. EVERYONE REUNITE FOR SLEEP AND IMMUNITY: In the warm adapted human Simultaneously, while sleep is rebuilding our cellular terroir (think levee one) , the immune system is also undergoing autophagic repair as well. That is anothe r reason why the temperature has to fall in our bodies. Usually, temperature ris es and this causes immune function to rise and more easily activate in response and duration in fever, stress and infections. This activation depletes our immun e system of its reserves during high light waking hours. Dropping our temperatur e as we sleep allows us to repair it. During sleep is when the body re-tools our immunity to function optimally the next day. What controls this entire orchestr a of hormonal regulation? It s all leptin mediated and the brain is the master rec eptive organ to its function. Sleep is a time for recycling and rebuilding to get us ready for the next day. I t is also a time when our immune system is retooled to fight the battle the next day. Wound healing has been shown to be affected by sleep. A study conducted by Gumustekin et al. in 2004 shows sleep deprivation hinders the healing of burns on rats. It has been shown that sleep deprivation affects the immune system function dire ctly. In a study by Zager et al. in 2007, rats were deprived of sleep for 24 hou rs. When compared with a control group, the sleep-deprived rats blood tests indic ated a 20% decrease in white blood cell count, a significant change in the immun e system. It is now possible to state that sleep loss impairs immune function and immune challenge alters sleep, and it has been suggested that mammalian species which invest in longer sleep times are investing in the immune system, as specie s with the longer sleep times have higher white blood cell counts. Rats kept awa ke indefinitely develop skin lesions, hyperphagia, loss of body mass, hypothermi a, and, eventually, fatal sepsis. It has now been shown that sleep increases telomere lengths on leukocytes in hum ans. Sleep has also been theorized to effectively combat the accumulation of fre e radicals in the brain, by increasing the efficiency of endogeneous antioxidant

mechanisms. These mechanisms are mediated by the hormone DHEA which is the majo r antioxident in the brain and correlates directly with effective sleep by lower ing IL-6 levels. Progesterone is another critical hormone for brain homeostasis and learning as well. Sleep is vital to mammals, but it is supremely vital to hu mans, because they have shrunk the benefits of hibernation into 2 short critical hours of their sleep cycle because of the massive growth of their brains exting uished the need to sleep through the winter months. Since man can directly control his environment, therefore, being awake during wi nter was naturally selected for in his direct ancestors before the primates spec ies because they have the same adaptations. The programs that control our fat ma ss (leptin) however still remain tied to our ability to sleep well. SLEEP GEEKS: The homeostatic sleep propensity (the need for sleep as a function of the amount of time elapsed since the last adequate sleep episode) must be bal anced against the circadian element for satisfactory sleep. These things are con trolled along with corresponding messages from the circadian clock; this tells t he body it needs to sleep. Sleep duration is affected by the DEC2 gene. The opti mal amount of sleep is not a meaningful concept unless the timing of that sleep is seen in relation to an individual s circadian rhythms. A person s major sleep epi sode is relatively inefficient and inadequate when it occurs at the wrong time of day; one should be asleep at least six hours before the lowest body temperature for optimal functioning. The timing is correct when the following two circadian markers occur after the middle of the sleep episode and before awakening: 1. maximum concentration of the hormone melatonin, and (you can test this but it s hard) 2. minimum core body temperature. (Easy to record with new Q self apps on iPhone s) SLEEP IMPLICATIONS: A University of California, San Diego psychiatry study of more than one million adults found that people who live the longest self-report sleeping for six to se ven hours each night. Another study of sleep duration and mortality risk in wome n showed similar results. Researchers at the University of Warwick and Universit y College London have found that lack of sleep can more than double the risk of death from cardiovascular disease, but that too much sleep can also be associate d with a doubling of the risk of death, though not primarily from cardiovascular disease. Professor Francesco Cappuccio said, Short sleep has been shown to be a risk factor for weight gain, hypertension, and Type 2 diabetes, sometimes leadin g to mortality. These all tie to a failure of autophagy in sleep stages 3 and 4 mentioned above. Here, we see why poor sleep links to sleep apnea and the neolithic diseases tha t are associated with sleep apnea. Growth Hormone is released in pulsatile fashi on from 12-3 AM during restorative sleep cycles 3 & 4, and this hormone facilita tes autophagy and recycling of proteins. In essence GH keeps us younger and in g reat shape when we sleep like a rockstar. The problem is modern man does not sle ep well because of his brain s creations. (Modern Technology) The metabolic phase during sleep at this time is anabolic which favors repair; a nabolic hormones such as growth hormones (as mentioned above) are secreted prefe rentially during sleep. If things are working well. things get repaired at night as we sleep; and if sleep is poor, repair is either absent or sub optimal. When this occurs chronically, stem cells are used to replace cells instead of using cellular recycling processes that are normally used. Sleep is vital for all our organs rebuilding and retooling. The human heart fails most commonly by autophagic failure. Heart disease is also the number one killer of both men and women so this means that physicians need to pay better attention to sleep. This is the most important question I assess i n an initial bio hack. Autophagy, GH, and sex steroids all strengthens muscle fi bers especially that of the cardiac muscle. Here we see the protective role of G

H on the cardiac muscle once again. Using the cold adapted pathway described in CT 6, is the best way to protect fro m all circadian erosions, considering we no longer hibernate and have to rely on the two hours of anabolic sleep we get as a replacement. Cold lowers all inflam matory cytokines across the board. In warm adapted humans, it becomes clear that inflammation is the single most de structive obstacle to human health. This implies that understanding how to contr ol leptin becomes paramount for the warm adapted human. TEMPERATURE VARIATION IN MENSTRUATING FEMALES: The average temperature falls slightly from infancy to puberty and again from pu berty to middle age, but after that stage is passed the temperature begins to ri se again, and by about the eightieth year is as high as in infancy. In humans, a diurnal variation in temperature has been observed dependent on the periods of rest and activity, lowest at 11 p.m. to 3 a.m. and peaking at 10 a.m. to 6 p.m. During the follicular phase (which lasts from the first day of menstruation unti l the day of ovulation), the average basal body temperature in women ranges from 36.45 to 36.7 C (97.6 to 98.1 F). Within 24 hours of ovulation, women experience an elevation of 0.15 0.45 C (0.2 0.9 F) due to the increased metabolic rate caused by sharply elevated levels of progesterone. The basal body temperature ranges b etween 36.7 37.3C (98.1 99.2F) throughout the luteal phase, and drops down to preovulatory levels within a few days of menstruation. Women can chart this phenome non to determine whether and when they are ovulating, so as to aid conception or contraception. Temperature and light have massive biological effects on our biochemistry. We ne ed to be aware of this. Up nextCT8

READERS SUMMARY: 1. CAN WE FUNNEL THE CT SERIES INTO 15 CONCEPTS: 2. WHAT IS THE MAIN PROBLEM MODERN HUMANS FACE? 3. WHAT IS THE EVOLUTIONARY BOTTLENECK THAT DRIVES THIS PROCESS? RADICAL THEORY #1 .If our brains can rewire, then Einstein s theories predict our bio chemistry should be able to as well. My Leptin Rx and the modern cochlea implant definitively prove this in modern humans. RADICAL THEORY #2: Considering that 90% of the earth s current biome lives in extr eme conditions on our own planet today still, we might need to consider that wha t we think is our normal environment is not so normal for most of life on our plan et or our evolutionary history. Life on Earth evolved in an environment much lik e we see on Titan today; in a deep ocean frozen solid at its surface with the ca pability of life buried deep with in it. The only escape was due to ejectants of water vapor from super heated water from underwater volcanoes. All these things are present today on Earth s crust too. There is one major difference now between the two. We are a lot warmer today than when life began. There are others, but when one looks at Titan we see a frozen giant moon with a monstrous ocean beneat h it.

All life on our planet came from the oceans first. We know this to be true as we ll. And because of this, studying extremophile forms of life here on earth today might explain the complexities of how biochemistry allows for life to exist at all in a thermoplastic environment. What the bio-astrophysics found on Titan with the Cassini Solstice mission, (htt p:// may be a huge clue that life first adapted to extreme environments and then was naturally selected and adapted to a cyclic wa rming trend on our planet s crust over time. Our hominid species may have adapted during this warming trend, but the DNA we i nherited came from animals that were cold adapted. Evolution uses epigenetics to determine adaptation to environments. We have discarded the strict definition o f genetic determinism in the last ten years. We know today that the power of epi genetics dictates a lot more about newer generations adaptations than we even kn ew since the 1950s. The implications of this information now has to make us look at some of our own long standing assumptions about how living cells work in col d and warm environments to see how our cells react to a thermoplastic environmen t. They may not have even made a big impact when hominids evolved 2.5 million years ago, because by all geologic accounts it was still warm. But it remains possibl e that the impact could be a lot larger than we expect as well. We may not fatho m this possibility but it is clearly in the realm of possibility. The modern science of epigenetics shows that who we came from and what they face d has a direct biologic effect upon subsequent generations DNA and phenotypes. I t is crystal clear today, but the biologic implications remain unexplored in all modern day literature. What is happening on Titan today, maybe, like opening up a black hole back to a reality that used to be our own. The ability to see Eart h at life s evolutionary beginning is now a possibility. RADICAL THEORY #3: One of my readers pointed out recently he was confused by Dr. Gamble s CT-2 video, when she said the normal pattern of sleep in a natural envir onment had two cycles. He wanted to know why her version and my version for slee p as written in my post Rx for the Leptin Rx were not congruent. It was a great question that really opens the discussion to the idea of evolutionary mismatches . These mismatches occur in many modern systems of biology and they are actually increasing in frequency and severity as time elapses. The reason is quite simpl e. Evolution is constantly getting faster as time goes on relative to the curren t state of our genome. Why is this happening? FACTOR X is the evolutionary reason and Factor X was an evol utionary bottleneck that resulted in the natural selection of the Ancient Pathwa y (leptin-melanocortin system) of the mammalian brain. I think most humans are n ot really ambiently aware of how how basic circadian mismatches destroy our biol ogy slowly via the slow erosion of metabolic function. This factor is the source o f most of our neolithic diseases modern hominids face today. We can now measure these mismatches with simple blood tests. I laid this out in the Paleo Summit ta lk with Sean Croxton and in my many panel discussions at Paleo fx. I strongly su ggest you review them when they become available. RADICAL THEORY #4: Sleep and cold the environment, were our ancestors primordial condition and as such, this was evolutions starting point for life on our plane t. This is why even today 90% of the living biome on Earth remains in a freezing cold environment. Humans believe because they are the penultimate species of ev olution there current environment is a more important factor than it really is. That is a very faulty assumption. Life on this planet evolved from the deep ocea ns to land. Therefore the biochemistry that dictate s modern energy generation can not be generalized to all life forms on this planet. It can be studied on those mammals, animals, and bacteria that have undergone natural selection to a warme r climate and have assumed a warm adapted diet. Just because we use and live thi s way, has no bearing on what we evolved from, or if energy generation is someho w more efficient or less efficient in a different thermoplastic environment. Sle

ep is the most important part of our biology for Optimal living in my opinion. I begin every hack I do in the clinic using sleep as the basis. RADICAL THEORY #5: Evolution speeds up as time progresses on. This is a known bi ologic fact. The faster this epigenetic evolution occurs the greater risks we fa ce at the hand of mismatches. We may then begin to see the real causes of why di abetes might occur. RADICAL THEORY #6: Modern epidemics are not caused by genetics. This is also a m edical clinical fact that gets lost in the modern scientific literature but you would never get that from reading the literature on diabetes. In fact the totali ty of the diabetes literature would have you believe the exact opposite. This is a neolithic thought that has hurt all modern diabetics and is at the seat of wh y modern medicine has failed to find a cure. Mother Nature has a cure for insuli n resistance in all eutherian mammals. That is cold exposure of there peripheral nervous systems. The stimulus to this pathway begins when the mammal is exposed to a high dietary carbohydrate diet that is found in long light cycles on this planet. This is how the gut senses the environment and this signals are transmit ted to the brain via the vagus nerve. Modern biochemistry books and biochemists stop here They immediately go to what we know about energy generation in cells. Bu t I am focusing in on what they have failed to realize. When dietary carbohydrates are high it stimulates the eutherian mammal to begin to upregulate omega 6 content into every cell membrane of their body slowly thro ugh the autumn while temperature falls. It speeds up as the temperature drops in winter. This process is completely independent of dietary sources as I laid out in CT-3. Why does this occur in all mammals? Because to cell membranes to funct ion in cold weather it requires all land based mammals from cold adapted ancesto rs to have an EFA ratio of 4:1 for optimal signaling. In water based mammals who are cold adapted, like whales, walrus, and seals they face steeper temperature gradients in the water that require a much lower EFA ratio (essential fatty acid s) in their cell membranes to function properly. This lowered ratio of EFAs also changes the biology of adipocyte biochemistry. It favors the accumulation of su rface fat but not of visceral fat. Visceral fat is used to burn first to maintai n core temperature in these animals. In land based cold adapted mammals like the polar bear the same is true. When they emerge from their den in spring they are shredded of all visceral fat and no longer insulin resistant, and have the bigg est and strongest muscles they will have all year. Their body composition is at its best at this time. They accomplish all this without needing any exercise to do so. This is in counter distinction to modern man beliefs. Why is this? The question is more complicated than the answer. The answer is again, simple. Modern man is further down the evolutionary path and a product of a faster evolution. This mea ns his evolutionary development was the product of a sped up epigenetic process for some reason. In essence, epigenetics also speeds up as time elapses. This al lowed for the human brain to develop faster than our body plan because our diet radical changed from our immediate ancestors, the chimpanzee. This ability cause d two simultaneous evolutionary adaptations to occur simultaneously. As our brai n expanded, our guts shrunk in length. We only needed a smaller gut when we beco me adapted to eat predominantly fat and protein from animals. A diet high in fat and protein was also used to fuel encephalization of hominids. Larger brains me ant we needed pelvic changes to become bipedal and it also extinguished the need to hibernate. Hibernation needs were shrunk into our sleep cycle during stage 3 and 4 sleep. As we became smarter we became able to control our environment. Th is is how a sped up epigenetic plan set up modern man to become more susceptible to many biochemical mismatches. When our recent ancestors lost the ability to hibernate, they also lost their be st way to fight insulin resistance. Since those ancestor mammals ate carbohydrat es in a proper circadian cycles, purely controlled by their seasonal growth, the biochemical systems in those mammals readily adapted to these new states withou t much problem. This biologic adaptation required alteration of the leptin recep

tor to function with higher levels of cytokines present. It appears natural sele ction also made adjustments to liver biochemistry and bioenergergenics to mirror those changes made in the brain. Every eutherian mammal born on this planet up until 2.5 million years ago had to live by the dictums of their environment. When hominids evolved, much later, th is situation radically was altered. Hominids remain the only mammal on the plane t who can 100% control its own environment. This allows our species to create mi smatches at great speed, as our brain continued to develop over the last 2.5 mil lion years. This trend dramatically speeds up all our chemical clocks in every c ell of our body that is controlled by circadian biology. This is well known by m odern science. The Nobel Prize of 2009 tied this all to telomere lengths in our cells. All mammals have circadian signaling hardware in their brains that wire d irectly tot he cell cycle machinery in every single cell of their bodies. This m eans that modern hominids are the most sensitive mammal to any circadian mismatc h compared to their ancestors. Moreover, since they have the most advanced brain in the mammalian family, they are subjected to the greatest risk of neolithic d iseases due to these mismatches. Humans get diseases that no other wild animal g ets for this reason. Humans get autoimmune disease when our most recent ancestor s, the chimp can not. They do not have zonulin and we do. The reason is because our guts are adapted to different diets that lead to our encephalazation. Animal s domesticated by humans suffer the same fates as we do, ironically. Wild mammal s tend not to get these issues because they live by the rule that Mother Nature determines for them in their own selected environments. The ultimate paradox of modern hominids is that they evolved the ability to live on a warm adapted diet and in a warm environment, but that they retain the cold adapted biochemistry buried in their brains even though they do not need to use it presently. Evolution has not extinguished this ability for a very good reaso n, in my view. One reason is that the geologic record shows that our planet unde rgoes cyclic cooling and warming over longer epochs. This will keep the pathway active epigenetically over thousands of years. The main reason it has not been e xtinguished in my opinion, is that this ancient pathway determines ultimate surv ival of the mammalian species and it was vital at one time in evolutionary histo ry. Modern hominids have an advanced nervous system, but they still are tied to the evolutionary family they come from long ago. They are not divorced from the rules of Mother Nature even though they act as if they are. This ties modern hum ans directly back to Factor X. The paradox is that they remain blind to it even today. RADICAL RULE #7: Since modern hominids are unaware of the thermoplastic nature o f their own biochemistry, they have never controlled for it in any modern bioche mical study or study on nutrition. This means that any assumptions made in bioch emical dogma now needs to be questioned. The hints of these paradoxes are found in NASA astronauts, the Sherpa abilities, Vasper Technology, Russian Winter Olym pic dominance, Lance Armstrong s ability to beat cancer and win 7 races, Michael P helps eight gold medals in one Olympics, Wim Hof s amazing abilities, and the use of cold in human transplantation harvesting, and modern neurosurgical procedures bring these paradoxes to life. They show us today they are not paradoxes at all . They remain abilities that evolution built into our ancestors and that were pa ssed down into our genome and hardwired into our brain for a reason. We remain b linded to it because few modern humans live in this environment. Today this rema ins completely unstudied as our population, while they get more sick and mediocr e with each passing decade. Elite athletes are the first humans to push these bo undaries and to open our eyes to this possibility that this may exist. We are in inning one of this ballgame right now. RADICAL THEORY # 8: Modern life is as bad to us as a vegan or SAD diet. Lab resu lts we draw on people show this. Cortisol patterns and hormone panels are a mess in humans when they are studied. Moreover, eating an ancestral paleolithic diet is a better choice than others, but it can hide the cellular effect of stem cel l depletion by other forms of modern circadian mismatches. technology use at nig

ht is an easy one. Modern paleos make this mistake way to often. The risk of a P aleo diet for them is that the diet is so good that it could blind your consciou sness that you might be depleting your life force. This will show up when diseas e develops in the back half of your life span. This implies that what you think is really safe may not be safe at all. Light after sunset from technology is as bad as eating the wrong diet for our Ferrari engines and our brains because it destr oys the cortisol diurnal rhythms. And it means that your ultimate proof wont com e until its too late for reversal unless you prove it to yourself today by testing. RADICAL THEORY #9: Modern humans cannot out exercise bad choices from diet or fr om technology. Modern life is plain stressful and can hurt us even if we remain oblivious to it. Moreover, just eating an ancestral template, while over exercis ing like mad and eating safe starches 24/7, is not justified by your activity le vel. If you also play on you computers, iPhone, and ipad all night long, and thi nk it has no biologic consequences to your stem cells is a neolithic thought tha t just might kill you early. Trying to get all cute and use food and supplements to hide bad decisions wont work either. Just increasing resveratrol, curcumin, and metformin won t allow you to out supplement poor choices. Exercise must be horme tic and within our circadian cycles too. If it s not, you will become a dead marat hon runner or a ex-NFL player with a short life span who people wonder why and h ow that body crashed so fast? You can t fool your telomeres, but you can fool your self with your thoughts or feelings . The quality of your health is a summation of great decisions consistently. These decisions are all based upon the quality of your thoughts presently RADICAL THEORY #10: Your modern beliefs are usually the cause of your ultimate d ecline. Become fully aware that the human mind is a wonderful servant but usuall y is a horrible master. This will be a tough one for you to swallow because it w as for me; but it is an ultimate truth. We are often our own worst enemy. This i s why we often why we see success in going against the grain in Wall Street, Med icine, and in fish, like salmon. Our community must beware of this rule. The pal eo tribe are experts at using modern technology to help it move forward ..but if it is not applied correctly it might make you a good looking corpse with no stem c ells when your telomeres are too short to change it. I do not want you to believ e me. On the contrary, I want you to test me! You can check my theory easily you rself. Draw your own telomere test right now at Spectracell labs and test your o wn dogma. RADICAL THEORY #11: Cold adapted mammals can do things warm adapted ones can t bec ause at extremes chemistry, physics, and biology change when the temperature is colder. All biochemical reactions slow down in cold so Mother Nature responded t o this environmental challenge by speeding up epigenetics. This is where Factor X plays its largest role in mammalian biology to compensate for the slowing of b iochemistry to speed up reproduction for survival. 90% of life on this planet is cold adapted as we speak today. Our anthropocentric point of view has resulted in the classification of cold-adapted organisms as extremophiles, even though en vironments of permanently cold temperatures (around 0C) abound on Earth, especial ly when one considers that these include not only the polar and alpine regions b ut also deep-sea waters. GEEK ALERT: Psychrophiles, both prokaryotic and eukaryotic, have successfully co lonized these cold environments and are able to grow efficiently at sub-zero tem peratures. This adaptation requires a vast array of structural and physiological adjustments in order to counteract the reduction in chemical reaction rates due to the low temperature of the habitat. Most scientists study human physiology i n mesophilic environmental conditions. This is a big problem. The reason is that humans have completely different abilities in cold and the resultant physiologi c changes are often 180 degrees opposite that one would expect. This fact has bl inded many scientists and physicians to some deep realities about human biology. Recently, fish have been found in our polar seas that are believed to be over 1 0,000 years old.

ORGANIC BIOCHEMIST GEEK ALERT: Temperature is one of the most important environm ental factors for life as it influences most biochemical reactions. Low temperat ures slow down and strongly inhibit chemical reaction rates catalyzed by enzymes , the work- horses of cell metabolism. The effect of temperature on chemical react ions is basically described by the Arrhenius equation: k = Ae -Ea/RT , where k i s the rate constant, A is Ea is the so-called activation energy, R is the gas co nstant (8.31 kJ mol ~1) and T is the temperature in kelvins. Accordingly, any de crease in temperature will induce an exponential decrease of the reaction rate, the extent of which depends on the value of the activation energy. The thermodep endence of the activity can be approximately expressed by the Q10 value that is normally close to 2- 3. This is the main factor preventing the growth, at low te mperatures, of non-adapted organisms. So biochemistry of cold says we should hav e slow growth patterns based upon the biochemistry. I told you earlier that evol ution has sped up tremendously as time has gone on. So the question remains is, how did evolution overcome slower growth? Since the cell cycle was slowed by col d it sped up epigenetics to compensate for the slower growth. That is the basis of FACTOR X. It is the most important part of my theory because it is why the hu man brain was naturally selected for in a mismatched environment. It is an evolu tionary factor by itself. RADICAL THEORY #12: The Ancient Mammalian Pathway naturally selects for the cold adapted paleolithic diet in all cold adapted eutherian mammals. To access this food source their nervous systems were adapted to remain insensate to pain after and adaptation period. This period differs across species but it is present eve n in humans after two weeks of peripheral surface cold sensation. The best food source then for a cold adapted mammals biochemistry would be a ket ogenic version of the paleolithic diet that has a high omega 3 content. The reas on is simple. More omega 3 s are needed in cold environments to provide for accura te cell membrane signaling due to increased double bounds in their chemical stru ctures. VLC WARNING: VLC in a warm adapted world has serious limitations. Be aware of th em. PALEO DIET WITH METCONS: carries even larger risks for the modern human. RADICAL THEORY #13: The leptin receptor is primordially a cold based electron co unter for nutrients from foods. I think it evolved the ability to function in wa rm environments as mammals evolved onto land and took the planet over. Our earli est ancestors however began in the cold polar seas and on cold polar land masses . The biochemistry we know today in textbooks only represents the warm adapted m ammalian pathways, and as such, are not complete in my view. TRAINING FICTION: Ketosis is most efficient mammalian fuel in the cold not carb loading. Carb loading is a thought born of only understanding the warm adapted m ammalian pathways. There are numerous examples of athletes using the cold adapte d pathways having superior performance to the warm adapted pathways. The issue i s that too few have decided to access it because it takes 24-36 months to reach those peak levels. The Sherpa s remain the best example of this in today s modern wo rld. They have been extensively studied by NASA. This blind spot needs to be stu died in depth by modern day scientists who are not just elite coaches. Burning f at (FFA) actually increases our VO2max when the ancient pathway is induced. This information is directly in counter distinction to published data because we rem ain unaware of the cold adapted pathways in humans. It is currently unstudied, b ut we have numerous examples of humans with exceptional performance in cold envi ronments that few can explain until now. At extremes, biochemistry changes in nature for our benefit. Evolution has a pla n for this because it tapped it many times before. REALIZE THAT modern trainers are oblivious to this therefore they regurgitate what is best from the literatur e that is based upon mammals who are warm adapted eating a warm adapted diet! Ca n you say major mismatch! The best example of this today is the technology of Va sper which can not be explained by the published data in modern exercise physiol ogy books. This should be a huge clue that we are missing some major factors. Va

sper is a known entity in NASA research. Vasper has licensed the NASA technology generated from the Sherpa s in the 1970 s. RADICAL THEORY #14: Why do humans remain blind to all this? They never face a tr ue winter any longer as do other wild mammals. Behavioral adaptation is most imp ortant for the survival of human species. It includes e.g., well heated houses, good thermal insulation of clothing, warm vehicles and short exposures to cold. In fact, behavioral adaptation can work so well, that no physiological adaptatio n is developed in winter, as shown in young urban residents. These neolithic cre ations are why we do not see the metabolic benefits of this pathway in modern hu mans often. When modern humans become aware of them and their benefits they may consider building a small part of their current environment for cold thermogenes is. Modern humans may find that when they cold adapt it will help treat diseases due to mismatches in circadian biology. Warm clothes and buildings are neolithic creations that kept us in the dark abou t the ancient pathways benefits. Wild mammals can t do what our brain allows us to do. Mismatches are not just not good for humans in our modern world where it co nstantly seems like it is summer time due to artificial light and 24/7 access to carbohydrates. RADICAL THEORY #15: Neolithic diseases of aging is total cellular chaos health is p erfect cellular order, in between is cellular mediocrity. We need to decide are searching for optimal or not. Optimal requires a cold adapted physiology ..sub optim al is found on the pathways in most modern biochemistry books. Up Next CT- 9


Many of you may not know this but I was asked to do to a TEDx event in Nashville on 3/31/2012. I have to say with about 6 days to prepare it was rushed, but it was a lot of fun. I want to publicly say thank you to Misty Williams and Michael Hart for making this happen. Many of you may not have heard about the event jus t yet because the videos are not posted on the TEDx Nashville site. It will be a nother few weeks before they are ready. In my talk I told 1200 people live on st age about the three thought experiments I came up with after reading, The Monk Wh o Sold His Ferrari . I actually conceptualized the Ancient Pathway soon after the reading was done but where the thought experiments came to me, was at the foot o f Michelangelo s David in Florence, when I was looking at him from behind. I reali zed that the major difference between him and I, was the world we both were livi ng had radically changed in 500 years. From this insight I realized that circadi an biology was the the major difference in David s perfection and my obesity. From this spark of wisdom I realized that obesity was an inflammatory brain cond ition. Because it was so, I could then reconstruct a signaling sequence to confu se my hypothalamus using signals from my vagus nerve and from the foods I ate us ing timing. Learning how the brain rewired in neural deafness using a cochlea im plant made this easy game for me as a neurosurgeon. I added Cold Thermogenesis t o this protocol to gain a stunning weight loss result in 11 months. The first tw o people, other than myself, to benefit from the Leptin Rx reset, where my son, Konnor and my nephew Kyle. I documented their results in the TEDx talk as well a

s a stunned audience gasped at the pictures and the time frames. I went on to ta lk about telomere biology and how this pathway might keep us young and healthy i f we lived in it for the majority of our life. I spoke about Elizabeth Blackburn s work and subsequent Noble Prize in 2009. I mentioned Lance Armstrong, Michael P helps, the Sherpa s and NASA astronauts and how they all had amazing capabilities at some level that was also tied to the cold. I mentioned Mr. Wim Hof and his truly amazing journey from a circus performer to a serious bio hacker, who modern science is now studying intently. Ray Cronise is working with Wim closely now in the Arctic. After viewing Wim s own TEDx event in 2010, I knew his abilities were not special to him, but tied to the cold. I k new they were built in by Mother Nature to each and everyone of us. Wim just hap pened to be cold adapted and he uncovered some of the amazing abilities this pat hway holds for us who choose to live in it. Take a look at this video to show yo u what Wim has proven to modern science today. Wim injected himself with endotoxins from dead bacteria via an IV and did not ge t sick. In fact, he raised his own endogenous cortisol to offset the toxin effec ts. This ability is biochemically expected in my theory, I proposed in CT-6 blog I wrote. It is clear from Wim s video, his doctors do not know that this is preci sely how the human brain reacts to cold when it is exposed to cold. POMC is incr eased in the hypothalamus when a mammal is cold and it is cleaved into ACTH and alpha MSH. The ACTH increases our cortisol production to provide us with ultimat e immunity. Ironically, Wim showed this exact ability in his own testing in the video I just asked you to watch. Coincidence or not? Wim was not unique in using testing done upon himself to prove the critics wrong . Dr. Edward Jenner did the same thing in the late 1700 s. He received this advice from the great physician, William Harvey during his training. In 1770 Jenner be came apprenticed in surgery and anatomy under surgeon John Hunter and others at St George s Hospital. The famous physician, William Osler recorded in his writings , that Hunter gave Jenner, some very famous advice in medical circles during thi s time. He told him, Don t think; but try. Jenner did just that. He was a man of act ion. The disease devastating mankind, at this time, was small pox. Voltaire reco rded that 60% of the population caught smallpox and 20% of the population died o f it. In 1765, Dr Fewster published a paper in the London Medical Society entitl ed Cow pox and its ability to prevent smallpox , but he did not pursue the subject further. A farmer named Benjamin Jesty, successfully vaccinated and induced immu nity with cowpox in his wife and two children during a smallpox epidemic in 1774 . It appears that Jenner read the 1765 paper and made the observation that Jesty s innoculation of his own family may have saved their lives from small pox. Jenne r went on to theorize that milkmaids were generally immune to smallpox. Jenner h ypothesized that the pus in the blisters that milkmaids received from cowpox pro tected them from the human version called smallpox. In May of 1796 Jenner inject ed an 8 year old boy with cowpox. He also injected 23 other people, including hi s two surviving children, and they all became immune to small pox. His discovery was hotly debated by medicine of the day, but the science prevailed. His discov ery was revolutionary because he refused to conform to the standards of the day. He let the findings and data dictate where he should go, and what he should do about it. In 1977, Dane Miller, a PhD, was working on Titanium alloys and felt they offere d huge advantages to modern medicine in orthopedic implant development but there was a lot of opposition to this at the time. Moreover there was no data to prov e his assertions true. So what did he do? He pulled a page from Jenner s playbook and went to his garage and cut himself open and placed a titanium rod in his arm and left it there for 9 months before he told anyone, to prove that titanium co uld be used in a human. His company, Biomet, revolutionized all modern orthopedi c and spinal instrumentation with this stunt. They went from 17,000 dollars in s ales to 2.5 billion in sales because Dane decided to think differently. See this LINK It appears it pays to think outside the box.

Then we have the story of Galileo. In 1610 the Catholic Church made all the rule s and they said that the skies were dominated by an Aristotelian scientific view of the universe. Galileo believed that the banished Copernican theory was, in f act correct, because of discoveries he made with his new telescope by viewing Ve nus and Jupiter. It turns out he was right, and the conventional wisdom dogma wa s wrong again. A more recent example of thinking differently was that of Dr. Barry Marshall from Australia. He and his wife came up with the idea that all human ulcers were not caused by stress, as modern medicine believed at the time in 1984. Instead, he b elieved that a spiral bacteria caused it. He could not test his theory on primat es because primates are not susceptible to this bacteria, as humans are, because of how our gut evolved. H. Pylori experiments failed in piglets and in primates . So what did Barry Marshall do? He drank a petri dish of H. Pylori and then he preformed a endoscopic procedure on himself to prove his theory correct. He then treated his own ulcers with antibiotics for a cure. Modern medicine called him a quack for a long time. There was big business around the surgical treatment of u lcer disease. So what happened to Dr. Marshall? He won the Nobel Prize for his d iscovery in 2005. So he went from crazy and a quack in 1984 to a genius in 2005. Again, this is another example of where thinking outside the box helped humanit y. LINK In 2010, I had a general surgeon in my hospital become acutely quadriparetic and have to have emergency surgery to save his spinal cord functioning. I talked ab out his case at my Paleo Fx lecture in Austin. The case shocked many in the audi ence. After his surgery, he did not improve, and his partner, a friend of mine, suggested he come see me. His dad was a neurosurgeon, so, I did not know what to expect from him. After meeting with him, and hearing his story and seeing the o utcome, I realized he felt his career was over. I told him that if he checked th e conventional wisdom we both learned in medical school at the door, that I migh t help him. In 6 weeks he went from not being able to walk or use his dominant h and to being able to run up stairs and coach his children s soccer game. In two mo nths, he was back to work full time with very little problems noted. I used some of the things I learned in the Ancient Pathway to help Brent regain his functio n and life. I introduced him to the paleolithic diet and to cold thermogenesis. Yes, I have a video of him too. Those of you who were at Paleo fx heard and saw his story. Then in November 2011, Dr. Terry Wahl s TEDx video on curing her MS hit the intern et. Terry inspired me to write my book. She used only her version of the paleo lithic diet to reverse secondary progressive Multiple Sclerosis. Her story captu red the hearts of many and really caught hold in the paleosphere. It caught medi cine off guard too, and I loved it. After her talk she motivated me to step up my game. I decided to execute the third and final thought experiment that I ori ginally had at the foot of the statue of Michaelangelo s, David. It was the hardes t of the 3 experiments to complete, because I knew what it meant I had to do. I had to perform the first ever evolutionary directed human experiment on a human, to prove that the paleolithic diet is the preferred diet of the Ancient Pathway . Moreover, that the Ancient Pathway still exists in all humans today by perform ing a surgery on a human without any antibiotics or local anaesthetics or narcot ic pain meds peri-opreratively. Finding someone to agree to this was not going t o be easy. Moreover, I had to raise the stakes to prove that immunity is up regu lated in the cold by using a nasty bacteria that modern medicine has trouble deali ng with. I knew that if I could use Cold Thermogenesis to block all the pain and use the cold to upregulate immunity by raising cortisol, that this could help m odern man immensely. So what did I do? I could not ask a modern human to do this ethically, so I asked the one person who I knew could consent to it. I used mys

elf. I sent the pictures of the id a 1.5 hour interview with me until I gave her the go ahead. other rule breakers above did,

event to a CBS reporter I met at Paleo fx. She d and told me she would keep the story under wraps I pulled the same page from the play book as the to prove a clinical point.

On January 9th 2012, I decided to perform the first ever evolutionary directed c linical experiment on a human being that I know of. I had an elective surgery do ne on myself with living bacteria injected into the proposed surgery region. Thi s was also done by me. Yes, after it was all completed, I told the surgeon and m y OR team. These people work with me daily, so I wanted to make sure they knew a bout it before anyone else did. I also wanted them to know why I did it too, and I showed them why too. Some, in the paleosphere think this was a risky move. It is only risky when you do not know or understand all the factors involved. I did not think this was ris ky at all based upon what I knew and what Wim Hof already showed me observationa lly in the video above. The hysteria that I have witnessed about this event is c learly made by people who have no clue how observational clinical studies can le ad to dramatic changes in understanding in science. Barry Marshall knew he had n o risk before he drank the H. pylori because he knew he could cure it. I felt pr ecisely the same way. In fact, this move has been used by many others before me too. I gave many examples at how this method was used in medicine and industry e arlier in this blog. My tact was not new at all; others have used it to make a p oint to doubters in the recent past. It appears many are unaware of this. My hypothesis for this evolutionary directed experiment was that I would not get an infection or need any pain medications, if in fact the Ancient Pathway was s till buried in my peripheral and central nervous system by Mother Nature. I felt the risk was very low because I had a ton of data I collected the last 6.5 year s, showing me it was present in all mammals for an evolutionary reason. Humans a re still classified as mammals by science last I checked, so I went ahead with m y third experiment confidently. The results were stunning and will be detailed i n my TEDx talk video and in my forthcoming book later this year. WHY DID I DO THIS? What made this all worthwhile for me? Well, let me tell you about Mr. Lonnie Dan iels. He has been a patient of mine for two years. Up until my Jan 9th experimen t modern healthcare could not help him further. He was relegated to pain managem ent for his condition because he was too high risk for a surgical option. This c aused him to accepted limited mobility and he even had to resort to use of wheel chair to live. He is a very fragile T2D who was not a candidate for any major sp inal surgery because of his poor medical condition. When he came to visit me onc e again in November of 2011, he was no longer able to walk into my office and he was in a wheel chair. He begged me to help him. See, Mr. Daniels has a zest for life, and he was not happy with the hand he was currently dealt. He is a very a ccomplished musician and he wanted to live life on his terms and not on the term s his health was dishing out to him. I told him that if he was willing to make s ome lifestyle changes that were dramatic immediately, that I might be able to he lp him. I told him that I needed him to eat a strict ketogenic paleolithic diet right away, and that he had to begin to ice his lower back and thighs for me dai ly. He told me the request sounded odd, but that if I was going to try to help h im he would do anything at this point because no one else had any answers for hi m. Lonnie is a fabulous man and person. Lonnie did exactly what I told him. I went on to tell Lonnie that I was taking a few weeks off in early January to test thi s theory out in humans before I could use it to help him in his upcoming surgery . I told him that if the experiment flopped, I would not be able to operate on h im and I would call him at once to cancel the surgery. He understood, and I told him I would call him on January 10th to let him know if it worked. Well, long s

tory short, it did work. I immediately scheduled Mr. Daniels for a major spinal reconstruction operation on January 27th 2012. I detailed the procedure in my TE D talk I did on 3/31/2012. I took the success of my idea, directly, to help Mr. Daniels less than three wee ks later. He was high risk for developing an infection, (hence the MRSA idea) be cause he was a fragile diabetic, and the proposed procedure he was having had a high complication rate in his case. In a healthy human, this operation would cal l for a 5-7 day recovery in the hospital with a 3 ?4 week stay in a rehab facili ty. During this time he would be on high dose narcotics to control his pain. Thi s alone could lead to other new problems like bowel obstruction or mental confus ion or a fall. The total recovery for this operation is 3-6 months in a normal p erson. In Mr. Daniels case, he might never recover, or be worse off. Mr. Daniels knew all this going in and told me he could no longer live the life he was livi ng. Before surgery I made sure Lonnie was still eating the diet I prescribed and usi ng the cold. He was. I told him that in his post operative state, he was not goi ng to like me much because I was going to freeze him on a 40 degree sheet of ice . I told him I would give him a narcotic pain pump to control his pain and I was going to start some medications on him that were not ordinary for this conditio n to help facilitate the cold in healing him and increasing his immune system. H e consented after knowing all the risks and benefits of the procedure and he the n had a four long surgery to open and completely reconstruct his spine. In this surgery I made a ten inch incision in his back from skin to spinal level on both sides and then proceeded to place 8, four inch screws in his back, whil e decompressing 80 years worth of osteoarthritis and degeneration caused by his longstanding diabetes and medical co-morbities. Lonnie tolerated the surgical pr ocedure and anesthesia risks the day of surgery. He left the hospital in 2.5 day s, far shorter than the prediction that one would find in most spinal textbooks of today. He used very little narcotics from his PCA pump because the ice blanke t took most of his pain away. The ice sheet was tough on him for sure, but he en dured it because I told him it was a must to get him through this operation safe ly. In the end, it worked well for Lonnie. His operation was several orders of magnitude greater than the one I had done on myself. If this worked on him I knew that this was a huge clinical finding I ha d made. Moreover, he also carried huge risks for infection because he was a diab etic with large metallic foreign bodies placed in his back during the surgery. L onnie got no infection at all during this and he also was in a hospital and reha b facility where MRSA is a present in abundance. He was a t high risk for DVT to o and he was not placed upon any medications to prevent it, and he got no DVT ei ther. In fact, he healed up faster than a person without diabetes, or who was 80 years old! He spent only 5 total days at rehab. I still find this hard to fatho m. This was better than I thought he would do. And when he was at rehab, I got r eports from the rehab team that he was playing his banjo for other patients as t hey recovered. He had no pain and only a decrease in stamina. I think what he ca lls a decrease in stamina and what I consider a decrease in stamina for a fresh post op 80 yr old diabetic is different. What Lonnie did was nothing short of re markable, to me, or to his family. In the hospital and the rehab facility, he used very little pain medicine too. H e went home after just 5 days in rehab. He came to see me in clinic about post o p day fourteen and he had a big smile on his face. Lonnie s face showed the result s of cold thermogenesis when he came back to see me two weeks after his operatio n. He walked in, with no wheelchair, walker, or walking stick and handed me his pain medications and told me this was the best he felt in 20 years! I was dumbfo unded. I thought he would do well ..but not this well. Here is the video Lonnie mad e with me about two weeks after his surgery.

Video I spoke about this case at my TEDx talk. TED is all about sharing good ideas. I think my theory about the Ancient Pathway is an idea worth sharing because the i mplications are immense for modern healthcare. Ideation without execution of the idea just leads to deletion of that idea. I no longer think my idea can die on the vine. The clinical results I am generating now in my clinic using what I learned from my own surgery on January 9th are nothing short of remarkable. I have many of th em documented now. I was the first human to show a remarkable recovery with no p ain or infection. Lonnie Daniels is the second. There are others too now. My last point to all of you reading this is simple. Sometimes to solve a problem we have to think differently about how to do it to become successful. Many of m y critics have said what I did to myself was reckless. I never believed it was r eckless because I already knew the concept was solid and theory had a ton of sup porting evidence present if they just had looked as I had. It is only reckless, when there is no evidence supporting it. They believed that there was none, henc e their false beliefs. I knew differently. Moreover, just because the critic is unaware of the supporting evidence, should not stop the person with the idea to further our progress. What was not present to them, was the written or experimen tal proof of the concept explained in modern hominids of today. On January 9th, 20 12, I proved to myself, that the Ancient Pathway was present in me. On January 27th I proved it was present in our species and it confirmed what Wim Hof led me to believe. Wim is a trailblazer. Critics will still doubt, and that is fine by me. In three weeks after my own surgery, I used what I had learned, to radica lly change the life of an elderly man who wanted help that modern medicine said was impossible. It also showed me that I could use it to help others get better where modern medicine could no longer help them. Progress doesn t just have to happen in the laboratory or on a research bench or v ia a conventional randomized controlled trial. This is a neolithic thought with no foundation. Sometimes being directionally accurate is all it takes to help a hu man clinically. This is why medicine is both an art and a science. The things th at trip up a scientist, do not have to make a clinician trip, if they evaluate t he clinical risk and deem it safe on a human before they apply it. I did just th at, by doing it on me first. Dane Miller, Barry Marshall, Einstein, Ghandi, Wim Hof, Dr. Terry Wahl, and many others have showed it can happen in every day life , through personal experiences, and challenging the status quo. Those personal e xperiences might help others quickly live a life that was closed to them in the older paradigm of health care. I took my experiment on January 9th and changed o ne man s fortune on January 27th. I knew this biology was present in us, so there was no risk to me at all. Sometimes the major question we face in life, is can we step outside our own com fort zone to make progress? A Paleo fx leader posted something on my FB wall that makes a great point for al l to consider. What was said, instead of criticizing me for doing what I did on myself on January 9th, why don t we ask the following questions to researchers to spur further research/inquiry: 1) What was different about Wim Hof and Jack Kruse that allowed their immune sys tems to be completely resistant to the endotoxin and/or MRSA? Is it just coincid ence that they were both cold adapted or not? In Wim s case we know his cortisol l evels were abnormally high to offset this according to the tests run on him duri ng his own experiment. Dr. Kruse s CT-6 blog lays that same foundational biochemis try in the neural circuits of the human brain. Is this also a coincidence? Why d

on t we know about this in modern textbooks? 2) What if biochemistry and biologic research studies have reached incorrect con clusions based on the fact that they are primarily done in warm adapted mammals? Should a cold adapted set of studies be funded and undertaken to dispel/prove w hat Dr. Kruse alleges to be the case? Can this be proven today in humans using a clinical study or would it require a detailed expensive trial? 3) What if cold adapted patients start showing up at clinics after surgery for t heir post-op checkups and start handing the surgeons and clinicians their pain m edications(unnecessary and unused)? Big implications for Big-Pharma and modern m edicine, no? There would be big implications for chronic management of pain in b oth the home and clinical setting as well, no? Doesn t this make the reasonable case for why a fresh look needs to be taken at the research, biologic assumptions and biochemistry of mammals (and humans) if there are any examples that this actually is possible? The potential benefits and implications are just too big to ignore I appreciate that leader sticking their neck out into the oncoming arrows of the P aleo elitists and their followers. But as most people who uncover new biological discoveries the science will eventually prove who is correct, and who is afraid t o push the boundaries of our knowledge. The only thing in real question left now , is the relative speed the rest of the world catches up to the thinkers of the new concepts or theories. Sometimes the thinkers are not the discovers of new sc ience or a thing at all. They just are more observant of present day paradox and ambiguity, and look to explain it, by using what they do know to be true. I thi nk Jenner, Galileo, and Einstein all fit that bill too. It seems that the zeitge ist of today, with its inherent power can color the acceptance or rejection of n ew ideas. I think what has occurred in the paleosphere lately fits that bill to a T, as well. All things are subject to interpretation, and whichever interpreta tion prevails at a given time is a function of the power of the day, and not to the ultimate truth it reveals. Frederick Nietzche was a smart dude for making th at quote long ago. In my view, there are far too many examples in our modern world where cold adapt ation does amazing things for humans that we remain blind too today. This parado x has fascinated me for over a decade now. So, I decided to seriously look into it as an observant clinician would to see if I could somehow understand it to he lp my patients in some fashion. Moreover, it has been shown even to the lay publ ic, in periodicals, that in biology, the genome may not be all that important in the grand scale of things. It now appears the epigenome, which is controlled by environmental factors, is the most important factor that affects genetic expres sion of our genes and how we respond to food and hormones. Read this link for so me eye opening findings that are true but the implications of most are currently not appreciated by my critics or by modern science for that matter because they have not been seriously studied. LINK WHAT EXAMPLES DO WE HAVE TO SHOW THIS PARADOX? Here is a small sample of a few articles that show many humans can do things the critics say they can t do. Well, when we know it truly has occurred, instead of d enying their existence as they have done to Wim Hof, maybe we should begin to lo ok for reasons why they can do it. Maybe in those answers we might find somethin g that can better humanity. We all have a duty to master the talents buried with in us in my view. A. LINK

B. LINK C. LINK D. LINK (Wim Hof) E. Douglas Mawson recounts his expedition in his epic book, Home of the Blizzard : This Australian was a key figure in the so-called Heroic Age of Antarctic Explo ration. His Australian Antarctic Expedition, which begun in December 1911, howev er, nearly saw the end of his adventures forever. He was the only survivor in hi s team after his fellow explorer, Lieutenant Ninnis, fell through a crevice with the dogs and supplies and were lost. The other member of his exploration team, Xavier Mertz, died from a combination of weakness, cold and vitamin A poisoning from eating dog livers. Ironically, Mawson fed the weaker Mertz the dog livers t hinking they were more nourishing than the muscle tissue of the dogs which led t o Hypervitaminosis A. Mawson, ironically was a vegetarian and he ate more of the skeletal muscle and less of the husky liver offal, continued on alone and fell into a crevasse and saved himself by wedging his sledge above him and using the cold ice to sustain his food source and his body to survive to travel the last 1 00 miles. So bad was his condition when he arrived at base camp, his rescuer exc laimed, My God, which one are you? But he survived without much food in the bitter cold. This was rather remarkable. F. The Andes Flight disaster that the book Alive is based upon: Uruguayan Air Fo rce Flight 571 was flying over the Andes on Friday 13 October 1972 when it crash ed into peaks hidden by cloud. It was carrying the Uruguayan Stella Marris Colle ge rugby team to a match in Chile, but only 16 lived to tell the tale. The other s died during the crash, in the days soon after from injuries or cold, and eight succumbed to an avalanche on the 17th day. The stranded survivors were left wit h no option but to eat the flesh of their dead teammates and adapt to living in the extreme conditions. The remaining men were found almost 10 weeks in cold tha t approached minus 30-40 degree F in deep snow falls, following the initial cras h when two members went on an expedition and flagged down a passing Chilean hors eman. G. Kenai girl credited with saving friends in Tustumena Lake accident | Alaska D ispatch One Friday, a father was taking his daughters and friends to a remote public use cabin on the shore of Tustumena Lake. They were traveling in an 18 ft skiff. Co nditions were good when they started across the lake. Tustumena Lake is about 25 miles long by about 6 miles wide. At its upper end it is fed by a large glacier . It is notorious for having strong winds come up suddenly off the glacier, lead ing to severe waves. The lake is relatively shallow in spots which makes the wav es even worse. Water temperature is around 40-45 deg F. Some say this is impossi ble, yet it still happened on our planet to a modern human. Why? Part way across the conditions became severe and swamped the boat, and all five people ended up in the water. The father was trying to tow one girl (according t o one report she was having problems with a poorly fitting pfd). He and that gir l died, apparently from hypothermia. However the other three girls were able to swim (wearing life jackets) for an estimated two hours in 40-45 F water and made it to shore. They then walked to another cabin, got a fire going, and were ulti mately rescued alive. (Some critics say Navy doctors all know this impossible, I guess the impossible can happen only when you are unaware of it?) To quote from the article: Although it s commonly believed by many in Alaska that i f you fall in water as cold as that draining off the Tustumena Glacier into Tust umena Lake you only have minutes to live, that belief is a now a myth to many of the locals because of this story. As long as people survive the sudden shock of the water, which can cause them to reflexively inhale and drown, they can survi

ve for hours, said Jeff Johnson, the state director of Boating Safety. PFDs, he added, are vital for surviving those first few seconds or minutes. People have b een known to hit the cold water in Alaska, sink out of sight, inhale water, and never come back up. A life jacket, however, will always bring them to the surfac e and at least give them a chance. The Tustumena accident, he said, underlines t he value of PFDs. BEGIN TO THINK DIFFERENTLY: A point I would like to make to all my readers is this; If you cold adapt using my protocol you will never drown by inhaling the cold water and die of sudden sh ock. This is the entire point of my Cold Thermogenesis protocol. Navy doctors ar e unaware of it because the people they treat are never cold adapted! Just becau se they are not cold adapted, does not also mean that the ability is not present in humans. Once they become adapted they have even more amazing abilities. Some have said it is just a hormetic ability. That is also a bad assumption based up on my own clinical observations and the things I have been able to use it for in my clinic. Soon you will see those abilities and results. Those results will fo rce you to consider that maybe there is a lot more to this cold adaptation. Critics are people who have lost there own ability to dream and create. Intellec tuals are people who believe that ideas are of more importance than values. That is to say, their own ideas and other people s values Negative feedback can make us b itter or it can make us better. When we let go of what we are and how we feel, i t allows us to become what we might be. Leadership always starts with thinking f or yourself. Liking me is not your job t is mine. I have to live with myself, and you with your self. I know that biology has an epistemologic foundation in evolutionary biology now. I need to prove that to modern medicine, now not to the paleosphere. I really d o not care if our community buys it or not, because I can tell you I have enough to prove it already clinically. Maybe that is the real problem for some. People want me to care what they think and want me to be a guy like Robb Wolf. I can t b e him. He swims in a different fish bowl than I do. Robb knows full well, what I am up against in my world of healthcare. He has voiced his opinion on the healt hcare complex in many venues. This is why I have to proceed differently. If that you percieve my methods different, they are that way, by design. But what I am telling you should not be discarded because you dislike how I am telling you. Yo u should listen to the results of what I have found in humans. Then you should t hink about the implications of what it might mean to your own currently held dog ma. Many smart people are already working on this biology. Just look at Wim Hof s vide o I showed you earlier. Ray Cronise, a former NASA scientist is also doing some amazing things in this arena. Soon scientists across many disciplines will prove me correct. Most elite athletes in profession sports are using CT today. NASA i s using it and they have recently sold technology to a company named VASPER in C alifornia to do some amazing things to the people who employ it. We need to begi n to use evolutionary biology in modern medicine to dictate the decisions we mak e. Moreover, what I have also found shows that the paleolithic diet is selected for specifically by Mother Nature. This should really make many of you out there , pleased. It has not. Too bad for you. How will I do it wont be to everyone s liking. I am fine with that too. I am not trying to convince people to try the die t as Robb or Mark are doing. They are the face of Paleo. I do not have the paleo label anywhere on my brand. The diet is a part of a larger story that I think w ill change medicine. For me, the diet is a tool I use to sculpt masterpieces. I am using it clinically to heal patients currently thought to be helpless. The

paleolithic diet is just a part of the Ancient Pathway. It is a tool for my clin ical practice. In the coming months you are going to hear a lot more about the t hings I am doing to help people get better using what I have learned. The soul of biology knows how to heal itself, the main modern challenge to success is to lea rn to silence the modern mind and thought mindset simultaneously. The power of observation is critical. We don t know who discovered water, but we k now it wasn t the fish. Reason, Observation, and Experience is the Holy Trinity of Science! Einstein didn t wait until he was Einstein to perform like an Einstein. Every prob lem we face in life has a solution, if we dig deep for it and do not fall back o n what we currently believe to be true. Just because we do not see it does not m ean it does not exist! We all need to begin to become aware of the things that a re present in life, but appear paradoxical, and try to explain them by the thing s we know. The key to winning is beginning to think, then executing on that idea . Every pro was once an amateur, and every expert was once a beginner. Your innate talent is your GIFT. It is your OBLIGATION to bridge the gap between your humanity to your DIVINITY. And I want to end CT 9 with this video Next up ..CT-10. Another rockstar star fish revealed.


Evolutionary strategy is based upon finding an environmental niche and exploitin g it. Evolution is based upon change and the natural adaptations to it. Today, we are going to explore how some environmental triggers might open a biochemical trap door. WHY IS CIRCADIAN BIOLOGY CRITICAL? For evolution to work, a cell first must adapt to its environment. So the first thing any living cell would see in an earth day is a period of day and night. I t also has to find food to make energy (ATP). In addition, it has to control its own cellular division. The epic battle for the cell is the circadian cycle has to yoke the metabolic cycle to its growth cycle. Most people know that the supra chiasmatic nucleus (SCN), is the circadian pacemaker that monitors this dance be tween darkness and light and the seasonal cold and hot temperatures in our envir onment. Evolution apparently agreed with this assessment, because we now know i

t to be true. What most people do not know is how leptin plays a massive role in regulating it . Research has revealed that leptin can induce expression of a neuropeptide gen e called vasoactive intestinal peptide (VIP) through the VIP cytokine response e lement. VIP actually is what sets the circadian pacemaker to light. Leptin yok es metabolism and sleep to the light and dark cycle. When temperature becomes t he dominant environmental trigger and not light cycles, leptin induces endotheli al nitric oxide synthetase (eNOS), that shuts down the photic effects of VIP on the SCN. This means that leptin forces the SCN not to be able to use light any longer to yoke circadian cycles! Once temperature begins to yoke the circadian rhythms, some very special things happen to our biochemistry that normally does not occur in other environments. These are ancient epigenetic programs that are hardwired into the DNA of every descendant of a eutherian mammal. We are desce nded from these animals. Take a look at this link. Kalsbeek A, Fliers E, Romijn JA, la Fleur SE, Wortel J, Bakker O, et al. The sup rachiasmatic nucleus generates the diurnal changes in plasma leptin levels. Endo crinology 2001;142:2677-85. SO WHAT HAPPENS IN NORMAL ENVIRONMENTS YOU ASK? When it is night time, the interior of our cells become more reduced chemically and electrically. (A lower redox state like we saw in the mitochondrial series) . During a low redox time, cells are usually recycling their components using a utophagy during sleep. Autophagy is critical to health and longevity in a mammal ian biochemistry. During the day, while energy is being made to explore the envi ronment, the cell is more oxidized because of increased leakiness of the mitocho ndria at cytochrome one. Remember the more we leak, the faster we age, and the more neolithic disease we sucuumb to. Another interesting coupling occurs between the circadian cycle with the cell cy cle. They are linked together via the PER 1 and PER 2 genes. PER 2 directly af fects the cell cycle when the cell divides. Cell division is called mitosis. M itosis is the phase in the cell that occurs just before cell division to generat e an offspring. The mammalian period 2 gene plays a key role in tumor growth in mice; Mice with a mPER2 knockout show a significant increase in tumor developme nt and a significant decrease in apoptosis (levee 19). It should be clear becau se of these links that just a simple mismatch in circadian cycles can lead to th e development of cancer and neolithic disease. Circadian biology is crucial to optimal health. The real kicker, that no one un til now has realized, is how biology accelerated time using the theory of relati vity for ultimate survival. It appears Mother Nature used power laws to fuel ex plosive growth in the species that we were descended from. I will explain in a later blog why this is a very critical factor in tying things together, but the result of it is what you need to pay attention to now. Evolution figured out a way to speed up. The consequence of this was that it also sped up epigenomics. This relative increase fueled human evolution, but also made us more susceptible to neolithic diseases if we do things against our circadian biology or our pale olithic genes. This can be worked out mathematically with power laws. This impli es we better pay attention to the factors that affect this equation. This caused a logarithimic change in how cells are guaranteed to become more oxidized (age faster) to circadian cycle mismatches as time proceeds. When epigenetics speeds up rapidly, it also changes the phenotype of the species affected by it. This is how we got the human brain from a primate model so quic kly in a small evolutionary window. The use of this biologic power law fueled th e development of our large brains from chimps. When you couple a super faster e pigenetic rate to a diet high in nutrients, you create the perfect storm for a b

iologic system to create disease. Modern humans fit this equation perfectly. Man y of these mismatches are not diseases at all, and we remain unaware of it even today. This is why we can t cure most of them either. This is why medicine has m any blind spots. HOW DOES CANCER OCCUR WHEN THE CIRCADIAN CYCLES ARE OFF? Time for some minor head hurting. I no longer think cancer is a strict disease e ither. It is caused by an acceleration of growth signals when there are no more stem cells left for adequate replacement. The cell has two choices, death or imm ortality. Guess what life chooses, by default, when it faces this decision? Onco genesis is that answer. Life is looking for an out to survive, but we have not evo lved a proper answer for it as yet. I think this is why we have found no cure f or cancer with the billions of dollars that have been spent on its research. Hon estly, I think the answer lies in FACTOR X. So how might this all occur you ask? This is thought to be caused by mPER2 circ adian deregulation of common tumor suppression and cell cycle regulation genes. Such as: Cyclin D1, Cyclin A, Mdm-2, and Gadd45I, as well as the transcription fa ctor c-myc, which is directly controlled by circadian regulators through E box-m ediated reactions. Sorry about the head hurting, but I have to show you I am not mad. I am a maven of Mother Nature. I connect things together. It is fine if you do not know abo ut all this. The key thing to remember is these epigenetic signals because our DNA to malfunction when there is a problem between leptin and circadian cycles. Defects in leptin biology are all linked to cancer generation and propagation. T his means that sleep is also tied directly into cancer, because it is wired into cell cycle functioning directly as explained above. It also is linked to cell m ediated immunity by evolutionary design as well! This means that lack of sleep c auses sepsis and can cause cancer in mammals whose biology is out of sync with t heir world. Research clearly shows that mammalian immunity is destroyed when sle ep is destroyed. It appears that sleep directly affects the chronic diseases of aging and likely plays a role in cancer development as well. Every bio hack in my office starts with a discussion of sleep. Mother Nature also used power laws to guarantee survival of our ancestors who we re cold adapted as well. These were the animals from which we evolved. Remember the currency of that biologic transaction is called epigenetics. This is control led 100% by the environment. Ten years ago, we did not know this. Eight years I ago, I began thought experiments in my head about what this could do to a cell over time, if applied over millions of years. This is the basis of FACTOR X. Power laws dictate that epigenetics had to speed up. It is required for ultimat e survival. It created the perfect situation for the development of a large huma n brain rapidly. This is not too controversial. But this implies that we should not have a lot of fossil ancestors. And guess what? We do not. This is why w e have found so few missing links. In fact, my theory says we are the missing li nk we are currently looking for! Radical? This is controversial. But, I believe it is based on firm science. If you want to see a modern world example of power laws effecting biology, I wan t you think about the recent TV program that starred Robb Wolf, called I-caveman . We all saw how that program turned out. We know what happened. I bet Robb h ad no idea how power laws dictated how he would be able to take down a large gam e animal to ensure survival. It is the same plan that Mother Nature employs. W e saw how some in the group gave up early. We saw how some of their decisions s ubjugated their biology. Do you remember what the vegan women said? Do you rem ember the gung-ho kid that gave up too early?

LINK Ultimate survival requires that out of the starting life forms, 80-90% will not make it because they die off or give up. Evolution does not ever give up. It ad apts to what it s given. Just like the Apollo 13 astronauts did to survive. Just as the surviving passengers did in the Andes plane crash, survivors did in 1972 stranded on the top of a mountain. Ultimate survival follows this basic power l aw. It is a core to biology. Robb survived with his group because of its appli cation. If this experiment was extended in real life, the others left behind wo uld have died for sure. Robb would not have and his success would have been exp losively selected for by his progeny. With Robb s success, it would have catapult ed him to a new understanding of how to successfully hunt and hone while Mother Nature was rewiring his biochemistry to make the most efficient use of the resou rces he procured. From this efficiency, it would speed up epigenetic control of his genome to cause extreme changes to his biology, to mandate his success. Th is is how evolution speeds up, and how it is transmitted to our genome in presen t time, and eventually epigentically transmitted to offspring. Maybe you have s ome insight why fat parents really make for fat infants now? It s a function of p ower laws. Evolution uses epigenetics to determine adaptation to environments. We have disc arded the strict definition of genetic determinism that came from Watson and Cri ck, as founders of DNA. We know today that the power of epigenetics dictates a l ot more about newer generations adaptations than we even knew ten years ago. The implications of this information now makes us look at some of our own long stan ding assumptions about how living cells work in cold and warm environments to se e how our cells ACTUALLY react to a thermoplastic environment. That is the essen ce of what I have found. I have put it all together in my mind and came up with three tests experiments t o disprove it. The Leptin Rx reset was step one. The results speak for themselve s. So I proved biologic plausibility with this experiment on myself, my family, and many of my patients now. I gave the world the Leptin Rx for free to test. I d say that has been a success in my practice and on the Internet. Now the last t wo experiments were tougher to figure out, but I think I did it in 2012. The la st two are steps in this ancient pathway that guaranteed success for survival. I have completed the other two. I did not disprove my theory either, but I do thi nk I destroyed lots of modern day dogma we all still suffer from.

GETTING BACK TO THE CANCER ISSUE: Is there a great recent, modern day example of my theory in action whose demise fits this theory today? Yes. We ll get to him soon enough. First, read this rec ent article and immerse your brain in it. ythm-disturbances.html

What does this article imply for us all, if this is true? Well, it is true in al l mammalian biochemistry. There is not a mammal alive that does not have this wi red into their hypothalamus. I m going to tell you what it means to me today. As the SCN function declines, it slowly destroys the chemical clocks in our head. When we are adapted and eat a warm climate diet, it INCREASES the decline of our metabolism and causes the inside of our cells to oxidize. The interior oxidatio

n pushes us toward a fork in our biologic road. That fork in the road is where cell suicide (apoptosis) or the choice of a cell to become immortal (oncogenesis ), occurs. If stem cells remain available, our biology uses them first. If none are left in our tissue stroma, we become senescent (non dividing with a poor fun ctioning organ) or we become cancerous. This implies that if we replenish stem c ells we may be able to alter the biology. The goal of longevity is to protect your stem cell supply at all costs as a youn g mammal. So having a program of living that does this is important. When we liv e outside our circadian cycles, we force our cells to make this decision too oft en, and we deplete those stem cells. We travel that road utilizing lifestyle beh aviors that subjugate our stem cells because we are unaware of how a circadian m ismatch may deplete our stem cells and force that decision to come to us earlier in life as future generations are born. This is why we see much more childhood cancers today as we did 120 years ago. It is a transgenerational epigenetic effe ct of our modern life. You need to go back and read what I wrote earlier in this blog about how circadi an biology is yoked to cellular metabolism. If epigenetics has sped up, and you eat a warm climate diet, you by definition increase mitochondrial ROS that slow ly kills you. As you age, it speeds up because epigenetics switches are designe d to react fast and furious for change. This is why neolithic disease all incre ase as we age. Name one that does not? Want more food for thought? Safe starches are in no way safe at all in a species that is derived from a cold adapted ancestor. Why? Re-read the NYT article. W hat are its implications given what I have just explained to you? This is more fuel or proof that the metabolic trap door I found makes all starches less safe wh en they are eaten outside of how our circadian biology accounts for them in our sped up systems. Evolution power laws have sped up too, simultaneously, to comp ound the issue. This explains why kids today are bigger than their preceding ge nerations. It explains also why they reach puberty faster today. It explains t hat when you add and carbs to their diet it speeds up neolithic disease generati on in modern man faster. This is why diabetes and cancer are now prevalent in y ounger age groups compared to 100 years ago. Colon cancer was the 37th leading cause of death in 1900. Today it is number two. Now you know why. CW is never going to answer these questions, because the manner in which they are approachi ng it is dead wrong. Review it all again. When the body used carbs for fuel, it generates more ROS in mitochondria. When you add this to a long light cycle, due to artificial lights of technology over time, you are actually causing your endogenous decline becau se it destroys your SCN clock for light. However, if you used cold it does not u se light. It uses a new signal (eNOS) that I will discuss in a later part of the series. That is not made unless carbs/starches are diminished in our diet. Carb s are a critical part of a warm adapted brain in the correct season, SUMMER. Bio logy says carbs can t grow in winter, when eNOS is selected to appear and the brai n wiring I uncovered proves that! Biology is telling us that we should not eat t hese things out of cycle. If we do, it is at our peril. This implies that there are no safe starches out of a normal cycle. That season is a summer cycle. In mammals, guess what signals that thermoplastic change of our environment? A gut hormone called VIP. Moreover, because of how this hormone is wired to the le ptin receptor, it becomes the initial stimulus to the metabolic trap door openin g for mammals. A gut hormone is what changes our entire metabolism in a few week s. And if you read my blog yesterday, you will see the start of all these proce sses begins first with a lot of dietary carb intake that stimulates PUFA increas e into our cell membranes of all mammals. It s the giant circle of life. Last tim e I checked, we are all mammals.

Now back to the original point of this section, cancer, oncogenesis, Apple, tech nology, carbohydrates, death, and Steve Jobs, are a prime example of this theory in our modern world. Diet alone was not the sole cause of his demise. That is a very bad assumption many in the paleo-world are making. In fact, they are co mmitting the same errors that a vegan does with their own dietary choices by usi ng technology out of cycle as well. The biologic effect of technology is buried far from their consciousness because they are eating a smarter diet for their biology, and they look and feel well o n the outside while their cells slowly oxidize and age. This implies that the p roof of my theory will be born out in the second half of their life with the ins idious chronic uncoupling of their biology from circadian biology. We can measur e the proof of my theory by checking their telomere lengths right now to see if what they believe today is in safe. If starches are safe, prove it. I put it to the test and they are not safe. Optimal is not Paleo by today s beliefs. RADICAL THEORY # 6: Modern life is as bad to us as a vegan or SAD diet. Eating b etter than the rest of the world will only hide its effects from your consciousn ess longer until you realize it. This implies that what you think is really safe may not be safe at all. It means that your ultimate proof won t come until it s too late for reversal unless you prove it to yourself today. Can we do that? Yes. Why do I know this? Because I tried to disprove it in 2006, 2009, and in 2012 . On February 27th, I use my talk at the Paleo Summit with Sean Croxton to delve i nto these mismatches further for you to consider. We must begin to question all our basic assumption of diet and all modern life and how it effects on our biol ogy. For example, are our neolithic brain s thoughts allowing us to live outside our biologic blueprint? How does this process manifest when you consider the ef fect of time with respect to epigenetic control of a modern mammal whose ancesto rs are cold adapted, and living in a modern world that is warm adapted 24/7? Ho w can we test it? Can it be reversed? Does it require us to optimize our diet as soon as we become aware of it, and limit ourselves to the exposure to technol ogy at the wrong times to get to an optimal life?

READERS SUMMARY: ARE YOU AWARE THAT YOU CAN EASILY CHANGE YOU METABOLISM BY YOURSELF AT HOME? DO YOU KNOW THAT YOU CAN CHANGE YOUR CALORIE NEEDS TOO? ARE YOU AMBIENTLY AWARE OF WHAT YOU DO NOT KNOW, BECAUSE YOU HAVE NOT CONSIDERED IT? CONSIDER THREE NEW RADICAL RULES THAT MIGHT INTRIGUE YOU TO KNOW MORE ABOUT CT Now that you understand that I believe lved, what implications does this hold ith this thought experiment we need to lution to fully conceptualize how cold for 4 short minutes. First, I want you Sleep Recently, one of my readers pointed out he was confused by Dr. Gamble when she s aid the normal pattern of sleep in a natural environment had two cycles. He want ed to know why her version and my version for sleep as written in my post Rx for cold environments were how life first evo for all life and humans today? I think w begin to talk about another aspect of evo works for biology. Let s talk about sleep to watch this video before you proceed.

the Leptin Rx were not congruent. It was a great question that really opens the discussion to the idea of evolutionary mismatches. These mismatches occur in ma ny modern systems of biology, and they are actually increasing in frequency and severity as time elapses. The reason is quite simple. Evolution is constantly getting faster as time goes on, relative to the current state of our genome. Th is is really how the cellular theory of relativity is currently affecting our own genome today. The speed of evolutionary change has far out stripped the ability of our paleolithic genes to catch up. This mismatch causes major problems for mo dern humans. When they further exacerbate the system with choices not congruent with our biology, the results are magnified in disease incidence and prevalence. She also mentioned in passing, early in her talk, that people who went deep into the ground have been found to be very productive while in a cold dark environment . She did not expand on this concept at all, but I would strongly suggest you r emember this as the cold thermogenesis series progresses on. There is a deep bi ologic reason this occurs. As we use this pathway, lots of things improve that w e do not expect.

She assumed in her talk that native polar people without artificial light sleep differently than we do today. She spoke about the effect of light cycles. She s aid that she felt that light cycle were the most important affect on our biology . Light cycles are important to all life, but this bright researcher is apparen tly unaware that mammals have an innate ability to change their internal chemica l clocks when their environment changes. We stop using the photic light cycles to yoke metabolism to our sleep when it is cold. There is an epigenetic switch in us that stops our suprachiasmatic nucle us from using light in cold environments. This is done by design by evolution be cause light cycles do not become important in freezing cold because carbohydrate s cannot grow in these environments. So evolution designed a plan to teach mamm als who cannot think as we can that the best way to yoke the season cycles at ou r poles is to use temperature instead. That is precisely what happens. I will explain the complex biochemistry later in the series and provide you with cites. Right now, I want you to be aware of this metabolic trap door. Its mere prese nce is shocking enough. But its implications are far greater for modern humans.

There is one larger problem with her assumptions in this TED talk. She said lig ht is the big deal. And I know it is not true any longer in cold. This means t hat if evolutionary biology gave up on light and uses cold, what else may happen to our metabolism in cold? Evolution does not do these things for no reason. S he was quick to point out that this ability has been lost in modern humans in he r estimation because of our discovery and widespread use of artificial light has become a huge game changer. We know Paris, France became the first city in our world that used fake light in 1924. I think most humans are not really aware of how basic circadian mismatches destroy our biology slowly via the slow erosion o f metabolic function. We know that humans die most from heart disease and heart failure. Heart failure is the number one cause of admission according to Medicare data. After this blo g is through, you might know why this makes complete sense. The reason has to wi th a slow erosion of the process of autophagy in humans due to the circadian mis matches created by our choices in life when they are married to the rapidity to the development of our neolithic brain. In essence, we got so smart so fast we b ecame able to control too much of our environment for our own epigenetic and gen etic good. The smarter we got, the more mismatches we created for our biology an d the less efficient autophagy became to fix and recycle proteins for repair. Re

duced autophagy leads to heart failure. So this means that biologic mismatches a re best measured in animals by looking at their rates of heart failure. For huma ns, the rates are staggering. That is a big clue that what we all believe to be true could be what is actually killing us slowly. Remember autophagy occurs when we sleep. Moreover, when one looks at the biology and biochemistry of sleep and truly unde rstands the power of autophagy for longevity, it becomes apparent that we may wa nt to consider that maybe sleep is our primordial condition and not wakefulness. Maybe, just maybe, we evolved consciousness over time. This theory I have follo ws the thoughts I have developed in my cold thermogenesis theory, because in ext reme cold environments, the process of autophagy becomes super sensitized to save energy while it increases our metabolic capabilities. Remember when Jessa Gambl e said that humans in dark deep holes become more energized and productive in he r TED talk? The reason why is cold dark environments super sensitize the human process of autophagy without us actually having to sleep at all. The cause is a n increased efficiency of autophagy by cold and dark. The metabolic trap door d oes something to us that we cannot do in long light cycles. To get suprasensiti ve autophagy in light we have to sleep well. This is an example of how metaboli sm and biochemistry can rewire or become thermoplastic in cold and dark environm ents. In fact, in cold, sleep is heavily selected for in terms of how mammalian nervou s systems are built by evolutionary design. Cold stimulus changes the behavior or eutherian mammals. This is why mammals can sleep so long underground in sub z ero conditions and survive. Sleep is heavily selected for in cold. Radical Rule #3: Sleep and cold environments were our ancestor s primordial condit ion and as such, this was evolutions starting point for life on our planet. Sounds more radical does it not? Let s consider these thoughts and facts today. If we assume this to be true, this thought explains why epigenetics has been fou nd as the dominant player in how genetics operate in biology. Why? Anything tha t promotes survival and reproductive fitness has to be passed to the next genera tions. This is evolutions main directive. I think evolution found that epigenet ic modifications to be quite effective way to pass on environmental information to succeeding generations. So successful, that it became a backbone law of geno mic functioning. Evolution follows fractal patterning. So it is also highly con served in all species. Today that appears to be true too. Life at its genesis w as likely static, and to get the nutrients it needed, it used passive diffusion because of proximity. This made food scarce to life at all times. To survive it had to overcome this impedance. This manner of nutrient collection is highly ine fficient, but the suprasensitivity of autphagy in cold made the process biologic ally plausible for great part of our evolutionary history. It appears that evol ution naturally adapted to improve access to nutrients and to do so, it had to e volve wakefulness to obtain them. Yes, you read that correctly. To complete this , it yoked metabolism to sleep early on in evolutionary biology so it could acco unt best for nutrients and autophagic repair to lead to optimal survival. I beli eve the use of timing became an easy evolutionary solution because of the rhythm of the sun and the freezing cold that these cells found them in could account f or these cycles. I believe that fractal organization of sleep and metabolism remains in every org anism studied today. If you ask sleep researchers, (I have) they have told me t his is a correct assumption. I believe that sleep and autophagic efficiencies a re extremely high conserved across all species on our planet. We still have yet to find a species that does not sleep some. I think as life evolved wakefulness and not sleep, because it had to account for its environment. Such evolution the n moved from a static model to a dynamic one, and then a whole new set of enviro

nmental problems had to be navigated to make life persist. Now you see why autop hagy sits at position 15 on the Quilt. It is a critical component of optimal li ving in all species, not just our own. This also signals where movement was first coupled to memory or actions in life. Even today, all learning in higher order animals is directly coupled to movemen t in their environment. The more one moves, the more intelligent one becomes. I just explained that to you in a recent blog on here.

We can prove this today because if we just get an Alzheimer s patient with a demol ished brain, when we introduce exercise, we can increase their cognitive functio n in a completely broken organ. In fact, in any neurodegenerative condition this happens by evolutionary design. That tells me a lot of how evolution thinks . The more I learn how she thinks, the more I learn. I hope this helps you understand how I think about life and how it all began. It is a foundational concept behin d my QUILT document. When you see my point of reference, you begin to see a new reality that you might have not anticipated before.

Let s continue on now to metabolism from the light and temperature story. There w as a recent paper done that showed mammals may have another unique ability that is thermoplastic we are also not aware of. It is currently assumed by researche rs and scientists that the only way a mammal can change its fatty acid concentra tion is by its diet. This article showed us that assumption might also not be t rue. ( Changes in Good Fatty Acid Concentration of Inner Organs Might Be Largely Ind ependent of Diet ) In this article, they state the following, it is generally beli eved that mammals are unable to alter the proportions of essential fatty acids i n their cell membranes except by changing their diets. Amazingly, the amount of so-called n-6? polyunsaturated fatty acids (those with t he final double bond at the sixth position) in the membranes was found to increa se dramatically before the start of hibernation. Apparently, to prepare the body , particularly the heart, for operation at very low temperatures. Consistent wit h this idea, the transition to a higher content of n-6 fatty acids in membranes takes place extremely rapidly just before the animals enter their hibernation ch ambers. The changes are reversed again, over a short time, around the terminatio n of hibernation in spring when the animals return to a life at high body temper atures. The fatty acids incorporated in the membranes probably stem from the marmots whit e adipose tissue. Surprisingly, however, fatty acids are not simply taken from t he fat stores at random but n-6 polyunsaturated fatty acids are transported pref erentially. The mechanism remains a mystery. These new and unexpected findings show that mammals can make highly significant and rapid seasonal changes to the lipid composition of their cell membranes. But the results go far beyond this. During and immediately after hibernation, marmo ts are unable to eat anything their food is under a thick layer of snow so the c hanges cannot be related to immediate dietary influences. Because the animals hibernate underground isolated from any external signals, th e changes are probably controlled by an endogenous clock as part of an annual cy cle. This article implies some more evidence for my theory on thermoplastic change. I is really not a theory, but an evolutionary dictum in all eutherian mammals. L et s examine why evolution may allow mammals to do this.

The critical points for us to consider in this article are twofold: 1. the stim ulus for hibernation in eutherian mammals and their descendants are tied to high dietary carbohydrate intake (proven fact already in science and not controversi al) and high placement of omega six intake into their cell membrane prior to hib erantion begins. This was not known until this article came out. It did not esca pe my view, because it makes total sense of why mammals in particular would do t his. The dietary stimulus of plentiful carbohydrate availability is a metabolic sign that they should soon den (fat and happy) and this seems to change what hap pens to the fatty acid synthetase enzyme in the mammalian gut lining. In this ne w research, scientists studied mice that are unable to make fatty acid synthase (FAS) in the intestine. FAS, an enzyme crucial for the production of lipids, is regulated by insulin, and people with diabetes or insulin resistance have defect s in FAS. Mice without the enzyme in the intestines develop chronic inflammation in the gut, which is a powerful predictor of insulin resistance. This is how ma mmals used to signal their body that it was time to lay down under ground and av oid the harsh arctic winters. This biology is now coming to light in humans and you can read about it in my second cite. It appears all the biology is lining up quite well with my theory. This signal is likely tied to signaling that the mammal should begin to replace its own cell membranes with PUFA s. Why would evolution do that? Why should we pa y attention to it? We should pay attention to it because it has major implicatio ns for modern humans who are direct descendents of these animals. Moreover, thi s evolutionary design feature allows for an interesting conundrum to potentially develop for us. It appears incorporation of PUFA s into cell membranes are a norm al signal in mammalian hibernation for them to den. I also found out from organi c chemistry that high cell membrane concentrations of PUFA s make the cell membran e of our cells very fluid in cold environments. This explains why mammals need t his adaptation to sleep and not freeze their cells. It is a cellular anti freeze . I also found out from Canadian frog biology that high glucose levels also act as antifreeze for animals in extreme environments. This information was nothing sh ort of shocking. Maybe diabetes is an ancient epigenetic program for survival an d not a disease at all? When I found this out I realized immediately why evoluti on needed to plan for this. In cold environments, if our cell membranes are fi lled with MUFA s and saturated fats they become too stiff to work. All cellular f unctioning in organ systems depend upon proper cellular signaling. Mother Nature knew it so it designed a system to incorporate PUFA s normally into all mammals c ell membranes to get optimal functioning in cold environments. Any organic chem ists can verify that this is a complete and factual statement. Here is another example of how biologic thermoplasticity occurs in nature. So it appears that dietary carbohydrates, which are only present in long, light cycles in the summer in cold places, induce mammals to add PUFA s to our cells to become fluid so we can function as we hibernate. This makes complete logical se nse when viewed from an evolutionary stand point. I asked several mammalian ver tebrate physiologists if this is how carbohydrates work for hibernating mammals and their answer was yes. This implied to me that maybe if this is how mammalian physiology was designed t o work to begin with. After all, they evolved in the polar environments on eart h. This implied something even bigger to me. Why would we need diabetes to surv ive? Then the answer occurred to me. I called it Factor X. I checked my facts, a nd continued to connect more dots. Diabetes is required in mammals who are desig ned to work for optimal adaptation in cold environments.

Maybe, just maybe, it has become thought of as a neolithic disease in humans bec ause we have simultaneously lost the ability to hibernate because we evolved the ability to control our environment completely? After all, we know evolution is moving faster today than our genome can adapt, Cordain and LaLonde have pointed out many times. Remember, we still have our mammalian paleolithic genes that control our use of dietary carbohydrates and the up-regulation of PUFA s in our cell membranes in us today. These biochemical pathways remain in us. This is another well known fact in the paleosphere. What is not so obvious to most, however, is that the rapidit y of our brains evolution created the ultimate mismatch in this system. I believe some perceive this mismatch, but no one has explained this as yet. So it then f ollows that when we create a biologic mismatch with our neolithic thoughts we ge t something we have been socialized to believe is a disease. It is not at all. I t is an evolutionary novelty created by our own rapid evolution secondary to our brain amazing development in the same time period? This is how I view it from a 30,000 foot level today. The skeptics will immedia tely jump down my throat and point out that type one diabetics and CW that says it is a genetic disease! I don t and never have. I think Type 1 and 1.5 diabetes are decidedly epigenetic phenomena of this mismatch that has been passed from e very eutherian mammal to us today, and we remain unaware of this possibility eit her! Epigenetics has also speeded up if evolution has. This is why humans have n o ability to stop diabetes once it starts unless they get in a cold environment. And this is why we assume that these two conditions are diseases, rather than c onsequences of a relative time frame shift in evolutionary time due to how fast ou r brains developed. This also explains why we have a paucity of hominid skeleton s in the fossil record. This time disruption is part of levee one, which I calle d the cellular theory of relativity. Time is something we failed to consider in ho w our species maybe its own missing link to this puzzle! Several of my friends have asked me, if this is not a disease then how does natu re cure diabetes on its own? The answer should be intuitive now to you. When y ou began this post you might have thought that where I was headed was counter in tuitive and frankly insane. Well, now you see how I think about it from a new p erspective. The biology we know to be true today lines up completely with this theory. But how are IR and DM cured? Well, can you really cure a disease that is not a disease to begin with? In IR, we get expansion of the fat mass to increase storage from carbohydrates w e ate during long light cycles. That implies to reverse this process, there has to be a system. There is, it s called hibernation in freezing cold. It means the cure is to live by your descendants biologic directs and in congruency with our evolved biology. Since we no longer hibernate maybe you need to consider how yo u eat carbohydrates within the circadian controls? Maybe what you thought was sa fe really is not? Final point in part two of this series. Doc, how does evolution eliminate these f at cells normally? What is the biologic process? The reason diabetic researchers can t find a cure is because their manner of looking at the problem is skewed and dead wrong. When you put on your evolutionary glasses, you see a different view of a perplexing issue. Cold environments are found as mammals hibernate in nor mal circadian biology. This completely reverses IR in mammals and wakes them up when conditions are better for life. Humans extinguished this ability rapidly in our evolutionary history because we are fully capable of controlling our enviro nment. There is no need to den any longer, because we control our environment re gardless of the temperature but we still have the machinery that acts within us. If we eat outside that directive, we get modern day diabetes. We can forage an d succeed all the time. We can obtain Chilean bananas on Dec 31 in the Arctic Ci rcle. Do you think evolution has a plan for this set of circumstances yet? Nop

e. The modern result is that we have created a world where carbohydrates and PUFA s a re available 24/7 while we no longer can access to evolutions solution for Insul in resistance. It also makes sense why we have no built in hard wired metabolic pathways for fat removal. But cold thermogenesis does it and does it remarkably well. That implies that our ancestors paleo genes remain dominant as we evolved out of the Savana. Or it could even mean that maybe other assumptions we have ma de are also wrong? Realize that because our brains development was so rapid, it allowed evolution to extinguish the ability to hibernate. But there is a lot mor e to this story yet to be told ss added biologic plausibility and maybe ultimate proof as to what is the optimal diet and what is just good enough. RADICAL RULE #4: Evolution speeds up as time progresses on. This is a known biol ogic fact. The faster this evolution occurs, the greater the dietary mismatch be comes, and then we begin to see the real causes of why diabetes might happen. RADICAL RULE #5: Epidemics are not caused by genetics. This is also a medical cl inical fact that gets lost in the scientific literature, but you would never get that from reading the literature on diabetes. Are you connecting any dots yet? Are you beginning to see how the QUILT was built we are just getting started Next up the mind bending biochemistry that backs up all I have said here. Prepare for some cranial work out.

READERS SUMMARY: WHAT REALLY IS A CONCUSSION? HOW DO I TREAT A CONCUSSION IF IT HAPPENS? WHAT THE MILITARY,NFL, NHL,MLB, NBA and NCAA SHOULD DO NOW? WHAT EVERY PARENT NEEDS TO KNOW NOW? Today marks the fourth blog in this series. Today also marked another early deat h in the NFL community. This time Orlando Zeus Brown was found dead in Baltimore. He was a mammoth offensive tackle who played in the NFL from 1994 to 2005. After hearing about it today I decided to post this blog tonight. I think this inform ation is critical and needs to be considered by everyone at risk right now. Concussion is a trauma-induced alteration in mental status that may or may not i nvolve loss of consciousness. Headache, confusion and amnesia are the hallmarks of concussion. The confusional episode and amnesia may occur immediately after t he blow to the head or several minutes later. I have also seen symptoms appear s everal days later from concussions especially in the younger patient and in the multiply concussed patient. Sources of Concussion: Blasts Vehicle crashes Projectiles Falls

Sports injuries Symptoms of concussion: Headaches or neck pain that do not go away; Slowness in thinking, speaking, acting, or reading; Getting lost or easily confused; Feeling tired all of the time, having no energy or motivation; Mood changes (feeling sad or angry for no reason); Changes in sleep patterns (sleeping a lot more or having a hard time sleeping); Difficulty remembering, concentrating, or making decisions; Light-headedness, diz ziness, or loss of balance; Urge to vomit (nausea); Increased sensitivity to light s, sounds, or distractions; Blurred vision or eyes that tire easily; Loss of sense of smell or taste and or r inging in the ears. Many use descriptive language in trying to relay information about what a concus sion is. Many call it a brain bruise This is very inaccurate. There are no finding s on imaging studies in most concussions. The best way to understand concussion biologically is that it is an energy disturbance caused by the abruptness of the trauma inflicted to the brain. Many studies of a concussed brain show blood flo w changes on functional MRI s and on PET scans. If EEG s are also done on patients o ften times there is low voltage findings on the study signifying decreased energ y efficiency that leads to acute changes in the neurocircuitry of the surroundin g neurons. This injury depletes neurons of energy and this puts the area of inju ry under much higher risk to future damage because of the accumulation of the re lease of excitotoxic neuro chemicals released by the cells injured. When these c hemicals are released by the damage neurons there is a simultaneous release of m agnesium and intracellular zinc and calcium. The calcium release can result in c ell death if the injury response is not contained by the brain s endogenous immune response and by the microglia and surrounding astrocytes. These cells re-uptake the toxic chemicals released and try to contain the release of the the metal io ns locally to limit damage. Concussion severity seems to correlate quite well to the release of these substances and the resulting decrease in cerebral blood fl ow to these areas. According to a recent statement by Dr. Robert Stern, co-director of CSTE, new ev idence shows that 85% of concussions require about three weeks of recovery (Abel, D., 2010). This is a longer time period than anything currently in the literatur e for return to play guidelines. I personally believe this statement does not co me close to going far enough for those with severe concussions or those who are multiply concussed. You also must realize that currently in 2011 there is no level one data on concuss ion risk, or treatment. Therefore there are no uniform agreed treatments. With t hat as a background one must entirely focus on the known biochemistry and pathop hysiology to make best guesstimates on how one should proceed once the concussion has occurred. HOW DO YOU PREVENT A CONCUSSION? 1. Avoidance of activities where there is risk for head trauma. 2. Avoiding situations where there are many angular momentum forces 3. Avoid severe flexion or extenuation of the neck and head. 4. If you are involved in a high risk activity you should consider limiting all glucose consumption for 6 hours prior to the activity. 5. You should maintain a ketogenic diet, loaded with medium chain triglycerides 6 hours before the at risk behavior to create a protective terroir for the brain if injury were to occur. 6. A properly fitted mouthguard should be worn at all times to avoid traumatic i

mpact of the mandibular condyles into the base of the temporal lobes. Many concu ssed patient have tongue lacerations because they are not wearing mouth guards a nd their concussion can be quite severe because the hippocampus is often severel y impacted by this type of impact. For athletes or soldiers who need to verbaliz e to act a voice controlled system should be developed using nanotechnology so t hey can wear the mouthguard. This should not be compromised due to the severe ri sks of what hippocampal damage can lead too. 7. All head gear should be mandatory and contain motion and impact detectors to help doctors understand injury vectors to predict injury and severity. ( IMPACT evaluation, Miltary Anam evaluation; Parallel biomarker study; Helmets with helm et blast sensors and cooling.) All helmets should have a cooling system built wi thin the helmet to keep the head temperature cooler than normal for the neuro-pr otective effects of cold temperatures as biomarkers 8. Cooling shirts should be designed and worn to protect the posterior and later al neck. This allows for a constantly controlled temperature across the vertebra l and carotid arteries to mitigate risk before concussion occurs. If this is not worn, Ice packs should be immediately placed and secured to this area for any t raumatic risk. Body and head cooling techniques should be used on the sideline, bench or in military theaters. 9. Prior to onset of high risk behavior one should consider supplementing with 2 5 mgs of zinc, 400 mgs of Magnesium. Ingestion of coconut oil in packet form sho uld be considered as soon as help arrives to improve the neuronal energy deficit and limit neuronal damage. All patents at risk should have baseline neuro-cogni tve batteries made mandatory. The younger the patient the more the testing will need to be enforced. 10. All at risk patients should avoid all MSG, artificial sweeteners, and excito -toxins to limit risk of neuronal damage pre and post injury occurrence. WHAT SHOULD BE DONE ONCE A CONCUSSION OCCURS? A. All people at risk should undergo fMRI pre and post injury/deployment as well as in game/theater scanning. Functional MRI/PET scanning should be required in all front line military and sports venues. B. Resting fMRI/PET scanning should be able to distinguish mTBI, PTSD as it has with 80-90% accuracy distinguished from neurodegenerative disorders. All fMRI sc anners should have minimum 3.0 tesla MR scan capability. All scanning needs to b e done during waking hours (sleep deprivation causes negative scan effects). C. Ketogenic packets, supplements available at all at risk events. Strict avoida nce of all glucose and fructose drinks or foods during at risk activities to lim it risk. D. All patients should be removed from all activities and assessed by a neurosur geon/neurologist with correct skill set. No exceptions should be made. E. Avoid excessive bright light in the eyes due to thalamic sensitivity/ lateral geniculate nucleus WHAT IS THE IDEAL STUDY FOR CONCUSSION AND CTE RISK? A. The ideal study of at risk patients: Combine/Preseason/Pre Deployment scans f or baseline with formal neuro-cognitve battery. B. Organ donor status made mandatory to allow postmortem exam of at risk patient s. Allow for concussion history; Thorough neuropsychology evaluation; Genetic Te sting for ApoE 4 allele C. Scanning in dedicated scanner before at risk activity begins (3T fixed scanne r) D. Parallel biomarker study modeling the VA s program for the military. (Banyan Bi omarkers)

E. Deployment/In Game injury: Scanned in theater/ City post concussion (3T fixed scanner) with Anam evaluation Parallel biomarker study, review of Helmet sensor and vehicle blast sensor data to assess risk. F. Post Deployment/Post Game management: Repeat scanning post deployment in exac t same scanner as pre-deployment/game assessment. Complete neuropsychology evalu ation with sequential brain examination using neurocognitive testing parameters like IMPACT/KIA Continued surveillance in civilian status through Veteran s Admini stration Parallel biomarker Study WHAT ARE THE SYMPTOMS OF IMPENDING CTE FOR THOSE AT RISK TO BE AWARE OF? The clinical symptoms associated with CTE vary in severity depending on which cl inical stage the individual is in (McKee, A.C., et. al., 2009). Initial early sy mptoms include the following: Deterioration in attention, concentration, memory, poor decision making Disorientation to person, place or time. Confusion that waxes and wanes. This is dramatic when the patient is int oxicated. Dizziness by spatial of visual cues. Headaches become very common. Cervical pain is also a common feature. Lack of insight, lack of empathy, and a personality change is apparent t o everyone who knows them Poor judgment involves use of drugs, alcohol, risky behavior, Overt dementia becomes obvious to friends and family. Slowed muscular movements with increased activity. Staggered gait and loss of balance is common. Impeded speech: Word finding difficulty is the first sign one usually re ports. Tremors and fibrillations in major muscle groups Vertigo at rest or during motion Deafness that can come one abruptly The individual may progress through three stages of the disease beginning in the first stage with affective disturbances and psychotic symptoms. The emotional l ability and change in personality are standouts of this stage. As the disease pr ogresses to stage two, the individual may suffer from social instability, errati c behavior, severe memory loss, and the initial symptoms of Parkinson s disease (M cKee, A.C.,, 2009) . Many functional movement disorders can be seen at th is stage of the disease progression. Family members should look for them to aler t the doctors of the progression. Alcoholism and drug abuse are particularly com mon in people developing CTE from their concussions. Generally, the more pathway s of inflammation that the patient sustains at this time the quicker the symptom s tend to progress. This can be from obesity, drugs, alcohol, or environmental t oxins. Sometimes, the symptoms progress rapidly when their are acute spikes in c ortisol, insulin, or in ingestion of excitotoxins. A new trauma or life stress c an also precipitate a serious neurological decline. The 3rd and final stage consists of a progressive deterioration to dementia and may have other symptoms including the signs associated with Alzheimer s disease or Parkinson s disease, speech difficulties, gait abnormalities, dysarthria (speech disorder characterized by neuromuscular weakness or lack of control of facial mu scles), dysphagia (difficulty swallowing), and ptosis (drooping eyelid) (McKee, A.C.,, 2009). How is CTE distinguished from other neurodegenerative tauopathies, (i.e. Alzheim er s Disease) A. CTE usually Involves superficial cortical layers, specifically neocortical la

yers 1 and 2. B. Patchy distribution in frontal and temporal cortices is the rule in CTE and n ot in AD or PD. C. Propensity for injury in sulcal depths as opposed to surface gyri Deposition of I?-amyloid occurs in <50% of cases - Marked accumulation of tau immunoreactiv e astrocytes (concentrated around glutamate receptors of the neocortex) D. Superficial cortical laminae: layers II and III Perivascular Patchy, irregula r Prominent glial tangles E. Key MRI findings: Often greatest at sulcal depths, Dot like tangles, spindleshaped neuritis, subcortical white matter defects on STIR or T2 imaging. Dilated ventricles due to cerebral atrophy, fenestrated septum pellucidum is extremely common in this group, atrophic mammillary bodies (due to memory loss), loss of t halamic volume, loss of neocortex volume, Loss of medial temp lobe structures re sulting in profound memory changes. F. Decreased Apo E and AI? spinal fluid concentrations in acute injury settings. Most patients do not have CSF examined but this should be considered by neurosu rgeon/neurologists rendering independent assessments in severe persistent concus sion symptoms. Regular MRI/CT is worthless in initial assessments. Functional MR I, connectome mapping and Diffusion tensor imaging should be considered gold sta ndard imaging testing for this group of patients. (tractographic imaging) G. Auto antibodies can show up 5-7 days post injury and can persist for years in at risk patients. This should be mandatory testing for all at risk patients pos t injury for their lifetime. (4 biomarkers in clinical testing) Conclusions: fMRI, through connectome mapping, will detect organic changes in functional neur al architecture after significant mTBI. These can all be made available in most cities supporting professional athletics of in the military theater. For younger patients parents should assess whether these treatment options exist in their a reas before consenting to allowing participation in at risk activities. The presence of these changes should serve as a warning that repeated exposure t o concussive forces may lead to the development of chronic traumatic encephalopa thy as the patient ages. This tool should be used in all cases in my opinion. Co st is steep but the cost of CTE is steeper to the patient and to their family du e to its debilitating and possibly lethal results. The pairing of RfMRI with other biomarker studies will provide cross validation of methods and the development of less complex methods of detection of significa nt mTBI, i.e., easily obtained serum biomarkers. (Banyan Biomarkers) Dietary and supplement regimens should be instituted at the time of injury. Neur osurgical or neurology consultation should be mandatory in all cases and decisio n tree analysis should be uncoupled from the employment/deployment situation in all cases.

READERS SUMMARY: 1. How does energy depletion link neurodegenerative, concussions, and diet? 2. Why are diabetics more at risk for concussion and neurodegenerative diseases? 3. What is the NMDA receptor and why should I care? 4. How does the NMDA receptor work normally and in diseases like concussion to p rotect us? 5. How does glutamate, aspartate, and glycine tie into this story?

This series of blogs is going to focus in on neuronal injuries and how they all have a common tie to defective energy metabolism. The initial blog will be heavy on biochemistry but it will set the tone for you gaining a deeper appreciation of how damage to a receptor in our brains may cause different diseases, but have very common symptoms. I have focused in on energy depletion in some neurodegene rative diseases already, but we need to expand the net to explain how cerebral c oncussions and dietary choices are linked and can cause a less than optimal resu lt for the person suffering from it. In this series I will also write a blog abo ut chronic traumatic encephalopathy (CTE) since football season is now in sessio n and this injury tends to make news in the fall sports sections. How this ties to diet may be new news for some of you. In my recent Alzheimer s blog, we spoke of how neurons in AD become deficient in e nergy as they slowly die off. This is an example of chronic energy depletion enh ancing a pathological cellular process. An example of acute energy depletion is that of a concussed athlete. Once the head is impacted, it causes a dramatic alt eration in the neurochemistry of the brain and leaves the person with a constell ation of symptoms based upon the severity and duration of the impact. We have al l seen pictures or heard stories of how concussions have caused athletes to miss games and have their career s threatened. The concept of energy deficiency is vit ally important to remember when we talk about neuronal injury types. The injury can be from metabolic damage, trauma, or from dietary toxins. We also showed how devastating magnesium depletion is in the development of insulin resistance and diabetes in this blog. Nutrient depletions can play major co morbid roles when energy is also lacking in neurons. These factors alone are bad enough for neuron s, but when they are combined, the summated results are even more problematic fo r the person to withstand. I have a few patients in my practice whose professional careers were ended becau se their healthcare providers and employers did not understand these dynamics an d how to optimally treat them. The loss of energy in a neuron is the initial cri tical event that can cause major pathologic problems to develop longer term. Thi s is especially true if the correct information is not given to the person at th is time. It is particularly bad if the person is already functioning sub-optimal ly and has compromised energy generation from leptin resistance, multiple trauma s, or other diseases processes that limit us in some way. Even if one is in the best physical and mental shape of their life, it might have devastating conseque nces if other critical factors are present simultaneously as well. In 1989, we learned that neurons deficient in energy became much more sensitive to the effects of excitatory neurotransmitters like glutamate and aspartate. I d istinctly remember giving several talks about this finding during my residency i n neurosurgery. These studies showed that if we took cerebellar neurons in a gla ss jar and the surrounding terroir was designed to contain high levels of glucos e (sugar) and magnesium, that even high levels of excitatory neurotransmitters c ould not cause neuron cell death. In impact studies we have also found that diab etics cannot withstand head impacts as well as those who were non diabetic. That stands to reason because the cells cannot use glucose normally and diabetics al l tend to be magnesium deficient. The most interesting effect occurred when gluc ose was removed from the neurons surroundings and it was made energy depleted. T hen even a small amounts of the excitatory glutamate or aspartate could kill the neurons. Many foods are loaded with these chemicals. The brain is usually prote cted from the dietary assault by its blood brain barrier, but this is not the ca se in trauma or in many neurologic conditions. This allows the brain to be furth er assaulted in these cases. For example, in traumatic injury, right after the i mpact their is a huge surge of these excitatory chemicals liberated from our dam aged brain cells. This clinical situation is important given what we learned fro m the 1989 experiments cited here. When the researchers then decided to also rem ove the magnesium from the experimental surroundings of the nerve cells as well,

even smaller doses of the glutamate were able to induce neuronal death. The dep letion of magnesium and glucose are clearly critical to energy generation in neu rons. Energy depletion sensitized the neurons to death or injury depending upon the level of insult. Even today in brain trauma or stroke care, physicians are t aught not to start IVs containing glucose so as to protect brain cells from dama ge and to supplement with magnesium to protect the brain from further injury. In the human brain glutamate is used as a neurotransmitter in over 50% of the sy napses in the neocortex of the frontal and temporal lobes. These are the areas o f the brain where many neurodegenerative disorders are also found. This is also happens to be the place where the brain is injured in most cerebral concussions as well. I believe this is not a coincidence either. Glutamate s main action is to excite the brain and prepare it for action. When this part of the brain is dama ged it causes memory loss, learning disability, inability to act and plan, and a loss of cognition. These symptoms are all commonly seen in neurodegenerative di sorders, trauma, and metabolic conditions that patients can suffer. These sympto ms tend to occur together when excessive glutamate or aspartate is allowed to re main around nerve cells no matter the cause. The action of glutamate occurs at several receptors. We will focus on the most c ommon receptor in this blog. The most common is the N-methyl-D-aspartate recepto r. We refer to it as the NMDA receptor for short. Glutamate, aspartate and glyci ne (dietary amino acids) can all stimulate this receptor. The NMDA receptor is a non-specific cation channel which can allow Ca2+, Na+, and K+ to pass into the nerve cell under normal conditions to facilitate neurochemical messages between cells. The net influx creates and excitatory post synaptic potential (EPSP) to o ccur between neurons. This is how nerve cells communicate in learning and memory and to initiate behavior. Mg2+ not only blocks the NMDA channel in a voltage-de pendent manner but also potentiates NMDA-induced responses at positive membrane potentials. This means that Magnesium glycinate and magnesium taurinate treatmen t can be used to produce rapid recovery from depression and in post concussive p atients. We know it is very effective in diabetics because of their inherent met abolic depletion. The reason Mg works, is that it blocks the NMDA receptor from firing constantly to cause neurons damage because of the low magnesium levels in those nerve cells. These findings are also seen in concussed depressed patients , those with diabetes, and those with AD or PD too. Na+, K+ and Ca2+ not only pa ss through the NMDA receptor channel in normal conditions but also modulate the activity of NMDA receptors. Zn2+ (zinc) and Cu2+ (copper) generally block NMDA c urrent activity in a noncompetitive and a voltage-independent manner. However, z inc may potentiate or inhibit the current depending on the surrounding neural ac tivity. The levels of Zn and Cu in the body are directly tied to diet, stress re sponse, and to the integrity of the gut s brush border. The NMDA receptor therefor e functions in the human brain as a molecular coincidence detector . Its ion channe l only opens when the following two conditions are met simultaneously: glutamate is bound to the receptor, and the postsynaptic cell is depolarized (which remov es the Mg2+ blocking the channel). This specific property of the NMDA receptor e xplains many aspects of long term potentiation (LTP) and synaptic plasticity and it confers to humans the ability to learn and adapt. NMDA receptor function is also strongly regulated by chemical reduction and oxid ation status, via the so-called redox modulatory site. Through this site, reductan ts dramatically enhance NMDA channel activity, whereas oxidants either reverse t he effects of reductants or depress native responses. It is generally believed t hat NMDA receptors are modulated by endogenous redox agents such as glutathione, alpha lipoid acid, and the essential nutrient pyrroloquinoline quinone (PQQ) wh ich is a B vitamin. Glutathione is the bodies major antioxidant and it acts to p rotect neurons under assault. Alpha lipoid acid and PQQ have major beneficial ef fects on mitochondrial function in nerve cells and improve energy utilization. I often consider prescribing these to patients who are concussed or suffer from n eurodegenerative diseases for this reason. (see my peripheral neuropathy post un der the AGE tab)

In the next blog we will see how excitatory amino acids in foods and introduced to our GI tract could cause us some problems with normal functioning, cause plat eaus, and interfere directly with weight loss. We will discuss how MSG and Splen da could wreck havoc with the human brain. This is especially true if that brain already has been concussed many times or is afflicted with some neurodegenerati ve disorder.

READERS SUMMARY: 1. 2. 3. 4. 5. What is the brain gut axis? What diseases likely are tied to its breakdown? Why might medical training force us to miss the importance of this axis? How did I discover the brain gut axis in my own clinical practice? Did evolution dictate where the initial battle of immunity should lie?

When many doctors hear me talk about the brain gut axis I get lots of funny look s. See, this is an axis that we do not formally learn about in anatomy in medica l school. We learn about systems in anatomy that are organized as tissues within organs. Physiology is where organ integration and its function is taught. Guess what? We did not learn about the brain gut axis there either. In fact, when I w as in medical school and residency, I never once heard or attended a lecture of this axis that I believe is the fifth most important levee in my cellular theory of health! I personally believe that medicine is going to revolutionized by the science that is uncovered in this axis over the next few decades. I believe the diseases that currently have no cure or known cause will be tied to this axis e ventually. Diseases like amyotrophic lateral scelerosis (ALS), MS, Lupus (SLE), Rheumatoid Arthritis, Autism, Depression, Crohn s disease, Parkinson s disease and A lzheimer s disease to name a few. When I tell this to my fellow physicians they ge t this look on their face like I am nuts. Then I began to explain WHY I believe this; and they stop and listen. The science is being discovered as we speak by c ountless researchers. Often, it is based completely on the sciences we already k now about. The biologic plausibility resides in neuroanatomy, biochemistry, and physiology of humans. I opened my textbooks 5 years ago and the answers were rig ht there but I just understood the problem from a new perspective. During residency training I had no time to even consider these issues because of the lack of time but scientific truth still exists even if I failed to recogniz e the pattern the connections before. Seeing diseases in my clinic and the opera ting room for the last 15 years made me have a 30,000 foot view of the larger is sues surrounding diseases. The microcosm world of biochemistry and physiology is often a myopic 30 foot view into clinical medicine. When you are down at that lev el you have no perspective on how certain biochemicals reactions effect organism s and disease states; or how they may modulate health. Most empirical knowledge is really one kind of knowledge. It s not real truth even when it appears to be so . Even with microscopes, what we see with our eyes is only a narrow spectrum of light between red and violet. We see only five percent of the real world. Most of what is out there remains hidden to the naked eye. Clinical medicine has allowed me a new way to look at old problem, osteoporosis. For many years I never saw it how young people could get osteoporosis from a gu t issue. In training when we encountered it, it was usually blamed upon genetic

determinism. I realize now that was an easy out back then from thinking about wh y this could happen. Then my thoughts changed about osteoporosis when I saw a yo ung woman below 30 years old come into the ER with severe osteoporosis about 5 y ears ago. She came into the emergency room partially paralyzed from severe degen erative disc disease and a broken vertebrae in her neck. She had zero risk class ic factors for this presentation. Her case changed my perspective big time. I wa nted to know why it happened to her. I found out it was related to her diet of e xtreme processed foods, coupled with low vitamin D levels, heavy use of grains, and very low testosterone and estrogen levels. Once we altered her diet and adde d back Vitamin D3 and K2 with some minerals she depleted from her leaky gut she magically improved over 18 months. She really changed the way I looked at all sp inal disorders as a neurosurgeon. The more I thought about her case the more I realized it was about co-evolution of our gut bacteria and our diet. We rely on our gut and our gut relies on us to maintain health and curb disease. If both are not congruent with one another th is symbiotic relationship will allow bad things to occur. My training was firmly entrenched in conventional medical principles and it was reductionistic in its logic. Her case forced me out of that box because I had no way to explain it. Th at bothered me. I was trained to look at individual layers of the organism and i ts structure and how they interacted. This is a good way to learn a large amount of data in four short years of medical school. I realized after my residency it fell short in treating chronic diseases of my patients in my office. So I embar ked on changing my paradigm of how I thought about disease. I put my iPod on and kept staring at the floor to see what all the textbooks had in common. And it d awned on me as I looked at a small book buried under my Grey s Anatomy book. It wa s evolution. Everything is tied to it. The evolution of the gut bacteria in a human usually is congruent with the type of chronic disease they will face in their life time. It appears the key in this levee 5 is to keep inflammation at low level as possible to retain your health. The types of food we eat and the quality of those foods appears to be directly proportional to the amount of inflammation we generate in our gut to promote dis ease. There are many complex interactions occurring within the gut between bacte ria and our own immune systems. It appears it is vital to our developing immune system to properly introduce bacteria so that immunity and its response develop properly. The links of many autoimmune diseases to gut health now are now being established in the gastrointestinal literature. It also appears that the basic a natomy of our gut may predispose us to certain diseases in certain locations of our gut. For example, I do not believe it is chance alone that colon cancer and ulcerative colitis are found far more commonly in the left descending colon beca use this territory of the gut is not protected by the brain with direct innervat ion for surveillance. It appears that the vagus nerve gives direct input to the brain via numerous tracts to monitor gut contents but also modulate gut health. There is also some interesting obesity research being done with vagal nerve stim ulators to show that stimulation may improve leptin sensitivity. In summary, the complex biochemical reactions that occur in the gut appear to be the genesis of where inflammation initially passes in to our body. We need to r ealize this and avoid eating the things that cause this inflammation. As I have said for close to five years now this means strict avoidance of omega 6?s, all g rains and especially wheat of any kind and very limited fructose (fruit or synth etic sources) The gut associated lymphatic tract (GALT) is the first place where our immune systems interact with the outside world. This occurs right below the intestinal brush border and is our first line of defense. It seems to me that e volution has dictated that this is precisely where the battle between health and disease begin in humans and why our immune system is set up ready on that battl e front.

READERS SUMMARY: WHY IS BAD LIVING TIED TO MEDIOCRE THINKING? WHAT DOES A MODERN HUMAN NEED TO KNOW ABOUT GALLBLADDERS? You must become aware of the high cost of low living by cheap thinking. In biolo gy, we often get what we deserve when we forget this. Today s CPC will illustrate that point for you. Wasting your time doing things that do not get you to Optima l is losing opportunity to improve yourself. Today .and every day from here become very aware of time. Be wise in the use of time. The question for living an Optim al life is never how much time do I really have it is in how you use the time you have. And when you realize that .you can begin to reverse the errors you made in th at time. There is a great lesson here for those willing to think. I hope the sharpness of this message strikes you in the correct fashion. When you think average you get average. Reject mediocre demand optimal from me, yo ur loved ones, and most importantly yourself. When you get this lesson you will understand why there is much harm in wasting your most valuable asset. TIME The more sand that has escaped from the hourglass of your life, the clearer we should see through it. If you continue to think the way you do your life s hour glass will remain opaque. Think, adapt, learn, become what you can only envision now through the actions those thoughts bring to you. ON TO THE SCIENCE AND MEDICINE Removing a gallbladder is one of the most common surgical operations done in the USA. The reason for this is two fold. If you eat a standard western diet, you a re helping cause an epigenetic signal to our gut that favors gallstone formation. The second one is that since this diet is so common it leads to major neolithic disease and symptoms that show up in our ER s and cause surgeons to do ultrasounds and HIDA scans to find the stones and sludge. Once they see a stone or sludge y ou will be loaded onto the fastest medical conveyor belt for having your gallbla dder removed faster than you can think about this comment. You will be told how simple the operation is and how slick it is. These are both true, by the way. Yo u will recover quickly and your risks are low from the surgery. These are also t rue. But what you won t be told is that once your have no gallbladder you become a tick ing time bomb for the development of neolithic disease because you begin to conc entrate a hormone slowly chronically that will eventually limit your longevity a nd kill you in some fashion. You also lose your ability to recycle vitamin K2. T his sets the stage for the development of heart disease and atherosclerosis. Sti ll think it is a simple decision? Remember heart disease is still the number one killer in men and women today.

This blog is the story of how a recipe for something simple and unobtrusive with low short term risks can morph into something that could scare the shit out of you. I think this CPC should give you pause to think before you get asked to sig n the consent form for having this gallbladder out. The best answer is make sure the gallbladder is really the cause of the disease and give yourself time to st op eating a standard diet and move to paleolithic diet that can REVERSE GALLSTON ES over time slowly. I twont be the easy choice when your miserable in pain, but I can assure you it is the an option you need to seriously consider. Some general surgeons believe the organ was put there for them to remove. Many v iew it as a useless organ. I do not believe that at all. I look at the gallbladd er as the pacemaker of the gut the most important thing it does for us is it relea ses massive amounts of CCK. This release is the pacemaker that sets up the amazi ng coordination of digestion of fats. It works in concert with leptin. There is a receptor in the mouth called CD36, (we heard about in the CT series) that is t he first fat sensor it is the canary in the coal mine for the gallbladder to tell it to get ready that a fat meal is coming. The type of fats at dinner are also c ritical but are typical in a ancestral template. Try to concentrate on 10-18 car bon fats because these are best at stimulating Cholecystokinin (CCK) that destro ys the night time appetite. I use coconut oil, ghee, pastured butter, and bacon lard to get this effect. I use the fat to cover the carbs and the protein most t imes in sauces. CCK signals the liver to begin to make bile to emulsify the fat in the meal. Peo ple who get gallstones stones tend to eat a high carbohydrate and low fat diet. The best evolutionary adapted diet for all mammals is a paleolithic diet. I will lay out why that is the case in my book. Most vertebrates have gallbladders, wh ereas invertebrates do not. There is a damn good reason for this evolutionary no velty to tied to the reason we are best adapted to this diet. Within the broad b oundaries of this diet lies the best type of diet for us the ketogenic paleolithic ve rsion. This is the one that confers to us the most evolutionary adaptations for maximum survival, in my opinion. It is also one that has the highest amount of f at within it. Becoming a lipophile allowed us to shorten our guts from our primate ancestors a nd it allowed us to increase our intake of fat to form the most amazing biologic machinery every created by evolution, the human brain. The evolution of the hum an brain has speed up the speed of evolution probably by a factor of 100 accordi ng to most evolutionary biologists. If this is true, than having a gallbladder b ecomes one of the most important things for the human GI tract because without i t we become suboptimal people to use the diet that is best adapted for our gut. If you look a medical text book of risk factors for gallbladder disease you will see these words somewhere in the chapter FAT, FEMALE, FORTY, and FERTILE. Every med ical doctor on the planet knows this information. You know what they do not appe ar to know though? Why is it that those four things really cause gallbladder dis ease. All four symptoms have one common tie. That is excessive estrogen producti on. The most common type of estrogen in people with gallbladder disease is estra diol, what we call E2 in medicine. GEEKS: People with gallbladder disease tend to be estrogen collectors in their t issues and have many estrogen dominant diseases that go with them. Estradiol is normally conjugated in the liver by sulfate and glucuronide formation and, as su ch, is excreted via the kidneys. Some of the water-soluble conjugates are excret ed via the bile duct (think gallbladder), and partly reabsorbed after hydrolysis from the intestinal tract. This enterohepatic circulation contributes to mainta ining estradiol levels. NON GEEKS: In English, this means that when fat is broken down it liberates E2 i nto our guts to get rid of the excess. If you no longer have a gallbladder you s

lowly begin to concentrate E2 in your body. The fatter you are the worse it gets . Fat people are estrogen sinkholes. This is why many neolithic diseases are tie d to obesity and high estrogen levels. This is the main reason for estrogen sens itive breast cancers in older females. Humans become estrogen dominant (both mal e and female) when they eat the standard Western diet. You need a gallbladder to rid your body of excess E2. It is a critical point. I could write 2000 diseases right here now that all have estrogen dominance as a cardinal feature. This is how an innocent error can lead to a magnificent mess twenty years latter when yo u get diagnosed with some new neolithic disease. No one in medicine today sees t he links from removing a gallbladder to that mess. If you show them this blog th ey will downplay it and tell you there is no good studies to prove this might be true. They are right about this, but its because they really do not want to know the a nswer and that is why the study will never be done by modern medicine. If you do n t look for something it is awfully hard to find the real answer. Just because th ere is no RCT on this does not make this not something for you to be concerned a bout. Evolution put your gallbladder there for a damn good reason, and to remove it you better have an even better one in my view. Remember most modern doctors will default to the standard RCT excuse. We saw in the article, Lies, Damned Lies , and Medical Science in the magazine the Atlantic, that most RCT are not worth t he paper they are written on. Most Ivory Tower doctors still tell you RCT is the gold standard. Remember what I just told you in CT 10 about Ivory Tower docs an d calls for moderation. I d like you to recall what veteran medical researcher, Dr . John Ioannidis had to say on this from the article in The Atlantic I linked ab ove. This article is the article that made it easy for me to question everything I believe I learned to be true in my medical career. It caused me to erase myse lf many of the beliefs I held as dogma. I do not believe any article I have read has ever made a greater impact in my life. Now you can see why understand how one system ties into another can lead to a bi ologic mismatch, alter signaling and cause cancer, heart disease, and atheroscle rosis over time .So the next time someone says, let s just remove your gallbladder arning echo in your head. I want you to rely on your primal instinct in your gut and not on the RCT that any medical student can spit at you as you are doubled over in pain in some ER. You wont hear this naked truth from my profession. Reme mber they honestly believe that God put the gallbladder there for us to remove w hen it has stones or sludge in it. I can not tell you how many time I have heard this in my training and from many surgeons. You might be thinking how in the world does this iatrogenic error happen? The re ason is simple. They have no idea about the connectiveness of the delicate micro machinery of how our gut evolved and why it shortened from our primate ancestors . There is no course in any doctors training about how all the information they cram in our head integrates and works like a symphony. We are left to figure tha t out by trial and error and thinking. Most surgeons honestly believe it has no real purpose because that is what we were taught. Do not blame them. I learned t his crap too as a surgery resident, and fell prey to it more than I care to admi t. The system propagates this nonsense as well. Reading the truth serum Dr. Ionn idis provided me years ago allowed me to question everything and go look for the real reason why gallbladder disease shows up so often and how it is best treate d using an evolutionary medicine perspective. So if you re missing a gallbladder consider supplementing NAC, MSM, and DMSO to sp eed up the removal of the serum estrogens like E2. You also better re read my Vi tamin K2 blog too. The links made here to heart disease and atherosclerosis are critical links for you to understand because your doc will minimize them. You ca n even do a test to check your clearance of estrogens from the liver. When it bu ilds up in men this is how they get man boobs. To become optimal you must handle dietary fats like a true champion. This requir


es a functional gallbladder. Always guard your guts from bad foods, bad diets, a nd bad medicine. Remember that iatrogenic medical thoughts of omission from my p rofession might lead to proximal harm as you age as I outlined here. That is my best advice to you why this organ is critical to a primal life. Protect your gut it will protect you.



This blog was specifically designed for the people who just experienced my Facto r X Webinar unveiling so it may not make total sense to those who did not attend . For those who did attend you now have the context to understand the following f ew modern diseases that just may not be diseases at all because of how an evoluti onary bottle neck sped up epigenetics. HEMOCHROMATOSIS: Iron is a element that is vital for life. In fact, every form of life on this p lanet uses it to some degree to make sense out of the random chaos of the chemis try of atoms that life orders together to make the beautiful musical composition that is life. For humans, metabolism requires Iron. Iron carries oxygen to ti ssues in our cells but it can paradoxically make the ocean water crystal blue cl ear and devoid of life. When Iron is present in abundance the water is green a nd filled with life. Without iron our immunity crashes, we become dazed and con fused, cold,and very lethargic. Our metabolic rates can plummet. Paleo eating supports eating small fish with high omega three levels like anchov ies. They concentrate omega 3?s at the bottom of the marine food chain. They g et their iron from dust storms of iron blown from land that concentrate in phyto plankton. In the ocean water where there is phytoplankton their is zooplankton. With out zooplankton, there are no anchovies. Without anchovies we do not get big Ahi tuna. With out Ahi tuna, I get cranky. If you think Iron is not amazing think about this geologic evolutionary trick th at occurred since India crashed into Asia to form the Himalayas. Without the fo rmation of the Mount Everest there would be no Sahara desert. The Sahara desert dumps billions of gallons of iron dust into the oceans to stimulate the phytopl ankton that supports the marine life of the North Atlantic. This is also why th e water in the North Atlantic is so green as well. But this iron dust also allo

ws the ocean to become a massive sump to generate massive plant growth in the oc ean that can absorb massive quantities of CO2 out of the atmosphere to offset al l the CO2 humans have been releasing into the air since the Industrial revolutio n. (Geritol Solution) So iron is a big factor for life in the seas. Most modern medicine men focus on low iron states. This leads to errors in judgement that makes us believe that more iron may be better for humans. This is precisely why modern processed food s like grains, flour and baby formula all have fortified iron in them. But iron in excess can be a very bad thing. In fact, parasites seek iron stores out in our body. Bacteria growth is stimulated to a great degree by iron. When serum ferritin levels rise with LR or inflammtion you can bet the risk of a co morbid infection is not far away. Dr. Eugene Weinberg proved in the 1950s that all bac teria undergo explosive growth when in the presence of excessive iron. The iron regulation in the body is extremely complex. When our skin defense are breached fluids like saliva, tears or mucous protect us by having metal chelators in the m to protect iron stores from bacteria who seek out our iron. When we first get ill and our defenses are mobilized and iron is placed under SECRET SERVICE protec tion by proteins that protect our endogenous stores from bacterial invaders who need it to survive. The same thing occurs when cells undergo oncogenesis and begin to spread. Cance r cells have huge hunger for iron. Drugs are designed to limit its availability when cancer is present. Some cancer patients are now instructed to cover their wounds with egg whites because the egg white protein protect the bodies iron st ores from toxic use. Why? Eggs shells are porous to many things, so an egg has a white part to protect the more important yolk portion from attack. It is the immune system of the egg. Iron is a big deal. THE BLACK DEATH: 1347-53 25 million people or half of Europe were wiped out by bubonic plague in two year s from 1347 to 1349. The plague has actually serially infected modern Europeans in every century until the 20th century to cause major death and illness but th e effect was greatest in 1347 because our genome was not adapted to it at that t ime. It is a bacterial disease caused by Yersina Pestis that collects in the ly mphatic system and cause massive swelling of the lymph nodes of the body cause a gruesome disease. When the lymph node explodes through the skin the bacterial infection becomes lethal. When it is airborne it kills 95% of people and it bec omes rapidly contagious. It is believed the plague came to Europe by way of sai lors on the sea who brought it to ports. As the death sentence raged through Eu rope observes noted that Jews during Passover did not get sick as often as other s did. The reason is that they did not eat grains at this time. The grains in Europe at this time were infested with rats who carried the bacterial and transm itted it to humans. Others observed that the plague seemed to spare some and be deadly for others. Women and children also fared better than adult men, for ex ample. In fact adult men, carried the highest risk of death from plague. Why w as this the case? New data pointed to iron levels as the real issue increasing their risk. Adult men had the highest iron content of humans alive in the 1300s. Women had lower i ron levels due to pregnancy, lactation, and menstruation and children were often malnourished and this protected them from Yersina. Adult males carried the hig hest risk because their iron levels were greatest. This is precisely what the e pidemiology of the plague showed occurred. So what did evolution do to combat th is epigenetic threat? It rapidly selected for men with the hemochromatosis genetic mutation to survive in Europe from 1347 all the way until 1900. This is why the incidence of hemoc hromatosis is so high in European Ancestral peoples even today by

m testing. Hemochromatosis, a disease modern humans fear, actually is the work of natural selection to protect Europeans from Yersina Pestis that has chronical ly afflicted their population from 1347 until today. Hemochromatosis, put iron stores in solitary confinement status in visceral organs. Most of the iron is sto red there so it can not wind up in the immune cells called macrophages in the li ver and lymphatic system. When macrophages lack iron in them they become mafia like killers of those with Ye rsina Pestis bacteria. This one move protects the adult male from the ravages of bubonic plague and allows them to live another day. There is a trade off Moth er Nature makes for this maneuver. With time, iron builds up in the viscera and causes organ failure, dysfunction and disease and possibly death but it happens slowly over a life span. This allows the human male to survive to reproductive fitness and provide progeny for the next generation. It is a highly protective epigenetic advantage that protects the adult European male from Bubonic Plague t hat has been chronically present in there environment for 500-800 years. This sped up epigenetics is a result of retrotransposons in our genome that just 15 years ago we thought was junk DNA . Today we know that 97% of our DNA is used t o alter our genome based upon epigenetic signaling. No other mammal on this plan et has more junk DNA than humans. This means we are very responsive to environme ntal changes and can rapidly mutate our genome using retrotransposons that can j ump to other parts of the genome. This essentially speds up genomic change using an epigenetic game plan. How did evolution come up with that idea? Survival is the short answer. As you saw in the Factor X webinar when faced with calamity wh at did evolutionary biology do to survive it? If you listened in to the Webinar you know precisely the answer now. And where the junk DNA came from maybe more shocking. It seems it came from para sites, like viruses that we faced in our remote and recent past. This implies th at infectious disease maybe a tool of evolution and not a disease state at all. They are the quickest mutators and fastest replicators in biology that we know o f. Several billion years ago we usurped bacteria and turned them into mitochondr ia to make energy. It appears our recent ancestors have now usurped viral RNA an d used reverse transcriptase to turn it into DNA and add it to our genome when i t was given the proper epigenetic signal from our environment. This helped us ra pidly develop an fast acting immune system and also help speed evolution from ou r primate ancestors as well. Today modern man looks at hemochromatosis as a disease when in reality it might be the result of epigenetic iron protection strategy that evolution used to keep a dult males alive to allow for modern humans to survive in Europe for the last 50 0 years. Today scientists realize that our junk DNA seems to have the epigenetic information of the last 1000 years of our biology built into to it so that we ca n use it to defend against pathogens and events we have recently faced so that w e can survive what ever life throws at us. It is our evolutionary bank account w e save for a rainy day. We now know that hemochromatosis was selected for by transgenerational epigeneti cs in the Viking men of the Northern coastline of Northern Europe. We believe t hat the harsh Tundra of the north was mineral deficient and that women with this genetic defect would have fared as better child bearers because they were able to absorb more iron to birth more children who also carried the hemochromatosis defect into the next generation. It is also believed that the Viking men might have survived the disease because their Gladiator type lifestyle was ferocious a nd they often faced serious blood loss that might have offset the iron defect. As Vikings settled down in Northern Europe the mutation grew by using the founder s effect caused by inbreeding due to small population sizes. The founder effect means that any non lethal defects are highly selected for and carried in the entir e population of a people. It is believed that the Viking defect was blended into

the the populations of Northern and Western Europe over 500 years to provide a s olution to the recurrent Yersina outbreaks that caused bubonic plague and almost extinguished humans in Europe. The chronicity of the infection was an epigentic signal phenomena that allowed for selection of the hemochromotosis gene to confe r reproductive fitness over longevity while the Yersina remained active in the h uman population. This remained true for close to 500-800 years. This irony may now explain why Ancient physicians were barbers and blood letters. We used to believe this practice was quackery but we now know that it was surviva l of fittest in action. Blood letting had a major role in conferring more longe vity to those with hemochromatosis of European descent. Until the 20th century bloodletting was standard practice. Then it was stopped and hemochromatosis bec ame a modern disease. Canadian physiologist Norman Kasting found that blood lett ing also released the hormone vassopressin (ADH) from the posterior pituitary, a nd this reduced their fevers and increased their immune function to act faster. This find is clearly was not causation but the correlation between bloodletting an d fever reduction is massive in the human historical record. Bleeding them down may have helped fight infection when it was present. It sounds crazy until you put on your Factor X lenses now. Consider that people in Africa live in a constant state of anemia because of malaria even today. In f act, if you replete them with iron to treat the anemia their rate of sepsis zoom s higher. Do you think evolution knows something modern science may not? Does this sound familiar to anyone who just listened to the Webinar? Maybe Type 1 and 2 diabetes were initially epigenetic adaptations that also beca me disease in our current modern world? Consider the following: There is a huge difference in the prevalence of type 1 and type 2 diabetes even today based upon geography. Type 2 diabetes is more common in the developed mode rn world and 85% of those with it also have co morbid obesity from the SAD and e nvironmental toxins. Consider these facts about Type 1 diabetes. It is much more common in in people of Northern European descent. Finland has the highest rate of juvenile diabetes in the world. Sweden is second and the UK and Norway are ti ed for third. As you head south the rate plummets. This disease is really uncomm on in African, Asian, and Hispanic descent even today. When a disease that is ca used at least partially by genetics is significantly more likely to happen in a specific population, this is when the observant of us raise our evolutionary pri mal sense and begin to look for an ancient evolutionary link as to why it happen ed. The reason is simple. When we see this occur it suggests that some aspect of tra it that causes a disease today likely helped our ancestors in our past to surviv e. In the case of diabetes, high blood glucose levels allows a person to deal be tter with extreme cold because it lowers the freezing point of blood! It is natu ral antifreeze that allows life to exist in the cold. Seawater does not freeze a t 32 degrees. It freezes at 28 degrees. Vodka does not freeze at 32 degrees in y our freezer even though it has 60% water in the alcohol. It freezes at minus 20 degrees. What about glucose in suspension? Ice wine does not freeze either at 32 degrees because of the sugar content of the wine hence its name. Alcohol, like sugar is a natural antifreeze. The higher the sugar content content in liquid th e lower the freezing point is. Sugar is what makes Slurpees a slush and why it nev er freezes! It took 7- Eleven 20 years to figure out how to make artificially sw eetened slurpees with an indigestible sugar moiety. To make Ice wine in late harvest around frost time, a grape begins to protect it self by rapidly reducing its water content and by raising its sugar content. It

tries to eliminate water when it gets cold. Now maybe you understand why you hav e the urge to urinate when you begin to use cold thermogenesis? You transiently are dumping water and raising your blood glucose levels just like a grape. But w hat happens in you is with longer adaptation you BG level drop as your fat mass shrinks. You eventually lose all your glucose stores and eventually just burn fa t to survive. Humans have this ability as we evolved ..but the Neanderthals likely did not. Why you may ask? Do ever wonder why they never won out in evolution against us? Modern science st ill struggles to figure out why? Could it be they could not become diabetic to s urvive the cold of the ancient past? After all we never find the Neanderthal ske letons in extreme Northern climates when the core ice samples show it was freezi ng cold? Coincidience or not? You decide. The moral here is that we need to be aware of just how much we really are not ev en aware of it. I think the evolutionary story of hemochromotosis from 1347 unt il 1900 represents what an epigenetic modification can look like when it is matc hed into the world it evolves. When the defect no longer fits the environmental model it can be than thought of as a disease and its major selective advantage c omplete lost to the modern world because they become unaware of what protective advantages it provided since the environment has also changed. If you heard my Factor X webinar you maybe connecting some dots to why I think F actor X is vitally important for the biologic sciences to understand. It is lik ely our Rosetta Stone or North Star in understanding how life makes sense out of the chaos that it is placed within. This story is eerily similar to the modern day plagues of diabetes and of cancer. Today modern medicine looks at both as disease states. In CT 2 and CT 3 I proposed that diabetes and cancer might not be diseases at all. They may be evidence of circadian mismatches brought out by mismatches in our environment. Back in February this sounded radical. When yo u consider what I explained to you here today about hemochromatosis and marry th at information to what you learned in the Webinar about Factor X, how radical a re things now? Might it be ingenious way of how evolutionary biology uses epige netics to control our biology to navigate life to get us to reproductive fitness to extend survival of our species? Inquiring minds will have much to ponder no w. Here is a teaser peek of for Type 1 diabetics to consider from: Summary The reasons for the uneven worldwide distribution of Type 1 diabetes mellitus ha ve yet to be fully explained. Epidemiological studies have shown a higher preval ence of Type 1 diabetes in northern Europe, particularly in Scandinavian countri es, and Sardinia. Recent animal research has uncovered the importance of the gen eration of elevated levels of glucose, glycerol and other sugar derivatives as a physiological means for cold adaptation. High concentrations of these substance s depress the freezing point of body fluids and prevent the formation of ice cry stals in cells through supercooling, thus acting as a cryoprotectant or antifree ze for vital organs as well as in their muscle tissue. In this paper, we hypothe size that factors predisposing to elevated levels of glucose, glycerol and other sugar derivatives may have been selected for, in part, as adaptive measures in exceedingly cold climates. This cryoprotective adaptation would have protected a ncestral northern Europeans from the effects of suddenly increasingly colder cli mates, such as those believed to have arisen around 14,000 years ago and culmina ting in the Younger Dryas. When life expectancy was short, factors predisposing to Type 1 diabetes provided a survival advantage. However, deleterious consequen ces of this condition have become significant only in more modern times, as life expectancy has increased, thus outweighing their protective value. Examples of evolutionary adaptations conferring selection advantages against human pathogens

that result in deleterious effects have been previously reported as epidemic pa thogenic selection. Such proposed examples include the cystic fibrosis mutations in the CFTR gene bestowing resistance to Salmonella typhi and hemochromatosis m utations conferring protection against iron-seeking intracellular pathogens. Thi s paper is one of the first accounts of a metabolic disorder providing a selecti on advantage not against a pathogenic stressor alone, but rather against a clima tic change. We thus believe that the concept of EPS should now include environme ntal factors that may be nonorganismal in nature. In so doing we propose that fa ctors resulting in Type 1 diabetes be considered a result of environmental patho genic selection (EnPS). Sound familiar to anyone? Sometimes when someone is real early with an idea they get branded a nut or a quack ..I like to think differently. Want some more interesting facts: Look up the wood frog called Rana Sylvatica an d researcher Ken Storey. The frog lives from the Arctic to the deep south in the USA. It freezes itself frozen solid in the winter but uses high blood glucose t o keep it in suspended animation until spring comes and it and comes alive once again. Ken s work was seminal to germ cell freezing and transplant medicine we use today. It appears that grapes, frogs and humans maybe able to all do this to so me degree. I believe that Ancient humans may used this ability survive over Nean derthals when the environment became abruptly cold. The last time this appears t o have happened was 13,000 years ago. It appears it helped our European Ancestor s survive the dramatic violent cold of the Younger Dryas. Diabetes maybe evoluti on working its magic for survival even in us today. The only problem is that we do not face a true winter today we just eat like we might face one. Many modern scientists believe the Young Dryas where the reason modern humans be gan to introduce modern agriculture to survive. How ironic is that notion to the paleo community? It appears that the abrupt onset of severe cold in Europe 13,000 years ago (an e pigenetic event) may have stimulated us to consider using agriculture to survive . When we did this what did we really do to ourselves? I think Dr. Loren Cordain previous research shows precisely how it hurt our species longer term, but the fact that we used agriculture initially to offset an environmental pressure is m ore interesting. Moreover, that previous evolutionary advantage is now killing us because our modern environment has changed while epigenetics has sped up simulta neously in modern humans. This puts us more at risk to any of these biologic mis matches now. This sounds a lot like the hemochromatosis and diabetes story to me today I have laid out here in this blog. Maybe this explains why we are seeing disease of aging 100 years ago now showing up in teenagers? All questions for yo u to think about now. Much of this blog was excerpted in total to give you a pre cise idea of how a modern disease may have begun as a naturally selected surviva l strategy. Most people are unaware of this genetic defect actually protects us today. It came to be because of the rapid epigenetic pressures placed upon human s by the bacteria because of the massive killing effect in 1347. Because the K-T event used a sped up epigenetic signaling program to allow eutherian mammals to sense changes in their environment quickly and adapt, modern humans have the mo st adaptable and fastest ability to change epigenetic program on this planet tod ay. We use junk DNA to first change DNA expression and with sustained pressure s elected for the genomic change and expanded it in survivors. This is a great mod ern example of how a sped up epigenetics works in us. We need to think about the good and bad it can do. It is definitely a double edged sword for modern humans . I believe this gives biology and modern medicine an epistemologic foundation in evolution and should put practitioners back on track who understand these implic ations. For modern patients it gives you a new understanding and a way to view d isease and health and save yourself from the current system.

I hope this stimulates some deeper thinking about the knowledge you re socialized to believe is correct today. We are the only mammals that falls prey to socializat ion in this manner. I hope you become aware of just how much we really are not e ven aware of at all, because of factors we are not considering today. This is a nother way a neolithic belief can subjugate our paleolithic genome when we have things in our blind spot.

READERS SUMMARY: HOW CAN A LEAKY GUT CAUSE ADRENAL FATIGUE? CAN OTHER THINGS COMPLICATE THIS LIKE A VIRAL INFECTION? CAN WE TREAT IT? HOW DO WE TREAT IT? CAN YOU HOPE FOR IMPROVEMENT TOO? A PATIENT TESTIMONIAL AFTER JUST 4 MONTHS OF TREATMENT We have talked at length on my forum about how a leaky gut can cause havoc for m odern humans. What many people do not realize is that humans having a leaky gut happened by design. Primates, our nearest relatives, do not have leaky guts by d esign because they do not have zonulin the protein that binds our gut cell membr anes where they join. Many people are shocked to find out that this make it impo ssible for a Primate to get an autoimmune disease. This is also true. Primates a lso can t get an infection of H. Pylori in their guts either. This is why Barry Ma rshall had to drink a vat of H. Pylori to prove it caused human ulcer disease in the last part of the 20th century. He had no animal models that would prove his hypothesis. Check out this detailed history of precisely what the establishment did to Dr. Marshall and his ideas for close to 20 years. LINK Choosing the correct animal to study at the right time of the year makes a huge difference in science. This is a fact that few people even consider when reading many of today s pub med articles. If you do not believe it is true consider that small doses of penicillin can kill a guinea pig during the winter time. During o ther seasons the guinea pig can tolerate massive doses of penicillin with out an y problems to their physiology. What if scientists had chosen to use guinea pigs to study penicillin instead of mice back in the 1940?s? Do you think we might h ave made some bad assumptions? Might antibiotic research taken a massive turn if we were not aware of what we did not know? When you realize that this kind of r esult can happen in a species, it has to make you consider the limitations of ex trapolating any data from one species of mammals to others and then drawing a co nclusion. Sadly, this is one of the biggest errors in all nutritional science to day, in my opinion. It is also why we see some much bad science being done and r egurgitated. Alexander Pope had it right when he said, The only proper way study of mankind is man. We must always remember that humans are not animals and what w e find in research done upon them rarely parallels the expected results to be fo und in us. This is why aftermarket data can cause a drug to be pulled from the m arket. Think of what happened to the diet drugs Phen/Fen or the recent COX2 inhi bitor drugs like Vioxx or Bextra. Evolutionary friend of foe round two? So why would a human have a leaky gut by design? Moreover, why don t we see it in primates? Like we saw in our last CPC #4 maybe this liability today used to be a huge evol utionary advantage in eons passed? I think that is precisely the case when you t

hink about the co-evolution of the gut and the development of the brain in human s. What happened between Ardi andLucy and Homo Habilis is a story that must be c onsidered by modern humans to get back to Optimal. I believe this transition in speciation within the hominid tree of life is just another way that Factor X hel ped fueled natural selection because of a rapidly changing environment that Ardi and Lucy found themselves in. You will soon find out in the next monster blog s eries why the differences in the human gut likely fueled our evolution into a ne w species. So today I am going to show you how a leaky gut can cause massive collateral dam age to many systems in a modern human. This shows you how a leaky gut can cause other body systems to fail because the gut is just not working as it was designe d too. It is a pleasure to share with you a video today from my clinic on a patient who had a severe leaky gut with dreadful adrenal fatigue. This patient came to me f or a pseudoarthrosis in her neck. This means her previous neck operation for a d isc herniation causing spinal cord compression never healed. She had this surger y done by another surgeon in Nashville. The cause of her leaky gut was a long st anding Hepatitis C infection that she got from a blood transfusion earlier in he r life. This viral infection was actually the real cause of why she never properly healed the fusion in her neck. When she first came to me for a revision surgery I told her it would never work unless I first treated her leaky gut and her Adr enal Fatigue first. How I did this was by making lifestyle changes. Some of the techniques I used on her I have not discussed on the blog to date. In her I used an Epi-Paleo dietary solution, spot CTing, control of night time light cycles, and a special supplement regimen to help her. I also sent her to a colleague for some special treatments to rapidly heal her leaky gut before and during her sur gery to make sure the osteoporosis would not hinder her healing once again. None of these things were done by her original surgeon in 2007 because they just tho ught these illnesses were bunk and would have little impact on her case. Take a look at this video here before going on and see if the surgeon in 2007 wa s correct or not. Conclusions: Leaky gut and adrenal fatigue are two modern diseases that were once evolutionar y adaptations that protected us. Both of these processes dramatical alter levee 5 called the brain gut axis. Today because of a modern lifestyle both of these a daptations can cause massive collateral damage in our bodies. This video clearly depicts how it can radically alter a persons life if adrenal fatigue proceeds t o wreck havoc. The good news is that once we become aware of just how much we do not know and we try to reverse the process we can also help a person. I am happ y to report that that her good fortunes continue using Cold Thermogenesis in hel ping her reverse her illness. You don t wear out, you flame out .limit inflammation a nd you control the burn rates for all neolithic diseases. This is case illustrates that cold is not just hormetic and many times in a deta iled clinical treatment plan can be curative for those who have it. We must alwa ys question our preconceived notions of what we believe. Sometimes when we do we can go to a place we did not think was possible. These neolithic diseases are c omplex presentations with numerous causes and solutions. Our job as clinicians i s to continue to look for solutions when patients show up in our clinics with pu zzling questions we can t answer for them. There are many ways to treat them but y ou first must consider them as possibilities in order to help a person with it. Healing her non healed neck fusion was a very complex situation that required an d outside the box approach using multiple modalities the moral of her story is that we should not settle when you do not feel well regardless of what an expert may

tell you. The joy is in creating your health not maintaining it.

Do not believe for one minute that you can not change your life when you take ba ck control of how you think about things. Sometimes we can t help people because w e remain blind to what we don t know.

READERS SUMMARY: 1. WHAT WAS I GOING TO SAY ON THE LOW CARB CRUISE? 2. HOW DID A MASTERPIECE OF ARTWORK INSPIRE MY THOUGHTS? 3. HOW DOES LEPTIN AND COLD THERMOGENESIS UNIFY INTO NEOLITHIC DISEASE CAUSED BY INFLAMMATION? 4. HOW DO EXAMPLES IN YOUR LIFE WHO USE COLD REMAIN IN YOUR BLIND SPOT? 5. WHAT IS FACTOR X? HOW DOES IT SPEED UP EPIGENETICS? Well, it has been a very interesting last few days but I am not the kind of pers on who looks in the rear view mirror to run my race. What happened happened and it will all come out in the wash eventually. I am a person who runs their own ra ce by looking forward via the windshield as I step on the accelerator pedal to l ive my life. If we focus on the past we lose sight of where we are headed and th e road to Optimal. A reader of mine, Dan K, sent this gem to me, I heard the Dala i Lama once say in a lecture that our worst enemies are your greatest teachers b ecause they allow you to examine the emotions of anger and revenge and then to t ranscend them. They give you the exact tools you need to elevate yourself to the spiritual energies that eliminate problems and provide solutions. So today, I am moving toward the Paleo template and away from the Paleo Radical Insurgency who i s steering the community into an abyss. There are too many people who need help and not the surrounding drama. The time has come to become, Epi-paleo, a term I mentioned at my Paleo fx speech, and that is what I will be building here on my blog and forum from here on out. An event that appears to be a tragedy to one, might reveal the seeds of unlimite d opportunity for another. On the Low Carb cruise I was going to present some of the things that happened i n my mind at the base of Michelangelo s David in help me realize that the missing piece to the obesity and insulin resistant story was the off switch in how we make fat and how we continue to make fat cells. Gary Taubes was scheduled to the fea tured speaker for the cruise but he could not attend it so Jimmy Moore asked me to step in his role. Gary wrote a book called, Why we get Fat but I clearly am not Gary Taubes, and I was not here to tell them why we get fat I was going to tell y ou how to reverse being fat and insulin resistant because unlike, Mr. Taubes, I ha ve done it myself and pretty successfully. Obese humans have a difficult life to live. I know the life they live because I was one of them for close to decade. It is very hard to take advice from someone who has never had obesity. To unders tand the mindset one has to have walked in the shoes. Most of the people giving out advice however have not had a successful track history of losing the weight and keeping it off. The reason for this is they are prisoners to modern dogma of fatness. What are we socialized to believe about fatness today?

Calories in / calories out is all that matters You need to exercise to burn fat You re fat because you re a glutton You re fat because you re lazy or a sloth You re body is too damaged to get fit / lean You don t have enough will-power You don t have self-control Eating fat makes you fat You can t get rid of fat cells; you can only shrink them Carbs make you to be fat Did that last one catch you off guard low carbers? Good. I never have believed that carbs made us fat intrinsically. The Paleo Radical Ins urgents who thought they knew what I was trying to convey to the readers often pu t many words in my mouth they thought they heard. My belief is far different bas ed upon the Ancient Pathway theory I have developed. When we add fat to adipocyt es we create new fat cells. Environmental toxins and dietary choices are what fi lls the fat cells and causes them to divide. We know what makes us fat biochemic ally from foods, but we are learning about the effects of fat generation from th e environmental toxins presently. The real gap in our knowledge is we do not und erstand the linkage between the brain and the fat cell s membrane and how they sig nal one another and how it is controlled at the hypothalamic level. The cell membranes of those fat cells are how the fat mass is communicated to th e brain is the critical step in understanding the obesity story in my view. The consequences of the fat collection results in increases of adipocytes. The more adipocytes we have the more insulin resistant, leptin resistant and adrenally re sistant we become. The goal of fat reversal and insulin resistance is to elimina te the excessive fat cell membranes present in us. How do we do that? In conventional medical practice today the advice we give to the obese who have insulin resistance is that they need to lose weight and diet and exercise. The o nly way for humans to lose fat cells today that we normally employ is to perform plastic surgery and remove the excessive number of adipocytes. Going on a low c arb diet is an excellent way for an obese person to lose weight, but it is not a n excellent way to sustain your weight loss forever. Many people in the low carb community are living this way now. I used to struggle with the same problem. Ho w do I know this for sure?. Because evolution uses its own version of plastic surg ery to remove the adipocyte, reduce leptin, raise adiponectin and change the bal ance of resistin in our fat mass. What is Mother Nature s scalpel? Cold Thermogene sis is the short answer. How did I come to this conclusion? The synthetic Leptin trial data from Amgen is that answer. Many people thought synthetic leptin would cure obesity and it did not. Amgen found that the synthetic leptin often did not work on the morbidly o bese. Initially, they lost weight on the drug but the weight loss could not be m aintained off the drug. Also they all had issue with glucose regulation. Their f asting BG, called the dawning phenomena, was often difficult to control. What so lved these patients problems? Plastic surgery did. When this subgroup of patient s had surgery they had unreal improvements across the board. Amgen researchers d id not put two and two together initially. The reason for this is plastic surger y removed the number of adipocytes in their body, which improved signaling betwe en the fat mass and the hypothalamus. It allows the brain thermostat to work ide ally. Amgen abandoned synthetic leptin as a pharmaceutical target and then began work on drug development on the TRPM8 channel receptors. What are they? They ar e the peripheral cold receptors. In May of 2012, a new protein was just linked t o the BAT receptors and just published after my theories were published here. Mo reover, Dr. Myers group also found new hypothalamic receptors that link directly to NOS, which I mention in CT-6 is the gateway chemical to the Ancient Pathway. All this was published in the last 6 weeks? Am I still nuts, as the Paleo Radica

l Insurgents have diagnosed me over the internet with their psycho babble crap? The surface cold receptor papers were one of the six papers that I was given whe n I hurt my own knee that I mentioned in Jimmy s original podcast with me in 2010. This linked the cold to adipocyte loss. Even today Amgen is still working on th is target. When I realized this I knew that the Leptin Rx reset would take care of the low carb portion of the equation to limit fat into cells. Moreover, I kne w that the cold would eliminate fat cells if I came up with a protocol to do it. So that is how I came up with marrying the Leptin Rx reset and the CT protocol together to change me in 11 months. My results with both are found in photo 1 (my before) and in photo 2 (my after) . Here you can see the day I explained the Leptin Rx reset to my son and my nephew at Walt Disney World.

Photo 4 is their after s shots.

So what happened at the foot of Michelangelo s statue to synthesize all this in my mind?

Listen to this podcast I did recently about the entire process. At the base of that statue I realized that the environmental control of the fat cell number was a critical part of the equation that remains in most people s blin d spot even today. The key factor was the temperature of the environment because it controls whether the adipocyte will be taken out of the body via apoptosis o r not. This was backed up in Amgen s synthetic leptin trials, NASA data on the She rpa s, and the work in developing Zeltiq at Mass General in 2008. The control of these fat cells is primarily controlled by the environment. Moder n humans never face a winter as I laid out in this podcast above. As time has pa ssed, evolution has speed up and so has epigenetic signaling. Epigenetic signali ng is how we control the adipocyte number the cell membranes it creates. The cel l membrane is the key to insulin resistance (IR). This is controlled by epigenet ics and the environment the mammal lives in. Genetic determination is dead these days and we know epigenetics are the prime mover for the human genome today. Wh at interacts first with the environment in our biology is the cell membrane in o ur skin and the surface cold receptors. The surface cold receptors are intimatel y linked to the Magnesium/ATPase where energy production is made or where calori es are burned as free and no ROS is generated. Decreased ROS means less aging a s well. This is why the cold preserves us and tissues. It why the Ancient Path way confers a longevity benefit. When one becomes Leptin resistant the Mg/ATPas e become inefficient and IR and diabetes are the eventual outcome if this contin ues chronically. This is common in modern humans as we never face a winter any l onger. This leads to issue with glucose control and fasting BG as well. Today we have 60 million pre or formal diabetics in the USA. At 357 pounds I kne w I had to think differently about my obesity than I was taught to. So I did. I first destroyed my cravings for the foods that helped fill my fat cells with the Leptin rx reset. It worked well. Then I used what I learned from Amgen, leptin, Sherpa s, NASA, and other eutherian mammals and applied to cold to decrease the n umber of fat cells and help expedite the fat loss. Again my results in 11 months

were extraordinary. The skeptics and haters still remain present, despite outst anding results. They did not know what I knew and many still don t believe in it b ut it has worked for me twice now. Once in 2007 when I lost 157 pounds, and rece ntly in 2012 during my TEDx bio-hack experiment. People have gotten the same res ults in my clinic in Nashville and many more can be found in my internet forum a nd my blog comments at my site. Denise Minger (awesome blogger and better person) recently said that anecdotes a re valuable for coming up with theories but theories need to be tested in an exp erimental design. My sensibilities are quite different today than that of Denise s , because I have to deal and treat these train wrecks daily as a surgeon. My persp ective is altered because of my clinical experience. Today s healthcare system is se t up to take care of only sick people and not designed to make them well permane ntly. We teach, and do things that are 180 degrees opposite to how we should be doing things. Those failures are obvious to us who are not blind. We see the res ults in health care statistics and in places like Wal-Mart and Walt Disney World daily. To those who call for Randomized Controlled Clinical Trials for my proto cols, who will pay to test a theory that no one can make money on? I hear nothin g but crickets from the NIH or the pharma industry!!!!! Ice water and cold are n ot going to make anyone money. The timing of eating foods and seasonality dieta ry choices are no cash cow either. Moreover, does the PALEO even have a RCT to sit upon today? No it does NOT, and yet, we have a community advocating for it violently with out that data? Ironic, no? Why the disconnect between the two? Dogma is the short answer. And this i s why I think Paleo Radical Insurgents connected to this community stole my identity and set me up to appear like a bio-terrorist. My version of Optimal or Epi-pale o scares them greatly for some reason. It seems when your ideas are different in conventional medicine and in the paleo world you might face the same response. I find that quite ironic. I also believe this is why so many leaders allowed this nonsense to go and remained silent. Well, now the consequences are in your lap and hopefully in your minds for years to come. It s time to step up and be counted in t he coming months. SO WHAT SHOULD WE CONSIDER DOING? When there is no money to be made in a cure (see the synthetic Leptin story) the re is NO SENSE in going to RCT in the literature to state your case because it w ill be never be done. The counterintuitive way to solve the problem is to offer it free to the obese and IR public to try for themselves for 30-60 days. Does th is sound familiar to any one? It sounds like what Robb Wolf says in his book tha t is considered the bible in this community. Patients are the one group of peopl e who love free ideas (think drug samples in CW terms) that they can try at home t o see if it s paleoquackery or ingenious. That is precisely why I went this route. We have 60 million people already sick and likely 100 million more in the que b ehind them. When you factor in my belief that epigenetics is sped up because of Factor X, the problem grows worse daily and disease shows up in children that sh ould be present in the elderly. Something is radically wrong, and yet we keep do ing the same shit over and over again and expecting a different result. Waiting for a RCT makes no sense to me as a clinician in today s world. I bet it makes a l ot of sense to someone who is a PhD researcher however. This is how they stay i n business. My job is to get people well today. Big difference here folks. This is where the theory of the ancestral template becomes divorced from the clinical g ravity of what I treat today. Should I remain quiet to the disconnect or do I t ry to shine light on it? This is where the hate mongering came from that lead to the LLCruise nightmare. In drastic times, we need to bring the battle to the fr ont lines for people to test. What we are doing today is not working. If we do t he same thing over and over again and get the same result we create insanity. Look at my pictures again, and remember my story. See what I did to my son and

my family. I have had two family member who were diagnosed as diabetics neither one is any lo nger. My own wife was a diabetic and she no longer is Success is 99% failure. We need to embrace our failure to find the freedom that can force us to think differently about a problem to solve it. When we live in our failures long enough and we remain observant sometimes from unconventional thoughts come extraordinary results. Medicine is a results driven business. Science is driven by reductive experimental design. I am a physician and surgeon first and not a scientist. The blogosphere mixes th ose true missions and this causes confusion in the community and hatred in some cases, as I was recently the victim of. I have a duty to do no harm and heal people with illness. I have no duty to crea te a RCT that will take 25 years to prove what I have found to work in my, my fa mily, and my patients while billions get ill and die needlessly. So I put my ideas on the internet for the world to dissect and try. Many critici ze it, and I turn the cheek, because I only care about the results people get. After all my oath was to do no harm So let me ask you, how harmful is the advice t o eat a seasonal diet of whole foods and make sure you never forget to feel a wi nter as the seasons change and our life goes on? I do this by forsaking synthetic drugs and look for big fixes for biologic misma tches. In my view, Optimal health is there for the taking if we are open to it and want i t. It is no longer a mystery unless you are blinded by modern day dogma. When we feed our mind a strict diet of exceptional thoughts, you stop trading yo ur greatest ideas for the illusion of security.