Dossier

Termo Te
FUXION Prolife Biotech

Compilación del Dr. Carlos Mena Herrera

(Medicina Interna . Endocrinología,
Fitofarmacognosia)

Componentes:
1. L-carnitina
2. Tamarindo malabar (Garcinia)
3. Ácido alfa lipoico
4. Ácido cítrico
5. Inositol
6. aceite esencial limón
7. Stevia

Garcinia

El tamarindo malabar (Garcinia gummi-gutta) también conocido por su antiguo nombre

científico Garcinia cambogia, es un arbusto que crece sobre todo en el sur de la India.
El género Garcinia, conformado por más de 200 especies tropicales, se origina en
el sudeste asiático, Polinesia y África, pero la mayoría de las especies se cultivan en la
India.

Garcinia gummi-gutta presenta copa redondeada y ramas horizontales o caídas;

tiene hojas compuestas, de color verde oscuro, brillantes, y que crecen de a dos por nudo;
y da flores apelotonadas de un color naranja rojizo. Su fruta —que contiene las semillas—
es un poco grande, lobular y levemente aplastada como una pequeña calabaza; se
compone de un pericarpio grueso y carnoso de color amarillo o anaranjado cuyo zumo es
agridulce; y es comestible cuando la fruta está madura en la estación húmeda entre junio
y octubre.

Las partes de la planta utilizada son la pulpa del fruto y su corteza que contiene
diferentes principios activos como el ácido hidroxicítrico y antocianósidos. Algunos
estudios realizados hace diez años señalaban la falta de actividad del ácido hidroxicítrico
en el metabolismo graso. Actualmente, nuevos estudios aclararon el mecanismo de
acción y hasta fotografiaron los resultados obtenidos en el adipocito.
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También se había citado la toxicidad sobre el hígado a

dosis elevadas, pero esto fue refutado y abandonado al
comprobarse que se trataba de una falsa garcinia
comprada por una única empresa sin certificación
adecuada. Sin embargo, las dosis exageradas pueden
provocar fibrosis en el hígado, especialmente si el hígado
ya se encuentra dañado.

El fruto puede desecarse o elaborar extractos fluidos que

solo o en combinación con otros principios activos como la
L-carnitina sirven para controlar el peso. El estudio
profundo de esta fruta ha abierto nuevos caminos en el conocimiento del metabolismo
graso.

Abstracts:
Food Funct. 2014 Mar 26;5(4):773-9. doi: 10.1039/c3fo60631g.

Evaluation of the satiating properties of a nutraceutical product

containing Garcinia cambogia and Ascophyllum nodosum extracts in healthy
volunteers.

Mayer MA1, Finlayson G, Fischman D, de Paz C, Telleriarte MR, Ferrero AJ, Bobillo
C, Fernández BE.

Abstract

A nutraceutical product composed of a combination of Garcinia cambogia, l-carnitine

and a seaweed extract of Ascophyllum nodosum has been recently developed. The
aim of the present study was to characterize its effects on subjective satiety sensations
and food preferences in healthy volunteers. In a crossover design, 28 subjects (21
females and 7 males, aged 31 ± 5, BMI 22.6 ± 1.7) were randomly assigned to receive
the active treatment (LIS) or placebo (PL) over one week. At the end of each treatment
period, subjects were instructed to consume ad libitum a test meal. Food preferences
and appetite sensations were evaluated by means of the Leeds Food Preferences
Questionnaire and visual analog scales, before and after meal, over three hours. There
were no differences in energy intake between study groups. LIS was associated with a
reduction in subjective hunger sensations (p = 0.018) and to an increase in satiety (p =
0.02) and fullness (p = 0.01) ratings. The preference for high fat foods was reduced
after consuming the test meal in both study groups. There was a significant effect of
LIS treatment on food explicit liking and implicit wanting, as evidenced by an increase
in preference for sweet foods (relative to savory foods; p = 0.03 and p = 0.004,
respectively), but no differences were observed regarding the preference for low or
high fat foods (NS). These results provide proof of principle for the satiating
properties of a nutraceutical containing Garcinia cambogia, Ascophyllum
nodosum extract and l-carnitine and suggest that it might be useful as an
appetite modulator.

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PMID:24563084 [PubMed - in process]

Phytother Res. 2013 Oct 17. doi: 10.1002/ptr.5076. [Epub ahead of print]

Hypolipemic Effect of Garcinia cambogia in Obese Women.

Vasques CA1, Schneider R, Klein-Júnior LC, Falavigna A, Piazza I, Rossetto S.

Abstract

Garcinia cambogia seems to promote weight reduction and improvement on lipid

profile by its major compound, hydroxycitric acid (HCA), blocking ATP-citratelyase,
potentially inhibiting lipogenesis. Furthermore, it is suggested that its extract is able to
change the adipokine levels. Thus, the aim of this study was to analyse the effect of
G. cambogia on the lipid profile, endocrine, calorimetric and anthropometric
parameters of obese women. The women (BMI > 25 kg/m2 ; age 25-60 years), divided
in treated (n = 30) and control (n = 13) groups, received 2.4 g (800 mg 3×/day)
of garciniaextract (50% of HCA) or placebo during 60 days, respectively, as well as
dietary control. Weight, BMI, waist-hip ratio and percentage of fat mass, resting
metabolic rate, respiratory coefficient, triglycerides (TG), total cholesterol, HDL and
LDL, leptin and insulin serum levels were evaluated. TG was significantly reduced in
the treated group (p = 0.0002) and the post-treatment variation was different compared
to the placebo group (p = 0.04). No significant response was observed on other
variables of the lipid profile, or on the anthropometric and calorimetric parameters.
Leptin and insulin levels did not change significantly after the treatment. The short-
term treatment with G. cambogia demonstrated a hypotriglyceridemic effect,
which does not appear to be related to changes in leptinemia. Copyright © 2013 John
Wiley & Sons, Ltd.

PMID: 24133059 [PubMed - as supplied by publisher]

Genes Nutr. 2008 Feb;2(4):353-8. doi: 10.1007/s12263-007-0070-1.

A mixture of the aqueous extract of Garcinia cambogia, soy peptide and L: -

carnitine reduces the accumulation of visceral fat mass in rats rendered obese
by a high fat diet.

Kim YJ1, Kim KY, Kim MS, Lee JH, Lee KP, Park T.

Abstract

The aim of the present study was to investigate the anti-obesity effect of a mixture
composed of Garcinia cambogia extract, soypeptide, and L: -carnitine (1.2:0.3:0.02,
w/w/w) in rats rendered obese by a high-fat diet (HFD). Sprague-Dawley rats were fed
either the high-fat control diet (CD) or the 0.38% mixture-supplemented HFD (CD + M)
for 9 weeks. The mixture significantly reduced body weight gain and the

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accumulation of visceral fat mass in a rat model of HFD-induced obesity.

Moreover, the mixture effectively lowered blood and hepatic lipid concentrations
and serum glucose, insulin, c-peptide, and leptin levels in rats with HFD-induced
obesity. Results from real-time reverse transcription-polymerase chain reaction
analyses indicated that the expression levels of leptin, tumor necrosis factor-alpha
(TNF-alpha), and sterol regulatory element binding protein 1c (SREBP1c) genes in the
epididymal fat tissue of rats fed the CD + M diet were 0.4-, 0.6-, and 0.48-fold,
respectively, of those found in the CD rats (P < 0.05), while expression of the
uncoupling protein 2 (UCP2) gene in epididymal adipose tissue was 1.25-fold (P <
0.05) of that found in CD rats. In conclusion, a mixture composed of
G. cambogia extract, soy peptide, and L: -carnitine attenuated visceral fat
accumulation and improved dyslipidemia in a rat model with HFD-induced
obesity.

PMID: 18850230 [PubMed] PMCID: PMC2478482

Lipids Health Dis. 2011 May 14;10:74. doi: 10.1186/1476-511X-10-74.

The relation of high fat diet, metabolic disturbances and brain oxidative
dysfunction: modulation by hydroxy citric acid.

Amin KA1, Kamel HH, Abd Eltawab MA.

Abstract

AIMS:

This study aimed to examine the effect of high fat diet (HFD) to modulate brain
dysfunction, and understand the linkages between obesity, metabolic disturbances and
the brain oxidative stress (BOS) dysfunction and modulation with hydroxyl citric acid of
G. Cambogia.

METHODS:

Rats were divided into 3 groups; 1st control, maintained on standard normal rat chow
diet, 2nd HFD, maintained on high fat diet along 12 week and 3rd HFD+G,
administered G. Cambogia for 4 weeks and each group include 8 rats. Blood, brain
and abdominal fat were collected for biochemical measurements.

RESULTS:

HFD group showed significant increase in energy intake, final BW and BW gain. Also
significant increase in weight of abdominal fat in HFD group. HFD induce metabolic
disturbance through increasing the lipid profile (LDL, TG, TC), γGT and α-amylase
activity, uric acid level and hyperglycemia, while decreasing creatine kinase (CK)
activity.These changes associated with lowering in brain nitric oxide (NO) level and

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rising in serum butyrylcholinesterase (BChE), brain catalase activity and MDA levels as
oxidative stress markers. These alterations improved by G. Cambogia that decrease
BOS and increased NO level.

CONCLUSIONS:

Rats fed HFD showed, metabolic disturbances produce hyperglycemia,

hypertriglyceridemia, hypercholesterolemia and increased LDL associated with
increased BOS. Involvement of BuChE, NO and oxidative stress associated with
metabolic disturbances in the pathophysiological progression in brain, suggesting
association between obesity, metabolic disorders and brain alteration while, using G.
Cambogia, ameliorate the damaging effects of the HFD via lowering feed intake
and BOS.

PMID: 21569551 [PubMed - indexed for MEDLINE] PMCID: PMC3104359

L-carnitina

La carnitona o 3-hidroxi-4-trimetilaminobutirato (conocida también como L-

carnitina o levocarnitina, debido a que en estado natural es un estereoisómero L) es
una amina cuaternaria sintetizada en el hígado, los riñones y el cerebro a partir de
dos aminoácidos esenciales, la lisina y la metionina.

A pesar de que se descubrió en 1905, no fue hasta mediados de los años 50 cuando
se demostró que el principal rol de la carnitina es acelerar el proceso de oxidación de
ácidos grasos (y de esta manera la ulterior producción de energía).

La deficiencia de carnitina conduce a una disminución sustancial de la producción de

energía y al aumento de masa del tejido adiposo (obesidad por déficit enzimático).

Las principal fuentes de carnitina son en particular las carnes rojas.

Los vegetales contienen cantidades muy pequeñas o incluso nulas de carnitina.

De todas formas, gran cantidad de la carnitina en nuestro organismo se sintetiza a

partir de lisina (aminoácido esencial) con ayuda de la metionina, otro aminoácido
esencial, tres vitaminas (vitamina C, vitamina B3 y vitamina B6) y el hierro. La
deficiencia de cualquiera de dichos nutrientes conduce a una deficiencia de carnitina.

La administración de carnitina ha demostrado ser eficaz en el tratamiento de una gran

variedad de enfermedades.

Se utiliza con frecuencia para tratar afecciones cardiovasculares y renales, sobre todo
cuando se intenta mejorar el rendimiento físico.

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– Enfermedades cardiovasculares: Angina de pecho, post infarto agudo de

miocardio, necrosis de miocardio, arritmias inducidas por el consumo
de drogas, trastornos cardíacos.

– Síndrome de fatiga crónica.

– Fibromialgia

– Concentraciones elevadas de colesterol asociado a LDL.

– Concentraciones elevadas de triacilgliceroles (triglicéridos).

– Bajo rendimiento físico. Trastorno distímico. Ansiedad.

– Enfermedad de Alzheimer, depresión senil y falta de memoria relacionada

con la edad.

– Enfermedades renales, trastornos hepáticos, cirrosis hepática.

– Diabetes.

– Bajo conteo y movilidad reducida de

los espermatozoides (infertilidad masculina).

– También se utiliza como un "quemador de grasa" (oxidación de ácidos

grasos y transporte a la mitocondria para formar ATP).

Como "quemador de grasa" se ha podido demostrar que durante una toma de 4 gr

diarios divididos en dos tomas durante 24 semanas, incrementó la L Carnitina a nivel
muscular en un 21% complementándolo con ejercicio aeróbico en bicicleta al 50% y
80% del esfuerzo máximo. Por lo tanto, mejoraría el envío de ácidos grasos de cadena
larga a las mitocondrias de las células. Sin ejercicio los resultados no serán los
mismos.

Abstracts

J Assoc Physicians India. 1998 Sep;46(9):801-5.

L-carnitine administration in coronary artery disease and cardiomyopathy.

Singh RB1, Aslam M.

Abstract

Myocardial ischaemia may be defined as a deficiency in cardiac energy supply relative

to energy demand. In coronary artery disease (CAD), oxygen supply is limited due to
coronary obstruction so energy production is not enough to meet the energy demands
for work. Several reports involving about 2500 patients of CAD where carnitine was

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administered for upto 1 year indicate some beneficial effects. There is reduction in
ischaemia showing reduced ST-segment depression and angina, greater effort
tolerance and decreased need of cardiac drugs. Carnitine can cause overall
improvement in cardiac performance in patients with CAD as well as in
cardiomyopathy. More studies are necessary to demonstrate where carnitine can
scavenge free radicals apart from its beneficial effect on fatty acid metabolism. Side
effects of carnitine are mild nausea and vomiting and dose upto 2 g/day in 3 divided
doses may not have any side effects. Intravenous L-carnitine acts rapidly and has no
side effects.

PMID: 11229253 [PubMed - indexed for MEDLINE]

Eur J Nutr. 2012 Feb;51(1):1-18. doi: 10.1007/s00394-011-0284-2. Epub 2011 Dec 2.

Role of carnitine in the regulation of glucose homeostasis and insulin

sensitivity: evidence from in vivo and in vitro studies
with carnitine supplementation and carnitine deficiency.

Ringseis R1, Keller J, Eder K.

Abstract

BACKGROUND:

Although carnitine is best known for its role in the import of long-chain fatty acids (acyl
groups) into the mitochondrial matrix for subsequent β-oxidation, carnitine is also
necessary for the efflux of acyl groups out of the mitochondria. Since intracellular
accumulation of acyl-CoA derivatives has been implicated in the development of insulin
resistance, carnitine supplementation has gained attention as a tool for the treatment
of insulin resistance. More recent studies even point toward a causative role
for carnitine insufficiency in developing insulin resistance during states of chronic
metabolic stress, such as obesity, which can be reversed by carnitine supplementation.

METHODS:

The present review provides an overview about data from both animal and human
studies reporting effects of either carnitinesupplementation or carnitine deficiency on
parameters of glucose homeostasis and insulin sensitivity in order to establish the less
well-recognized role of carnitine in regulating glucose homeostasis.

RESULTS:

Carnitine supplementation studies in both humans and animals demonstrate an

improvement of glucose tolerance, in particular during insulin-resistant states. In
contrast, less consistent results are available from animal studies investigating the
association between carnitinedeficiency and glucose intolerance. The majority of

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studies dealing with this question could either find no association or even reported
that carnitinedeficiency lowers blood glucose and improves insulin sensitivity.

CONCLUSIONS:

In view of the abovementioned beneficial effect of carnitine supplementation on

glucose tolerance during insulin-resistant states,carnitine supplementation might be an
effective tool for improvement of glucose utilization in obese type 2 diabetic patients.
However, further studies are necessary to explain the conflicting observations from
studies dealing with carnitine deficiency.

PMID: 22134503 [PubMed - indexed for MEDLINE]

Phytomedicine. 2008 Aug;15(8):595-601. doi: 10.1016/j.phymed.2008.02.026. Epub

2008 Jun 9.

Dietary l-carnitine supplementation improves bone mineral density by

suppressing bone turnover in aged ovariectomized rats.

Hooshmand S1, Balakrishnan A, Clark RM, Owen KQ, Koo SI, Arjmandi BH.

Abstract

Postmenopausal bone loss is a major public health concern. Although drug therapies
are available, women are interested in alternative/adjunct therapies to slow down the
bone loss associated with ovarian hormone deficiency. The purpose of this study was
to determine whether dietary supplementation of l-carnitine can influence bone density
and slow the rate of bone turnover in an aging ovariectomized rat model. Eighteen-
month-old Fisher-344 female rats were ovariectomized and assigned to two groups: (1)
a control group in which rats were fed ad libitum a carnitine-free (-CN) diet (AIN-93M)
and (2) another fed the same diet but supplemented with l-carnitine (+CN). At the end
of 8 weeks of feeding, animals were sacrificed and bone specimens were collected for
measuring bone mineral content (BMC) and density (BMD) using dual energy X-ray
absorptiometry. Femoral microarchitectural properties were assessed by
microcomputed tomography. Femoral mRNA levels of selected bone matrix proteins
were determined by northern blot analysis. Data showed that tibial BMD was
significantly higher in the rat fed the +CN diet than those fed the -CN (control) diet.
Dietary carnitine significantly decreased the mRNA level of tartrate-resistant acid
phosphatase (TRAP), an indicator of bone resorption by 72.8%, and decreased the
mRNA abundance of alkaline phosphatase (ALP) and collagen type-1 (COL),
measures of bone formation by 63.6% and 61.2%, respectively. The findings suggest
that carnitine supplementation slows bone loss and improves bone
microstructural properties by decreasing bone turnover.

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J Strength Cond Res. 2003 Aug;17(3):455-62.

The effects of L-carnitine L-tartrate supplementation on hormonal responses to

resistance exercise and recovery.

Kraemer WJ1, Volek JS, French DN, Rubin MR, Sharman MJ, Gómez AL, Ratamess
NA, Newton RU, Jemiolo B, Craig BW, Häkkinen K.

Abstract

The purpose of this investigation was to examine the influence of L-carnitine L-tartrate
(LCLT) supplementation using a balanced, cross-over, placebo-controlled research
design on the anabolic hormone response (i.e., testosterone [T], insulin-like growth
factor-I, insulin-like growth factor-binding protein-3 [IGFBP-3], and immunofunctional
and immunoreactive growth hormone [GHif and GHir]) to acute resistance exercise.
Ten healthy, recreationally weight-trained men (mean +/- SD age 23.7 +/- 2.3 years,
weight 78.7 +/- 8.5 kg, and height 179.2 +/- 4.6 cm) volunteered and were matched,
and after 3 weeks of supplementation (2 g LCLT per day), fasting morning blood
samples were obtained on six consecutive days (D1-D6). Subjects performed a squat
protocol (5 sets of 15-20 repetitions) on D2. During the squat protocol, blood samples
were obtained before exercise and 0, 15, 30, 120, and 180 minutes postexercise. After
a 1-week washout period, subjects consumed the other supplement for a 3-week
period, and the same experimental protocol was repeated using the exact same
procedures. Expected exercise-induced increases in all of the hormones were
observed for GHir, GHif, IGFBP-3, and T. Over the recovery period, LCLT reduced the
amount of exercise-induced muscle tissue damage, which was assessed via magnetic
resonance imaging scans of the thigh. LCLT supplementation significantly (p < 0.05)
increased IGFBP-3 concentrations prior to and at 30, 120, and 180 minutes after acute
exercise. No other direct effects of LCLT supplementation were observed on the
absolute concentrations of the hormones examined, but with more undamaged tissue,
a greater number of intact receptors would be available for hormonal interactions.
These data support the use of LCLT as a recovery supplement for hypoxic exercise
and lend further insights into the hormonal mechanisms that may help to mediate
quicker recovery.

Ácido alfa lipoico

El ácido lipoico ha demostrado ser hepatoprotector, mejorar la circulación del hígado,

tratar enfermedades crónicas del hígado, tales como la ictericia, la hepatitis, cirrosis,
coma hepático, diabetes, alteraciones del metabolismo de los
carbohidratos, neuropatía diabética, trastornos metabólicos de la histidina,
alteraciones de los niveles de lactato y piruvato, enfermedades psiquiátricas,

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envenenamiento con antimonio, envenenamiento por mercurio, aterosclerosis,

aterosclerosis coronaria, enfermedades cerebrovasculares,, envenenamiento
por cianuro de potasio, intoxicación por estreptomicina, envenenamiento por setas,
bajar el colesterol, invertir anestesia barbitúrica, reducir experimentalmente la
ingesta voluntaria de alcohol y aumentar la tolerancia de potasio.

Es una ayuda indispensable para prevenir y mejorar muchas patologías :

 Neutralizar toxinas generadas por agentes oxidantes como el tabaco y el

alcohol.
 Incrementar la asimilación de la glucosa en pacientes diagnosticados con
diabetes tipo II y prevenir diversas complicaciones relacionadas con esta
enfermedad.
 Equilibrar los niveles de la presión sanguínea y mejorar la circulación .
Reducir el estrés oxidativo de las células , causa del envejecimiento
precoz.
 Mejorar las enfermedades neurológicas .
 Prevenir la formación de cataratas.
 Combate el Síndrome de Fatiga Crónica.
 Ayuda a mejorar la salud cardiaca aumentando la eficiencia del músculo
cardiaco. Protege las arterias, capilares y venas.

Recupera las formas reducidas de la vitamina C y la vitamina E, además de otras sustancias.

Esto ahorra la pérdida de estas moléculas una vez usadas por las células.

El Acido Alfa Lipoico entra al cerebro y protege directamente las células donde mas lo
necesita, una vez en el cerebro el Ácido Lipoico incrementa los niveles de glutatión
protegiéndolo de los radicales libres. Investigaciones han probado que niveles bajos de
glutation en el cerebro se asocian con desordenes cerebrales como: Parkinson, Alzheimer y
Demencia.

 Activa la función inmunitaria.

 Actúa como protector hepático.
 Ayuda a paliar los efectos de las radiaciones.
 Remueve de nuestro cuerpo metales pesados como el mercurio, cobre y el plomo.

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Abstracts:

Eur J Nutr. 2013 Mar;52(2):779-87. doi: 10.1007/s00394-012-0384-7. Epub 2012 Jun 5.

Effects of lipoic acid on AMPK and adiponectin in adipose tissue of low- and high-fat-fed
rats.
Prieto-Hontoria PL1, Pérez-Matute P, Fernández-Galilea M, Alfredo Martínez J, Moreno-Aliaga
MJ.
Abstract

BACKGROUND:

Lipoic acid (LA) is an antioxidant with antiobesity and antidiabetic properties. Adiponectin is an
adipokine with potent anti-inflammatory and insulin-sensitizing properties. AMP-activated
protein kinase (AMPK) is a key enzyme involved in cellular energy homeostasis. Activation of
AMPK has been considered as a target to reverse the metabolic abnormalities associated with
obesity and type 2 diabetes.

AIM OF THE STUDY:

The aim of this study was to determine the effects of LA on AMPK phosphorylation and
adiponectin production in adipose tissue of low-fat (control diet) and high-fat diet-fed rats.

RESULTS:

Dietary supplementation with LA reduced body weight and adiposity in control and high-fat-
fed rats. LA also reduced basal hyperinsulinemia as well as the homeostasis model assessment
(HOMA) levels, an index of insulin resistance, in high-fat-fed rats, which was in part
independent of their food intake lowering actions. Furthermore, AMPK phosphorylation was
increased in white adipose tissue (WAT) from LA-treated rats as compared with pair-fed
animals. Dietary supplementation with LA also upregulated adiponectin gene expression in
WAT, while a negative correlation between adiposity-corrected adiponectin levels and HOMA
index was found. Our present data suggest that the ability of LA supplementation to prevent
insulin resistance in high-fat diet-fed rats might be related in part to the stimulation of AMPK
and adiponectin in WAT.

PMID: 22664981 [PubMed - indexed for MEDLINE]

Diabetes Metab Res Rev. 2013 Jul;29(5):327-33. doi: 10.1002/dmrr.2397.

Whither pathogenetic treatments for diabetic polyneuropathy?
Boulton AJ1, Kempler P, Ametov A, Ziegler D.
Abstract

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Diabetic distal symmetric polyneuropathy (DSPN) occurs in around one-third of patients with
diabetes and is associated with significant morbidity and increased mortality. Diagnosis and
clinical assessment of DSPN remain a challenge, not only for the physician in clinical practice
but also for clinical trials. Optimal diabetes control is generally considered an essential first
step in the prevention and management of DSPN. However, glycaemic control alone may be
insufficient to prevent the development or progression of DSPN, especially in type 2 diabetes.
Near-normoglycaemia is also difficult to achieve in a significant proportion of patients.
Although considerable advances have been made in symptomatic pain management, these
have not addressed the problem of sensory deficits and have no impact on the underlying
pathogenesis of DSPN. There remains a lack of treatment options that effectively target the
natural history of the disease. Several pathogenetic treatment approaches have been
investigated, but evidence from clinical trials is limited with a number of treatments having
shown disappointing results. However, some pathogenetic therapies have shown clinically
relevant improvements in neuropathic endpoints in randomised controlled trials, in particular
α-lipoic acid and Actovegin. These advances in DSPN disease modification need to be
confirmed with further robust evidence from clinical trials together with a better
understanding of the mechanisms of action of promising treatments.

Copyright © 2013 John Wiley & Sons, Ltd.

PMID: 23381942 [PubMed - indexed for MEDLINE]

Expert Opin Pharmacother. 2013 Sep;14(13):1829-38. doi: 10.1517/14656566.2013.813483.

Epub 2013 Jun 22.
Lipoic acid in animal models and clinical use in diabetic retinopathy.
Nebbioso M1, Pranno F, Pescosolido N.
Abstract
INTRODUCTION:
Oxidative stress, a consequence of excessive production of reactive oxygen species (ROS), is a
factor in the development of many diseases, including diabetes and its complications. Alpha-
lipoic acid (ALA), a natural thiol antioxidant, has been shown to have beneficial effects on
oxidative stress parameters in various tissues. This article is an up-to-date review of current
thinking regarding ALA and its use in providing antioxidant (AO) drug therapy for ocular
dysfunction due to diabetic retinopathy (DR).
AREAS COVERED:
ALA prevents micro- and macro-vascular damage through normalized pathways downstream
of mitochondrial overproduction of ROS, and preserves pericyte coverage of retinal capillaries.
In addition, clinical studies suggest that oral administration of ALA can improve insulin
sensitivity in patients with type-2 diabetes. Moreover, ALA treatment has been shown to
suppress expression of vascular endothelial growth factor (VEGF), angiopoietin 2 and
erythropoietin via blockade of superoxide formation.
EXPERT OPINION:

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The diverse beneficial effects of ALA, many of which have only recently been uncovered,
suggest that it acts by multiple mechanisms on oxidative stress parameters. Consequently, ALA
supplementation is an achievable adjunct therapy to help prevent vision loss
indiabetic patients. Finally, further research to better understand the mechanism of ALA will
be useful for the development of more effective therapies in patients affected by DR.
PMID: 23790257 [PubMed - indexed for MEDLINE]

Stevia rebaudiana
Se le considera un edulcorante no calórico y , aunque inicialmente se reportó toxicidad en ratas a
dosis muy elevadas, posteriormente se ha desechado ese concepto, habiendo tenido un uso por
años en la sociedad japonesa.

Abstracts:
Int J Toxicol. 2013 Jul;32(4):261-73. doi: 10.1177/1091581813492828. Epub 2013 Jun 13.

Metabolism and toxicity studies supporting the safety of

rebaudioside D.
Nikiforov AI1, Rihner MO, Eapen AK, Thomas JA.

Abstract
Rebaudioside D (Reb D) is one of the several glycosides found in the leaves of Stevia rebaudiana
(Bertoni) Bertoni (Compositae) which has been identified as a potential sweetener. The metabolism
of Reb A and Reb D was evaluated in various in vitro matrices (simulated gastrointestinal fluids, rat
liver microsomes, and rat cecal contents) and through analysis of plasma collected from rats in a
dietary toxicity study. Reb A and Reb D showed similar stability when exposed to simulated
stomach and small intestine fluids, with susceptibility to hydrolytic degradation by enteric bacteria
collected from the cecum. Incubations with rat liver microsomes indicated that neither compound is
expected to be metabolized by the liver enzymes. Plasma concentrations of Reb D, Reb A, and/or
the final hydrolysis product of each compound, free/conjugated steviol, were consistent between
animals administered either Reb D or Reb A in the diet. A repeated exposure dietary toxicity study
was conducted to compare the safety of Reb D, when administered at target exposure levels of
500, 1000, and 2000 mg/kg body weight (bw)/d to Sprague-Dawley rats for 28 days, to that of Reb
A administered at a target exposure level of 2000 mg/kg bw/d. There were no treatment-related
effects on the general condition and behavior of the animals and no toxicologically relevant,
treatment-related effects on hematology, serum chemistry, or urinalysis. Macroscopic and
microscopic findings revealed no treatment-related effects on any organ evaluated. Results were
comparable between the group administered 2000 mg/kg/d Reb D and the group administered
2000 mg/kg/d Reb A.

PMID:23766392 [PubMed - indexed for MEDLINE]

Safety Evaluations
The U.S., international regulatory agencies, and international food safety panels have thoroughly
reviewed the biological, toxicological and clinical data on stevia and steviol glycosides. Most
notably, JECFA over the years has evaluated steviol glycosides multiple times. The majority of
these safety reviews focused on mixtures of steviol glycosides. Some of the earliest toxicology

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reviews revealed possible adverse health effects such as decreased fertility and kidney effects,
but results from better toxicology studies with modern test protocols and use of purer test
materials resolved these earlier safety concerns. Additionally, JECFA raised questions about
clinical effects on blood pressure and glucose metabolism in hypertensive and diabetic
individuals, respectively, in comparison to normal human subjects. These uncertainties prompted
additional clinical testing on high purity test materials, and by 2006, sufficient favorable data
were generated to resolve concerns about these health matters.

Merisant and Cargill strengthened JECFA’s safety assessments of steviol glycosides with well-
conducted investigations on Reb A that were incorporated into their respective GRAS
notifications.

Pharmacokinetic work revealed that stevioside and Reb A are not absorbed per se but are
converted to steviol in the gastrointestinal tract. In both humans and rats, steviol is rapidly
converted to the glucuronide, and the glucuronide is not further metabolized but is efficiently
excreted. It is important to recognize that Reb A is handled pharmacokinetically similarly to
stevioside.

In November 2011, the Commission adopted Regulation EU 1131/2011 which granted

authorisation of the use of steviol glycosides as a sweetener in food. The food additive was
assigned number ‘E 960’ and added to the official EU list of authorised food additives.

Cómo tomar el Termo Té de FUXION

La bolsa se disuelve en agua caliente.
Puede tomarse dos y hasta tres veces por día, siempre una hora antes de las comidas de
mayor volumen (desayuno y almuerzo, generalmente). La dosis puede después reducirse a
una sola bolsa diaria antes de la comida más abundante. Y posteriormente, puede tomarse
interdiario.
Es imprescindible realizar algún ejercicio aeróbico (gastador de calorías, que hace sudar….)
como puede ser media hora de marcha agitada, o en caminadora, etc.
El período recomendado es de 12 semanas, descansar un mes y repetir el período de 12
semanas.
Es recomendable una dieta razonable, según el tipo de trabajo, actividad y clima.
Cuando el uso es en otras enfermedades, o preventivo, basta con una bolsa diaria.

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