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ALIMENTOS FUNCIONALES
Definiciones
4
Expectativa de vida
Evolución
5 http://www.casamerica.es/otras-miradas/impacto-visual/fernando-botero
6
ALIMENTOS FUNCIONALES
9
ALIMENTOS SALUDABLES
Presentación al CPIE
18 de marzo de 2016
ALIMENTOS FUNCIONALES
Definición
Alimentos funcionales Los alimentos funcionales son aquellos que contienen componentes biológicamente
activos que ofrecen beneficios para la salud y reducen el riesgo de sufrir
enfermedades.**
*http://www.inta.cl/Consumidor/tripticos/funcionales/index.asp?offset=1
**Alimentos Funcionales. FECYT. ISBN 84-689-4204-9
15 16
ALIMENTOS FUNCIONALES ALIMENTOS FUNCIONALES
Ejemplos: Naturales y elaborados Aspectos operativos de la definición*
Debe producir efectos beneficiosos sobre las funciones orgánicas, además de sus
efectos nutricionales intrínsecos, apropiados para mejorar la salud y el bienestar,
Antioxidantes Ácidos grasos poliinsaturados Jugo + fibra
(Antocianinas) (Omega-3) (Agua+Fibra soluble) reducir el riesgo de enfermedad (no prevenir), o ambas cosas.
* ILSI Europe
18
✓ Probióticos, prebióticos
✓ Fibra dietaria
✓ Vitaminas y minerales
✓ Derivados fenólicos
✓ Carotenoides y derivados
Arándano Suplemento Alimenticio Nutracéutico
(cápsulas)
✓ Ácidos grasos y fitoesteroles
(alimento) (polvo)
✓ Compuestos Azufrados
20
EXAMPLES OF FUNCTIONAL COMPONENTS* Plant Stanols/Sterols
Free Stanols/Sterols** corn, soy, wheat, wood oils, fortified foods and beverages may reduce risk of CHD
Stanol/Sterol esters** fortified table spreads, stanol ester dietary supplements may reduce risk of CHD
Class/Components Source* Potential Benefit
Carotenoids
Polyols
Sugar alcohols**—Xylitol, Sorbitol, Mannitol, Lactitol some chewing gums and other food applications may reduce risk of dental caries
Beta-carotene carrots, pumpkin, sweet potato, cantaloupe neutralizes free radicals, which may damage cells; bolsters cellular antioxidant defenses;
can be made into vitamin A in the body Prebiotics
Lutein, Zeaxanthin kale, collards, spinach, corn, eggs, citrus may contribute to maintenance of healthy vision Inulin, Fructo-oligosaccharides (FOS), Polydextrose whole grains, onions, some fruits, garlic, honey, leeks, may improve gastrointestinal health; may improve calcium absorption
Lycopene tomatoes and processed tomato products, watermelon, may contribute to maintenance of prostate health fortified foods and beverages
red/pink grapefruit
Probiotics
Dietary (functional and total) Fiber Yeast, Lactobacilli, Bifidobacteria, and other specific certain yogurts and other cultured dairy and may improve gastrointestinal health and systemic immunity; benefits are strain-specific
Insoluble fiber wheat bran, corn bran, fruit skins may contribute to maintenance of a healthy digestive tract; may reduce the risk of some strains of beneficial bacteria non-dairy applications
types of cancer
Beta glucan** oat bran, oatmeal, oat flour, barley, rye may reduce risk of coronary heart disease (CHD) Phytoestrogens
Soluble fiber** psyllium seed husk, peas, beans, apples, citrus fruit may reduce risk of CHD and some types of cancer Isoflavones—Daidzein, Genistein soybeans and soy-based foods may contribute to maintenance of bone health, healthy brain and immune function; for
women, may contribute to maintenance of menopausal health
Whole grains** cereal grains, whole wheat bread, oatmeal, brown rice may reduce risk of CHD and some types of cancer; may contribute to maintenance of
healthy blood glucose levels Lignans flax, rye, some vegetables may contribute to maintenance of heart health and healthy immune function
Caffeic acid, Ferulic acid apples, pears, citrus fruits, some vegetables, coffee may bolster cellular antioxidant defenses; may contribute to maintenance of healthy vision
21 and heart health NATURE|Vol 444|2 November 2006
February 2007
22
Source: International Food Information Council Foundation NEWS
O. FRANKEN/CORBIS
Vinos
Enfermedades crónicas no transmisibles
Polifenoles
Vegetales
Fibras
Aceite Alimentos
Obesidad
Oliva funcionales
Pescados
W3–W6
Dieta Rosy prospect? A compound found in red wine might help to protect against the health problems associated with obesity.
groups from 18–24 months, when most of our analyses were per- Although resveratrol increased survival, it was important to ascer-
1. Compuesto polifenólico clasificado
formed. There como ARTICLES
was also no difference estilbeno
in producido
body temperature (Table 1), por variasquality
tain whether plantas
of life was maintained. One way to assess this was NATURE | Vol 444 | 16 November 2006
también denominadofood
fitoalexina
consumption (propiedades
(Supplementary Fig.antibacterianas or to measure balance and motor coordination, which we did by exam- Sin resveratrol
y antifungicas)
1a, b), total faecal output Con resveratrol
ining the ability to perform on a rotarod. Surprisingly, the resvera-
lipid content (Supplementary Fig. 1c, d), or post-mortem body fat
distribution (Supplementary Fig. 2). trol-fed HC mice steadily improved their motor skills as they aged, to ARTICLES NA
At 60 weeks of age, the survival curves of the HC and 39 HCR groups the point where they were indistinguishable from the SD group
2. Es posible encontrarlo beganen uvas,and
to diverge vino
havetinto
remained y algunas
separated by berries.
regeneration ,
a 3–4-month is of Su concentración
note
inter- because its
(Fig. 1c). It is possible variathat
activity dethe improved rotarod performance might
is known to be sup- might reveal pathways common to the enhancement of health and
pressed in the in liver by highhave caloric diets anddifferences
shows an age-related longevity.
this as Of the 36 different pathways identified by AGEMAP , isas
acuerdo a factores como: origen geográfico, exposición a hongos, especie, been due
condiciones
to minor in body weight but we view
val (Fig. 1b). A similar effect on survival was observed a previous 39
regeneration of note because its activity is known to be sup- might reveal pathways common to
unlikely because we found no correlation between 40,41 body weight
study of one-year-old C57BL/6 micedecline on caloricin activityultimately
restriction, that is attenuated by caloric restriction . beingand significantly altered by caloric restriction, there was sufficient
pressed in the liver by high caloric diets and shows an age-related longevity. Of the 36 different pathw
de producción, etc. resulting in a 20% extension of mean lifespan 17
. With the present age
A few of the pathway changes
performance within groups and rotarod performance was also
were unanticipated.SDAlthough alteredthat is attenuated by caloric restriction .
decline in activity 40,41
being significantly altered by caloric
ofARTICLES
the colony at 114 weeks, 58% of the HC control animals have died improved for resveratrol-treated mice (R.deC.we and K.P., overlap
unpub-to compare 19 of them to our data (Fig. 4e). Pathways A few of the pathway changes were unanticipated. Although we
had observed NATURE | Vol 444 | 16 November 2006 overlap to compare 19 of them to ou
(median lifespan 108 weeks), as compared to 42% of thean HCR increase
group in lishedmitochondrial
data). These data number are reminiscent in the of theHCR in the same direction by caloric restriction and resveratrol
resveratrol-mediated included
had observed an increase in mitochondrial number in the HCR
increase in motor activity in older individuals of the vertebrate fish in the same direction by caloric rest
el group, there was a a14.3 decrease in
-1*the transcription of 10numerous mito-
and 42% of the SD controls. Although we cannot yet confidently the downregulation of IGF-1 and mTOR signalling, group, downregulation
3. Su concentración enpredict vino the se encuentra
ultimate mean en lifespan rango
extension,de:Cox ND proportional mg Lspecies Nothobranchius furzeri . there was a decrease in the transcription of numerous mito- the downregulation of IGF-1 and m
groups from 18–24 months, when most chondrial genes,
of our analyses suggesting
were per- that
Although the turnover
resveratrol
hazards regression shows that resveratrol reduced the risk of death tain whether quality of life was maintained. One way to assess this was
of mitochondrial
increased survival, it was important pro- to of glycolysis, and upregulation of Stat3 signalling. chondrial
ascer- One interesting
genes, suggesting that the turnover of mitochondrial pro- of glycolysis, and upregulation of S
formed. There was also no differenceteins in body was temperature
reduced. (Table
This 1),resultIncreased
was unexpected, but is consistent with a teins was reduced.
from
food the HC diet by(Supplementary
consumption 31% (hazard ratio Fig. 51a,0.69, P 5 0.020),
b), total to a point
faecal output
insulin sensitivity
or to measure balance and motor coordination, which we did by exam-
difference was that cell cycle checkpoint and apoptotic pathways wereThis result was unexpected, but is consistent with a difference was that cell cycle checkpo
where it was not significantly previous
different from the report
SD groupshowing(hazard thatIn SIRT1-dependent
humans, high-calorie activation
diets cause numerousof PGC- pathological condi- previous report showing that SIRT1-dependent activation of PGC- elevated in the caloric restriction gro
lipid content (Supplementary Fig. 1c, d), or post-mortem body fat ining the ability to perform on a rotarod. Surprisingly, the resvera- elevated in the caloric restriction group but downregulated 1a does
bynot
resver-enhance transcription of mitochondrial genes27.
ratio 5 1.03, (Supplementary
P 5 0.88). tions HC including increased glucose andmotor insulin levels . leading
as27they to
to dia- do not favour the interpretation that atrol. We do not favour the interpret
distribution Fig. 2). 1a does not enhance transcription
At 60 weeks of age, the survival curves of the HC and of HCR groups
trol-fed
thebetes,
point cardiovascular
where
of mitochondrial
mice steadily
they were
improved
disease
their
and non-alcoholic
indistinguishable
genes
skills
from fatty
aged,
the 18liver
atrol.
SD groupdisease,We a Ratones peso normal
the resveratrol-treated
Upregulation of complement, which occurs in obese and aged mice, livers were undergoing less apoptosis
Upregulation complement, which
condition
1c). It is for
occurs
which in
there obese and
is no effective aged mice,
treatment . The livers
HC-fed were undergoing less apoptosis because levels of
wasASTalso and ALT,
observed in the HCR group for reasons that are currently two indicators of hepatic apoptosis,
began toadiverge
60
and have remained separated by a 3–4-month inter- (Fig. possible that the improved rotarod performance might
val (Fig. 1b). A similar effect on survival was was also observed
observed in the HCR
in a previous mice
have group
beenhaddue tofor
alterations
minor reasons
in plasmathat
differences levels
in body are currently
of markers
weight that
but wepredict
view this theasonset
two indicators of hepatic apoptosis, were unchanged unclear.
(see Table 1). Perhaps the downregulation of cell c
study of one-year-old
50 C57BL/6 mice unclear.
on caloric restriction, ultimately
resulting in a 20% extension of mean lifespan17. With the present age
It is notable that resveratrol
of diabetes
lin, glucose within
performance
and a
and IGF-1
shorter
groups
lifespan,
unlikely because we found no correlation between body weight
(Table and1).rotarod
including
The HCR
increased
group hadwas
performance
levels of
and
Perhaps
significantly
also ENSAYO INICIAL-RESVERATROL-LONGEVIDAD
insu-
the downregulation of cell cycle checkpoints isItlinked is notable that resveratrol opposed the effects of high caloric
to the
intake in 144 out of 153 significantly altered pathways (Fig. 4c). In
recent discovery that inhibition of c
increases stress resistance and lifes
lower opposed
levels of these the effects
markers, of
micehigh
paralleling thecaloric
SD group.
K.P., An recent
oral glu- discovery that inhibition of checkpoint function fact, in
theC. elegans
Body weight (g)
Liver pathology
50
diabetes and
different froma shorter
mice inlifespan,
the SD group including (Fig. increased
2b, d). levels of insu- a 600 b 30,000
restriction data set for C57BL/6 mice
lin, glucose and known
IGF-1 as
(Table AGEMAP,
1). The
Next, we investigated possible mechanisms behind these meta-HCR hypothes-
group had significantly 3
500 25,000
(AU)
40 bolic effects. AMPK a metabolic regulator that promotes insulin 2
20 Standard diet AMPK occurs on a calorically restriction diet and has been proposed Standard diet 10,000
0.4 500 resistance, gave scores 25,000 of 2.5 for SD, 8.8 20 for HC and 3.5 for HCR, 0
Glucose (mg dl–1)
High caloriediet
Standard as a longevity strategy for mammals . Consistent with this idea, SD100HC HCR High calorie
confirming improved sensitivity (HCR versus HC, P 5 0.01). High calorie + resveratrol 5,000
AUC (mg dl–1)
10 High
Highcalorie
calorie+ resveratrol additional copies of the AMPK gene are sufficient to extend lifespan
0.2 High calorie + resveratrol 400 Although the 21persistence 20,000 of high glucose * levels for morecthan d 0
0
#0 10 20 30 40 50 60
22
0 60inmin following. Because
C. elegans an oral dose we and others for
is unusual have
young observed
mice, that resveratrol
it is typical 4 SD HC HCR
300 Time (min)
Heart pathology
55 60 65 70 75 80 85 90 95 100 105 110 can activate AMPK1915,000 in cultured cells
for older animals . Compared to the HC controls, the areas under through an indirect mechanism
c 12 d 400
0 Time (weeks) 200 (Fig. 2e; see also Supplementary 3a–d), we examined whether AMPK 3 Standard diet #
50 60 70 80 90 100 110
the curves for both10,000glucose and insulin levels were significantly High calorie e
b Standard dietactivation occurred in the livers of theand resveratrol-fed group. Res- 10
(AU)
decreased in the resveratrol-fed HC group were not significantly
18 months 0 * 10 20 30 bolic 40 50 60
140 activity,
effects. namely
AMPKphosphorylation of acetyl-coA carboxylase
that promotes at Ser 79
insulin
SD HC acid HCRsynthase (Supplementary 4
fall from rotarod
21 months Timerisk
31% (min)
ofand
death
sensitivitydecreased
and expression
fatty acid of fatty
oxidation. Its activity correlates tightly 0 100
120 SD HC
0.6
c 12#
24 months Fig.phosphorylation
with 3e, f). d 400 at Thr 172 (p-AMPK). Chronic activation of 2 HCR
100 Standard diet # diet and has been proposed e f
Proportion
Mitochondria per
AUC (ng ml–1)
High calorie
# Time (min)
+ resveratrol 100
cell (% of SD)
60 8 additional
At 18 months copiesofofage theitAMPK gene arethat
was apparent sufficient to extend lifespan
the high-calorie diet greatly
High calorie + resveratrol #
Latency to
0.2 21 22
AR
inincreased
C. elegans the . Because weweight
and others have observed that resveratrol
size and of livers and
* an indirect
that resveratrol prevented 80
µM esv .
5 0 r sv
40 6 in200
12 SO IC
re .
.
sv
µM re
can activate
these changes AMPK (Fig. cultured
3a–c; seecells
alsothrough
Supplementary Fig.mechanism
4a, b) without 60 e
25 µM
f
DM µM
20
0 l
3.0
50 tro
0 (Fig. 2e; seeplasmaalso Supplementary 3a–d), we 1). examined whether AMPK of
100 4 110
altering lipid levels (Table Histological examination 40 #
.5
on
050 60 70 80 90 activation occurred in100 the livers of the resveratrol-fed group. Res-
AMPK phosphorylation
liver sections by staining with haematoxylin and eosin or oil red O 20 2.5
in liver (p-AMPK/total)
SD Time (weeks)
HC HCR
2 veratrol showed a strong tendency towards
revealed a loss of cellular integrity and the accumulation of large lipid inducing phosphoryla- j
c 0 p-AMPK i IgG HC HC + resv.
* nature 444 (2006): 337-342
(% of control)
survival curves. Hazard ratio for HCR is 0.69
group, 2.8 for the HC group and 0.8 for the HCR group (Fig. 3b). 1.0 PGC-1α
HC, and 1.03100 (x2 5 0.022, P 5 0.88) versus# SD. The hazard ratio for HC
Intensity
AR
# 150
µM esv .
2
80 (x 5 5.75, P 5 0.016).
versus SD is 1.43 c, Time
# to fall from an accelerating Decreased organ pathology AMPK
12 SO IC
re .
.
# # 0.5
sv
A
µ r
rotarod was measured every 3 months for all survivors # from a pre-designated in the HC group and was significantly reduced by resveratrol 100
25 µM
60
50 tro
9 (HCR). Asterisk, P , 0.05 (Table 1). The reasons for the elevation#of plasma amylase levels in Tubulin 0
50 Figure 3 | Resveratrol improves liver hi
.5
on
40 P , 0.05 versus SD. Error bars indicate s.e.m. increased the size and weight of livers and that resveratrol prevented SD HC HCR
versus HC; hash, the HC group are unclear given that pancreatic sections of all animals
C
AMPK phosphorylation
these changes (Fig. 3a–c; 2.5see also Supplementary Fig. 4a, b) without number and decreases acetylation of PG
in liver (p-AMPK/total)
20 0
j
PGC-1α acetylation
338 altering plasma lipid levels (Table 1). Histological examination of 1.2 Figure 2 | Resveratrol improves insulin sensitivity and activates AMPK. development of fatty liver, as assessed by
27 p-AMPK i IgG HC HC + resv. 28
AL
– CR
+ sv.
.
sv
0 ©2 0 0 6 Natu re Pu liver
blishinsections
g Gro u p by staining with haematoxylin and eosin or oil red O (b) and decreased fat accumulation as me
2.0 1.0 a–d, Plasma levels of glucose (a, b) and insulin (c, d) were measured after a
(Ac-Lys/total)
Re
Re
SD HC HCR
revealed a loss of cellular integrity and the accumulation of large lipid
Ac-Lys 0.8 2 g kg21 oral glucose dose. Areas under the curves (AUC) were significantly arbitrary units. d, Pathology of heart sec
Figure 1 | Resveratrol increases survival and improves rotarod droplets in the livers 1.5 of the HC but not the HCR group. Blinded reduced by resveratrol treatment. e, Activation of AMPK by resveratrol in heart and aorta is shown in Supplementa
performance. a, Body weights of mice fed a standard diet (SD), high-calorie
p-ACC scoring of the liver sections for overall pathology on a scale of 0–4 Total 0.6 CHO cells. In the presence of resveratrol or 5-aminoimidazole-4- electron microscopy of liver sections (e)
diet (HC), or high-calorie diet plus resveratrol (HCR). b, Kaplan–Meier
survival curves. Hazard ratio for HCR is 0.69 (x2 5 5.39, P 5 0.020) versus
(with 4 being the most 1.0 severe) gave mean values of 1.3 for the SD PGC-1α 0.4 * carboxamide-1-b-D-ribofuranoside (AICAR) as a positive control, g, h, Mitochondrial number in HeLa cells
HC, and 1.03 (x2 5 0.022, P 5 0.88) versus SD. The hazard ratio for HC group, 2.8 for the HC group and 0.8 for the HCR group (Fig. 3b). 0.2 phosphorylation of AMPK and its downstream target, acetyl-coA fed (AL) or calorically restricted (CR) ra
2 AMPK
versus SD is 1.43 (x 5 5.75, P 5 0.016). c, Time to fall from an accelerating Plasma amylase, which 0.5
can indicate pancreatic damage, was elevated 0.0 carboxylase (ACC), are increased. f, AMPK activity in liver. Phosphorylation Mitotracker green FM. i, j, Resveratrol re
rotarod was measured every 3 months for all survivors from a pre-designated in the HC group and was significantly reduced by resveratrol HC HC +ofresv.
AMPK (f), acetyl-coA carboxylase (Supplementary Fig. 3e) and decreased known SIRT1 target and regulator of mit
subset of each group; n 5 15 (SD), 6 (HC) and 9 (HCR). Asterisk, P , 0.05
Tubulin
(Table 1). The reasons for 0 the elevation of plasma amylase levels in expression of fatty acid synthase (Supplementary Fig. 3f) are indicative of 1a was immunoprecipitated from liver e
versus HC; hash, P , 0.05 versus SD. Error bars indicate s.e.m. the HC group are unclear givenSD HC HCRsections of all animals
that pancreatic Figure 3 | Resveratrol improves liver histology, increasesenhanced mitochondrial
AMPK activity. Asterisk, P , 0.05 versus HC; hash, P , 0.05 (i) and quantified (j). Asterisk, P , 0.05 v
338 number and decreases acetylation of PGC-1a. a–c, Resveratrol prevents
versus SD. n 5 5 fortheall groups. Error bars indicate s.e.m. n 5 5 for b and d; n 5 3 for f and j. Error
Figure 2 | Resveratrol improves
©2 0 0 6 Natu re Pu blishin ginsulin
Gro u p sensitivity and activates AMPK. development of fatty liver, as assessed by organ size (a), overall
340
pathology
Un comprimido no puede “mimetizar” esta mezcla natural y equilibrada
de fitoquímicos que comemos con los alimentos que, además, tienen
otras muchos bioactivos
t h bi ti di t t t l
dieta total.
dieta total
Incluso las MEGADOSIS
MEGADOSIS pueden tener el efecto contrario!!
Hormesis: Muchas veces, de lo bueno, ¡cuánto más … peor!
No se recomienda el consumo de alcohol, pero si bebes, hazlo con moderación Carbajal, 2013
Resveratrol
Hormesis Curve
Hormesis: del griego ὁρμάω "estimular"
Inhibición‐tóxxico | Estimulación‐benefficioso
(Mattson, 2008; Vaiserman, 2011; Calabrese y col., 2012)
+
Hormesis respuesta bifásica:
b fá
• A dosis bajas (o intermitente)
respuesta adaptativa beneficiosa
Fibra Dietaria
• A dosis altas: efecto tóxico
Hormetic Zone
‐ (averages 10‐ to 20‐fold)
Increasing Dose
29
30
Aceite de Oliva
Aceite de Oliva Aceite de Oliva
Propiedades saludables
37 38
Aceite de Oliva
Propiedades saludables
1. Ácido oleico (18:1 W-9) suprime la sobre expresión de HER2 (erbB-2), un oncogene
que juega un rol crucial en la etiología, invasión, progresión y metástasis de varios
cánceres que afectan a los seres humanos. [Curr Pharm Biotechnol. 2006; 7(6):495-502.]
39
of Edinburgh, Summary points
Edinburgh als and the public are increasingly interested in their
EH16 4SB role in the prevention and management of coronary
Jehangir N Din Coronary heart disease is still the most
heart disease. In this era of multiple pharmacological
research fellow cause of death in the United Kingdom
treatments for cardiovascular disease many believe that
David E Newby
reader simple dietary interventions or nutritional supple- Omega 3 fatty acids from fish and fish o
Royal Infirmary of ments may be a more natural and acceptable method protect against coronary heart disease
Edinburgh, of providing benefits.
Edinburgh Several areas of uncertainty remain. The optimal
EH16 4SA There is evidence to support the use of
Andrew D Flapan
intake of omega 3 fatty acids is not firmly established, oil supplements after myocardial infarct
consultant nor is their mechanism of action fully understood.
cardiologist Some studies have produced conflicting results, and The mechanisms by which fish oils conf
Correspondence
Downloaded from bmj.com concerns
on 10to:December 2007have been increasing about environmental benefits are not fully understood
J N Din contamination of certain fish. This article reviews the
Clinical review jehangirdin@
current evidence regarding fish oils and cardiovascular Unravelling these mechanisms may iden
OMEGAS
hotmail.com
disease, their possible mechanism of action, and therapeutic targets and could help guid
BMJ 2004;328:30–5 humans and trials are
potential future currently under
developments andway in patients
research strategies. development of future treatments for co
Box 1: Possible mechanisms of action of omega with implantable defibrillators. heart disease
PROPIEDADES
3 fatty acids
• Antiarrhythmic SALUDABLES Thrombosis
Sources and selection criteria
Activation of platelets and their deposition at sites of Future trials may identify other patients
• Antithrombotic unstable plaque rupture
We searched PubMed promotes thrombus
for relevant formation,
articles by using the could benefit, such as those with stable a
• Antiatherosclerotic and these
key critical
words events
“fish,” haveoils,”
“fish become a common
“omega 3 fattythera-
acids,” and risk factors for coronary heart disease, o
• Anti-inflammatory peutic target in acute coronary syndromes. However, the ventricular dysfunction
• Improves endothelial function effects of omega 3 fatty acids on platelet function and
• Lowers blood pressure thrombosis are controversial. Large doses reduce plate-
La asociación entre W-3 y let aggregation, but smaller amounts have modest plate-
• Lowers triglyceride concentrations
enfermedades cardiovascular fue let inhibitory effects.17 Omega 3 fatty acids have “cardiovascular disease.” References iden
inconsistent effects on fibrinolysis and little effect on search are on bmj.com
establecida por las observaciones blood coagulability.18 Therefore, although omega 3 fatty
Mechanism of action
al pueblo Inuit de
Ácidos grasos omega-3 y 6
realizadas acids have an antithrombotic effect, its relevance to the
Groenlandia,
Although the weightquienes
of evidencea outlined
pesar abovede mortality reduction seen with lower doses is unclear. Omega 3 polyunsaturated fatty
supports a protective effect of omega 3 fatty acids on Atherosclerosis The association between omega 3 fatt
consumir
coronary heart una dieta
disease, rica en grasas
the mechanisms through Omega 3 fatty acids may also influence the atheroscle- cardiovascular disease was established f
presentaban
which they confer una
thesebaja mortalidad
benefits por
remain unclear. rotic process. Fish oil fed to experimental animals pro- observation that the Greenland Inuit had l
Omega 3 fatty acids have several potentially cardiopro-
enfermedades cardiovasculares tects against progression of atherosclerotic plaques.w3 w4
from coronary heart disease despite a die
tective effects (box 1), although the relative contribu- In humans with coronary heart disease omega 3 fatty
tion of each of these is not fully understood. in fat. In the 1970s the Danish investigato
acid supplementation versus placebo for two years
En 1970 los investigadores Daneses resulted in modest improvements in atherosclerosis as Dyerberg proposed that this could be be
Arrhythmias high content of omega 3 fatty acid in th
TheBang y Dyerberg
benefits propusieron
of fish oils were que esta
originally thought to be
assessed by angiography.w5 These effects may be due to
which consisted largely of fish, seal, and w
a reduction in lipids, inflammation, production of
due to their antithrombotic effects, but recent evidence
baja mortalidad se podía deber al
has indicated that the predominant effect may be
growth
Fig 1 factor,
GreenlandorInuit
suppression of in
gutting a seal smooth
the earlymuscle cell diet
1900s. Their
contenido de
antiarrhythmic. In W-3 en la dieta Inuit*
the GISSI-Prevenzione trial the
proliferation. w6
Anofimportant
consisted largely fish, whale,recent study
seal, and randomised
walrus, resulting in a high Additional references (w1-w15) are on bmj.c
patients
intake ofawaiting
omega 3 carotid endarterectomy
fatty acids. to fish used
Copyright Arctic Institute, oil with
decrease in mortality was largely due to a reduction in
capsules,
permissionsunflower oil capsules,
from Leif Vanggaard, or control until
Arctic Institute
sudden death,11 and, as in DART,10 no reduction in the
surgery and then assessed morphology of the plaque.19
rate of non-fatal myocardial infarction occurred. Fish
Omega 3 fatty acids were readily incorporated into
oil supplementation increases heart rate
* BMJ 2004;328;30-35 30 variability in BMJ VOLUME 328 3 JANUARY
atherosclerotic plaques in the fish oil group, and these
patients after myocardial infarction, which correlates
41 plaques were more likely to have thick fibrous caps and 42
with a lower risk of mortality and malignant
less inflammatory infiltrate. These features imply a
arrhythmia.15 In animal models fish oil protects against
plaque that is less vulnerable to rupture and indicate
ventricular fibrillation after surgical occlusion of a cor-
that fish oils may be important in establishing stability
onary artery.16 The addition of eicosapentanoic acid or
of the plaque.
docosahexanoic acid can prevent or terminate
pharmacologically induced arrhythmias in cultured Inflammation
cardiomyocytes from newborn rats.16 However, studies Inflammation has a central role in the development
are necessary to show a direct antiarrhythmic effect in and progression of coronary artery disease. Omega 3
OMEGAS T able 1 Effect of marine derived omega 3 fatty acids on death from coronary heart disease in secondary prevention of myocardial
infarction
Absolute risk Relative risk
proteína C reactiva, IL-6, selectina E, etc. Por lo tanto tendría una actividad beneficiosa directa patients after
myocardial infarction
sobre el proceso inflamatorio de la aterogénesis. Nilsen et al13 Randomised
double-blind placebo
Fish oil (EPA+DHA
3.5 g/d)
5.3 5.3 — — — Small size,
reasonable intake of
controlled, 1.5 year fish among general
follow up, 300 population
Numerosos estudios observacionales han concluido que el consumo de W-3 es inversamente patients after
myocardial infarction
proporcional al riesgo de padecer enfermedades cardiovasculares y muerte por ellas, sin *P<0.01 between control and intervention groups.
embargo la ultima revisión sistemática publicado por Cochrane library* concluyó que no hay **P=0.024 between control and intervention groups.
EPA=eicosapentanoic acid, DHA=docosahexanoic acid, ALA=" linolenic acid.
una evidencia clara sobre el efecto de los W-3 sobre la mortalidad combinada por
enfermedades cardiovasculares o cáncer. 32 BMJ VOLUME 328 3 JANUARY 2004 bmj.com
* BMJ 2006;332;752-760
43 * BMJ 2004;328;30-35 44
Boletín de la Sociedad de Pediatría de Aragón, La Rioja y Soria
CLA
isomería trans (t). Por ello pueden existir ácidos grasos le identifica también como «ácido ruménico». Existe otra
conjugados di-insaturados con isomería c,c, hecho poco vía metabólica para la formación de ALC, que puede
probable, o c,t, o t,c o t,t. Cada isómero puede jugar un tener lugar en el hígado de los rumiantes, y posiblemen-
papel fisiológico diferente y la efectividad del ALC varía
según las proporciones de los isómeros.
Definiciones
te también en los mamíferos no rumiantes. El ácido vac-
cénico (18:1, 11t) producido por hidrogenación del ácido
linoleico en el rúmen puede ser desaturado en el carbo-
El ácido linoleico (ácido 9,12-octadecadienoico) Ácido linoleico conjugado (conjugated linoleic acid, CLA) son un grupo de
no 9 por desaturasas intestinales y/o hepáticas de los
(Figura 1) es un ácido graso de 18 átomos de carbono y moléculas grasas poliinsaturadas
rumiantes, transformándose en la forma 9c-11t de ALC.que químicamente son diasteroisomeros del
dos instauraciones, o dobles enlaces, situados en las posi-
Ello explicaríaácido
que seoctadecadienoico
encuentre ALC en algunos tejidos y
ciones 9 y 12 respectivamente. Las cadenas C1-C8 y
secreciones, como la leche.
C13-C18 están en posición cis respecto al sistema de
dobles enlaces. Es un ácido graso esencial omega-6 muy
Los isomeros
En los tejidos animales elcisALC y trans están ubicados
se encuentra en los principalmente en las posiciones 8 y 10,
abundante en el reino vegetal y en el animal. La mayoría 9 y 11,
fosfolípidos, como 10 y 12 y 11 yde
fosfatidiletanolamina 13.las membranas
de los aceites vegetales, con excepciones como los de celulares.
790 Cuando el aporte A. dietético de etácido
Bhattacharya linoleico
al. / Journal es
of Nutritional Biochemistry 17 (2006) 789 – 810
Ácidos grasos conjugados oliva, palma, o coco, aportan cantidades significativas de alto, en experiencias animales es posible encontrar ALC
ácido linoleico. También se encuentra en la grasa animal, en hígado, pulmones, y tejidos muscular y adiposo. En
junto con ácidos grasos saturados y monoinsaturados. humanos también se ha observado la presencia de ALC,
en la leche o en el plasma sanguíneo. En la leche humana,
ALC EN TEJIDOS ANIMALES los isómeros más frecuentes son el 9c-11t, y el 7t-9c. En
el suero sanguíneo humano el isómero 9c-11t llega a
Puesto que ALC se encuentra en los alimentos de los constituir hasta el 0,4-0,5% del total de los lípidos circu-
rumiantes, ello puede significar que estos animales son los lantes. Los niveles de ALC en los humanos son variables
que transformen el ácido linoleico en alguno de los isó- dependiendo de la cantidad y tipo de carne que se con-
meros del ALC. Dentro de la abundante y variada flora sume y de la alimentación de los animales.
microbiológica del rúmen, la bacteria identificada como
Butyrivibrio fibrisolvens, la que al realizar la hidrogenación APORTE DIETÉTICO DE ALC Fig. 1. Structures of parent LA, c9t11 and t10c12 CLA.
del ácido linoleico para transformarlo en un ácido graso
monoinsaturado genera como intermediario del proceso Tras lo mencionado, es posible deducir que la mejor fuen-
c9t11 and t10c12 isomers. With the advent of technology, (47% c9t11+47.9% t10c12) decreased weight gain and fat
te dietética de ALC es el consumo de carnes y produc-
los diferentes isómeros del ALC. Por su origen, al ALC se enriched or purified c9t11 and t10c12 CLA preparations mass, whereas dietary intake of CLA containing 91% c9t11
tos
havelácteos
become procedentes
commerciallyde rumiantes
available (Tablas
in 17
recent1, 2, 3). Con
*Figura from Journal of nutritional biochemistry (2006)years,
789-810 had no effect on these parameters, proving that t10c12 is the
45 laleading
incorporación de una mejor
to studies examining tecnología
the effects para
of these el análisis
individual isomer responsible for loss of fat mass [20]. In vitro studies 46
eisomers
identificación de los ácidos
in health-related grasos
disorders. componentes
Most de gra-
of the studies have using purified c9t11 and t10c12 isomers and cultured 3T3-
sas,
useddeCLA aceites o de
isomer muestras
mix, de evidence
but recent tejidos, essuggests
posiblethatiden- L1 adipocytes provided further supportive evidence that
Ácido linoleico Ácido linoleico conjugado
(9 cis-12 cis) (9 cis-11 trans) tificar
c9t11 que and en todamay
t10c12 muestra
have de aceiteeffects
myriad o de grasa, particu-
in different t10c12 was the isomer responsible for the fat-lowering
larmente
biological en aquellas
systems. de origen
Indeed, animal,
it has been foundpuede estarthepre-
that both effects of CLA [6,41].
isomers
sente unaexhibit significant
pequeña biological
cantidad de ALC.activities, whichgraso
Este ácido often se Here we summarize recent information on the impact of
CLA
may be similar or opposite. This review focuses on the CLA or its isomers on body composition. Navarro et al.
CLA
presenta con diferentes isomerías, aunque siempre pre-
biological role of CLA and its purified isomers (c9t11 and studied the effect of 6 weeks of supplementation of 0.5%
domina
t10c12) la in estructura 9c-11t.ofSihealth-related
different models bien el ALCdisorders
se encuentrain LA, c9t11 CLA or t10c12 CLA in atherogenic diet-fed Ácido linoleico conjugado: ácido graso con isomería t
cell culture, animals and clinical studies. Unless otherwise hamsters. Although there was no difference in body weight,
Definiciones Contenido
mentioned in thisen alimentos
review, CLA refers to a mixture
containing equal levels of c9t11 and t10c12 isomers.
fat mass decreased significantly in t10c12-fed hamsters [42].
In a related study, intake of diet containing 0.5% t10c12
Tabla I. Contenido en ALC de alimentos. CLA
Tablafor
II. 6 weeks decreased
Contenido en ALC defatalimentos.
mass in atherogenic diet-fed Tabla IV. Algunos de los efectos saludables
hamsters [43], but failed to prevent insulin resistance (IR)
Isomería
2. Conjugated LA and body composition associated with intake of atherogenic diet. Wargent et al.
CLA tienen como fuente natural los alimento provenientes de rumiantes como carnes y
Isomería
cis Productos lácteos mg/g de grasa Carnes/Pescados mg/g grasa Proporciona efectos anticarcinogenético
Isomería [44] recently showed that intake of t10c12 CLA isomer for
leche cis trans
2.1. Animal studies
Leche homogeneizada 5,5 3 weeks in genetically
Carne picada de buey obese mice decreased gain in4,3 body Estimula la función inmunitaria
Park2%
et al. [5] showed for the first time that intake Disminuye la inflamación
Leche 4,1 of weight
Ternera and white fat pad weight. In a study using wild-type 2,7
CLA es producido en bacteria presentes en el rumen que (bio)hidrogenan al ácido 0.5%
Nata CLA in ICR male and female mice (50% c9t11 6,1 and and stearoyl-CoA desturase 1 (SCD1) null mice, t10c12 Disminuye los efectos catabólicos de la e
Cordero 5,8
50%
Lechet10c12) results in decreased body fat mass 7,0 and CLA decreased fat mass and enhanced mRNA expression of Disminuye el asma en modelos animale
linoleico condensada
increased lean body mass. The mechanisms proposed Cerdo 0,6
Mantequilla 5,4were lipogenic enzymes, fatty acid synthase (FAS) and uncou-
Polloprotein 2 (UCP-2), suggesting that antiobesity effects 0,9
Disminuye la aterosclerosis
increased lipolysis, increased fatty acid oxidation or reduced pling Estimula el crecimiento de roedores jóv
Nata ácida 4,6
CLA fue descubierto por accidente por el Dr. Pariza en 1985* cuando investigaba fatty acid uptake in adipocytes. Subsequent studies in
Helados 3,6
of Carne
t10c12picadaCLA isdeindependent
pavo of SCD1 gene expression 2,6and
Disminuye la ganancia de grasa corpora
compuestos carcinogénicos presentes en carne asada y contrariamente encontraron different animal models corroborated the findings and Salmónactivity [45].
enzyme 0,3
Yogurt pobre en grasa 4,4 Aumenta la ganancia de masa magra co
Átomo de carbono showed that CLA containing equal proportions of both iso- Somederecent
Yema huevostudies have evaluated the impact 0,6 of the
ácidos grasos anti-carcinogénicos Átomo de hidrógeno Yogurt en natilla 4,8
mers decrease fat mass and enhance lean mass [21,29 – 34]. type of dietary fat on the antiadiposity effects of CLA. A Disminuye los efectos negativos de diet
Átomo de oxígeno Yogurtstudies
These entero and others have been discussed in reviews
4,8 recent study showed that CLA isomer mixture (1.5%, Disminuye los síntomas de diabetes en
Yogurt congelado
published elsewhere [35 – 39]. 2,8 4 weeks) had no effect on adiposity in Sprague– Dawley Disminuye la hipertensión
Figura 1. Estructura química del ácido linoleico (9 cis-12 cis) y de uno Queso Cheddar medium 4,1 in
The availability of purified isomers or CLA enriched Tablarats
(SD) III. when
Contenido
givenenalongside
ALC de alimentos.
diets rich in either saturated
de los isómeros del ácido linoleico conjugado (9 cis-11 trans). Queso
either Americano
c9t11 procesado
or t10c12 isomers prompted new in vivo5,0 and in fat (coconut oil) or unsaturated fat [corn oil (CO)] [46].
vitro studies, which identified t10c12 isomer to be primarily Aceitesrecent
Another vegetales
study examined the effects of 14 mg/g
daysgrasa
of con antioxidantes sintéticos como
involved in reduction of fat mass, and not the c9t11 isomer. CLA mixture intake on body fat in mice previously treated (BHT), y en numerosas revisiones s
When hamsters were fed with a hypercholesterolemic diet Aceite
with diets cártamo
containing soy oil as control, coconut 0,7 oil
56 Antonio Sarría Chueca dad antioxidante comparable a la de
containing 1% CLA, 0.2% c9t11 CLA or 1% LA, CLA Aceite girasol
[essential fatty acid-deficient (EFAD)] and fish oil 0,4 for
isomer mix-fed animals had the lowest weight gain [40]. 42 days [47]. Conjugated LA significantly decreased body téticos convencionales. Sin embargo
Yet, another study showed that intake of t10c12 isomer- weight and epididymal fat mass, but not retroperitoneal fat los efectos antioxidantes del ALC,
enriched diet decreases body fat significantly compared to mass in both control
en pequeñas and EFADendiet-fed
proporciones aceitesmice. The study
vegetales, su con- mente, se le atribuyen efectos pro-o
diet enriched in c9t11 isomer [6]. In a study in Zucker suggested that CLA seems to be more effective in lowering
centración es particularmente alta en la carne y en la
* Carcinogenesis 1985;6:591-593
47
diabetic fatty (ZDF) rats, dietary intake of 1.5% of CLA
*PhD these of Dr. Silke Gnädig
48
fat mass when diet was deficient in essential fatty acids
leche de los rumiantes, donde puede alcanzar hasta un
b) Efectos hipocolesterolémico
0,65% de los lípidos totales. En modelos experimentales de h
ALC ha demostrado producir dism
En una dieta mixta promedio occidental se estima
plasmáticos de colesterol, con respu
que el consumo de ALC puede ser hasta 1,5 g/día, aun-
las que se obtienen con los ácidos
que es muy variable y depende de los hábitos de cada
hámsteres alimentados con dietas
país y también del porcentaje de ALC aportado por las
ALC, con un aporte además de 1,1
carnes de animales rumiantes. Por ejemplo, Australia pre-
se produce una disminución progre
senta los valores más altos (1,5-1,8 g/día), en tanto que
ingesta de ALC, del colesterol-LDL
Alemania muestra los más bajos (0,5 g/día). En Estados
CLA
Ácido linoleico conjugado: ácido graso con isomería trans potencialmente beneficioso
Efectos beneficiosos
en ALC de alimentos. Tabla IV. Algunos de los efectos saludables del ALC.
Ajo Chilote
Disminuye el asma en modelos animales
0,6
Disminuye la aterosclerosis
0,9
Estimula el crecimiento de roedores jóvenes
pavo 2,6
Disminuye la ganancia de grasa corporal
0,3
Aumenta la ganancia de masa magra corporal
0,6
Disminuye los efectos negativos de dietas para perder peso
Disminuye los síntomas de diabetes en algunos modelos
Disminuye la hipertensión
en ALC de alimentos.
Isoaliina
Metiina
Discusión:
Mercado
58
57
59 60
Alimentos funcionales
Ejemplos Chilenos
61 62
LEAFA-UDEC
Muchas gracias! Universidad de Concepción
Facultad de Farmacia
Contacto: Texto
maranda@udec.cl or maranda@gmx.net
!63