Professional Documents
Culture Documents
long-chain
for
polyunsaturated cardiovascular
fatty acids disease
and
health benefits
Translated from «Oméga-3 et bénéfice santé», published by the Centre d'Etude et d'Information
sur les Vitamines, Roche Vitamines France, Neuilly-sur-Seine.
I. Introduction
3
II. Omega-3 and omega-6
polyunsaturated fatty acids
1. Definition
PUFAs are natural constituents of animal and vegetable fats. They
are made up of a carbon chain with a methyl group at one terminal
and an acid group at the other. These fatty acids are said to be
polyunsaturated because they contain several double bonds.
■
H3C
Omega-3 LC PUFAs
Eicosapentaenoic acid (EPA)
Docosahexaenoic acid (DHA) COOH
Stearic acid (saturated)
H3C 3 5
1
2 4 6 COOH
Linoleic acid (n-6 PUFA)
H3C 1 3
COOH
-linolenic acid (ALA, n-3 PUFA)
H3C 1 3
COOH
eicosapentaenoic acid (EPA, n-3 PUFA)
2
COOH
H3C 1 3
-linolenic Linoleic
acid acid
(ALA, C18:3) (C18:2)
Prostaglandins -linolenic
■ acid
The enzyme reactions C18:4 (GLA, C18:3)
responsible for LC fatty acid Thromboxanes
acid
(EPA, C20:5)
Arachidonic
Prostaglandins acid
(AA, C20:4)
C22:5 Thromboxanes
C22:4
Docosahexaenoic
acid
C22:5
(DHA, C22:6)
Figure 2: PUFA metabolism
5
Two PUFAs, linoleic acid (omega-6 PUFA) and a-linolenic acid
(omega-3 PUFA), are termed essential in that they cannot be
synthesized by the body (whether animal nor human) and have to
be supplied by the diet.
The body stores these fatty acids, uses them as an energy
source, or transforms them, using elongase and desaturase
enzymes common to both PUFA families, into elongated
PUFAs with additional points of desaturation.
However, these reactions are slow and limited, and may fail to
satisfy the body’s LC PUFA requirements.
The diet needs to supply appropriate amounts not only of
essential fatty acids but also of their LC derivatives.
2. Sources
Omega-6 PUFAs are found mainly in vegetable products. Linoleic
acid is found in soybean, corn, nut, sunflower and olive oils, -lino-
lenic acid (GLA) in borage, evening primrose and blackcurrant seeds,
and omega-6 LC PUFAs such as arachidonic acid mainly in animal
products.
Omega-3 PUFAs are found in vegetable products (rapeseed, soybean
and nut oils) and animal sources (mainly fish and fish oils). The
richest sources of Omega-3 LC PUFAs are fish, particularly oily fish
(mackerel, herring and salmon) while smaller amounts are found in
meat (Table 1).
■ Source (EPA + DHA) g/100 g
Omega-3 LC PUFAs are
found mainly in oily fish. Mackerel 2.5
Salmon 1.8
Herring 1.6
Tuna 1.6
Beef 0.25
Table 1: Lamb (leg) 0.5
Omega-3 LC PUFA content of common
animal products1 Pork 0.7
6
3. Role and metabolism of polyunsaturated fatty acids
7
III. Omega-3 polyunsaturated fatty acids
and cardiovascular diseases
1. Epidemiology
Omega-3 PUFA research was originally inspired by the very low
incidence of cardiovascular diseases among the Greenland Inuits
(10–30% lower than in Denmark) 2,3. The Inuit diet is based on oily
fish and marine mammals containing high omega-3 LC PUFA
concentrations. The average Inuit consumes 10 g of omega-3 PUFA
for every 3000 kcal, therefore having high plasma levels of DHA
and EPA and low levels of arachidonic acid. This results in a lower
platelet reactivity and a longer bleeding time. The same metabolic
profile has been observed in other populations with a high fish
consumption (e.g. Japan) 4,5.
■ ENDOTHELIAL
PLATELETS
Omega-3 LC PUFAs decrease CELLS
Arachidonic Arachidonic
EPA EPA
acid acid
Lipase
4. Clearance of the Remnants from the
Remnants
blood by liver receptors.
Formation of triglyceride rich VLDL
lipoproteins from remnants, alcohol, Brain
carbohydrates and proteins in the
liver.
Remnant receptor
HDL
5. Hydrolysis of VLDL into LDL.
Triglycerides are split off. 4
LIVER
LDL 6
Scavenger receptor
Peripheral cell
LDL receptor
Macrophage
of the arterial
wall
All nutritional factors that can help to control high plasma trigly-
ceride levels have therefore a potential role in cardiovascular disease
prevention.
15
Many studies have shown that omega-3 LC PUFAs lower high
plasma triglyceride levels63. They do so by lowering hepatic
triglyceride synthesis and by decreasing the release of trigly-
ceride-rich VLDL into the blood 64–69.
■ EPA and DHA act via transcription factors (small proteins that bind
Omega-3 LC PUFAs lower to the regulatory domains of a gene). Binding of an omega-3 LC
plasma triglyceride levels. PUFA to a transcription factor modifies the structure of the factor
and its ability to activate or inhibit the target gene (Figure 5). To
date, two transcription factors are known to interact with LC PUFAs:
peroxisome proliferator activated receptor (PPAR) and sterol regula-
tory element binding protein (SREBP)70,71. PPAR appears to be
involved in the activation of fatty acid oxidation65 and SREBP in the
inhibition of triglyceride synthesis pathways.
Blood circulation
cytosol
nucleus
inactivated SREBP
inactivated PPAR
activated
activated
PPAR
SREBP
transcription
or repression
✔ Effect on adrenoceptors
20
This as yet unexplained metabolic effect of omega-3 LC PUFAs
on energy production could be an important factor in myocar-
dial cytoprotection since it is based on the principle of
reducing the oxygen cost of cardiac contraction.
21
Such channel effects could influence arrhythmias but the mechanism
remains unelucidated. It may involve a direct effect on the channels
concerned or a general effect on membrane characteristics, fluidity
in particular.
■ 3. Conclusion
Omega-3 LC PUFAs
moderate cardiovascular Prevention of such a multifactorial entity as cardiovascular disease
risk factors such as means taking all the risk factors involved into account. A number of
elevated triglyceride drug treatments are currently available which slow the course or
levels, arrhythmias and reduce the incidence of cardiovascular diseases by acting on these
hypertension. risk factors (blood pressure, cholesterol, triglycerides etc). But as the
age of the population increases, the long-term efficacy of these
treatments is largely unknown and there is a high risk of side
effects.
22
Dietary correction of the omega-3/omega-6 ratio in healthy
subjects and omega-3 LC PUFA supplementation at nutritional
doses combined with tailored treatments in high-risk subjects
constitute solidly documented strategies in cardiovascular
disease prevention.
23
IV. Omega-3 long-chain polyunsaturated
fatty acids and inflammation
Inflammation, the body’s non specific response to trauma and
chemical or microbial aggression, is classically associated with rubor,
tumor, calor and dolor (redness, swelling, heat and pain). These
symptoms result from the release of mediators derived primarily
from leukocyte activation. They include two eicosanoid mediators,
prostaglandin E2 and leukotriene B4, whose precursor in both cases
is arachidonic acid.
Omega-6 Omega-3
inhibition
excitation Arachidonic acid Eicosapentaenoic acid
PROSTAGLANDIN E2 LEUKOTRIENE B4
Stimulus
n local
inflammation
n fever
n blood
coagulation
n septic shock
Macrophages or neutrophils T and B lymphocytes
Figure 6: Omega-3 PUFAs and the
inflammatory response (Calder103)
24
These mediators are produced via reactions involving cyclooxygenase
and 5-lipoxidase, respectively (Figure 2).
25
1. Omega-3 long-chain polyunsaturated fatty acids
and rheumatoid arthritis
■ Epidemiological evidence supports the hypothesis that consumption
Regular fish consumption of oily fish prevents the development of rheumatoid arthritis : preva-
correlates with a lower lence is decreased among Inuits eating large amounts of fish and
incidence of rheumatoid marine mammals with a high omega-3 LC PUFA content107; rheu-
arthritis. matoid arthritis also takes less severe forms in Faroe Islanders, who
have a high-fish diet108; lastly, a case-control study showed that the
consumption of baked or grilled fish is associated with a decreased
risk of rheumatoid arthritis109 (particularly rheumatoid factor-positive
disease, which is considered to have a poorer outcome)109.
3. Conclusion
28
V. Omega-3 long-chain polyunsaturated
fatty acids and cancers
The molecular and biological properties associated with the interac-
tions between omega-3 LC PUFAs and other nutrients (omega-6,
antioxidants), give a strong indication of the role of these fatty
acids in cancer prevention and cancer treatment130,131.
Noding et al. observed that the sensitivity of tumor cells to DHA and
its oxidation products, depends on their antioxidant status151.
The presence of vitamin E blunts antitumor activity and apoptosis
induction by omega-3 LC PUFAs152. Timmer-Bosscha et al. found
29
that DHA potentiated the toxicity of an anticancer agent (cis-
diamine-dichloroplatinum II) in malignant human embryonic cell
lines153.
30
VI. Omega-3 long-chain polyunsaturated
fatty acids and brain function
Nervous tissue has the second highest concentration of fatty acids
■ after adipose tissue. LC PUFA levels are particularly high in the retina
Omega-3 LC PUFAs are and cerebral cortex. DHA can account for up to 50% of phospho-
heavily involved in cerebral lipid fatty acids in these tissues, suggesting that it is heavily involved
and visual function. in neuronal and visual functions156 –158. Vision would in fact be
impossible without the presence of DHA.
32
2. Omega-3 long-chain polyunsaturated fatty acids
and brain development
■ Omega-3 LC PUFAs play a now well-documented role in the brain
Omega-3 LC PUFAs are development of the foetus and child. However, a consensus has yet
essential for neonatal brain to be reached on the recommended dietary allowance (RDA)186.
development. Premature infants require particular attention as they have no
reserve adipose tissue. These reserves are not generally built up until
the third trimester. Premature infants are therefore closely depen-
dent on dietary intake.
34
VII. Recommendations
Our current diet encourages an excessive intake of saturated fats
without meeting our dietary requirements for PUFAs, in particular
omega-3 PUFAs. Yet it is now accepted that a limited intake of
saturated fatty acids and compliance with a correct omega-3/
omega-6 PUFA ratio have documented health benefits, in particular
in cardiovascular prevention.
35
Source Omega-6/Omega-3 Omega-3 EPA + DHA
ratio recommendations
Nordic Nutrition Committee, None 0.5%* (1-2 g/day)
1989193
NATO Workshop, None 0.27%*
1989194 (0.8 g/day)
Scientific Review Committee, 5:1 - 6:1.5 0.5%* (1-2 g/day)
Canada,1990195
British Nutrition Task Force, 6:1 0.5%* (1.1 g/day)
1992196
Scientific Committee for Food, 4.5:1 - 6:1.5 0.5%* (1-2 g/day)
EU, 1993197
FAO/WHO Expert Committee, 5:1 - 10:1
1994198
Committee on Medical Aspects None 0.2%* 0.1-0.2 g/day
of Food Policy, 1991, 1994199,200
National Nutrition council None 0.5%* (1-2 g/day)
(Norway), 1996201
NIH Workshop, 1%* (2.22 g ALA) 0.3%* (0.65 g/day)
1999202
ANC 2000, 5:1 2-2.5 g/day 0.12 g/day (DHA)
France203
FDA, 2000204 1 g/day
AHA, 2000205 0.9 g/day
The Japanese Society of Nutrition 4 :1
and Food Science, RDA for the
Japanese, 6th revision 2000
*% calorie intake.
36
VIII. Conclusion
The great number of studies on omega-3 LC PUFAs reflect the
interest aroused by this fatty acid family in the scientific community.
The studies have shown the importance of omega-3 LC PUFAs in
the diet, even though these micronutrients are not considered
essential as they are synthesized in low amounts by the body. They
are critical to brain development and function. They are therefore
particularly important in pregnant and breastfeeding women and in
infants.
38
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