High
Intakes of Alpha Linolenic Acid (ALA) Reduce Risk of Cardiovascular
Diseases
Populations with high intakes of alpha-linolenic acid (ALA)*
have a low risk of cardiovascular diseases such as coronary
heart disease (CHD) and stroke. ALA is an essential omega-3
fatty acid found mainly in plants-flaxseed, for example, is
the richest source of ALA in the North American diet.1 ALA
is the precursor of the long-chain omega-3 fatty acids eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA).
It has been known since
the 1970s that native fishing populations in Greenland, Japan
and Alaska have low rates of CHD, despite eating a high-fat diet.
Their low CHD risk is associated with their high intake of EPA
and DHA from marine fish and mammals.2, 3 (Fish contain
only trace amounts of ALA.4)
These long-chain omega-3
fatty acids have been shown to reduce blood triglycerides, increase
blood HDL-cholesterol, reduce blood pressure, reduce platelet
reactivity and reduce neutrophil activity-all actions that help
lower CHD risk.5, 6 ALA also offers protective effects
against both CHD and stroke, and its effects appear to be distinct
from those of EPA and DHA.
What Are the Effects of ALA
on Blood Lipids and CHD Risk?
ALA, like other dietary
polyunsaturated fatty acids, influences physiological processes
and disease risk. Results of relevant clinical and epidemiologic
studies are described below.
Results of Clinical Studies
In clinical trials,
ALA exerts positive effects on blood lipids. One study found
that dietary ALA was as effective as oleic acid (18:1n-9) and
linoleic acid (18:2n-6) in lowering plasma total cholesterol,
LDL-cholesterol and VLDL-cholesterol in eight healthy men aged
20-34 years.7
Another study of 10 young,
healthy men and women found that plasma total cholesterol was
reduced 6% and LDL-cholesterol was reduced 9% following the consumption
of flaxseed muffins providing 50 g flaxseed/d for four weeks.
Plasma HDL-cholesterol and triglycerides did not change during
the flaxseed supplementation period.8 In 15 hyperlipidemic
men and women who had just completed a study of the effect of
vitamin E supplementation on serum lipids and lipid oxidation
products, the addition of 15 g milled flaxseed to their daily
diet produced significant reductions in blood total cholesterol
(-7%) and LDL-cholesterol (-11%)
without changing HDL-cholesterol levels. Blood triglycerides
decreased slightly but not significantly during the intervention.9
The effect of flaxseed
on blood lipids was confounded in the latter two studies by
the fibre content of flaxseed. Flaxseed mucilage gum, like
other soluble dietary fibres,10 affects serum cholesterol
levels, as demonstrated in a study of the effects of partially
defatted flaxseed on serum lipids. Partially defatted flaxseed
was chosen because it is high in mucilage gums, but it has
a lower ALA content than full-fat flaxseed. Twenty-nine hyperlipidemic
adults ate muffins containing either partially defatted flaxseed
(about 50 g/d) or wheat bran (control) for three weeks in a
randomized, crossover design. Partially defatted flaxseed reduced
total cholesterol, LDL-cholesterol, apolipoprotein B and apolipoprotein
A-1 but did not affect serum lipoprotein ratios.11
Overall, the findings
from clinical studies suggest that modest reductions in total
cholesterol and LDL-cholesterol levels can be achieved, without
a change in HDL-cholesterol levels, by adding flaxseed to the
diet. Substituting ALA for saturated fats in the diet enhances
its beneficial effect.12
Results of Epidemiologic
Studies
The results of epidemiologic
studies suggest that ALA has particular effects related to
CHD risk. Researchers with the Lyon Diet Heart Study hypothesized
that ALA may have unique antiarrhythmic and antithrombotic
properties that significantly reduce fatal CHD events. All
participants in this study had previously survived a myocardial
infarction. Those who consumed a Mediterranean-type diet rich
in ALA experienced a reduction in myocardial infarction (MI)
and cardiac deaths of nearly 70%, without a reduction in blood
cholesterol and triglycerides, compared with a control group
who consumed their usual Western-type diets.13 In
an extended follow-up to this study, the protective effect
of the Mediterranean diet was maintained. As in the original
analysis, ALA-but not EPA and DHA-was significantly associated
with protection against recurrence of MI.14
Data from the Health Professionals
Follow-up Study, which began in 1986 with a cohort of 51,529
health professionals aged 40 to 79 years, found a specific preventive
effect of ALA. An age-adjusted analysis of dietary fat intake
and risk of MI among 43,757 men who participated in the 1992
survey, found that ALA as a proportion of total energy was inversely
associated with risk of MI and fatal coronary disease. The effect
of ALA was independent of other dietary and non-dietary
risk factors. Intake of marine omega-3 fatty acids (EPA and DHA)
was not associated with MI risk in this study, suggesting that the
cardiovascular effects of ALA are different from those of EPA and
DHA.15
In the Multiple Risk
Factor Intervention Trial (MRFIT), ALA intake as a percentage
of total energy was inversely associated with mortality from
CHD, cardiovascular diseases and all causes among subjects
assigned to the usual care intervention. MRFIT was a primary
prevention trial among 12,866 men aged 35-57 years who had
a high risk of developing CHD due to their smoking, blood pressure
and blood cholesterol status.16
An analysis of data from
the Nurses' Health Study likewise showed that female nurses (n=76,283)
in the highest quintile of ALA intake had a lower relative risk
of fatal and nonfatal MI compared with those in lower quintiles.
The Nurses' Health Study began in 1976 with a cohort of 121,700
female, registered nurses aged 30-55 years.17 These
findings support the hypothesis that higher intakes of ALA protect
against fatal cardiac events.
What Are the Effects of ALA
on the Risk of Stroke?
ALA may reduce the
risk of stroke, according to data from the MRFIT trial. An
analysis of MRFIT subjects with fatal or nonfatal incident
strokes who been followed for 6.9 years found that the ALA
content of blood cholesterol esters and phospholipids was inversely
associated with stroke risk. Each standard deviation (SD) increase
in ALA was associated with a 30% reduction in stroke risk.18
How Does ALA Protect against
Cardiovascular Diseases?
ALA has two biologic effects
that may explain how it protects against stroke, arrhythmia,
myocardial infarction and other cardiovascular events. These
effects include the following:
ALA Modifies Membrane
Phospholipids: The ALA content of blood phospholipids,
triglycerides and/or cholesteryl esters can be increased 2-8
fold by supplementing the diet with flaxseed or flaxseed oil
and spread for four weeks.19-21 Increasing the omega-fatty
acid content of membrane phospholipids increases membrane fluidity
and alters membrane function, changes that may reduce cardiovascular
disease risk by influencing calcium ion exchange across the
cell membrane.2
ALA
Interferes with Eicosanoid Production: ALA competes with linoleic acid and the
delta-6-desaturase enzyme
that converts linoleic acid to arachidonic acid (20:4n-6).
Arachidonic acid is the precursor of eicosanoids (i.e.,
prostaglandins, thromboxanes and leukotrienes), many
of which promote platelet aggregation,
vasoconstriction and other thrombotic activities.22 Interventions
that reduce the formation of these eicosanoids may
help protect against cardiovascular diseases. Caughey
and co-workers23 reported, for example,
that the synthesis of thromboxane B2 (a
metabolite of thrombozane A2) and prostaglandin
E2 was significantly decreased by ~30% in healthy men who consumed a flaxseed oil
diet for four weeks.
The study of ALA's
protective effect against cardiovascular disease is
in its infancy. Future research will clarify its biological
effects and its benefits in reducing the morbidity
and mortality associated with cardiovascular diseases.
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References
|
|
1. Connor
WE. Am J Clin Nutr. 1999;69:827-828.
|
|
2. Bang
HO and Dyerberg J. Acta Med
Scand. 1972;192:85-94.
|
|
3. Keys
A. Circulation. 1970;41(Suppl
I):I-62-I-79.
|
|
4. Nettleton
JA. J Am Diet Assoc. 1991;91:331-337.
|
|
5. Rotondo
D. Biochem Soc Trans. 1995;23:291-296.
|
|
6. Harris
WS. Am J Clin Nutr. 1997;65(Suppl):1645S-1654S.
|
|
7. Chan
JK, et al. Am J Clin Nutr. 1991;53:1230-1234.
|
|
8. Cunnane
SC, et al. Am J Clin Nutr. 1994;61:62-68.
|
|
9. Bierenbaum
ML, et al. J Am Coll Nutr. 1993;12:501-504.
|
|
10.
Spiller RC. Pharmacol Therap. 1994;62:407-427.
|
|
11.
Jenkins DJA, et al. Am J Clin
Nutr. 1999;69:395-402.
|
|
12.
Nelson GJ and Chamberlain JG. In: Flaxseed in Human
|
Nutrition. Cunnane
SC and Thompson LU, eds. Champaign,
|
|
IL: AOCS Press,
1995, pp. 187-206.
|
|
13.
de Lorgeril M, et al. Lancet. 1994;343:1454-1459.
|
|
14.
de Lorgeril M, et al. Circulation. 1999;99:779-785.
|
|
15.
Ascherio A, et al. Br Med
J. 1996;313:84-90.
|
|
16.
Dolecek TA. Proc Soc Exp Biol
Med. 1992;200:177-182.
|
|
17.
Hu FB, et al. Am J Clin Nutr. 1999;69:890-897.
|
|
18.
Simon JA, et al. Stroke. 1995;26:778-782.
|
|
19.
Cunnane SC, et al. Br J Nutr. 1993;69:443-453.
|
|
20.
Mantzioris E, et al. Am J
Clin Nutr. 1994;59:1304-1309.
|
|
21.
Li D, et al. Am J Clin Nutr. 1999;69:872-882.
|
|
22.
Nair SSD, et al. J Nutr. 1997;127:383-393.
|
|
23.
Caughey GE, et al. Am J Clin
Nutr. 1996;63:116-122.
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* The chemical
formula for ALA is 18:3n-3, which denotes the number
of carbon atoms (18), the number of double-bonds
(3), and the family of the fatty acid (n-3). The
family name specifies the position of the first double
bond as the number of carbon atoms from the methyl
end of the fatty acid chain.
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Flax Council of
Canada, 4654-167 Lombard Ave., Winnipeg, MB, Canada R3B
0T6, email: flax@flaxcouncil.ca
Web site: http://www.flaxcouncil.ca/
