ANTIOXIDANT
VITAMINS AND CARDIOVASCULAR DISEASE
Published in Journal of Saudi Heart
Association
Hassan Chamsi Pasha,
FRCP, FACC
Department of Cardiology
King Fahd Armed Forces Hospital
Jeddah, Saudi Arabia
Over The past several years,
there has been an increasing interest in the role of free radical scavengers,
particularly antioxidant vitamins in cardiovascular disease prevention. Free
radicals are common by products of many oxidative biochemical reactions in the
body. They can damage or destroy biological molecules and have the potential
for causing serious tissue and organ damage. They have been implicated in aging
and chronic disease processes, including atherosclerotic coronary heart
disease. Substantial laboratory, animal, and human data suggest that oxidation
of low density lipoprotein (LDL) cholesterol is an important step in the
pathogenesis of atherosclerotic lesions1.
Antioxidants vitamins
presumably exert their effects through the protection of oxidation. However,
some studies have shown that these vitamins may also preserve endothelial
function 2, affect hemostasis3, and lower LDL cholesterol
level4.
The predominant
antioxidants protecting the LDL molecule are a tocopherol, retinyl stearate,
gamma tocopherol , and beta carotene. Being lipid soluble, these agents are
incorporated into the LDL molecule. a Tocopherol, the most active isomer of the
vitamin E family, is the principal lipid soluble antioxidant in tissues and
plasma57. Ascorbic acid, on the other hand, is the first line of
defense against oxygen free radicals in the water soluble compartment 6,7.
Vitamin E supplementation
was found to reduce the risk of coronary heart disease in a study in which
39,910 male health professionals with no history of cardiovascular disease were
followed for 4 years9, About 17% of the men took vitamin E
supplements. The adjusted relative risk reduction (RRR) of coronary heart
disease in men taking at least 100 IU of vitamin E supplements for at least 2
years compared with the men not taking vitamin E supplements was 44% (CI, 19%
to 56%).
In a study of 34,486
postmenopausal women10 with no cardiovascular disease followed up
for 7 years, the intake of vitamin E from food was inversely associated with
the risk of death from coronary heart disease and that such women can lower
their risk without using vitamin supplements. By contrast, the intake of
vitamins A and C was not associated with lower risks of dying from coronary
disease11.
Vitamin C clearly reduced
risk in only one large cohort study (in which vitamin E intake was not
ascertained) and in none of the small cohort studies. In a prospective study of
11,348 American adults, researchers found a 34% lower standardized mortality
ratc (CI, 18% to 47%) among participants who received 50 mg of vitamin C/day or
more (by dietor supplements) compared with persons who received less vitamin C12.
In another cohort study, Galc and colleagues13 examined the 20year
survival of 730 elderly persons who had no initial history of vascular disease.
The incidence of stroke in subjects in the highest tertile of vitamin C intake
(mean,> 45 mg/day) was significantly reduced (RRR of 50%). However, no such
reduction was seen in mortality from coronary heart disease.
Experimental data suggest
that vitamin C lowers blood pressure by a small amount, that 2 g daily lowers
serum cholesterol concentration and prevents oxidation of LDL and that a
similar dose may increase fibrinolytic activity in those with coronary heart
disease14,15. However, evidence is required to show more benefit
than harm from treatment16.
Reliable estimates of
efficacy of antioxidant vitamins can only be obtained from large scale
randomized trials. None of the completed randomized trials showed any clear
reduction in cardiovascular disease with vitamin E, vitamin C, or beta carotenc
supplementation. The trials were not specifically designed to address
cardiovascular disease, did not provide data on nonfatal cardiovascular end
points, may have had insufficient treatment duration, and used suboptimal
vitamin E doses12.
More recently, however,
the Cambridge Heart Antioxidant Study (CHAOS) looked at the effects of vitamin
E in the secondary prevention of coronary heart disease17, 2002
patients with angiographically confirmed coronary artery disease were randomly
assigned to take vitamin E or placebo. Half the patients who had vitamin E were
randomized to receive 800 IU daily for 2 years while the other half had 400 IU
for 1 year. The primary end points were a combination of cardiovascular death
plus nonfatal myocardial infarction. Vitamin E reduced these two end points
significantly by 36%;and 66% respectively. There is still much uncertainty
about the dose of vitamin E in primary and secondary coronary heart disease
prevention. The follow-up of patients receiving 800 IU daily dose was twice as
long, yet the number of nonfatal myocardial infarction in the 400 IU daily
group seems to have been reduced more18.
The Alpha Tocopherol,
Beta Carotene and Cancer Prevention Study (ATBC) of 29,133 middle aged heavy
smokers in Finland were followed for 6.1 years20. The participants
were treated with vitamin E (50 mg/day), beta carotene (20 mg/day), both, or
neither. There was no reduction in the incidence of lung cancer nor was there
any significant reduction in the incidence of coronary heart disease. The dose
of vitamin E was probably too low but the dose of beta carotene was adequate.
The participants were heavy smokers and therefore at high risk of both lung
cancer and coronary heart disease. It is conceivable that this was a group of
men with advanced atherosclerosis. A legitimate question is whether their
disease was so far advanced which limits the validity of the trial19.
Recently, the data of two
large placebo controlled studies have been published. In the Physicians Health
Study, 22,071 American male doctors treated with 50 mg of beta carotene or
placebo every other day were followed for an average of 12years20.
There were virtually no early or late differences in the overall incidence of
malignant neoplasm or cardiovascular disease, deaths from cardiovascular
disease, or in the overall mortality.
The Beta Carotene and
Retinol Efficacy Trial (CARET) studied 18,314 persons at high risk for lung
cancer because of exposure to asbestos or cigarette smoking. They were treated
daily with a combination of 30mg of beta carotenc and 25,000 IU of retinol
(vitamin A) or with placebo for an average of 4 years20. The trial
was stopped 21 months earlier than planned when researchers recognized an
elevated risk of death from lung cancer in the group receiving the supplements.
The study showed that the
combination of beta carotene and vitamin A had no benefits and may have had an
adverse effect on the incidence of lung cancer and on the risk of death from
lung cancer, cardiovascular disease, and any cause in smokers and workers
exposed to asbestos20.
The results of these last
two trials send a clear message to the public , the tens of millions of dollars
spent annually on beta carotene supplements should now be diverted to more useful
purposes21.
Randomized trials of
sufficient power to establish the effectiveness of higher dose antioxidant
supplementation in preventing coronary heart disease are currently unerway.
In all trials of vitamin
E, doses greater than 3IU/day are being used; such doses should be sufficient
to increase serum levels at least two to threefold. A future metaanalysis or a
systematic overview of the cumulative numbers from these trials should, by the
end of the decade, provide clear answers about the efficacy and safety of the
various antioxidant vitamins12.
The combined evidence
currently does not support the routuse of antioxidavitamins apreventive measure
against cardiovascular disease.
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