Vitamin E and Protection Against Coronary Disease
By Matthew Sorrentino, MD, FACC
Coronary artery disease is the No. 1 killer of men and women in the United States. Many patients are aware of the link between cholesterol levels—particularly low density lipoprotenin (LDL) cholesterol in the blood as a predictor of heart disease. This awareness creates an opportunity for patients to look at their diet and its effect on reducing accumulation fo LDL-cholesteroal on artery walls. Vitamin E is one of the antioxidants that have been shown to have a postive effect for many patients in preventing atherosclerosis and subsequent complications such as myocardial infarction and storkes. Here is the latest information on strategies such as dietary manipulation and medical treatment using Vitamin E.The oxidation of low-density lipoprotein (LDL) is thought to be an important step in the development of atherosclerotic lesions. Vitamin E is a fat-soluble antioxidant that may inhibit the progression of coronary artery disease by preventing this oxidation process. Antioxidant vitamins have become increasingly popular, and it is estimated that approximately 20% of the U.S. population currently takes vitamin E supplements.
Mechanism of Action
Vitamin E is a fat-soluble vitamin found in vegetable oils. The vitamin is absorbed through the gastrointestinal tract, and 90% of the vitamin is found in LDL particles. In vitro, the vitamin has been shown to inhibit the proliferation of smooth muscle cells and reduce the oxidation of LDL particles. It is not known if inhibition of oxidation of LDL particles also occurs in the subendothelial layer of coronary arteries.
Clinical Studies
A few observational epidemiological studies have suggested that vitamin E supplementation may help prevent the progression of coronary artery disease. Vitamin E intake and the risk of coronary disease events was evaluated in the Nurses’ Health Study.1 Vitamin E supplementation was assessed by questionnaire in a cohort of more than 80,000 nurses. The subgroup of nurses taking the largest amount of vitamin E (median 208 IU/day) had a significantly lower risk of major coronary disease events compared with those taking the lowest amount (median 2.8 IU/day). The Health Professionals Follow-up Study reported similar findings for men in the highest quintile of vitamin E intake (median 419 IU/day).2
Not all studies, however, have linked vitamin E supplementation to lowering coronary risk. The Iowa Women’s Health Study demonstrated that the intake of vitamin E from food lowered coronary risk, but the same effect was not seen in women who took vitamin E supplements.3 Observational studies have been criticized, however, because of possible bias in patient selection.
Two prospective trials using vitamin E supplementation have been reported. In the Finnish alpha-tocopherol, Beta Carotene Cancer Prevention Study supplementation of 50 mg/day of vitamin E showed no effect on mortality from coronary disease.4 The Finnish study, however, may have used too small a dose since at least one study suggests that greater than 100 mg/day of vitamin E is required to prevent the progression of atherosclerotic lesions.5 The prospective secondary prevention trial CHAOS (Cambridge Heart Anti-Oxidant Study) demonstrated that treatment of coronary heart disease with higher doses of vitamin E reduced non-fatal myocardial infarction by 77%.6 The dose of vitamin E was either 400 or 800 IU. All subjects in the CHAOS trial had documented coronary artery disease. No large scale prospective randomized trials using vitamin E supplementation for primary prevention (in subjects without known heart disease) have been completed, although studies such as the Women’s Health Initiative may help clarify the role of vitamin supplementation.
Adverse effects
Adverse effects of vitamin E supplementation are rare at the most commonly suggested doses of 100 to 800 IU per day. Rare cases of hepatic toxicity and necrotizing enterocolitis have been reported in neonates with intravenous preparations of vitamin E but has not been seen in adults using oral supplements.7 Vitamin E may interfere with vitamin K dependent carboxylase leading to coagulopathy or bleeding. Because of this potential interaction, vitamin E is not recommended in patients treated with warfarin anticoagulation. There are no other known drug interactions.
Dosage
Vitamin E is readily available at pharmacies as an over the counter vitamin supplement in dosage forms of 100, 200, 400, 800 and 1,000 IU. Vitamin E is also a component of many multivitamin preparations but usually in doses of 30 IU or less. Studies suggest that at least 100 IU/day is required to give a cardiovascular benefit. Prices range from $3 to $7 per 100 vitamins depending on the dose selected.
Conclusion
Epidiemiologic data suggests that a diet high in vitamin E or vitamin E supplementation may help prevent the progression of coronary artery disease and prevent complications of the disease. Vitamin E may prevent oxidation of LDL cholesterol which is a crucial component of the atherosclerosis process. Well-designed prospective trials are underway to evaluate the effect of vitamin E supplementation in patients at risk for coronary disease. At doses between 100 and 1000 IU there is no significant toxicity. Based on the available literature, a dose of 100 IU or greater is recommended to decrease the risk of coronary disease. A similar benefit may also be achieved from a diet high in vegetable sources of the vitamin.
References
1. Stampfer MJ, et al. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med 993; 328:1444-1449.
2. Rimm EB, et al. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 993;328:1450-1456,.
3. Kushi LH, et al. Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. N Engl J Med 996;334:1156-115X. (NEED NUMBER)
4. The Alpha-Tocoperol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 994;330:1029-1035.
5. Hodis HN, et al. Serial coronary angiographic evidence that antioxidant vitamin intake reduces progression of coronary artery atherosclerosis. JAMA 995;273:1849-1854.
6. Stephens NG, et al. Randomized controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 996;374:781-786.
7. Meyers DG, Maloley PA, Weeks D. Safety of antioxidant vitamins. Arch Intern Med 996; 156:925-935.
Dr. Sorrentino is Associate Professor of Medicine, University of Chicago, Pritzker School of Medicine
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