Vitamin E and Cardiovascular Disease: The Human Studies and Trials

Dr. James Meschino D.C., M.S., R.O.H.P.

The evidence that Vitamin E supplementation is an important means to prevent heart attack and other vascular problems continues to be reported in human studies.

In 1987 Geyet all published the results of a large cross-sectional survey in Europe. The researchers collected blood samples from healthy men who lived in areas with high heart disease mortality (Southwest Finland, North Karelia, and Scotland), medium mortality (Northern Ireland) and low mortality (Switzerland and Southern Italy). The average blood vitamin E levels were found to be significantly higher in regions with low heart disease mortality compared with vitamin E blood levels in regions with higher rates. In a subsequent, more detailed study of 16 European population samples in the Monica Study, Gey et al reported a remarkably strong relationship between, higher blood vitamin E levels and lower rates of heart disease mortality, even among the 12 populations with similar heart disease mortality rates.

In patients with angina, Riemersma et al, in a case-control study, found lower vitamin E levels in newly documented angina patients (105 patients) compared with normal subjects (382 control subjects). Individuals with the lowest 20% blood levels of vitamin E had a 2.7 times greater risk of developing angina.

Kok et al followed 10,532 people in a Dutch nested case-control study. After 9 years, 68 cardiovascular deaths were documented (mostly heart disease). In this study subjects with the lowest 20% of vitamin E blood levels had a 1.5 times greater risk of cardiovascular disease mortality.

A similar finding was reported by Street et al in the Washington County MD Study. Individuals with the lowest 20% blood levels of vitamin E had a 1.4 times greater risk of heart disease.

In a 14 year study of 5,133 Finnish men and women aged 30-69, Knekt found that individuals consuming the most vitamin E (top 1/3 intake level) had the lowest rates of heart disease.

In another Finnish study Salonen found that low vitamin E status (from diet) was associated with increased risk of heart attack only if vitamin C status was also low. Because vitamin C is required to regenerate vitamin E, this finding could explain the lack of protective effect of vitamin E reported in a few studies, which go against the body of evidence. Hence, future studies should consider both vitamin E and vitamin C status as vitamin C helps to maintain optimal function of vitamin E. With lower vitamin C status, vitamin E is used up faster and can not be recycled back to an effective antioxidant state to provide continual protection against heart disease.

In the largest study to date Stampfer et al reported results from the Nurses’ Health Study. In this prospective cohort study, dietary data were collected in 1980 from 87,245 US female nurses aged 34-59 years old, who were free from diagnosed cardiovascular disease and cancer at the beginning of the study. After 8 years of follow up the study showed that nurses who consumed vitamin E supplements (greater than/or equal to 100 I.U.) for at least 2 years had a 41% reduction in risk of heart disease compared with other nurses. As with other studies this finding held true even after factoring in other heart disease risk factors.

In this same study, the risk of ischemic stroke was also reduced 29% in nurses using vitamin E supplementation at or above 100 I.U. per day.

Very similar findings were seen in men in the Health Professionals Follow-up Study as reported by Rimm et al. This study followed 39,910 men aged 40-75 years old in 1986 who were free of prevalent cardiovascular disease, diabetes, or high cholesterol at the beginning of the study. Once again the men using vitamin E supplementation showed the greatest reduction in risk of heart disease (46% reduction in risk) compared with non supplement users. This fact remained unchanged after factoring in other known risk factors such as age, smoking, high blood pressure etc. The protective vitamin E supplementation dosage was found to be 100-350 I.U. per day in this study. As in the Nurses’ health Study vitamin E supplementation below 100 I.U. per day did not provide significant protection against heart disease. Hence, regular multiple vitamins, which contain vitamin E at does of 12 I.U. to 30 I.U. are an insufficient means of attaining protective vitamin E intake levels. An antioxidant-enriched multiple vitamin, or a separate vitamin E supplement are required to achieve 100 I.U. or more of vitamin E from supplementation sources.

In a most remarkable study, Hodis et al assessed the progression of coronary artery narrowing by using serial, quantitative coronary angiographic methods. He found that in 162 nonsmoking men aged 40-59 years old, men who took vitamin E supplements had a significant reduction in the narrowing of coronary arteries compared with non supplement users. The apparent benefit was once again limited to those taking greater than 100 I.U. of vitamins E per day. In this study subjects receiving cholesterol-lowering medication and who also took vitamin E supplements showed regression (reversal) in coronary artery narrowing. No other group demonstrated this finding. The ability to reverse heart disease by this form of combination therapy is indeed, a remarkable finding, which has important implications for society.

Other intervention trials using vitamin E supplementation have also been effective. In a study of patients with severe claudication from atherosclerosis (narrowed arteries) in peripheral vessels, the improvement in symptom-free walking distance in the vitamin E group (n=24) was twice as great as the results achieved in the placebo group (n=9).

DeMaio conducted a study in 100 patients who underwent coronary angioplasty. They were given either a placebo (n=48) or vitamin E at 1,200 I.U. (n=52) for 4 months after the procedure. Among those given the placebo, 50% had significant restenosis (narrowing), whereas only 35% of those in the vitamin E group had significant restenosis.

Similar findings were observed by DuBroff et al in 440 patients with coronary angioplasty. The restenosis rate was only 15% in the vitamin E users versus 31% in those taking no supplements and 32% in those taking vitamin C supplements.

An attractive feature of vitamin E is that it has little toxicity, making it a very safe supplement to take. The preceding human studies discussed in this review suggest that vitamin E supplementation (greater than 100 I.U. per day) may represent a simple and extremely effective way to significantly reduce the risk of the number one killer in our society (heart disease). The magnitude of this effect may be in the order of a 40% reduction in risk for heart attack and other cardiovascular problems related to atherosclerosis (narrowing of arteries).

Unless otherwise indicated my view is that healthy adults should consider ingesting 300 – 400 I.U. of natural vitamin E succinate each day as an important prevention strategy.

References:

Stampfer MJ and Rimm EB Epidemiologic evidence for vitamin E in prevention of cardiovascular disease. AM J ClinNutr 1995;62(suppl):1365S-9S.

Gey KF, Brubacher GB, Stahelin HB. Plasma levels of antioxidant vitamins in relation to ischemic heart disease and cancer. AM J ClinNutr 1987;45(suppl):1368-77.

Gey KF, Moser UK, Jordan P, Stahelin HB, Eichholzer M, Ludin E. Increased risk of cardiovascular disease at sub-optimal plasma concentrations of essential antioxidants: an epidemiological update with special attention to carotene and vitamin C. Am J ClinNutr 1993;57(suppl):787S-97S.

Riemersma RA, Wood DA, Macintyre CCA, Elton RA, Gey KF, Oliver MF. Risk of angina pectoris and plasma concentrations of vitamins A, C and E and carotene. Lancet 1991;337:1-5.

Kok FJ, de Bruijn AM, Vermeeren R, et al. Serum selenium, vitamin antioxidants, and cardiovascular mortality: a 9 y follow-up study in the Netherlands. AM J ClinNutr 1987;45:462-8.

Street DA, Comstock GW, Salkeld RM, Schuep W, Klag M. Serum antioxidants and myocardial infarction: are low levels of carotenoids and a-tocopherol risk factors for myocardial infarction? Circulation 1990;90:1154-61.

Knekt P, Reunanen A, Järvinen R Seppänen R, Heliövaara M Aromaa A. Antioxidant vitamin intake and coronary mortality in a longitudinal population study. AM J Epidemiol 1994;139:1180-9.

Salonen R, Nyyssönen K, Porkkala E, et al. Low vitamin E status is associated with increased risk of myocardial infarction only if vitamin C status is low: a population study in men in Eastern Finland. Circulation 1995;91:933(abstr).

Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, Willet WC. A prospective study of vitamin E consumption and risk of coronary disease in women. N Engl J Med 1993;328:1444-9.

Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC. Vitamin E consumption and risk of coronary heart disease among men. N Engl J Med 1993;328:1450-6.

Hodis HN, Mack WJ, LaBree L, et al. Serial angioghaphic evidence that antioxidant vitamin intake reduces progression of coronary artery atherosclerosis. JAMA 1995;273:1849-54.

Williams HTG, Fenna D, Macbeth RA. Alpha-tocopherol in the treatment of intermittent claudication. SurgGynecolObstet 19971;132:662-6.

Gillilan RE, Mondell B, Warbasse JR. Quantitative evaluation of vitamin E in the treatment of angina pectoris. AM Heart J 1977;93:444-9.

DeMaio SJ, King SB, Lembo NJ, et al. Vitamin E supplementation, plasma lipids and incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA). J Am CollNutr 1992;11:68-73.

Meydani SN, Meydani M, Rall LC, Morrow F, Blumber JB. Assessment of the safety of high-dose, short-term supplementation with vitamin E in healthy older adults. Am J ClinNutr 1994;60:704-9.

Bendich A, Machlin L. Safety of oral intake of vitamin E. Am J ClinNutr 1988;48:612-9.