Does Vitamin E Cause Heart Failure?

Does Vitamin E Cause Heart Failure?
Nutritional Medicine A Textbook by Alan R. Gaby, MD

Some practitioners reported in the 1940s and 1950s that vitamin E in doses of 200-600 IU/day produced clinical improvement in CHF patients.15 Intramuscular administration of 300-400 IU/day of vitamin E for 4-5 days was said to produce rapid and dramatic diuresis (usually within 12 hours of the first injection) in patients with severe heart failure.16 However, other practitioners found that vitamin E in doses of 150-800 IU/day was not beneficial for patients with CHF.17-20

More recently, controlled trials have shed an unfavorable light on vitamin E. In a double-blind study of patients with advanced CHF (NYHA class III or IV) administration of 1,000 IU/day of vitamin E for 12 weeks did not improve heart function or quality-of-life scores, compared with placebo.21 Moreover, in a double-blind study of patients with vascular disease or diabetes, those who received 400 IU/day of vitamin E for a mean of 7 years had a 19% higher incidence of CHF (14.7% vs. 12.6%; p = 0.007) and a 40% higher incidence of hospitalization for CHF (5.8% vs. 4.2%; p = 0.002), when compared with those who received placebo.22

The negative results observed in many vitamin E studies might be explained by the fact that virtually all of these studies used pure alpha-tocopherol, whereas vitamin E as it occurs naturally in food consists of 4 isomers: alpha-, beta-, gamma-, and delta-tocopherol.

Studies in humans have shown that supplementation with alpha-tocopherol can deplete gamma-tocopherol.23 Gamma-tocopherol is metabolized largely to 2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman (gamma-CEHC), which may function as a natriuretic hormone, since it is involved in the body’s response to sodium-induced plasma volume expansion. 24-26 It is possible that alpha-tocopherol-induced gamma-tocopherol depletion could lead to impaired regulation of sodium and water balance, potentially increasing the risk for heart failure.

If high-dose alpha-tocopherol does adversely affect cardiac function in some people, one might reasonably expect that mixed tocopherols, which contain all 4 isomers of vitamin E, would not have the same negative effects, and might even be beneficial. The clinical trials that used alpha-tocopherol should therefore be repeated using mixed tocopherols.27

15. Vogelsang A, Shute EV. Effect of vitamin E in coronary heart disease. Nature 1946;157:772.
16. Vogelsang A. Intramuscular administration of vitamin E. Lancet 1950;1:734.
17. Eisen ME, Gross H. Vitamin E in arteriosclerotic heart and peripheral vascular disease. NY State J Med 1949;49:2422-2424.
18. Berger H. The failure of vitamin E to alleviate the signs and symptoms of congestive heart failure. NY State J Med 1950;50:441-443.
19. Levy H, Boas EP. Vitamin E in heart disease. Ann Intern Med 1948;28:1117-1124.
20. Baer S, Heine WI, Gelfond DB. The use of vitamin E in heart disease. Am J Med Sci 1948;215:542-547.
21. Keith ME, Jeejeebhoy KN, Langer A, et al. A controlled clinical trial of vitamin E supplementation in patients with congestive heart failure. Am J Clin Nutr 2001;73:219-224.
22. Lonn E, Bosch J, Yusuf S, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 2005;293:1338-1347.
23. Huang HY, Appel LJ. Supplementation of diets with alpha-tocopherol reduces serum concentrations of gamma- and delta-tocopherol in humans. J Nutr 2003;133:3137-3140.
24. Murray ED Jr, Wechter WJ, Kantoci D, et al. Endogenous natriuretic factors 7: biospecificity of a natriuretic gamma-tocopherol metabolite LLU-alpha. J Pharmacol Exp Ther 1997;282:657-662.
25. Wechter WJ, Kantoci D, Murray ED Jr, et al. A new endogenous natriuretic factor: LLU-alpha. Proc Natl Acad Sci 1996;93:6002-6007.
26. Uto H, Kiyose C, Saito H, et al. Gamma-tocopherol enhances sodium excretion as a natriuretic hormone precursor. J Nutr Sci Vitaminol 2004;50:277-282.
27. Gaby AR. Vitamin E supplementation, cardiovascular events, and cancer. JAMA 2005;294:425.

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