Durk Pearson & Sandy Shaw’s®
Life Extension NewsTM
Volume 15 No. 5 • September 2012

New Data Helps Explain Why Large Vitamin E Human Clinical Trials Have Not Consistently Provided Cardioprotection

A new paper1 offers additional clues on why large randomized human clinical trials of vitamin E have not substantiated the benefits of vitamin E found in in vitro and animal as well as short-term human mechanistic studies.

The researchers explain, in their paper’s introduction, that despite promising results in cell culture and animal studies, the results of cohort and supplementation studies with alpha tocopherol have been inconsistent. They note that the Nurses’ Health Study of over 80,000 nurses found a 30% reduction in the risk of developing coronary artery disease in subjects who took vitamin E supplements as compared to those who didn’t (after adjusting for age, smoking status, and intakes of beta carotene and vitamin C). A cohort study of 5133 Finnish residents taking vitamin E supplements and followed for 14 years, however, revealed no reduction in the incidence of coronary artery disease. Moreover, the Physicians’ Health Study of over 80,000 male physicians reported no association between vitamin E supplementation and mortality due to cardiovascular disease. There are many more studies, some showing protective effects of vitamin E and others reporting no such protection or protection only for certain classes of subjects (e.g., those with deficiencies of vitamin E) and even increased risk of disease.

Attempts at explanations (and there have been many) have run up against the difficulty of determining causality in large trials in which there are so many variables (some unknown at the time the study was designed and conducted). The new study examined the effects of vitamin E supplementation on the production of inflammatory cytokines in 160 apparently healthy middle aged men who took either 75 IU (low dose) or 600 IU (high dose) alpha-tocopherol for a period of 6 weeks. The production by their peripheral blood mononuclear cells (PBMCs) of pro-inflammatory TNF-alpha and IL-1beta, IL-6, and the anti-inflammatory IL-10 was measured at baseline and then again after 6 weeks. In addition (and this is something that only became possible very recently) the genetic polymorphisms (variants) in genes involved in inflammation or in responses to oxidative stress were also determined in the subjects.

The results showed that the ability of alpha-tocopherol to affect the levels of various proinflammatory cytokines (TNF-alpha, IL-1beta, or IL-6) was influenced by the polymorphisms of genes that regulate the production of those cytokines by PBMCs.

Thus, “[i]n healthy control subjects, the effect of alpha-tocopherol supplementation on the production of inflammatory cytokines appears to be dependent on an individual’s genotype. These genotype-specific differences may help explain some of the discordant results in studies that used vitamin E.”1 Thus, the authors propose, their “data suggest that individuals with a lower antioxidant capacity might be those who would benefit most from intake of alpha-tocopherol.”


  1. England et al. Variants in the genes encoding TNF-alpha, IL- 10, and GSTP1 influence the effect of alpha-tocopherol on inflammatory cell responses in healthy men. Am J Clin Nutr 95:1461-7 (2012).

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