Variants in the genes encoding TNF-α, IL-10, and GSTP1 influence the effect of α-tocopherol on inflammatory cell responses in healthy men

Am J Clin Nutr. 2012 Jun;95(6):1461-7. doi: 10.3945/ajcn.111.012781. Epub 2012 May 9.


Background: Despite evidence of antioxidant effects of vitamin E in vitro and in animal studies, large, randomized clinical trials have not substantiated a benefit of vitamin E in reducing inflammation in humans. An individual's genetic background may affect the response to α-tocopherol supplementation, but this has rarely been investigated.

Objective: The aim of this study was to explore the role of genetic polymorphisms on changes in LPS-stimulated inflammatory cytokine production from peripheral blood mononuclear cells (PBMCs) after α-tocopherol supplementation.

Design: A total of 160 healthy, middle-aged male volunteers (mean age: 52.7 y) were given dietary supplements of either 75 IU (low dose; n = 57) or 600 IU (high dose; n = 103) α-tocopherol/d for 6 wk. The production of TNF-α and IL-1β, -6, and -10 by PBMCs after LPS stimulation was measured at baseline and after 6 wk. Polymorphisms in 15 genes involved in inflammation or responses to oxidative stress were characterized in the subjects.

Results: The ability of α-tocopherol to affect TNF-α production by LPS-stimulated PBMCs was influenced by the TNFA -238 polymorphism (P = 0.016). The ability of α-tocopherol to affect IL-6 production was influenced by the GSTP1 313 polymorphism (P = 0.019). The ability of α-tocopherol to affect IL-1β production was influenced by the IL10 -592 and -1082 polymorphisms (P = 0.025 and P = 0.016, respectively).

Conclusions: In healthy control subjects, the effect of α-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / pharmacology
  • Dietary Supplements
  • Glutathione S-Transferase pi / genetics*
  • Humans
  • Inflammation / chemically induced
  • Inflammation / genetics*
  • Inflammation / metabolism
  • Interleukin-10 / genetics*
  • Interleukin-1beta / biosynthesis
  • Interleukin-1beta / genetics
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics
  • Interleukins / genetics*
  • Interleukins / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Lipopolysaccharides
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Tumor Necrosis Factor-alpha / genetics*
  • alpha-Tocopherol / pharmacology*


  • Anti-Inflammatory Agents
  • Interleukin-1beta
  • Interleukin-6
  • Interleukins
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Glutathione S-Transferase pi
  • alpha-Tocopherol