expert opinion

Genes may affect vitamin E needs

September 1, 2011


Dr. Marian L. Neuhouser, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Vitamin E is an important antioxidant that prevents free radical reactions and lipid peroxidation. It is this oxidative stress preventing function that may be particularly relevant in relation to the development of several cancers, including prostate. However, a major controversy over the association of vitamin E with prostate cancer risk prevails, because a beneficial effect of vitamin E supplements was found in a randomized controlled trial of smokers (1) but not in two other trials not specifically recruiting smokers (2, 3). Whether the beneficial association exists only among smokers or other factors, such as genetic polymorphisms related to oxidative stress, play a role is inconclusive. A hypothesized mechanism of oxidative stress in relation to prostate cancer involves four important enzymes: MnSOD8, GPX1, CAT, and MPO.

The primary objective of this new study (4) was to examine associations of serum alpha- and gamma-tocopherol with prostate cancer risk in the randomized controlled CARET trial (5), using a nested case-control study design. Alpha- and gamma-tocopherol concentrations were assayed among 684 male heavy smokers and asbestos-exposed workers with incident prostate cancer and 1441 controls. We further investigated whether the genetic variants (polymorphisms) in the four selected oxidative stress regulatory enzymes, MnSOD, GPX1, CAT, and MPO, modified these associations.

The study results showed that

  • Higher serum alpha- and gamma-tocopherol concentrations were associated with reduced risks of aggressive prostate cancer among current smokers.
  • Current smokers with the highest serum concentrations of alpha-tocopherol had a 38% decreased risk of prostate cancer compared to those with the lowest concentrations.
  • Participants with the highest serum gamma-tocopherol concentrations had a non-significant, 31% reduced risk of aggressive prostate cancer.
  • Genetic variations in the oxidative stress regulatory enzyme MPO were associated with a nearly two-fold increased risk of aggressive prostate cancer among current smokers with low serum alpha-tocopherol levels.

In conclusion, our data suggest that, among current smokers, high serum alpha- and gamma-tocopherol concentrations are associated with reduced risks of aggressive prostate cancer. High serum alpha-tocopherol concentrations may be particularly important among men with genetic variation in MPO in reducing prostate cancer risk. As the MPO variations were present in 40% of our study population, our observations are important from a public health perspective, because these genotypes are not rare in the general population.”

Washington, July 2011

Addendum: Past studies which failed to find a protective benefit of vitamin E supplementation on prostate cancer risk did not consider the potential effect of genetic polymorphisms on vitamin E metabolism. Genetic polymorphisms seem to be relevant for micronutrient efficacy: vitamin E, for example, provides cardiovascular protection to individuals with diabetes and a certain haptoglobin (HP 2-2) genotype (6). Re-evaluations of two trials (HOPE and ICARE) found that vitamin E supplementation (400 IU daily) significantly decreased risk of cardiovascular death and myocardial infarction in individuals with diabetes mellitus and the HP 2-2 genotype (7). Given that Americans 2 years and older are consuming only 7.7 mg vitamin E daily (8) – about half of the recommended 15 mg per day – dietary supplementation may be beneficial.


  1. Heinonen O. P. et al. Prostate Cancer and Supplementation With α-Tocopherol and β-Carotene: Incidence and Mortality in a Controlled Trial. J Natl Cancer Inst. 1998; 90 (6): 440–446.
  2. Gaziano J. M. et al. Vitamins E and C in the Prevention of Prostate and Total Cancer in Men. The Physicians' Health Study II Randomized Controlled Trial. JAMA. 2009; 301(1):52–62.
  3. Lippman S. M. et al. Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other CancersThe Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2009; 301(1):39–51.
  4. Cheng T.-Y. D. et al. Genetic Variation in Myeloperoxidase Modifies the Association of Serum α-Tocopherol with Aggressive Prostate Cancer among Current Smokers. J. Nutr. July 2011.
  5. Omenn G. S. et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med. 1996; 334:1150–1155.
  6. Farbstein D. et al. Vitamin E therapy results in a reduction in HDL function in individuals with diabetes and the haptoglobin 2-1 genotype. Atherosclerosis. June 2011.
  7. Blum S. et al. Vitamin E reduces cardiovascular disease in individuals with diabetes mellitus and the haptoglobin 2-2 genotype. Pharmacogenomics. 2010; 11(5): 675–684.
  8. What We Eat in America, NHANES 2007-2008. Table 1.