Vitamin E, Genetics, and Inflammation

Vitamin E is an antioxidant often promoted as a supplement that prevents cardiovascular disease and the oxidation of LDL cholesterol. It is an essential nutrient found in a variety of foods including wheat germ, almonds, hazelnuts, sunflower seeds, and peanut butter.

The RDA for adults is 15 mg/day (22.4 IU/day), and the upper tolerable limit is 1,00 mg (1,500 IU).  This is one vitamin that has several drug interaction warnings including antidepressants and blood thinners.  Check on drug interactions if you are taking a medication daily.

There are two forms of Vitamin E: tocopherol and tocotrienol.  Those forms are subdivided into alpha-, beta-, gamma-, and delta-.  Alpha-tocopherol is the only one that is known to be necessary for people.  It is the most common form to find in supplements and enriched foods.

Not living up to the hype for heart disease:
A headline-grabbing study in 1993 of 90,000 nurses found that those who supplemented with Vitamin E had fewer incidences of cardiovascular disease.  Since then, large clinical trials haven’t upheld the idea that Vitamin E prevents cardiovascular disease.

In fact, two studies, HOPE and HOPE TOO, actually found that in a randomized controlled trial of over 10,000 people, supplementing with Vitamin E did not lower the risk of heart disease.  There was actually a slight increase in mortality due to heart problems in those who supplemented with Vitamin E vs. placebo.

One possible reason for the inconclusive studies is genetic variations.  A more recent study showed that indeed there is a genetic component to whether a person benefits from supplementing with Vitamin E.

For some people, vitamin E increases inflammation:

A 2012 study published in the American Journal of Clinical Nutrition showed that supplementing with 75 IU of alpha-tocopherol (a common, supplement form of Vitamin E), increased inflammatory cytokines depending on the genotype.  Specifically, for the GSTP1 polymorphism, rs1695, those with A/A and A/G had an increase in interleukin-6.

IL-6 genetic variants:
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Check your genetic data for rs1695 (23andMe v4, v5; AncestryDNA):

  • A/A: increased interleukin-6 with supplementing alpha-tocopherol
  • A/G: increased interleukin-6 with supplementing alpha-tocopherol
  • G/G: decreased  interleukin-6 with supplementing alpha-tocopherol

Members: Your genotype for rs1695 is .

So what is interleukin-6?  It is a cytokine that is involved in inflammation. It induces an inflammatory response and is implicated in several autoimmune diseases including diabetes, arteriosclerosis, and rheumatoid arthritis.

What about cancer risk?

A new study out in the Journal of the National Cancer Institute shows that there is an interaction between the COMT gene and vitamin E supplementation also. Basically, the study showed that for people carrying the COMT Val/Val genotype there was an increased risk for cancer with vitamin E (alpha-tocopherol) supplement.  [ref]

Check your genetic data for rs4680 (23andMe v.4 and v.5):

  • G/G: higher COMT activity, (val/val) increased the overall rate of cancer with alpha-tocopherol supplementation[ref]
  • A/G: intermediate COMT activity
  • A/A: lower COMT activity, met/met, decreased overall rate of cancer with alpha-tocopherol supplementation

Members: Your genotype for rs4680 is .


In summary, for some people, vitamin E supplementation may be beneficial, but for others, there may be no benefit or even possible detrimental effects.  One-size fits all recommendations don’t work here.