I often think that if a little bit of something is good for you, more should be even better…  But that is often not the case when it comes to health.  arge, population-wide studies of different macronutrients (e.g. fats vs carbs) or micronutrients (e.g. folic acid) often give conflicting results – or show no overall effect at all.  This can be confusing when compared with animal studies showing that a vitamin or diet is the super-duper best-est thing in all the land.

Vitamin E is one of those micronutrients with conflicting studies. It is an antioxidant, and we often jump to the conclusion that more is better with antioxidants.

For cancer prevention, a new study that was just published in the Journal of the National Cancer Institute shows that vitamin E supplementation decreases the risk of cancer for some people — but for others, it can actually increase the risk of cancer.

The difference seems to be which version of the COMT gene you carry.  If you carry the more active version of COMT (val/val), your body produces a 3 to 4-fold more active enzyme than if you carry the met/met version. If you carry the met/met version, your body produces less active enzyme. And those with the val/met genotype are in the middle. All three variants are very common. For most population groups, the val/val genotype is the most common, occurring in 30-50% of the population.

The COMT gene codes for the enzyme catechol-o-methyltransferase. The enzyme is responsible for the breakdown of neurotransmitters (dopamine, epinephrine, norepinephrine) as well as catechol-containing molecules throughout the body.

The study on vitamin E and COMT used the data from two large studies that examined the cancer rate in a 10 year follow-up period after trials involving supplementing with vitamin E.  All in all, more than 50,000 people were involved in the trials.The results showed that people with the COMT val/val (rs4680, GG) genotype who took supplemental alpha-tocopherol had an increased overall rate of cancer (HR=1.18). Those with the met/met (rs4680, AA) genotype had a decreased risk of cancer (HR=0.88).  And those with val/met genotype had no statistical effect on cancer risk from vitamin E.

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

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


This seems to be pretty straight forward. Vitamin E as alpha-tocopherol increases cancer risk (a little) if you carry the val/val genotype. The study doesn’t answer the question of whether vitamin E from foods or from mixed tocopherol supplements would have the same effect.

Is this a big enough deal to worry about?  The increase in the risk of cancer was 18%, so it isn’t a huge increase. This is similar to the overall increase in the risk of colon cancer from eating 50g of processed meat per day, also estimated at 18%. (read about it here with a good explanation of the statistics) Compare this to the 20-fold increase in lung cancer risk from smoking and you can see that the increase is small. But even a small increase in risk isn’t worthwhile if you aren’t getting a greater benefit elsewhere from taking vitamin E…  you will need to weigh the risk vs. reward for yourself.

Categories: Disease Prevention

1 Comment

Jeanne · January 10, 2019 at 3:50 pm

This is very interesting. I wonder if this gene snp works in tandem with other genes. In my family, we are “bleeders”, due to fragile capillaries and possibly Von Willebrands disorder. If take vitamin E supplements, the bruising and bleeding gets worse. I am G/G….so higher rate of cancer with vitamin E supplementation. It’s like my body is trying to discourage my intake of high levels of vitamin E by sending me the bruising/slow clotting signal. I wonder how many other gene snp’s work in tandem, like that, to keep us healthy.

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