Selenium, vitamin E, and prostate cancer research

Why this trial still matters

For years, smaller and earlier studies had suggested that selenium or vitamin E might be linked with fewer prostate cancers. Some of those studies were not designed to answer that question. The Selenium and Vitamin E Cancer Prevention Trial, called SELECT, was designed to answer it directly. It was a randomized trial funded primarily by the National Cancer Institute and run by SWOG. Enrollment ran from 2001 to 2004 at more than 400 sites in the United States, Puerto Rico, and Canada. The National Cancer Institute reports that more than 35,000 men, age 50 and older, took part.

Men were assigned by chance to selenium plus vitamin E, selenium plus a placebo, vitamin E plus a placebo, or two placebos. Neither the men nor the researchers knew the assignment. The vitamin E was 400 international units a day of dl-alpha-tocopheryl acetate. The selenium was given as l-selenomethionine. The National Cancer Institute’s public questions-and-answers page, which is the source for the numbers below, does not restate the selenium dose in the sections used for this article, so this page does not invent one.

The supplements did not prevent prostate cancer

The trial was planned to last at least seven years. On September 15, 2008, the independent safety committee found that selenium and vitamin E, alone or together, did not prevent prostate cancer. Participants were told in October 2008 to stop the study capsules.

The first results, published in JAMA in January 2009 by Lippman and colleagues, found no statistically significant difference in prostate-cancer rates among the four groups. There were more prostate cancers in the vitamin E-only group, but that difference was not yet significant, which means it could have been chance. There were also more new diabetes diagnoses in the selenium-only group. That finding was not significant either, and later follow-up did not show a higher diabetes risk. The groups did not differ in lung cancer, colorectal cancer, cancers overall, deaths overall, or cardiovascular events overall.

A 2011 update by Klein and colleagues added follow-up through July 5, 2011, after men had stopped the capsules. The average observation was about seven years: 5.5 years on supplements and 1.5 years afterward. Men who had taken vitamin E alone had a 17 percent relative increase in prostate cancers compared with men on placebo. That difference was statistically significant. In numbers the National Cancer Institute uses to explain the 17 percent: among men on placebo, 65 prostate cancers were diagnosed per 1,000 men over seven years; among men assigned to vitamin E alone, 76 per 1,000 were diagnosed. That is 11 additional diagnoses per 1,000 men. Men on selenium alone, or on both supplements, also had more prostate cancers than the placebo group, but those smaller increases were not statistically significant.

Baseline selenium changed the picture again

A 2014 analysis by Kristal and colleagues, described by the National Cancer Institute, looked at selenium in toenail clippings taken when men joined. Men who started with high selenium and then took the selenium supplement had almost double the chance of high-grade prostate cancer compared with men who started with low selenium and took selenium. Men who started with low selenium and took vitamin E had double the chance of high-grade prostate cancer. The National Cancer Institute’s reading is that extra selenium may have offset some of the vitamin E effect in men whose selenium was low at the start, which may help explain why the combination arm did not show the same overall increase as vitamin E alone. The mechanism is still unclear.

These findings come from men in a prevention trial, using particular forms and a particular vitamin E dose. They should not be turned into a claim about a different product, a different dose, or a man who already has cancer.

What the National Cancer Institute says men should do

The institute’s answer is direct: men should not take vitamin E or selenium supplements to prevent cancer. Scientists do not have a full account of how these supplements interact with each other, with food, or with medicines. The men who took both supplements did not have a significant increase in prostate cancer, and they also had no reduction in prostate cancer, other cancers, or heart disease.

The Office of Dietary Supplements adds the everyday context. Adults need about 55 micrograms of selenium a day. Most people in the United States get enough from food, including seafood, meat, eggs, dairy foods, grains, beans, and nuts. Deficiency is uncommon here. The adult upper limit is 400 micrograms a day from all sources, and some experts recommend a lower ceiling. Too much selenium can cause hair and nail changes, stomach illness, nerve problems, and, at very high intakes, more serious harm. Brazil nuts are naturally high in selenium. A supplement taken “for the prostate” can push a person who already eats a varied diet toward that excess.

What this does not say

SELECT does not prove that food sources of selenium are harmful. It does not measure every form sold online. It does not mean a clinician will never have a reason to address a documented deficiency. It does mean that advertising a selenium or vitamin E pill as protection against prostate cancer is not supported by this trial, and that vitamin E at the dose studied was associated with more prostate cancers, not fewer.