Men in a large prostate cancer prevention trial who took vitamin E supplements had a higher risk of developing the disease than men who took a placebo, according to extended follow-up of trial participants. Dr. Eric Klein of the Cleveland Clinic and his colleagues reported the finding October 12 in JAMA.
The results are from the Selenium and Vitamin E Cancer Prevention Trial (SELECT), which included more than 35,000 relatively healthy men at average risk for prostate cancer. The trial was stopped early in 2008, when a planned interim analysis indicated that vitamin E and selenium—whether alone or in combination—were unlikely to prevent prostate cancer.
At the time, participants were told to stop taking the supplements, and researchers continued to follow the men. The interim analysis also suggested that vitamin E might be associated with an increased risk of prostate cancer, though the result was not statistically significant at the time.
But with additional follow-up, the researchers detected a 17 percent increased risk of prostate cancer among men who took 400 international units of vitamin E per day (IU/d) compared with men who took a placebo, a difference that was statistically significant.
The Evidence on Vitamin E
In reporting their results, the researchers noted that, by and large, vitamin E has failed to show a benefit for preventing a number of diseases. “The totality of the evidence shows that vitamin E does not prevent other diseases, and we now have evidence that it may increase the risk of prostate cancer,” said Dr. Klein.
Consumers need to be skeptical of health claims for over-the-counter products when strong evidence of a benefit demonstrated by clinical trials is lacking, the study authors stressed.
“Studies like SELECT make us take a step back and realize that any pharmaceutical agent we give has the potential for benefit and, as remote as it may be, also the potential for harm,” said co-author Dr. J. Michael Gaziano of Brigham and Women’s Hospital.
—Dr. Eric Klein
“That’s why we engage in these large-scale randomized studies, especially for agents that are in widespread use,” he added.
More than half of all men over age 60 in the United States are taking supplements containing vitamin E, and 23 percent are taking the dose used in SELECT, the study authors noted. Therefore, the finding of an increased risk of prostate cancer has “substantial implications.”
The increased risk of prostate cancer emerged only after the men had stopped taking the supplements. “These agents seem to have longer-lasting effects,” said Dr. Klein, noting that researchers who design clinical trials need to consider this possibility.
“This study is yet another cautionary tale about the potential risks of high-dose nutritional supplements,” said Dr. JoAnn Manson of Harvard Medical School, who was not involved in the research. “We’ve seen this before, and it shows why it is so important to have these randomized trials.”
In the early 1980s, she noted, beta-carotene was widely regarded as “a magic bullet for good health” until clinical trials showed that it was harmful to those at elevated risk for lung cancer, particularly smokers.
Another large randomized trial, the Physicians Health Study II, linked vitamin E to an increased risk of bleeding-related strokes.
Although deficiencies in certain nutrients can cause health problems, high doses of supplements may have health risks that outweigh the benefits, noted Dr. Manson, who is leading a large randomized trial of vitamin D and omega-3 fatty acids.
“With many nutrients, there is an optimal range of intake and blood levels, and more is not necessarily better,” she added.
Most Prostate Cancers Found Early
More than 400 sites in the United States, Canada, and Puerto Rico participated in SELECT, which was coordinated by SWOG, a federally funded cancer research cooperative group. Doctors monitored the participants according to contemporary community standards of screening and biopsy. This ensured that, as in general practice, some men had PSA tests and others did not.
During the 7 years of the trial (5.5 years of taking supplements and 1.5 years of not taking them), doctors diagnosed 65 cases of prostate cancer for every 1,000 men in the placebo group. In comparison, doctors diagnosed 76 cases for every 1,000 men in the vitamin E-only group.
—Dr. J. Michael Gaziano
Most of the detected cancers were found early, and therefore “the risk of a man dying from the disease is not very great,” said co-author Dr. Ian Thompson of the University of Texas Health Science Center at San Antonio.
He pointed out, however, that most men diagnosed with prostate cancer in the United States end up being treated with surgery or radiation, which can impair a man’s sexual and urinary functions.
“If a man is taking vitamin E, he should either stop taking it or talk to his doctor about a reason he should take it,” Dr. Thompson said. “And I can’t think of a reason he should take it.”
It is not clear why SELECT showed an increased risk for prostate cancer when earlier studies that led to the randomized trial showed that vitamin E protected against the disease. The study populations were different, however, and the original results may have been chance findings, the researchers said.
In fact, the prospective randomized trial, the gold standard in medical evidence, was launched precisely because the earlier studies were not definitive and needed to be confirmed.
The SELECT investigators have biological samples from the participants, and they intend to explore questions raised by the trial. For instance, men who took both supplements did not have an increased cancer risk, so there may have been an interaction between selenium and vitamin E.
The current results are an example of “rigorous scientific exploration,” noted Dr. Howard Parnes of NCI’s Division of Cancer Prevention, another co-author. “The idea of science is to put your observations to the test and see if they are correct,” he said. “You often learn the most from the studies that overturn conventional wisdom.”
Deadline Extended for Research Proposals Using SELECT and PCPT Samples
With the publication of new data from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) that show an increased risk of prostate cancer in men taking vitamin E, the deadline for proposals to use biorepository samples from the study has been extended. SWOG, formerly known as the Southwest Oncology Group, is making resources from SELECT and the Prostate Cancer Prevention Trial (PCPT) available to the wider research community for the development of novel translational research projects, including those that might help decipher the role of vitamin E in prostate cancer.
Researchers interested in using samples from SELECT or PCPT must submit a letter of intent to SWOG by 5:00 p.m. ET on November 14, 2011. Full applications are due by 5:00 p.m. ET on December 15, 2011. SWOG will review proposals in January 2012 and send notifications in April 2012.
Together, SELECT and PCPT randomly assigned more than 53,000 men without prostate cancer to intervention or placebo, generating substantial clinical data related to the risk of developing prostate cancer, as well as corresponding biorepositories for molecular, epidemiologic, and other studies.
Source: National Institute of Cancer