The Selenium and Vitamin E Cancer Prevention Trial (SELECT) involved 35,000 men randomly assigned to receive selenium (L-(+)-Selenomethionine) plus vitamin E (dl-alpha-tocopheryl acetate), selenium plus placebo, vitamin E plus placebo, or two placebos.
The initial data from the trial (published in JAMA in December 2008) indicated that, after almost five and half years, no significant differences were observed between any of the groups in relation to prostate cancer risk.
And now?
Ongoing analysis of the study’s participants, published this week in the Journal of the American Medical Association, revealed that vitamin E supplements only were associated with a 17% increase in the risk of prostate cancer.
On the flip side, no increase in risk was observed in the combination selenium-vitamin E group, a result that suggests “that selenium may have a protective effect by dampening the increased risk associated with vitamin E alone”.
"We report an observation of important public health concern that has emerged with continued follow-up of SELECT participants," wrote the authors, led by Eric Klein, MD, of the Cleveland Clinic.
"Given that more than 50% of individuals 60 years or older are taking supplements containing vitamin E and that 23% of them are taking at least 400 IU/d despite a recommended daily dietary allowance of only 22.4 IU for adult men, the implications of our observations are substantial."
New SELECT data
Dr Klein and his co-workers analyzed the final data collected by the study until July 5, 2011. Results showed that, during the whole study period 529 men in the placebo group developed prostate cancer, compared with 620 in the vitamin E group, 575 in the selenium group, and 555 in the combination group.
After crunching the numbers, the researchers report that the association was only statistically significant in the vitamin E alone group.
“Despite the lack of a mechanistic explanation, the findings show that vitamin E supplementation in the general population of healthy men significantly increases the risk of being diagnosed with prostate cancer,” wrote the researchers.
Prostate cancer
Over half a million new cases of prostate cancer are diagnosed every year worldwide, and the cancer is the direct cause of over 200,000 deaths. More worryingly, the incidence of the disease is increasing with a rise of 1.7 per cent over 15 years.
A number of studies have previously reported beneficial links between the intakes of vitamin E, selenium, and other nutrients, and prostate cancer risk. For example, the Alpha-Tocopherol, Beta Carotene (ATBC) trial reported that 50 mg/d of vitamin E was associated with a 35% reduction in the risk of prostate cancer.
Industry reaction
Reacting to the study's conclusions, Cara Welch, PhD, VP of scientific & regulatory affairs or the Natural Products Association (NPA) told NutraIngredients-USA: “This study may reveal a need for greater examination into the relationship between vitamin E and prostate cancer but I don’t believe it should immediately affect the benefit of vitamin E supplementation for certain groups.”
Harry Rice, PhD, VP of regulatory and scientific affairs for the United Natural Products Alliance (UNPA) added: "Given the initial report of the SELECT was towards a nonsignificant increase in prostate cancer risk with vitamin E, the present results, although disappointing, should not be a surprise.
"While the present results are statistically significant, there remains the question as to their clinical significance. In general, prostate cancer is a slow growing cancer. In the present study, it's likely that the majority of the cases of prostate cancer would not have been detected had it not been for the aggressive diagnostics (prostate specific antigen (PSA) testing) that were employed as part of the experimental design. In fact, subject recruitment was based on PSA test results.
"As of last week, the U.S. Preventive Services Task Force (USPSTF) now recommends against PSA-based screening for prostate cancer because it is of no benefit and leads to overdiagnosis.
"Consumers should engage in a lifetime of healthy habits which includes, but is not exclusive of, taking dietary supplements."
Out of context?
The study was described as "well-designed and well-executed in the confines of the drug model" by Duffy MacKay, ND, VP of scientific and regulatory affairs for the Council for Responsible Nutrition (CRN).
"However, it also evidences the risks of examining a nutrient in isolation.
"With a reductionist approach to the benefits of nutrition, the study showed that a dose of 400 IU vitamin E was not likely to provide benefit for preventing cancer, and the authors found an increased risk for developing prostate cancer. Interestingly, when vitamin E was combined with selenium, the risk was reduced to a non-significant statistic, perhaps even the result of chance.
"This reinforces the theory that vitamins work synergistically and that drug-like trials of nutrients, when used in isolation from other nutrients, may not be the most appropriate way to study them.
"This study provides an important addition to the knowledge base, but we should be reminded it is one study. We will be interested to see the results of the serum level analysis which the researchers have indicated will be published at a future date as that will provide even further information about the role of vitamin E and prostate cancer," added Dr MacKay.
Source: JAMA
2011, Volume 306, Issue 14, Pages 1549-1556
“Vitamin E and the Risk of Prostate Cancer: The Selenium and Vitamin E Cancer Prevention Trial (SELECT)”
Authors: E.A. Klein, I.M. Thompson Jr, C.M. Tangen, J.J. Crowley, et al.