(25-05-11) No Evidence That Selenium Supplements Protect Against Cancer

Roxanne Nelson
May 12, 2011 ? Selenium is a trace mineral that is essential to human health, but its role as a chemopreventive agent has been controversial. Studies have reported conflicting results on the risks for specific cancers and selenium exposure, and published data have, overall, been inconsistent.
However, a new mega-analysis reports that reliable conclusions regarding a causal relationship between low selenium exposure and an increased risk for cancer cannot be drawn at this time.
A Cochrane Systematic Review reported that thus far, there is no "convincing evidence" that selenium supplements can prevent cancer in any population.
The authors note that in some of the epidemiologic data, there was a decreased incidence of cancer (odds ratio [OR], 0.69) and mortality (OR, 0.55) among individuals with higher selenium exposure. This reduction in cancer risk was more pronounced in men (incidence: OR, 0.66) than in women (incidence: OR, 0.90).
However, these findings have potential limitations because of factors such as study design and the quality and heterogeneity of the data, the authors note, as factors such as these can complicate the interpretation of the summary statistics.
"These conclusions have limitations because the data came from a wide variety of trials, and so it is difficult to summarize their findings," said lead author Gabriele Dennert, MD, from the Institute for Transdisciplinary Health Research, Berlin, Germany, in a statement.
However, when the authors reviewed randomized controlled trials, there was no evidence of a protective benefit against nonmelanoma skin cancer or prostate cancer. Study results for the prevention of liver cancer with selenium supplements were inconsistent and had an unclear risk for bias, the authors write.
"In fact, the results of the Nutritional Prevention of Cancer Trial and the Selenium and Vitamin E Cancer Prevention Trial [SELECT] raised concerns about possible harmful effects from long-term use of selenium supplements," Dr. Dennert pointed out.
Inconsistent Data
To date, the data have been inconsistent when evaluating the role of antioxidants, including selenium, and the role they may play in preventing cancer or increasing the risk for certain malignancies.
As previously reported by Medscape Medical News, the results from the Vitamins and Lifestyle (VITAL) study found there was no association between the use of antioxidant supplements, including selenium, and a higher risk for melanoma (Arch Dermatol. 2009;145:879-882).
The findings from VITAL contrast those from the Supplementation in Vitamins and Mineral Antioxidants study, which found a 4-fold higher melanoma risk in women ? but not in men ? who used nutritionally appropriate doses of antioxidant supplements (J Nutr. 2007;137:2098-2105).
The authors of the VITAL trial noted that their findings are consistent with those from several case-control studies that examined serum levels of antioxidants including selenium and did not identify any association with an increased risk for melanoma.
"Our study only examined daily supplementation with nutritionally appropriate doses of vitamins C and E, beta carotene, selenium, and zinc and melanoma risk," lead author Maryam Asgari, MD, MPH, dermatologist and research scientist at Kaiser Permanente in Oakland, California, told Medscape Medical News at that time. "Therefore, I do not think we can make sweeping generalizations about antioxidants and melanoma risk."
In prostate cancer, the SELECT showed that supplementation with selenium had no effect on the incidence rate. Larry Baker, MD, chairman of the Southwest Oncology Group, which coordinated the trial, and professor of medicine at University of Michigan Medical School in Ann Arbor, told Medscape Medical News that "the results to date speak for themselves."
The SELECT is a much larger trial than previous trials that suggested benefit, he pointed out. "This is the definitive study, and anyone who argues that is ignoring the facts," said Dr. Baker.
The results of another study that appeared in 2009 in the Journal of Clinical Oncology suggested that there was potential harm from selenium supplementation for men who already have prostate cancer (2009;27:3577-3583). A high level of selenium in the blood was associated with a slightly elevated risk for aggressive prostate cancer.
No Solid Evidence
The just-published Cochrane meta-analysis reviewed 49 prospective observational studies, which included more than 1,078,000 participants, and 6 randomized controlled trials with a total of 43,408 participants (94% men).
Overall, some of the data showed that individuals with higher levels of selenium levels or a higher intake experienced a lower frequency of certain cancers, including bladder or prostate cancers, but there was no difference in the incidence of other malignancies such as breast cancer. However, the authors point out that it was not possible to determine from these data whether selenium levels or intake was the actual reason for the lower cancer risk seen in some persons.
Other factors could influence cancer risk independent of selenium, they note. These include a healthier nutritional intake or lifestyle and more favorable living conditions.
However, the randomized controlled trials with the most reliable results showed that organic selenium did not prevent prostate cancer in men and elevated the risk for nonmelanoma skin cancer in persons of both sexes. Although other trials showed a decrease in liver cancer among persons using selenium salt or organic supplements, "this evidence was less convincing" because of the trials' methodological shortcomings.
"We advise further investigation of selenium for liver cancer prevention before translating results into public health recommendations," the authors conclude. "We also recommend that there should be further evaluation of the effects of selenium supplements in populations according to their nutritional status as they may differ between undernourished and adequately nourished groups of people."
The study was partially funded by the Dr. Ernst and Anita Bauer Foundation, the EU-CAM-Cancer Project, the German Cancer Aid, and National Center for Complementary and Alternative Medicine. The authors have disclosed no relevant financial relationships.

Source: Cochrane Database Syst Rev. 2011;5:CD005195.

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