More Evidence of Harm From Selenium in Prostate Cancer

Pam Harrison

January 08, 2015

A new analysis has found that men diagnosed with nonmetastatic prostate cancer who consumed more than 140 μg a day of supplemental selenium had over a two-and-a-half–fold excess risk for death from prostate cancer compared with nonsupplement users.

"There is no evidence for benefit from taking selenium after a prostate cancer diagnosis and now we have evidence for harm," lead author Stacey Kenfield, ScD, University of California, San Francisco, told Medscape Medical News.

"Based on these findings, prostate cancer patients should avoid selenium supplements," she said, "although further research evaluating high-dose selenium intake is needed to confirm our results and inform clinical guidelines for prostate cancer survivors." 

The new finding comes from the Health Professionals Follow-Up study (HPFS) and was published online December 12, 2014, in the Journal of the National Cancer Institute.

Dr Kenfield and colleagues prospectively followed 4459 men initially diagnosed with nonmetastatic prostate cancer from 1988 through to 2010.

Participants completed detailed information on the use and dosage of supplements, including multivitamins and individual vitamins and minerals, every 2 years beginning in 1986.

Total selenium supplement intake was calculated as the sum from multivitamins and selenium supplements. Men were categorized according to how much selenium they were taking: less than 80 μg daily, 80 to 130 μg daily, between 140 and 250μg daily, and 260 μg daily or more. There was also a "don't know" category.

During a median follow-up of 8.9 years, investigators documented 965 deaths, 23.4% of them due to prostate cancer and 27.7% due to cardiovascular disease.

"Compared with nonusers, selenium supplement users had an increased risk of prostate cancer mortality," the investigators report.

On the basis of multivariable analyses, men who consumed the lowest amount of selenium (1 to 24 μg/day) after being diagnosed with prostate cancer had an 18% higher risk for prostate cancer mortality compared with nonusers (hazard ratio, 1.18).

This risk increased by 33% in men who consumed between 25 and 139 μg of supplemental selenium a day (HR, 1.33) and by 60% among men who consumed 140 μg of supplemental selenium or more per day (HR, 2.60).

Investigators also analyzed the risk for biochemical recurrence of prostate cancer and the amount of selenium supplementation consumed.

On the basis of an analysis of 3718 men followed for a median of 7.8 years, they observed no statistically significant association between selenium supplementation after prostate cancer diagnosis and the risk for biochemical recurrence.

On the other hand, there was a modest 12% inverse association between selenium supplementation and the risk for overall mortality (HR, 0.88) among men who took 140 μg of a selenium supplement or more per day compared with those who didn't use supplements.

Although not a statistically significant finding, investigators also noted that men who used the highest doses of selenium supplements after prostate cancer diagnosis had a statistically significant 36% decreased risk for cardiovascular mortality (HR, 0.64; P for trend = 0.38). However, the researchers also point out that these men were generally more healthy. At diagnosis, men who consumed 140 μg of selenium supplements or more per day did more vigorous physical activity, smoked less, used other supplements, and were more likely to have clinical T1 stage cancers, although use did not vary by biopsy Gleason score, as investigators observe.

Supplements to Protect Against Cancer?

As Dr Kenfield pointed out, guidelines from the American Institute for Cancer Research and the American Cancer Society for cancer survivors agree that no evidence indicates that supplements are beneficial and so should not be relied upon to protect against cancer progression.

On the other hand, the Physicians' Health Study, evaluating the impact on men using a regular multivitamin supplement demonstrated a modest 8% reduction in total cancer incidence in men taking a multivitamin.

Further, the subgroup of men with a baseline history of cancer in the same study had a 27% reduction in total cancer during the study.

"Therefore, the available evidence suggests that a regular multivitamin is safe and may be beneficial in this group," Dr Kenfield observed.

Two Sides to the Story

Asked to comment on the study, epidemiologist Theodore Brasky, PhD, from the Ohio State University College of Medicine, Columbus, told Medscape Medical News that there are two sides to this story: the relation between selenium intake and prostate cancer occurrence and the relation between selenium intake and prostate cancer survival among men who have already been diagnosed with prostate cancer.

"In the SELECT trial (Selenium and Vitamin E Cancer Prevention Trial), which was an incredibly large trial of over 35,000 men, investigators found no effect on prostate cancer risk from selenium supplements compared with placebo," Dr Brasky noted.

On the other hand, the same trial showed that men who had high baseline levels of selenium and who were also given selenium supplements were significantly harmed by supplementation.

As reported by Medscape Medical News, the risk for high-grade cancer was increased by 91% in men in SELECT with high baseline selenium levels who took 200 μg a day of selenium supplements.

"I think the current study really highlights concern that too much of this substance can be a bad thing," Dr Brasky said.

The recommended dietary allowance (RDA) for selenium in the United States is 55 μg a day, Dr Brasky points out in an accompanying editorial that was coauthored with Alan Kristal, DrPH, Fred Hutchinson Cancer Research Center, Seattle, Washington (who was the lead author of the SELECT study).

The 140 μg a day supplementation used by some men in the HPFS was clearly in excess of the recommended daily dosage and again underscores that levels of selenium achieved by supplementation in men with already adequate levels of selenium are harmful for those with and without a diagnosis of prostate cancer, Dr Brasky commented.

"We recommend avoiding any supplement containing more than the US RDA of 55 μg a day of selenium" he emphasized.

"But we need to be clear that that covers men who might be taking a multivitamin, because multivitamins marketed specifically for men's prostate health have double the US RDA for selenium at around 100 μg."

 
[U]rologists should make sure that their patients are indeed avoiding these supplements Dr. Theodore Brasky
 

"So what we are saying, regardless of how the multivitamin's marketed, is that people should avoid these multivitamins and we think urologists should make sure that their patients are indeed avoiding these supplements if they have been diagnosed with prostate cancer," Dr Brasky said.

Selenium is a nonmetallic trace element found in plant in foods such as rice, wheat, and Brazil nuts and in seafood and meat.

On average, men in the United States consume 134 μg of selenium per day.

The study was supported by the National Cancer Institute. The authors have disclosed no relevant financial relationships.

J Natl Cancer Inst. Published online December 12, 2014. Abstract Editorial

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