High-Dose Selenium May Increase Prostate Cancer Risk

Dietary supplement companies tout the mineral selenium as possibly being able to reduce the risk of prostate cancer. The Food and Drug Administration (FDA) allows companies to make this claim, despite the lack of evidence that selenium has any positive effect on cancer rates. In fact, recent evidence from a large clinical trial has shown that high doses of selenium may actually increase the risk of prostate cancer.

Selenium is essential to humans in small amounts. The recommended dietary allowance (RDA) for adequate intake for adults is 55 micrograms per day.[1] Foods that are rich in selenium include Brazil nuts; many fresh- and saltwater fish, such as tuna, halibut and sardines; beef and poultry; and grains.[2] Variations in the soil can affect how much selenium is absorbed by plants, so selenium content in grains and other plant-based foods varies depending on the geographic area where the plants are grown (geographic area tends to have less impact on selenium levels in animal-based foods).

Because selenium is found naturally in the soil and is, therefore, available in many foods, selenium deficiency is uncommon in the U.S.[3] Nonetheless, some health conditions — such as certain conditions associated with HIV infection, kidney dialysis and others — are linked with low selenium levels in the body.

Over the past several years, selenium has attracted attention because of its antioxidant properties, which some researchers suspect may protect cells from damage.[4] A study that analyzed national survey data showed that about 19 percent of American men reported taking a dietary supplement that contained selenium.[5] This study also showed that about 30 percent of men over age 50 are taking a supplement containing selenium. However, current national surveys do not provide information on men who are using high-dose selenium (i.e., doses that are higher than the RDA).

Prostate cancer

Prostate cancer is the most common type of non-skin cancer among men in the U.S., occurring in approximately 16 percent of American men.[6] However, for many men diagnosed with prostate cancer, the disease progresses very slowly and does not cause symptomatic illness. This is reflected in the high survival rates for men who are diagnosed: 95 percent of men diagnosed with local and regional prostate cancer (i.e., cancer that has not yet spread throughout the body) live 10 years or longer following diagnosis. Most American cases are diagnosed at an early stage because of current prostate cancer screening practices. But prostate cancer treatment is costly,[7] and complications associated with treatment are common.[8]

Prostate cancer is rare in men under the age of 40, and the chance of developing prostate cancer increases with age.[9] Men with a family history of prostate cancer are at a higher risk of developing the disease than those without family history. Notably, prostate cancer occurs more frequently among African-American men than among white men. Testosterone may play a part in the development of prostate cancer.[10] Based on how the changes in the prostate gland cells look under the microscope, prostate cancer can be classified as low-, medium- or high-grade cancer.[11] A low-grade prostate cancer grows more slowly and is less likely to spread than a high-grade cancer.

Research on selenium and prostate cancer risk

In 2003, the FDA allowed companies that make foods and dietary supplements containing selenium in daily doses of up to 400 micrograms to state on their labels that while “some scientific evidence suggests that consumption of selenium may reduce the risk of certain forms of cancer [including prostate cancer] ... FDA has determined that this evidence is limited and not conclusive.”[12]

Unfortunately, the FDA’s decision to allow companies to make the claim that selenium supplements may help prevent prostate cancer was based in large part on results from a single clinical trial: the 1996 Nutritional Prevention of Cancer (NPC) trial.[13] As acknowledged by the FDA,[14] and according to many critics of the study, prostate cancer was not a primary outcome being evaluated as part of the design of the NPC trial, and therefore the finding of a reduction in prostate cancer risk seen in analyses of data from this trial is not robust.

Indeed, the strongest evidence regarding the effect of selenium on prostate cancer risk comes from a more recent large, multisite, randomized clinical trial called the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Initiated by the National Cancer Institute in 2001, the SELECT trial enrolled over 35,000 male North American participants ages 50 and older (for enrolled African-Americans) or 55 and older (for all other races) who tested negative for signs of prostate cancer. The trial was specifically designed to test the efficacy of selenium and vitamin E, alone or in combination, in preventing prostate cancer.[15]

In the SELECT trial, men took daily doses of 200 micrograms of selenium and 400 international units (IU) of vitamin E (the RDA is 22 IU per day).[16] Four groups were compared: men who took selenium only, men who took vitamin E only, men who took both and men who took a placebo. The study was double-blind, meaning neither the subjects nor the researchers knew which men were taking selenium or vitamin E and which were taking a placebo.

An interim analysis of the SELECT trial appeared in a 2009 article in The Journal of the American Medical Association and showed no benefit from the supplements. The analysis even found a non-statistically-significant increase in the incidence of Type 2 diabetes (maturity-onset diabetes mellitus or non-insulin dependent diabetes mellitus, which accounts for about 75 percent of diabetic cases) in men taking the selenium supplements. Therefore, the supplements were stopped early in 2008 at the recommendation of the trial’s independent data and safety monitoring board, but subject follow-up was continued.[17]

The next follow-up analysis of prostate cancer risk from the SELECT trial was published in 2011. It used data from 521 participants who were diagnosed with prostate cancer between the time the trial was initially conducted and July 2011.[18] In these cases, there was a small increase in the risk of prostate cancer in the men taking vitamin E, selenium or both compared to the placebo group: For every 10,000 men taking the supplement for one year, there were 16 additional cases of prostate cancer for men taking vitamin E, eight for men taking selenium and four for men taking the combination. However, this difference was statistically significant only for the group taking vitamin E alone.

A more compelling analysis of the evidence from the SELECT trial was published Feb. 21, 2014, in the Journal of the National Cancer Institute. The researchers used trial subjects’ toenail samples to determine the level of selenium already in their bodies before they began taking the selenium and vitamin E supplements.[19] The researchers then re-analyzed the data to see if the amount of selenium already present in the body made any difference when it came to prostate cancer risk.

The researchers compared the 1,739 men from the SELECT trial who were diagnosed with prostate cancer during the study period with a random sample of 3,117 age- and race-matched men without prostate cancer who had also participated in the study. The results showed that existing selenium levels did make a difference: Taking selenium supplements increased the risk of high-grade prostate cancer by 91 percent among men with already high selenium levels.[20] Among men with low selenium levels, taking vitamin E increased their total risk of prostate cancer by 63 percent and their risk of aggressive prostate cancer by 111 percent.

The researchers stated that it is unlikely that there will be another trial of high-dose selenium or vitamin E supplementation for the primary prevention of prostate cancer.[21] Therefore, they made the following recommendation: “Given the [prostate cancer] risks and lacking evidence of benefit for other diseases of equal or greater public health importance than [prostate cancer], men aged greater than 55 should avoid supplementation with either vitamin E or selenium at doses that exceed the recommended daily intake.”

What You Can Do

Men should avoid taking high-dose selenium supplements for the prevention of prostate cancer or any other type of cancer or health condition. However, dietary supplements with the recommended daily allowance for selenium are safe to use. Consumers may report serious adverse events with drugs or product quality problems to the FDA’s MedWatch Adverse Event Reporting System online by visiting www.fda.gov/Safety/MedWatch/ or by calling 800-332-1088.

References

[1] Institute of Medicine. Dietary Reference Intakes (DRIs): Recommended Dietary Allowances and Adequate Intakes, Elements. 2014. http://iom.edu/Activities/Nutrition/SummaryDRIs/~/media/Files/Activity%20Files/Nutrition/DRIs/RDA%20and%20AIs_Vitamin%20and%20Elements.pdf. Accessed May 9, 2014.

[2] National Institutes of Health, Office of Dietary Supplements. Selenium Dietary Supplement Fact Sheet. July 2, 2013. http://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/#h3. Accessed May 22, 2014.

[3] Ibid.

[4] Dennert G, Zwahlen M, Brinkman, et al. Selenium for preventing cancer. Cochrane Database Syst Rev. 2011:5.

[5] Bailey RL, Gahche JJ, Lentino CV, et al. Dietary supplement use in the United States, 2003-2006. J Nutr. 2011;141:261-266.

[6] Brawley OW. Prostate cancer epidemiology in the United States. World J Urol. 2012;30(2):195-200. doi:10.1007/s00345-012-0824-2.

[7] Roehrborn CG, Black LK. The economic burden of prostate cancer. BJU Int. 2011:108(6);806-813. doi:10.1111/j.1464-410X.2011.10365.x.

[8] Potosky AL, Davis WW, Hoffman RM, et al. Five-year outcomes after prostatectomy or radiotherapy for prostate cancer: the prostate cancer outcomes study. J Natl Cancer Inst. 2004:96(18),1358-1367. doi:10.1093/jnci/djh259.

[9] Prostate Cancer Foundation (PCF). Prostate Cancer Risk Factors. 2014. http://www.pcf.org/site/c.leJRIROrEpH/b.5802027/k.D271/Prostate_Cancer_Risk_Factors.htm. Accessed May 7, 2014.

[10] National Cancer Institute. Prostate Cancer Prevention. 2014. http://www.cancer.gov/cancertopics/pdq/prevention/prostate/Patient/page3#Keypoint14. Accessed May 9, 2014.

[11] Cancer.Net. Prostate Cancer. 2013. http://www.cancer.net/cancer-types/prostate-cancer/stages. Accessed May 12, 2014.

[12] U.S. Food and Drug Administration. Labeling & Nutrition — Selenium and Certain Cancers (Qualified Health Claim: Final Decision Letter) (Docket No. 02P-0457). April 28, 2003. http://www.fda.gov/Food/IngredientsPackagingLabeling/LabelingNutrition/ucm072780.htm. Accessed May 9, 2014.

[13] Clark LC, Combs GF, Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin: A randomized controlled trial. J Am Med Assoc. 1996;276(24):1957-1963.

[14] U.S. Food and Drug Administration. Labeling & Nutrition — Selenium and Certain Cancers (Qualified Health Claim: Final Decision Letter) (Docket No. 02P-0457). April 28, 2003. http://www.fda.gov/Food/IngredientsPackagingLabeling/LabelingNutrition/ucm072780.htm. Accessed May 9, 2014.

[15] Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). J Am Med Assoc. 2009;301(1):39-51. doi:10.1001/jama.2008.864.

[16] National Institutes of Health, Office of Dietary Supplements. Vitamin E Fact Sheet. October 11, 2011. http://ods.od.nih.gov/factsheets/VitaminE-QuickFacts. Accessed May 29, 2014.

[17] Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). J Am Med Assoc. 2009;301(1):39-51. doi:10.1001/jama.2008.864.

[18] Klein EA, Jr IMT, Tangen CM, et al. Vitamin E and the Risk of Prostate Cancer. J Am Med Assoc. 2011;306(14):1549-1556.

[19] Kristal AR, Darke AK, Morris JS, et al. Baseline selenium status and effects of selenium and vitamin E supplementation on prostate cancer risk. J Natl Cancer Inst. 2014;106(3):djt456. doi:10.1093/jnci/djt456.

[20] MedlinePlus. Vitamin E, Selenium Supplements Might Double Chances of Prostate Cancer. 2014. http://www.nlm.nih.gov/medlineplus/news/fullstory_144752.html. Accessed May 9, 2014.

[21] Kristal AR, Darke AK, Morris JS, et al. Baseline selenium status and effects of selenium and vitamin E supplementation on prostate cancer risk. J Natl Cancer Inst. 2014;106(3):djt456. doi:10.1093/jnci/djt456.