In 2013, Dr. Margaret Rayman, University of Surrey, United Kingdom, reviewed the published reports of randomized controlled trials in which a selenium supplement had been used as a single-agent treatment option and in which there had been a follow-up or sub-group analysis of the effect of the selenium supplementation on the risk of type-2 diabetes.
Dr. Rayman found 5 such studies. I want to summarize Dr. Rayman’s review, and then I want to see what studies have been done since 2013.
Selenium and diabetes studies
Nutritional Prevention of Cancer (NPC) study
In 2007, Dr. Saverio Stranges published the results of a post hoc analysis of the data from the Nutritional Prevention of Cancer study. In the NPC study, supplementation for an average of 4.5 years with 200 micrograms of a high selenium yeast preparation resulted in significant reductions in the risk of lung cancer, colon cancer, and prostate cancer [Clark 1996]. The age of most participants in the study was 63 years, plus or minus 10 years.
In his after-the-fact analysis, Dr. Stranges found that the risk of type-2 diabetes was higher only in the highest tertile (the highest third) of the study participants. These were the study participants with baseline plasma selenium concentrations greater than 121.6 micrograms per liter [Stranges].
Selenium and Vitamin E Cancer Prevention Trial (SELECT) study
In the SELECT study, a study enrolling males only, there was a study group in which the treatment option, compared with placebo group, consisted only of the 200 micrograms/day selenium supplement (without the vitamin E supplement). The follow-up period in the SELECT study was 5.5 years. The age of most participants was 64 years, plus or minus 6 years.
The selenium supplement used in the SELECT study was a synthetic selenomethionine preparation, different from the selenized yeast preparations that were used in other prevention of cancer studies that Dr. Rayman reviewed :
- the NPC study
- the PRECISE study
- the Watchful Waiting study
- the HDEL and selenium study
The SELECT study did not show significant reductions of the risk of cancer, and the study was halted early. The difference in the form of the selenium supplement and the difference in the beginning serum selenium levels of the participants were thought to be plausible explanations for the selenium supplementation’s non-effect on the risk of cancer in the SELECT study [Kristal 2008].
The mean baseline serum selenium concentration in the SELECT study was 136 micrograms per liter, considerably higher than the baseline level in the NPC study (114 micrograms per liter) and the PRECISE study (92 micrograms per liter).
In any case, analysis of the results of the selenium-only arm of the SELECT study showed that there was no statistically significant risk of type-2 diabetes with the selenium supplement [Klein 2011].
Prevention of Cancer by Intervention with Selenium (PRECISE) Study
The PRECISE study was shorter in duration than the NPC and SELECT studies. It lasted six months, enrolled elderly participants aged 60 – 74 years, and compared the effects of daily supplementation with 100, 200, or 300 micrograms of an organic high-selenium yeast preparation with the effects of a matching placebo treatment.
The mean baseline plasma selenium level in the PRECISE study was 92 micrograms per liter. There was no effect of the selenium supplementation on plasma adiponectin levels. Plasma adiponectin is a recognized bio-marker for and independent predictor of the risk of type-2 diabetes [Rayman 2012]. By extension, then, there was no effect of the selenium supplementation in the PRECISE study on the risk of developing diabetes.
Watchful Waiting Trial study
In the Watchful Waiting study, another all-male study, the participants were assigned randomly to a 200 micrograms/day group, an 800 micrograms/day group, or a placebo group for a five-year period. The selenium preparation used was a selenized yeast preparation. The age of most of the participants in the study was 73 years, plus or minus 6 years.
Serum glucose samples were collected every six months for the five-year period. There was no effect of the selenium supplementation, at either level — 200 micrograms/day or 800 micrograms/day — on the serum glucose levels [Algotar 2010].
HDEL and selenium study
Iranian researchers reported the results of a study designed to test whether daily supplementation with l-arginine and selenium alone or together increases the effect of a hypocaloric diet enriched with legumes (HDEL) in healthy premenopausal obese women over a six-week period. The selenium supplement was 200 micrograms daily of a selenized yeast preparation.
The researchers found that the selenium supplementation significantly lowered the fasting serum insulin levels and significantly lowered the levels of a marker for insulin resistance [Alizadeh 2012]. The selenium supplementation seemed to reduce the risk of diabetes and indicated a beneficial effect on insulin resistance.
Selenium studies since the Rayman review
Systematic analysis and meta-analysis
In 2013, Rees et al analyzed the data from 12 randomized controlled trials in which selenium was the only intervention substance used. The 12 studies enrolled a total of 19,715 study participants and tested the effect of selenium supplementation on the risk of heart disease. Their analysis showed a small increased risk of type-2 diabetes, but the increase was not statistically significant [Rees]. The small increase could have been caused by chance.
Selenium and prevention of type-2 diabetes
In 2014, S. Mao and colleagues did a meta-analysis of study data from four randomized controlled trials of selenium supplementation. The four trials had enrolled a total of 20,294 study participants of Caucasian background. In the analysis of the study data, the researchers did not see any significant change in the risk of developing diabetes [Mao]. In meta-regression analyses, neither age nor study length showed any impact on the relative risk [Mao].
Advancing age a possible co-variable
Thompson et al in the SEL/CEL trial of selenium supplementation for the prevention of recurrent colorectal adenomas found no overall increase in the risk of diabetes with selenium. The study participants took 200 micrograms of a high selenium yeast supplement or a placebo for a median 33 months. When the researchers did a sub-analysis, dividing the study participants into two groups — those under 63 years of age and those 63 years or older — there was an association between older age and selenium supplementation and diabetes risk [Thompson].
Selenium supplementation and pregnancy and insulin sensitivity
In 2016, J. Mao and Rayman and colleagues reported the results of a randomized controlled trial of the selenium supplementation of pregnant women at the rate of 60 micrograms per day. The pregnant women took the selenium supplements from the 12th week of gestation until delivery. The selenium supplementation had no adverse effect on insulin sensitivity and insulin resistance [Mao 2016].
Need for more studies
Clearly, before we draw any conclusions, we need evidence from more randomized controlled studies in which selenium is used as the single-agent intervention. Specifically, we need studies that investigate the association, if any, between selenium intakes and the risk of diabetes with a focus on the following differences in the study participants:
- baseline selenium status
- body weight (overweight? obese?)
- extent of exercise
- form and dosage of the selenium supplement
At issue is the determination of the optimal intake, given a specified baseline selenium status, to achieve the following health benefits:
- protection against oxidative damage to the cells
- enhancement of immune system function
- prevention of cancer and heart disease
- promotion of good thyroid function
Selenium is involved in the body’s glucose metabolism in ways that are not completely understood at present.
The evidence from clinical trials does not show definitively that selenium supplementation increases or decreases the risk of type-2 diabetes.
In the words of Professor Holger Steinbrenner of the Friedrich-Schiller-Universität in Jena, Germany, the selenium levels in normal diets and in dietary supplements are probably not enough to cause overt diabetes in healthy individuals [Steinbrenner].
The evidence from randomized controlled trials shows that the only increased risk of type 2 diabetes has been reported in individuals with unusually high baseline selenium levels. Moreover, this influence has been seen only in males. It may be that men and women respond to selenium in different ways [Ogawa-Wong].
Algotar, A. M., Hsu, C., Singh, P., & Stratton, S. P. (2013). Selenium supplementation has no effect on serum glucose levels in men at high risk of prostate cancer. Journal of Diabetes, 5(4), 465-470.
Alizadeh, M., Safaeiyan, A., Ostadrahimi, A., Estakhri, R., Daneghian, S., Ghaffari, A., & Gargari, B. P. (2012). Effect of L-arginine and selenium added to a hypocaloric diet enriched with legumes on cardiovascular disease risk factors in women with central obesity: a randomized, double-blind, placebo-controlled trial. Annals of Nutrition & Metabolism, 60(2), 157-168.
Clark, L. C., Combs, G. J., Turnbull, B. W., Slate, E. H., Chalker, D. K., Chow, J., & … Taylor, J. R. (1996). Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA, 276(24), 1957-1963.
Klein, E. A., Thompson, I. J., Tangen, C. M., Crowley, J. J., Lucia, M. S., Goodman, P. J., & … Baker, L. H. (2011). Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Jama, 306(14), 1549-1556.
Kristal, A. R. (2008). Are clinical trials the “gold standard” for cancer prevention research? Cancer Epidemiology, Biomarkers & Prevention, 17(12), 3289-3291.
Mao, J., Bath, S. C., Vanderlelie, J. J., Perkins, A. V., Redman, C. G., & Rayman, M. P. (2016). No effect of modest selenium supplementation on insulin resistance in UK pregnant women, as assessed by plasma adiponectin concentration. The British Journal of Nutrition, 115(1), 32-38.
Mao, S., Zhang, A., & Huang, S. (2014). Selenium supplementation and the risk of type 2 diabetes mellitus: a meta-analysis of randomized controlled trials. Endocrine, 47(3), 758-763.
Ogawa-Wong, A. N., Berry, M. J., & Seale, L. A. (2016). Selenium and Metabolic Disorders: An Emphasis on Type 2 Diabetes Risk. Nutrients, 8(2), 80.
Rayman, M. P., Blundell-Pound, G., Pastor-Barriuso, R., Guallar, E., Steinbrenner, H., & Stranges, S. (2012). A randomized trial of selenium supplementation and risk of type-2 diabetes, as assessed by plasma adiponectin. Plos One, 7(9), e45269.
Rayman, M. P., & Stranges, S. (2013). Epidemiology of selenium and type 2 diabetes: can we make sense of it? Free Radical Biology & Medicine, 651557-1564.
Rees, K., Hartley, L., Day, C., Flowers, N., Clarke, A., & Stranges, S. (2013). Selenium supplementation for the primary prevention of cardiovascular disease. The Cochrane Database of Systematic Reviews, (1), CD009671.
Steinbrenner, H. (2013). Interference of selenium and selenoproteins with the insulin-regulated carbohydrate and lipid metabolism. Free Radical Biology & Medicine, 65, 1538-1547.
Stranges, S., Marshall, J. R., Natarajan, R., Donahue, R. P., Trevisan, M., Combs, G. F., & Reid, M. E. (2007). Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Annals of Internal Medicine, 147(4), 217-223.
Thompson, P. A., Ashbeck, E. L., Roe, D. J., Fales, L., Buckmeier, J., Wang, F., & Lance, P. (2016). Selenium Supplementation for Prevention of Colorectal Adenomas and Risk of Associated Type 2 Diabetes. Journal of The National Cancer Institute, 108(12), djw152.
Wang, X., Yang, T., Wei, J., Lei, G., & Zeng, C. (2016). Association between serum selenium level and type 2 diabetes mellitus: a non-linear dose-response meta-analysis of observational studies. Nutrition Journal, 15(1), 48.
Disclaimer: remember, please, that the information in this article is not intended as medical advice and should not be used in that way.