The evidence for the use of selenium supplementation in cancer prevention is still inconclusive. Rataan et al suggest that the fault may lie in the design of the existing studies. At least two factors have contributed to this lack of conclusive evidence:
- the use of different compounds in the tests of selenium and cancer
- the different blood selenium levels of the study participants at baseline
As an example, Rataan et al cite the differences between the Nutritional Prevention of Cancer (NPC) trial and the Selenium and Vitamin E Cancer Prevention Trial (SELECT). In the NPC study, the researchers used a selenium-enriched yeast supplement. This yeast formulation contained mostly selenomethionine but also contained several other selenium species including Se-methylselenocysteine. In the SELECT study, the researchers used a 100% selenomethionine supplement. It now seems clear that the chemopreventive effect of selenium that was seen in the NPC study but not seen in the SELECT study must have come from some selenium species other than selenomethionine. The most likely chemopreventive selenium species is the Se-methylselenocysteine [Rataan 2022; Marshall 2017].
Note: In this review article, we are discussing cancer prevention, not cancer treatment.
Selenium-Deficient and Selenium-Replete Status
Moreover, in the NPC study, the study participants had, for the most part, low serum selenium levels at baseline. The study participants in the SELECT study were healthy individuals with replete serum selenium levels when they started the study [Rataan 2022]. In the NPC study, the mean baseline plasma selenium was 115 mcg/L. The upper boundary of the lowest plasma selenium tertile was 105 mcg/L. In the SELECT study, the median baseline serum selenium level was 135 mcg/L. Only 20% of the SELECT study participants had serum selenium levels below 121.6 mcg/L [Marshall 2017].
Rationale for Selenium Supplementation in Cancer Prevention
Adequate selenium status has a positive effect on the endocrine and immune systems. Adequate selenium status is necessary for apoptosis and for DNA repair. Adequate selenium status enhances selenium’s antioxidant properties. Given these factors, Rayman et al have hypothesized that selenium may play a role in the prevention of cancer [Rayman 2018].
- At low dietary selenium intakes, selenium supplementation may confer protection by increasing the concentration or activity of antioxidant selenoproteins.
- When dietary selenium intake is adequate, selenium supplementation is not needed and should be discouraged.
- A plasma selenium concentration of approximately 125 mcg/L is sufficient to cause complete expression of the selenoproteins.
Poor Planning and Coordination of Selenium and Cancer Studies
Demircan et al have shown that the studies investigating the effect of selenium supplementation cannot be used for direct comparison and for generalizability [Demircan 2024]:
- studies of healthy individuals, cancer patients, or individuals with a high risk of cancer incidence
- studies of individuals with widely different blood selenium status at baseline
- studies using different forms and different dosages and different durations of selenium supplementation
Much time and much money have been used to conduct many observational and experimental studies. The studies have generated masses of data. However, the data cannot be used, for the most part, to reach conclusions. This is the result of having a decentralized competitive-grant research system.
Recent Evidence: Selenium and Cancer Prevention
German ESTHER Study
In February 2024, Schöttker et al published data from the German ESTHER study, a cohort study that enrolled 7,186 participants aged 50–74 years at baseline. After 17 years, 2,126 study participants (30%) had died. Cancer accounted for 696 (10%) of the deaths.
The tertile of study participants with the lowest levels of selenium at baseline had selenoprotein P concentrations below 4.21 mg/L (= roughly 76 mcg/L of serum selenium). The study participants in the highest tertile of selenium level had selenoprotein P concentrations above 5.25 mg/L (= roughly 95 mcg/L of serum selenium). Comparing the top tertile to the lowest tertile, Schöttker et al found that the individuals in the top tertile of selenium status had a 1.3-fold better chance of not being diagnosed with cancer [Schöttker 2024].
The protective effect of selenium against cancer mortality was much stronger in men than in women. Selenium’s protective effect was also stronger in individuals with no history of cancer than in individuals with a history of cancer [Schöttker 2024].
Note: In this cohort study, higher selenium status also conferred strong protection in other conditions:
- 35% better all-cause survival
- 24% better cardiovascular survival
- two times better respiratory disease survival and gastrointestinal disease survival
Kuria meta-analysis and systematic study
In 2020, Kuria et al reported the results of a meta-analysis of 39 studies of the association between dietary intake of selenium and risk of different cancers. The data showed that selenium intake was inversely associated with overall cancer risk. Selenium intakes equal to and greater than 55 mcg/day decreased the risk of cancer. Moreover, additional selenium intake from supplements was protective against cancer at intake levels equal to or greater than 55 mcg/day [Kuria 2020; Alexander & Olsen 2023].
Conclusion: Selenium and the Prevention of Cancer
In individuals with low selenium intakes, selenium supplementation may enhance resistance against certain cancers when the chemical form and the dosage is appropriate. Zhang et al have summarized the evidence for this assertion [Zhang 2023].
Despite the publication of numerous human studies, it is not possible to reach fully unified conclusions about selenium supplementation and cancer prevention. Observational studies seem to suggest an inverse association between selenium intake/status and over-all cancer risk in populations low in selenium. However, the effect varies by cancer type [Alexander & Olsen 2023, Kuria 2020].
The outcome of the selenium supplementation and cancer prevention studies seems to depend on the chemical form of the selenium compound, the administered dosage, the baseline selenium status of the study population, and the type of cancer [Radomska 2021].
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Kuria A, Fang X, Li M, Han H, He J, Aaseth JO, Cao Y. Does dietary intake of selenium protect against cancer? A systematic review and meta-analysis of population-based prospective studies. Crit Rev Food Sci Nutr. 2020;60(4):684-694.
Marshall JR, Burk RF, Payne Ondracek R, Hill KE, Perloff M, Davis W, Pili R, George S, Bergan R. Selenomethionine and methyl selenocysteine: multiple-dose pharmacokinetics in selenium-replete men. Oncotarget. 2017 Apr 18;8(16):26312-26322.
Radomska D, Czarnomysy R, Radomski D, Bielawska A, Bielawski K. Selenium as a bioactive micronutrient in the human diet and its cancer chemopreventive activity. Nutrients. 2021 May 13;13(5):1649.
Rataan AO, Geary SM, Zakharia Y, Rustum YM, Salem AK. Potential role of selenium in the treatment of cancer and viral infections. Int J Mol Sci. 2022 Feb 17;23(4):2215.
Rayman MP, Winther KH, Pastor-Barriuso R, Cold F, Thvilum M, Stranges S, Guallar E, Cold S. Effect of long-term selenium supplementation on mortality: Results from a multiple-dose, randomised controlled trial. Free Radic Biol Med. 2018 Nov 1;127:46-54.
Schöttker B, Holleczek B, Hybsier S, Köhrle J, Schomburg L, Brenner H. Strong associations of serum selenoprotein P with all-cause mortality and mortality due to cancer, cardiovascular, respiratory, and gastrointestinal diseases in older German adults. Eur J Epidemiol. 2024 Feb;39(2):121-136.
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The information presented in this review article is not intended as medical advice. It should not be used as such.
15 Dec 2024