On its Selenium: Fact Sheet for Health Professionals website, the US Office of Dietary Supplements, an agency of the National Institutes of Health, writes that selenium might play a role in the prevention of cancer for the following reasons:
- selenium’s role in DNA repair
- selenium’s role in apoptosis
- selenium’s role in the endocrine and immune systems
- the antioxidant properties of certain selenoproteins
Different Selenium Compounds Have Different Effects on Cancer
The evidence from scientific research into the effect of selenium on cancer prevention can be confusing. Two observations about selenium supplementation may help to explain the confusing results from existing selenium and cancer studies:
1. Different selenium containing compounds differ widely in their ability to prevent cancer. Study results may vary according to the form of the selenium supplement tested.
2. Selenium supplementation may be more effective at cancer prevention in study participants with low baseline selenium status (below 100 mcg/L) and less effective in study participants with high baseline selenium status (above 135 mcg/L).
The most blatant example of this confusion was the choice of synthetic selenomethionine exclusively for use in the SELECT study (Selenium and Vitamin E Cancer Prevention Trial).
- Several selenium researchers have said that it would have been better to test a natural high-selenium yeast compound, which contains several different forms of organically bound selenium in addition to selenomethionine, e.g. selenocysteine, methyl-selenocysteine, etc.
- Moreover, it would have been better to test selenium in the study participants with a lower mean baseline serum selenium concentration (SELECT study: mean 135 mcg/L serum selenium).
Richie et al. [2014] have shown, in a direct comparison study, that high-selenium yeast supplements are associated with significant reductions in blood bio-markers of oxidative stress whereas selenomethionine supplements are not. The results from the Richie study suggest that it is not selenomethionine but, instead, other selenium-containing compounds that account for the decrease in oxidative stress.
A 2019 review done by Tan et al. suggests that the right selenium compounds, under the right circumstances, can be potent anticancer agents.
Inverse Relationship Between Selenium Intake and Overall Cancer Risk
In a 2020 meta-analysis and systematic review, Kuria et al. found an inverse relationship between selenium intake and overall cancer risk after they had adjusted for such potentially confounding factors as age, body mass index, and smoking. Their findings suggested that selenium is protective against cancer overall. It is to be expected that selenium’s anti-cancer effects vary with the form of the cancer.
A review of observational studies has shown an inverse association between selenium status and the risk of colorectal, prostate, lung, bladder, skin, esophageal, and gastric cancers [Dennert 2011].
A 2016 meta-analysis of 69 observational studies has shown that the extent of selenium exposure has different effects on different types of cancer. Higher selenium exposure is associated with decreased risk of breast cancer, lung cancer, esophageal cancer, gastric cancer, and prostate cancer but was not associated with reductions in the incidence of colorectal cancer, bladder cancer, and skin cancer [Cai 2016].
A 2011 meta-analysis investigated the preventive effect of selenium supplements on cancer in nine randomized controlled trials enrolling 32,110 study participants in supplement groups and 120,428 study participants in placebo groups [Lee 2011].
The pooled data from the nine randomized controlled trials showed that selenium supplementation alone had an overall preventive effect on cancer incidence. The relative risk for the selenium supplementation was a statistically significant 0.76, meaning that the relative risk was 24% less in the supplement groups than in the placebo groups [Lee 2011].
The authors of the study concluded that there is evidence for the use of selenium supplements alone for cancer prevention in low baseline serum selenium level populations and in populations at high risk for cancer [Lee 2011].
Selenium Supplementation and Prostate Cancer
Results from the randomized controlled Nutritional Prevention of Cancer Trial in the US showed that 200 mcg/day selenium from a high-selenium yeast preparation was associated with a 52% to 65% lower risk of prostate cancer [Duffield-Lillico 2003]. The anti-cancer effect was strongest in men who had a baseline serum selenium concentration of 121 mcg/L.
In a 2018 systematic review and meta-analysis of 38 studies with 36,419 cases and 105,293 controls, Sayehmiri et al. found an aggregated relative risk relationship between selenium and prostate cancer of 0.86, meaning that higher selenium status conferred a statistically significant 14% lower risk of prostate cancer.
- Case-control studies: 11% risk reduction
- Cohort studies: 23% risk reduction
- Randomized controlled studies: 10% risk reduction
In ten studies of selenium status and advanced prostate cancer, the relative risk of advanced prostate cancer was 33% lower with higher selenium status [Sayehmiri 2018].
In a 2012 systematic review and meta-analysis of 12 studies with a total of 13,254 participants and 5007 cases of prostate cancer, Hurst et al. found that the prostate cancer risk decreased with increasing plasma/serum selenium status from 60 mcg/L up to 170 mcg/L.
Serum Selenium Status and Various Types of Cancer
Breast cancer
In a prospective cohort study, researchers took blood samples from 538 women diagnosed with first primary invasive breast cancer. Each patient was assigned to one of four quartiles based on the distribution of serum selenium levels in the whole cohort. The researchers followed the patients from diagnosis until death or until last known alive date (mean follow-up 7.9 years).
The 10-year actuarial cumulative survival rate was 65.1% for women in the lowest quartile of serum selenium (52.1-76.7 mcg/L), compared to 86.7% for women in the highest quartile (94.7-171.5 mcg/L). The difference was statistically significant [Szwiec 2021].
In a study in which 1066 breast cancer cases were compared to controls regarding their pre-diagnostic serum selenium levels, researchers found lower overall mortality among women in the highest serum selenium quartile compared to the lowest serum selenium quartile. The hazard ratio was 0.63, indicating a 37% relative reduction associated with the higher serum selenium status [Sandsveden 2020].
Cervical cancer
Serum selenium levels in cervical cancer cases were significantly lower than in controls; subgroup analysis showed consistent results [He 2017].
Colorectal cancer
Serum concentrations of selenium are lower in colorectal cancer patients [Nawi 2019; Al-Ansari 2020].
Laryngeal cancer
In a prospective study of 296 patients diagnosed with laryngeal cancer, the five-year survival rate after diagnosis was 82.0% for individuals in the highest quartile of serum selenium status (above 66.8 mcg/L) and was 28.6% for individuals in the lowest quartile (below 50.0 mcg/L) [Lubinski 2018].
Oral cancer
In a case-control study of 235 oral cancer cases and 406 controls, researchers found that the highest tertile of serum selenium status was associated with significantly lower risk of oral cancer than the lowest tertile of serum selenium status. The researchers concluded that serum selenium levels may be significantly associated with oral cancer risk [Bao 2020].
Prostate cancer
Two meta-analyses of case-control studies have shown an inverse correlation between prostate cancer risk and higher serum selenium concentrations, suggesting a possible protective role for selenium [Cui 2017; Sayehmiri 2018].
Conclusions: Selenium to Reduce Cancer Risk
The jury is still out. The evidence from observation studies is stronger than the evidence from randomized controlled trials. A big reason for the inconclusiveness is the use of 100% synthetic selenomethionine in the SELECT study.
On the Selenium: Fact Sheet for Health Professionals, there is a qualified health claim for foods and dietary supplements containing selenium that states that while “some scientific evidence suggests that consumption of selenium may reduce the risk of certain forms of cancer… the FDA has determined that this evidence is limited and not conclusive.”
More research is needed to determine whether selenium supplements can help prevent various forms of cancer.
It is difficult to estimate one’s selenium intakes, so having one’s serum selenium status tested may be important.
The best evidence to date shows a beneficial effect of serum selenium status in the range from 100 mcg/L to approximately 170 mcg/L.
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The information presented in this review article is not intended as medical advice and should not be used as such.
15 June 2021