All-cause mortality, cancer mortality, and cardiovascular disease mortality are all three significantly associated with selenium status in the blood. Higher selenium status correlates with lower mortality risk. In particular, the inverse relationship with all-cause mortality was strong among different study populations in different countries and in different study regions. The inverse relationship was strong with different selenium measurement methods, with different study recruitment years, and with different study sizes and study follow-up lengths [Cui 2025].
These are the conclusions from a systematic review and meta-analysis of 20 observational studies that enrolled 67,534 study participants. The studies included 17 studies of all-cause mortality, 7 studies of cancer mortality, and 9 studies of cardiovascular disease mortality. The review shows that a concentration increase of one standard deviation in serum or plasma selenium biomarkers was associated with 13% lower all-cause mortality, 15% lower cancer mortality, and 11% lower cardiovascular mortality [Cui 2025].
Cui et al urge that well-designed randomized controlled trials of the health effects of selenium supplementation be carried out in study participants with low selenium status. Such RCTs could perhaps confirm that a cause-effect relationship exists between selenium status and mortality risk. The researchers suggest that selenium supplementation of individuals with low selenium intakes could perhaps be a “highly cost-effective and safe intervention” to prolong the healthy life-span of older adults who do not get enough selenium in their food [Cui 2025].
Observational Studies versus Randomized Controlled Trials
Cui et al note that the pooled results from existing RCTs do not show the same statistically significant relationship between selenium status and mortality that the observational studies show. The researchers attribute this anomaly to the inclusion of data from the very large SELECT trial in the pertinent meta-analyses.
SELECT Randomized Controlled Trial in the USA
The Selenium and Vitamin E Cancer Prevention Trial (SELECT) enrolled over 35,000 men in the United States, Canada and Puerto Rico. The study participants lived in regions with high concentrations of selenium in soil. The SELECT study participants had serum selenium levels (median: 135 mcg/L) much higher than the sub-optimal serum selenium concentration (less than 100 mcg/L). Consequently, the SELECT study participants did not benefit from selenium supplementation. The great majority of the study participants did not need selenium supplementation [Lippman 2009].
With such a large number of study participants, the data from the SELECT trial overwhelm the results from other selenium supplementation studies [Cui 2025].
PRECISE Randomized Controlled Trial in Denmark
Cui et al clarify some points of confusion about the Denmark PRECISE study.
- Denmark is a country with low selenium intakes, i.e., Denmark is an appropriate place to study the effect of selenium supplementation.
- Comparison of all-cause mortality rates in the treatment group that received 300 mcg/day for five years with the placebo group showed a non-significant rise in all-cause mortality at the end of the five-year treatment period.
- Comparison of all-cause mortality rates in the 300 mcg/day treatment group and the placebo group after an additional ten years of no supplementation showed a surprising significant increase in all-cause mortality.
Cui et al note that the period in which 80% of the deaths occurred was the unsupplemented follow-up period. Many unknown things could have happened to the study participants during the unsupplemented period. These unexplained factors during the unsupplemented period could well be the cause of increased mortality.
What is needed is a new RCT with a full 10 years of selenium supplementation compared with placebo [Cui 2025].
KiSel-10 Study in Sweden
In Sweden, Prof. Urban Alehagen and a team of researchers conducted a study of elderly live-at-home Swedish citizens. At the study start, the participants were notably low in selenium: average serum selenium concentration of 67.1 mcg/L. For four years, Prof. Alehagen et al administered combined selenium and Coenzyme Q10 supplements or matching placebos to the study participants. The supplementation regime reduced cardiovascular mortality significantly [Alehagen 2022].
Conclusions: Selenium Status and Mortality Risk
Perhaps as many as a billion people worldwide have low selenium intakes and sub-optimal selenium status.
Low selenium status is associated with significantly increased mortality risk.
People living in selenium-poor regions of the world may need selenium supplementation.
Sources
Alehagen U et al. Improved cardiovascular health by supplementation with selenium and coenzyme Q10: applying structural equation modelling (SEM) to clinical outcomes and biomarkers to explore underlying mechanisms in a prospective randomized double-blind placebo-controlled intervention project in Sweden. Eur J Nutr. 2022 Sep;61(6):3135-3148.
Cui et al. Associations of selenium status with all-cause and cause-specific mortality: a systematic review and meta-analysis of cohort studies. Redox Biology. 2025;103755. Journal PrePub.
Lippman SM 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). JAMA. 2009;301(1):39-51.
Rayman MP et al. Effect of long-term selenium supplementation on mortality: Results from a multiple-dose, randomized controlled trial. Free Radic Biol Med. 2018;127:46-54.
The information presented in this review article is not intended as medical advice. It should not be used as such.