Selenium, antioxidants, cardiovascular disease, and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials.

The American journal of clinical nutrition. 2020;112(6):1642-1652

Plain language summary

Oxidative damage is a shared characteristic in chronic diseases such as cardiovascular disease (CVD), diabetes, cancer and ageing. Antioxidants mitigate the impact of oxidants and have been widely investigated in ageing and disease. However, the evidence for supplementary antioxidants has been mixed and some authorities have advised against the use of certain single nutrients for the prevention of CVD or cancer. This systematic review and meta-analysis focused on selenium due to its vital role in the antioxidant system and associations of low selenium blood levels with increased risk of CVD, cancers and death. The study included 43 randomised controlled trials (RCTs) evaluating the effect of supplemental selenium and antioxidants with or without selenium and their impact on CVD risk, cancer and all-cause mortality. Overall supplemental selenium or antioxidants alone did not seem to be associated with CVD outcomes, cancer, CVD and cancer mortality, or all-cause mortality. On close examination, a decreased risk was seen for CVD mortality when antioxidants were combined with selenium, whilst antioxidant mixtures without selenium demonstrated an increased risk in all-cause mortality. The findings did not seem to be influenced by dietary selenium intake. The authors suggested that inclusion of selenium as part of an antioxidant mix could be key for an antioxidant associated risk reduction. However, in the absence of further long term studies, a balanced antioxidant-rich diet was advocated as the safest approach. In clinical practice, where antioxidant support beyond diet is warranted, supplemental antioxidant use should be concurrent with adequate selenium supplementation, with dose benefits of 50-200mcg observed.


BACKGROUND Antioxidants have been promoted for cardiovascular disease (CVD) risk reduction and for the prevention of cancer. Our preliminary analysis suggested that only when selenium was present were antioxidant mixtures associated with reduced all-cause mortality. OBJECTIVE We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the effect of selenium supplementation alone and of antioxidant mixtures with or without selenium on the risk of CVD, cancer, and mortality. METHODS We identified studies using the Cochrane Library, Medline, and Embase for potential CVD outcomes, cancer, and all-cause mortality following selenium supplementation alone or after antioxidant supplement mixtures with and without selenium up to June 5, 2020. RCTs of ≥24 wk were included and data were analyzed using random-effects models and classified by the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS The meta-analysis identified 9423 studies, of which 43 were used in the final analysis. Overall, no association of selenium alone or antioxidants was seen with CVD and all-cause mortality. However, a decreased risk with antioxidant mixtures was seen for CVD mortality when selenium was part of the mix (RR: 0.77; 95% CI: 0.62, 0.97; P = 0.02), with no association when selenium was absent. Similarly, when selenium was part of the antioxidant mixture, a decreased risk was seen for all-cause mortality (RR: 0.90; 95% CI: 0.82, 0.98; P = 0.02) as opposed to an increased risk when selenium was absent (RR: 1.09; 95% CI: 1.04, 1.13; P = 0.0002). CONCLUSION The addition of selenium should be considered for supplements containing antioxidant mixtures if they are to be associated with CVD and all-cause mortality risk reduction. This trial was registered at as CRD42019138268.

Lifestyle medicine

Fundamental Clinical Imbalances : Immune and inflammation
Patient Centred Factors : Mediators/Cardiovascular disease
Environmental Inputs : Diet ; Nutrients
Personal Lifestyle Factors : Nutrition
Functional Laboratory Testing : Not applicable

Methodological quality

Jadad score : Not applicable
Allocation concealment : Not applicable