Selenium supplementation for the primary prevention of cardiovascular disease

Abstract

Background

Selenium is a key component of a number of selenoproteins which protect against oxidative stress and have the potential to prevent chronic diseases including cardiovascular disease (CVD). However, observational studies have shown inconsistent associations between selenium intake and CVD risk; in addition, there is concern around a possible increased risk of type 2 diabetes with high selenium exposure.

Objectives

To determine the effectiveness of selenium only supplementation for the primary prevention of CVD and examine the potential adverse effect of type 2 diabetes.

Search methods

The following electronic databases were searched: the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 of 12, October 2012) on The Cochrane Library; MEDLINE (Ovid) (1946 to week 2 October 2012); EMBASE Classic + EMBASE (Ovid) (1947 to 2012 Week 42); CINAHL (EBSCO) (to 24 October 2012); ISI Web of Science (1970 to 24 October 2012); PsycINFO (Ovid) (1806 to week 3 October 2012); Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database and Health Economics Evaluations Database (Issue 4 of 4, October 2012) on The Cochrane Library. Trial registers and reference lists of reviews and articles were searched and experts in the field were approached. No language restrictions were applied.

Selection criteria

Randomised controlled trials on the effects of selenium only supplementation on major CVD end‐points, mortality, changes in CVD risk factors, and type 2 diabetes were included both in adults of all ages from the general population and in those at high risk of CVD. Trials were only considered where the comparison group was placebo or no intervention. Only studies with at least three months follow‐up were included in the meta‐analyses, shorter term studies were dealt with descriptively.

Data collection and analysis

Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information.

Main results

Twelve trials (seven with duration of at least three months) met the inclusion criteria, with 19,715 participants randomised. The two largest trials that were conducted in the USA (SELECT and NPC) reported clinical events. There were no statistically significant effects of selenium supplementation on all cause mortality (RR 0.97, 95% CI 0.88 to 1.08), CVD mortality (RR 0.97, 95% CI 0.79 to 1.2), non‐fatal CVD events (RR 0.96, 95% CI 0.89 to 1.04) or all CVD events (fatal and non‐fatal) (RR 1.03, 95% CI 0.95 to 1.11). There was a small increased risk of type 2 diabetes with selenium supplementation but this did not reach statistical significance (RR 1.06, 95% CI 0.97 to 1.15). Other adverse effects that increased with selenium supplementation, as reported in the SELECT trial, included alopecia (RR 1.28, 95% CI 1.01 to 1.62) and dermatitis grade 1 to 2 (RR 1.17, 95% CI 1.0 to 1.35). Selenium supplementation reduced total cholesterol but this did not reach statistical significance (WMD ‐ 0.11 mmol/L, 95% CI ‐ 0.3 to 0.07). Mean high density lipoprotein (HDL) levels were unchanged. There was a statistically significant reduction in non‐HDL cholesterol (WMD ‐ 0.2 mmol/L, 95% CI ‐ 0.41 to 0.00) in one trial of varying selenium dosage. None of the longer term trials examined effects on blood pressure. Overall, the included studies were regarded as at low risk of bias.

Authors' conclusions

The limited trial evidence that is available to date does not support the use of selenium supplements in the primary prevention of CVD.

Plain language summary

Selenium supplements for the prevention of cardiovascular disease

Use of selenium enriched foods, supplements and fertilizers has increased in recent years in many countries because of the perception that selenium may reduce the risk of cardiovascular disease and other chronic conditions. Therefore, it is important to understand the effects of a nutrient that is frequently supplemented on common conditions such as cardiovascular disease or diabetes. This review assessed the effects of providing selenium supplements to healthy adults in order to prevent the occurrence of cardiovascular disease. Whether selenium supplements would reduce the risk factors associated with heart disease was also examined. We found 12 trials in which 19,715 healthy adults were randomly assigned to receive selenium supplements or placebo. The vast majority of participants involved in these trials were male individuals from the US, where people are already well nourished and take large amounts of selenium from natural foods. Overall, the included studies were regarded as at low risk of bias. In our review, providing selenium supplements to healthy adults did not prevent the occurrence of major cardiovascular disease. The increased risk of developing type 2 diabetes when taking selenium supplements, as suggested in some previous studies, could not definitely be ruled out in our review. In summary, this review of the available evidence to date suggests that taking selenium supplements is neither beneficial nor harmful for cardiovascular disease, but it is probably unnecessary for those who are already well nourished and who take large amounts of selenium from natural foods.