Vitamin D supplementation for prevention of mortality in adults
Abstract
Background
The available evidence on vitamin D and mortality is inconclusive.
Objectives
To assess the beneficial and harmful effects of vitamin D for prevention of mortality in adults.
Search methods
We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded, and Conference Proceedings Citation Index‐Science (to January 2011). We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials.
Selection criteria
We included randomised trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention. Vitamin D could have been administered as supplemental vitamin D (vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol)) or an active form of vitamin D (1α‐hydroxyvitamin D (alfacalcidol) or 1,25‐dihydroxyvitamin D (calcitriol)).
Data collection and analysis
Six authors extracted data independently. Random‐effects and fixed‐effect model meta‐analyses were conducted. For dichotomous outcomes, we calculated the risk ratios (RR). To account for trials with zero events, meta‐analyses of dichotomous data were repeated using risk differences (RD) and empirical continuity corrections. Risk of bias was considered in order to minimise risk of systematic errors. Trial sequential analyses were conducted to minimise the risk of random errors.
Main results
Fifty randomised trials with 94,148 participants provided data for the mortality analyses. Most trials included elderly women (older than 70 years). Vitamin D was administered for a median of two years. More than one half of the trials had a low risk of bias. Overall, vitamin D decreased mortality (RR 0.97, 95% confidence interval (CI) 0.94 to 1.00, I2 = 0%). When the different forms of vitamin D were assessed separately, only vitamin D3 decreased mortality significantly (RR 0.94, 95% CI 0.91 to 0.98, I2 = 0%; 74,789 participants, 32 trials) whereas vitamin D2, alfacalcidol, or calcitriol did not. Trial sequential analysis supported our finding regarding vitamin D3, corresponding to 161 individuals treated to prevent one additional death. Vitamin D3 combined with calcium increased the risk of nephrolithiasis (RR 1.17, 95% CI 1.02 to 1.34, I2 = 0%). Alfacalcidol and calcitriol increased the risk of hypercalcaemia (RR 3.18, 95% CI 1.17 to 8.68, I2 = 17%). Data on health‐related quality of life and health economics were inconclusive.
Authors' conclusions
Vitamin D in the form of vitamin D3 seems to decrease mortality in predominantly elderly women who are mainly in institutions and dependent care. Vitamin D2, alfacalcidol, and calcitriol had no statistically significant effect on mortality. Vitamin D3 combined with calcium significantly increased nephrolithiasis. Both alfacalcidol and calcitriol significantly increased hypercalcaemia.
PICOs
Plain language summary
Vitamin D supplementation for prevention of mortality in adults
Numerous observational studies and randomised trials have observed that optimal vitamin D status has a positive effect on our health and may reduce cancers and cardiovascular diseases. However, a number of systematic reviews and meta‐analyses on vitamin D for prevention of mortality have reported variable results.
This systematic review analysed the influence of different forms of vitamin D on mortality. In the 50 trials that provided data for our analyses a total of 94,148 participants were randomly assigned to either vitamin D or no treatment or a placebo. All trials came from high‐income countries. The mean age of participants was 74 years. The mean proportion of women was 79%. The median duration of vitamin D administration was two years. Our analyses suggested that vitamin D3 reduces mortality by about 6%, which corresponds to 200 participants that need to be treated over a median of two years to save one additional life. Another supplemental form of vitamin D, vitamin D2 (ergocalciferol), as well as the active forms of vitamin D (alfacalcidol and calcitriol) had no significant effect on mortality. We also found evidence of adverse effects including renal stone formation (seen for vitamin D3 combined with calcium) and elevated blood levels of calcium (seen for both alfacalcidol and calcitriol). In conclusion, we found evidence that vitamin D3 decreases mortality in predominantly elderly women who are mainly in institutions and dependent care.
