Vitamin D supplementation for prevention of mortality in adults.

The available evidence on vitamin D and mortality is inconclusive. To assess the beneficial and harmful effects of vitamin D for prevention of mortality in adults. 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. 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 D(3) (cholecalciferol) or vitamin D(2) (ergocalciferol)) or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol) or 1,25-dihydroxyvitamin D (calcitriol)). 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. 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, I(2) = 0%). When the different forms of vitamin D were assessed separately, only vitamin D(3) decreased mortality significantly (RR 0.94, 95% CI 0.91 to 0.98, I(2) = 0%; 74,789 participants, 32 trials) whereas vitamin D(2), alfacalcidol, or calcitriol did not. Trial sequential analysis supported our finding regarding vitamin D(3), corresponding to 161 individuals treated to prevent one additional death. Vitamin D(3) combined with calcium increased the risk of nephrolithiasis (RR 1.17, 95% CI 1.02 to 1.34, I(2) = 0%). Alfacalcidol and calcitriol increased the risk of hypercalcaemia (RR 3.18, 95% CI 1.17 to 8.68, I(2) = 17%). Data on health-related quality of life and health economics were inconclusive. Vitamin D in the form of vitamin D(3) seems to decrease mortality in predominantly elderly women who are mainly in institutions and dependent care. Vitamin D(2), alfacalcidol, and calcitriol had no statistically significant effect on mortality. Vitamin D(3) combined with calcium significantly increased nephrolithiasis. Both alfacalcidol and calcitriol significantly increased hypercalcaemia.

Stern, Cindy BHSc (Hons), PhDa; Young, Charlotte F. PhD, RNb,*; Skorga, Phyllis PhD, RN, CCMb,* Author Information

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the beneficial and harmful effects of vitamin D supplementation for prevention of mortality in adults.

Faculty Opinions recommendation of Vitamin D supplementation for prevention of mortality in adults.

The medical and legal risks associated with prescribing unlicensed vitamin D products were recently highlighted in the article by Davies et al. 1. This prompted a letter from Rhein who raised the concern that this may dissuade practitioners from prescribing vitamin D 2, and exacerbate the failure to address adequately the widespread problem of vitamin D deficiency and insufficiency 3. Rhein asks whether European licensed preparations could be used in the absence of suitable or affordable UK licensed preparations, with appropriate checks. We address this point with a practical approach to understanding the licensed status of different preparations of vitamin D and the relevance with respect to prescribing and dispensing them, particularly with the recent licensing of vitamin D. We are not setting out to provide guidance on the specific requirements for vitamin D replacement in vitamin D deficiency and insufficiency, or advice on specific dosing regimens, or selection of specific vitamin D preparations, for which we encourage the reader to consult their local or national guidelines. However, when following such guidelines, the prescriber should be reasonably satisfied that the likely benefits of prescribing higher doses of vitamin D products exceed the likely risks of harm. For example, with respect to evidence of benefit in terms of mortality, the Cochrane Review on vitamin D supplementation for prevention of mortality in adults by Bjelakovic et al. 4 which included 32 trials of vitamin D3, found that a dose of vitamin D3 below 800 units a day significantly decreased mortality (RR 0.92, 95% CI 0.87, 0.97, P = 0.005, I2 = 0%). However, a dose of vitamin D3 ≥ 800 units a day had no significant effect on mortality (RR 0.96, 95% CI 0.92, 1.00, P = 0.07, I2 = 0%). No effect on mortality was found with vitamin D2. In this commentary we present the risks of different categories of vitamin D products, with respect to their licensed status, within the context of the medico-legal framework.