Vitamin D Supplementation and Total Mortality: A Meta-analysis of Randomized Controlled Trials


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Vitamin D Supplementation and Total Mortality: A Meta-analysis of Randomized Controlled Trials

By Philippe Autier, MD; Sara Gandini, PhD; Arch Intern Med. 2007;167:1730-1737.
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Background: Ecological and observational studies suggest that low vitamin D status could be associated with higher mortality from life- threatening conditions including cancer, cardiovascular disease, and diabetes mellitus that account for 60% to 70% of total mortality in high-income countries. We examined the risk of dying from any cause in subjects who participated in randomized trials testing the impact of vitamin D supplementation (ergocalciferol [vitamin D2] or cholecalciferol [vitamin D3]) on any health condition.

Methods: The literature up to November 2006 was searched without language restriction using the following databases: PubMed, ISI Web of Science (Science Citation Index Expanded), EMBASE, and the Cochrane Library.

Results: We identified 18 independent randomized controlled trials, including 57 311 participants. A total of 4777 deaths from any cause occurred during a trial size–adjusted mean of 5.7 years. Daily doses of vitamin D supplements varied from 300 to 2000 IU. The trial size– adjusted mean daily vitamin D dose was 528 IU. In 9 trials, there was a 1.4- to 5.2-fold difference in serum 25-hydroxyvitamin D between the intervention and control groups. The summary relative risk for mortality from any cause was 0.93 (95% confidence interval, 0.87- 0.99). There was neither indication for heterogeneity nor indication for publication biases. The summary relative risk did not change according to the addition of calcium supplements in the intervention.

Conclusions: Intake of ordinary doses of vitamin D supplements seems to be associated with decreases in total mortality rates. The relationship between baseline vitamin D status, dose of vitamin D supplements, and total mortality rates remains to be investigated. Population-based, placebo-controlled randomized trials with total mortality as the main end point should be organized for confirming these findings.

Author Affiliations: International Agency for Research on Cancer, Lyon, France (Dr Autier); and the European Institute of Oncology, Milano, Italy (Dr Gandini).

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