Ordinary Doses of Vitamin D Linked to Lower Mortality

September 13, 2007 — Intake of ordinary doses of vitamin D supplements seems to be associated with decreases in total mortality rates, according to a meta-analysis of randomized controlled trials published in the September 10 issue of Archives of Internal Medicine.
"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," write Philippe Autier, MD, and Sara Gandini, PhD, from the International Agency for Research on Cancer in Lyon, France. "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."
The investigators searched PubMed, ISI Web of Science (Science Citation Index Expanded), EMBASE, and the Cochrane Library for trials of vitamin D supplements and identified 18 independent, randomized, controlled trials published in any language through November 2006.
These trials enrolled a total of 57,311 participants, and daily doses of vitamin D supplements varied from 300 to 2000 IU, with a trial size–adjusted mean daily vitamin D dose of 528 IU.
During a trial size–adjusted mean of 5.7 years, there were 4777 deaths from any cause. Nine trials showed a 1.4- to 5.2-fold difference between the intervention and control groups in serum 25-hydroxyvitamin D. The summary relative risk (RR) for all-cause mortality was 0.93 (95% confidence interval [CI], 0.87 - 0.99), and this did not change based on the addition of calcium supplements in the intervention. There did not appear to be any evidence of heterogeneity or publication biases.
"Intake of ordinary doses of vitamin D supplements seems to be associated with decreases in total mortality rates," the authors write. "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."
Limitations of the meta-analysis include those inherent in the trials themselves, lack of data concerning timing of deaths during trials, and inability to draw any conclusion on optimal vitamin D daily dose associated with mortality reduction.
"Our results also provide reassurance that at ordinary doses, long-term vitamin D supplementation does not seem to be associated with an overall adverse effect," the authors conclude. "Mechanisms by which vitamin D supplementation would decrease all-cause mortality are not clear."
The authors have disclosed no relevant financial relationships.
In an accompanying editorial, Edward Giovannucci, MD, ScD, from the Harvard School of Public Health in Boston, Massachusetts, notes that this analysis was not able to consider the specific causes of death.
"Research on vitamin D should be continued to clearly elucidate the specific benefits and optimal intakes and levels of vitamin D," Dr. Giovannucci writes. "Nonetheless, based on the total body of evidence of health conditions associated with vitamin D deficiency, abetted with the results from this meta-analysis, a more proactive attitude to identify, prevent, and treat vitamin D deficiency should be part of standard medical care. From a broader public health perspective, the roles of moderate sun exposure, food fortification with vitamin D, and higher-dose vitamin D supplements for adults need to be debated."
Dr. Giovannucci has disclosed no relevant financial relationships.
Arch Intern Med. 2007;167:1709-1710, 1730-1737.