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Vitamin D supplements reduce mortality in a meta-analysis of 18 randomized trials.

Design & Participants: This is a meta-analysis of 18 randomized trials of which 13 were blinded or partially blinded. It includes 57,311 combined subjects from the 18 trials, of whom 4,777 died during a mean follow-up of 5.7 years

Study Medication & Dosage: Vitamin D, mostly as cholecalciferol ([D.sub.3]) at 300-2,000 IU/day (mean dose: 528 IU/day), mostly from oral supplementation, with two trials using injectable vitamin D

Primary Outcome Measure: Mortality data

Key Findings: The risk of dying during the course of follow-up declined a statistically significant 7% in those assigned to vitamin D supplementation (95% CI, 0.87-0.99). An 8% reduction was found in trials lasting at least three years.

Practice Implications: Gone are the days in which irradiated ergosterol ([D.sub.2]) and [D.sub.3] are considered interchangeable, with [D.sub.3] coming out the clear winner in terms of bioavailability. Gone are the days when 400 IU/day was considered an adequate supplemental dose, increasingly being replaced with calls for doses in the 1,000-2,000 IU/day range. Most importantly, gone are the days in which vitamin D is viewed as simply a way to affect calcium metabolism and bone health.

Evidence showing immune-enhancing and anti-cancer actions have been accompanied by new data proving the existence of extra-renal bioconversion from semi-activated 25(OH)[D.sub.3] to fully-activated 1,25(OH)[.sub.2][D.sub.3]. These new findings paired with the fact that vitamin D receptors exist in many parts of the body outside of bone have excited the research community, and rightly so. The consequences are of potentially great importance, and one way to gauge those consequences is through measurement of the one end-point no one can argue with--mortality.

Perhaps the worst way to gauge a drop in mortality, particularly cancer mortality, is through relatively short-term trials, as was the case with most of the trials that were studied in this meta-analysis. Yet despite this severe limitation, a significant reduction in mortality was reported. In an accompanying editorial, noted Harvard researcher Edward Giovannucci reminds us, "If vitamin D had an additional effect on the development of chronic diseases, which tend to have long latencies, these studies would have underestimated the total benefit of vitamin D supplementation. For cancer, there is some evidence for an influence of vitamin D on both incidence and survival." He goes on to remind us that 800 IU/day is insufficient to achieve even the bottom end of optimal serum 25(OH)[D.sub.3] levels, yet most of the subjects in these trials received far lower doses. He concludes by wondering, "Would even a greater reduction in mortality accrue than that suggested in this meta-analysis if intakes of vitamin D were higher, if compliance was improved, if higher levels of 25-hydroxyvitamin D were attained, and if the duration of supplementation was longer?"

Unfortunately, the meta-analysis did not separate data on the basis of cause of death. Nonetheless, we have reason to expect that despite the relatively short follow-up, much of the reduction may well have been due to a drop in cancer-related deaths.

Arguably--at least for Americans--vitamin D has rapidly become the single most important component in multivitamins (with the possible exception of folic acid for women who could become pregnant). Vitamin D has also become the vitamin for which doses typically found in multis is the most inadequate. This deficit is likely to change rapidly.

Autier P and Gandini S. "Vitamin D supplementation and total mortality--a meta-analysis of randomized controlled trials." Arch Intern Med, 2007; 167:1730-7.

By Steve Austin, N.D.
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Author:Austin, Steve
Publication:Original Internist
Geographic Code:1USA
Date:Dec 1, 2007
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