Pietras and colleagues1 report that medium-term vitamin D2 (ergocalciferol) supplementation, 50 000 IU fortnightly, increases mean serum levels of 25-hydroxyvitamin D (25[OH]D) from 23.4 ng/mL (to convert to nanomoles per liter, multiply by 2.496) to 47 ng/mL. The achieved 25(OH)D levels exceed those observed in all but 3 of 394 international studies of healthy individuals.2 Pietras et al state that their practice is to continue such treatment indefinitely in order to prevent vitamin D deficiency.1 This recommendation is predicated on the results of observational studies that have reported associations between lower levels of 25(OH)D and an increased risk of an array of diseases, including autoimmune disorders, infectious diseases, cardiovascular diseases, and cancer.3 However, clinical trial evidence of efficacy of vitamin D supplementation does not exist for any of these diseases. Interventional studies do exist for skeletal end points. Meta-analyses of clinical trials of vitamin D coadministered with calcium demonstrate a marginal (relative risk reduction, 13%) protective effect against fractures, that is largely restricted to institutionalized elderly women,4 but vitamin D alone is ineffective and may even increase the risk of hip fracture (relative risk 1.15; 95% confidence interval 0.99-1.33).5
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