Endocrine Abstracts

Vitamin D deficiency is associated with several adverse skeletal and extra-skeletal outcomes including cancer, cardiovascular diseases, and mortality. Large randomized controlled trials (RCTs) have been conducted over the last few years with the aim to evaluate the cause-and-effect relationship of vitamin D and health outcomes. These RCTs failed to document significant effects of vitamin D on their primary outcome measures, whereas explorative analyses and meta-analyses suggest potential benefits of vitamin D regarding cancer mortality, acute respiratory infections, and asthma as well as chronic pulmonary disease exacerbations. Findings from vitamin D RCTs did not indicate significant safety concerns, except for RCTs in severely ill patients or with intermittent high-dose vitamin D treatment. Drawing final conclusions on vitamin D is, however, limited as the majority of vitamin D RCTs was not conducted in participants suffering from vitamin D deficiency and because many of these RCTs allowed for vitamin D supplementation in the placebo groups. Thus, the design of vitamin D RCTs adhered to drug RCTs and did not sufficiently account for vitamin D as a nutrient with a unique metabolism including its role as a precursor for the hormone calcitriol. Moreover, recently published RCTs did not specifically address the role of vitamin D in the prevention and treatment of rickets and osteomalacia, that remain the scientific basis for vitamin D guidelines. The learnings from the scientific history of vitamin D with its probably overwhelming hype based on observational studies and the severe limitations of large vitamin D RCTs, that still leave us with many knowledge gaps, will hopefully inform the design of future research activities on vitamin D and other research fields.