Vitamin D plays critical roles in many physiological processes, such as calcium balance, blood pressure regulation, immune function, and cell growth. Poor vitamin D status is implicated in the pathogenesis of many acute and chronic diseases, including rickets, osteoporosis, multiple sclerosis, and cancer. Data from a study presented at the European Endocrine Society’s recent conference suggest that free, circulating levels of vitamin D predict future disease risk in aging men better than measures of total vitamin D.

Vitamin D is a steroid hormone synthesized in the body in a multistep process following skin exposure to ultraviolet B light. The primary end-products in the process are 25-hydroxyvitamin D, or 25(OH)D (the major circulating form of vitamin D) and 1α,25-dihydroxyvitamin D, or 1,25(OH)2D (the active steroid hormone). The vast majority of these end-products in serum is bound to the vitamin D binding protein](https://academic.oup.com/jcem/article-abstract/63/4/954/2674725?redirectedFrom=fulltext). Total measures of 25(OH)D) and 1,25(OH)2D are associated with death rates from all causes. Some researchers have posited that only the free, unbound portion of vitamin D can exert its biological effects.

The authors of the study drew on data from the European Male Ageing Study, which involved nearly 2,000 men between the ages of 40 and 79 years. They measured total and free levels of 25(OH)D) and 1,25(OH)2D in the men’s blood.

They found that low total 25(OH)D) and 1,25(OH)2D levels among the men were associated increased risk of death. However, only low free 25(OH)D but not free 1,25(OH)2D levels predicted death from all causes. It’s noteworthy that this was an observational study, and the causal relationships and underlying mechanisms were not identified.

• Link to press release (and study abstract).