Vitamin D's role in health and disease: How does the present inform our understanding of the past?

While the role of vitamin D in supporting bone homeostasis during growth and maintenance is well substantiated, emerging evidence from ecological and observational studies suggests that a deficiency of vitamin D is associated with some cancers, immune disorders, cardiovascular disease, abnormal glucose metabolism, and neurodegenerative diseases. Biological plausibility for extraskeletal functions originated with the discovery of the vitamin D receptor in many body tissues and knowledge that the conversion of 25-hydroxyvitamin D (25(OH)D) to its active metabolite 1,25(OH)(2)D occurs in many cell types in addition to the kidney. The association of vitamin D status in humans as an etiological factor in developmental programming of bone, in some chronic diseases, and in all-cause mortality, in addition to skeletal morbidity, is supported by some but not all observational studies and randomized controlled trials. These clinical observations have implications for paleopathology, both in terms of specific comorbidities and the potential role of vitamin D in individuals who display no evidence for skeletal disease. This paper outlines recent clinical research on vitamin D metabolism and its novel biological roles, and explores the possible relevance to paleopathological research designs, theoretical models, and interpretations of disease experience.