Expanding non-calcaemic roles of vitamin D in therapeutics and their mechanisms

Vitamin D is a fat-soluble secosteroid that has a major role in calcium homeostasis in humans. The non-calcaemic roles of vitamin D have been extensively studied in the past few decades, and it is associated with various diseases, including cardiovascular, central nervous system, respiratory, infectious, autoimmune, metabolic disorders, and carcinomas. This review aimed to analyse the available evidence on non-calcaemic roles of vitamin D. We found that most observational studies concluded that low levels of vitamin D are associated with the incidence of many diseases, and some of the interventional studies supported this by positive outcomes after vitamin D supplementation. However, most of the systematic reviews and meta-analyses concluded that vitamin D supplementation has no therapeutic benefit, although these had limitations of heterogeneity of studies and inclusion of low-quality studies. We conclude that further high-quality randomized controlled trials with vitamin D supplementation should be conducted in diseases where there is a strong association between low levels of vitamin D and disease incidence in large observation studies.