Physiology of Vitamin D—Focusing on Disease Prevention

Vitamin D is a crucial micronutrient, critical to human health, and influences many physiological processes. Oral and skin-derived vitamin D is hydroxylated to form calcifediol (25(OH)D) in the liver, then to 1,25(OH)2D (calcitriol) in the kidney. Alongside the parathyroid hormone, calcitriol regulates neuro-musculoskeletal activities by tightly controlling blood-ionized calcium concentrations through intestinal calcium absorption, renal tubular reabsorption, and skeletal mineralization. Beyond its classical roles, evidence underscores the impact of vitamin D on the prevention and reduction of the severity of diverse conditions such as cardiovascular and metabolic diseases, autoimmune disorders, infection, and cancer. Peripheral target cells, like immune cells, obtain vitamin D and 25(OH)D through concentration-dependent diffusion from the circulation. Calcitriol is synthesized intracellularly in these cells from these precursors, which is crucial for their protective physiological actions. Its deficiency exacerbates inflammation, oxidative stress, and increased susceptibility to metabolic disorders and infections; deficiency also causes premature deaths. Thus, maintaining optimal serum levels above 40 ng/mL is vital for health and disease prevention. However, achieving it requires several times more than the government’s recommended vitamin D doses. Despite extensive published research, recommended daily intake and therapeutic serum 25(OH)D concentrations have lagged and are outdated, preventing people from benefiting. Evidence suggests that maintaining the 25(OH)D concentrations above 40 ng/mL with a range of 40–80 ng/mL in the population is optimal for disease prevention and reducing morbidities and mortality without adverse effects. The recommendation for individuals is to maintain serum 25(OH)D concentrations above 50 ng/mL (125 nmol/L) for optimal clinical outcomes. Insights from metabolomics, transcriptomics, and epigenetics offer promise for better clinical outcomes from vitamin D sufficiency. Given its broader positive impact on human health with minimal cost and little adverse effects, proactively integrating vitamin D assessment and supplementation into clinical practice promises significant benefits, including reduced healthcare costs. This review synthesized recent novel findings related to the physiology of vitamin D that have significant implications for disease prevention.