It is now clear that Cholecalciferol (D3) has important roles in addition to its classic effects on calcium and bone homeostasis. As the vitamin D receptor is expressed on immune cells (B cells, T cells and antigen presenting cells) and these immunologic cells are all are capable of synthesizing the active vitamin D metabolite, vitamin D has the capability of acting in an autocrine manner in a local immunologic milieu. Vitamin D can modulate the innate and adaptive immune responses. Deficiency in vitamin D is associated with increased autoimmunity as well as an increased susceptibility to infection. As immune cells in autoimmune diseases are responsive to the ameliorative effects of vitamin D, the beneficial effects of supplementing vitamin D deficient individuals with autoimmune disease may extend beyond the effects on bone and calcium homeostasis.
The immune system defends the body from foreign, invading organisms, promoting protective immunity while maintaining tolerance to self. The implications of vitamin D deficiency on the immune system have become clearer in recent years and in the context of vitamin D deficiency, there appears to be an increased susceptibility to infection and a diathesis, in a genetically susceptible host to autoimmunity.
Vitamin D has been used (unknowingly) to treat infections such as tuberculosis before the advent of effective antibiotics. Tuberculosis patients were sent to sanatoriums where treatment included exposure to sunlight which was thought to directly kill the tuberculosis. Cod liver oil, a rich source of vitamin D has also been employed as a treatment for tuberculosis as well as for general increased protection from infections.
There have been multiple cross-sectional studies associating lower levels of vitamin D with increased infection. One report studied almost 19,000 subjects between 1988 and 1994. Individuals with lower vitamin D levels (<30 ng/ml) were more likely to self-report a recent upper respiratory tract infection than those with sufficient levels, even after adjusting for variables including season, age, gender, body mass and race. Vitamin D levels fluctuate over the year. Although rates of seasonal infections varied, and were lowest in the summer and highest in the winter, the association of lower serum vitamin D levels and infection held during each season. Another cross-sectional study of 800 military recruits in Finland stratified men by serum vitamin D levels. Those recruits with lower vitamin D levels lost significantly more days from active duty secondary to upper respiratory infections than recruits with higher vitamin D levels (above 40nmol). There have been a number of other cross-sectional studies looking at vitamin D levels and rates of influenza as well as other infections including bacterial vaginosis and HIV. All have reported an association of lower vitamin D levels and increased rates of infection.
The beneficial effects of vitamin D on protective immunity are due in part to its effects on the innate immune system. It is known that macrophages recognize lipopolysacharide LPS, a surrogate for bacterial infection, through toll like receptors (TLR). Engagement of TLRs leads to a cascade of events that produce peptides with potent bacterialcidal activity such as cathelocidin and beta defensin. These peptides colocalize within phagosomes with injested bacteria where they disrupt bacterial cell membranes and have potent anti-microbacterial activity.