Review: Vitamin D3 deficiency results in dysfunctions of immunity with severe fatigue and depression in a variety of diseases.

Recent immune data on vitamin D3 deficiency help to more clearly understand chronic fatiguing illnesses, such as autoimmune disorders, cancer and chronic fatigue syndrome (CFS). The vitamin D3 pathway is activated by stress and requires sufficient stores of precursor 25-hydroxyvitamin D3 for proper cell and immune functions. In vitamin D3 deficiency, secretion of the antimicrobial peptide cathelicidin is reduced, leading to impaired auto/xenophagy. As a result, phagocytosis, cytotoxicity, antigen processing and antigen presentation become dysregulated. In addition, vitamin D3 deficiency affects T- and B-lymphocyte activation, as well as quantity, maturation and function of regulatory natural killer T-cells and their counterparts in the gut, i.e. T-cell receptor-αβ, cluster of differentiation-8αα-positive intraepithelial lymphocytes. Consequently, innate and adaptive immunity become de-regulated, with microbial effects contributing further to this. Persistent infections, chronic inflammation and fatigue follow. Vitamin D3 substitution in such conditions may help to prevent or to ameliorate such chronic conditions, even in patients with cancer.