Vitamin D is often recognized for its impact on bone metabolism, but it is also an important regulator of immune function.

In patients suffering from sepsis, parathyroid hormone (PTH) typically increases while calcium levels decrease. In normal physiologic circumstances, PTH would stimulate increased conversion of the substrate 25(OH)D to the active 1,25(OH)D via the 1α-hydroxylase enzyme primarily found in renal tissues. 

As sepsis continues, though, PTH levels tend to decrease while calcium levels typically remain depressed. This altered relationship indicates that other factors are altering the regulation of this pathway (Endoc Metab Immune Disord Drug Targets 2013;13:135-142). It is known that various other tissues also express 1α-hydroxylase activity, and the purpose primarily may be for immunologic responses (J Steroid Biochem Mol Biol 2007;103:316-321).


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Active 1,25 (OH)D stimulates the vitamin D nuclear receptor in neutrophils and macrophages to upregulate the production of cathelcidin and defensin. These peptides have antimicrobial properties and improve overall immune function.

Vitamin D and sepsis

Although 1,25(OH)D is the active form of vitamin D, the body keeps this hormone more tightly regulated than its substrate, 25(OH)D. Thus, the substrate is more often used to assess vitamin D status and deficiency. Multiple studies have found increased risks of sepsis and mortality with low vitamin D status. 

Patients with vitamin D deficiency (serum 25(OH)D 15 ng/mL or less) and insufficiency (25(OH)D 15-30 ng/mL) have an increased risk for sepsis (Crit Care Med 2013; published online ahead of print). Those with deficiency had a 1.5 times increased risk. 

Each 5 ng/mL increase in 25(OH)D was associated with a 4% reduction of risk. Mortality risk after 30 days was 1.6 times greater in septic patients with deficient or insufficient vitamin D. In subanalyses of patients with more defined physiologic data for analysis of APACHE II-defined sepsis, every 5 ng/mL increase in 25(OH)D resulted in a 19% reduced risk of sepsis or septic shock.