The Serum 25-Hydroxyvitamin D Response to Supplemental Vitamin D Is Temporarily Blunted with Elevated Circulating Cytokines at Baseline

This investigation examined whether initially elevated serum cytokine concentrations associate with a lower serum 25-hydroxyvitamin D (25(OH)D) increase shortly after initiating supplemental vitamin D. This secondary analysis combined data from separate randomized, double-blind, placebo-controlled studies consisting of reportedly healthy adults and individuals with knee osteoarthritis who received supplemental vitamin D. Subjects were separated into 2 groups based on serum IL-6 concentrations at baseline (Bsl; prior to supplemental vitamin D): (1) non-elevated IL-6 (<2.5 pg/mL; n = 22) or (2) elevated IL-6 (≥2.5 pg/mL; n = 11). Reportedly healthy adults and knee osteoarthritis subjects with elevated IL-6 were matched (1:2) to those with non-elevated IL-6. Matching was based on condition (healthy adults and knee osteoarthritis), age (±3.0 y ), sex, body mass index (±3.0 kg/m ² ), and dose of supplemental vitamin D (cholecalciferol, 4,000 or 8,000 IU/d). Serum cytokine concentrations at Bsl and serum 25(OH)D concentrations at Bsl and following 7 and 28-d of daily vitamin D supplementation are reported here. Serum IL-6 and other cytokines (GM-CSF, IL-10, IL-13, IL-1β, IL-2, IL-4, IL-5, IL-7, IL-8, and TNF-α) were significantly increased in the elevated compared to the non-elevated IL-6 group at Bsl (all P < 0.05). Serum 25(OH)D concentrations at Bsl, 7-d, and 28-d were not significantly different between IL-6 groups. The increase in serum 25(OH)D from Bsl to 7-d (7-dΔ) was significantly lower in the elevated compared to the non-elevated IL-6 group ( P < 0.05). The 7-dΔ in serum 25(OH)D displayed modest inverse associations with Bsl serum 25(OH)D (β = −0.46, P < 0.01) and IL-6 (β = −0.43, P < 0.01). However, the 28-dΔ in serum 25(OH)D was inversely associated with Bsl serum 25(OH)D (β = −0.57, P = 0.01) but not with Bsl serum IL-6 (β = 0.10, P = 0.31). We conclude that the serum 25(OH)D response to supplemental vitamin D is temporarily blunted with elevated baseline circulating IL-6 and other cytokines, but this response diminished as supplementation continued.