Effects of Vitamin D Supplementation and Seasonality on Circulating Cytokines in Adolescents: Analysis of Data From a Feasibility Trial in Mongolia

Abstract

Vitamin D deficiency is prevalent in human populations and has been linked to immune dysfunction. Here we explored the effects of cholecalciferol supplementation on circulating cytokines in severely vitamin D deficient [blood 25(OH)D << 30 nmol/L] adolescents aged 12-15 from Mongolia. The study included 28 children receiving 800 IU daily cholecalciferol for 6 months spanning winter and spring, and 30 children receiving placebo during the same period. The levels of 25(OH)D were assessed at baseline, 3 and 6 months. Twenty-one cytokines were measured in serum at baseline and at 6 months. Changes in 25(OH)D and cytokines were assessed using paired parametric tests. The median blood 25(OH)D concentration at baseline was 13.7 nmol/L (IQR = 10.0-21.7). Supplementation tripled blood 25(OH)D levels (p < 0.001) and was associated with elevated interleukin (IL)-6 (p = 0.043). The placebo group had reduced macrophage inflammatory protein (MIP)-1α (p = 0.007) and IL-8 (p = 0.034) at 6 months. Although limited by a small sample size, these findings suggest that cholecalciferol supplementation and seasonality may impact systemic immunity in adolescents, identifying chemokines as potentially important biomarkers of vitamin D status in this Northeast Asian population. Larger clinical trials are warranted to validate these results. Clinical Trial Registration: www.ClinicalTrial.org, Identifier: NCT01244204.

Keywords: Mongolia; Northeast Asia; adolescents; chemokines; cholecalciferol supplementation; cytokines; vitamin D deficiency.

Figure 1

Longitudinal changes in blood 25(OH)D concentrations in Mongolian children. Measurements were performed in vitamin D3 supplemented (n = 25) and placebo (n = 30) groups. Circles and bars denote means and 95% confidence intervals, respectively. Intraindividual changes within each group and inter-group differences were assessed by paired t-test and one-sample t test (p < 0.05), respectively. *p-values <0.001, NS, not significant.

Figure 2

Longitudinal changes in blood cytokine concentrations in Mongolian children. Measurements were performed on serum samples from vitamin D supplemented (n = 25) and placebo (n = 27) groups. Circles represent means of difference between log-transformed cytokine concentrations at the 6 month follow-up visit and baseline. Bars are 95% confidence intervals. Cytokine change is considered significant when its respective confidence intervals are found entirely on the positive or negative sides of the x-axis and are not spanning the “0” reference line. Stars denote the cytokines (MIP-1α, IL-8, IL-6) exhibiting statistically significant changes (p < 0.05) see Supplementary Figure 1 for participant-level data for these cytokines.