Background: In vitro and animal studies suggest that vitamin D has anti-inflammatory properties, which are thought to occur via inhibition of the nuclear factor kappa-B (NFkB) pathway. However, the association between vitamin D and in vivo NFkB activity in humans has not previously been reported. We investigated the associations between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and NFkB activity in peripheral blood mononuclear cells (PBMCs) as well as plasma inflammatory markers in healthy individuals. We hypothesized that 25(OH)D concentrations would be negatively associated with NFkB activity and pro-inflammatory markers downstream of NFkB, and positively associated with anti-inflammatory markers.
Methods: In 49 healthy normoglycaemic adults, we measured serum 25(OH)D concentrations (chemiluminescent immunoassay); anthropometry: BMI, waist-to-hip ratio, and %body fat (dual X-ray absorptiometry); plasma pro- and anti-inflammatory markers: high sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and IL-10 (ELISAs); and NFkB activity in PBMCs (DNA-binding assay).
Results: Twenty-one males and 28 females completed the study (age=31.6±10.2 years (mean±SD); BMI= 28.4±4.6 kg/m2; %body fat=30.2±9.3%). Mean 25(OH)D concentration was 48.2±24.5 nmol/l. There were no differences in 25(OH)D concentrations between genders and no association between 25(OH)D concentrations and age, BMI, or %body fat (all p>0.1). Serum 25(OH)D concentrations were positively associated with NFkB activity in PBMCs (r=0.48, p=0.0008) but not with any of the pro- or anti-inflammatory markers measured (all p>0.1). After adjustment for age, sex, and %body fat, 25(OH)D concentrations remained positively associated with NFkB activity in PBMCs (β=0.55, p<0.001).
Conclusion: Although in-vitro and animal studies suggest that vitamin D inhibits NFkB activity, our novel cross-sectional data from a cohort of healthy individuals suggest that vitamin D may regulate rather than inhibit the NFkB pathway. Large-scale intervention and mechanistic studies are needed to further investigate the effects of vitamin D on NFkB activity in vivo in humans.