BACKGROUND:  
Systemic inflammation is common in obesity and is a key risk factor in the development and progression of type 2 diabetes. In vitro and animal studies suggest that vitamin D has anti-inflammatory functions, which are thought to occur via inhibition of the nuclear factor kappa-B (NFκB) pathway. However, existing clinical trials of vitamin D supplementation are limited by short durations, low doses of vitamin D, and variability in participants’ vitamin D deficiency status, and no previous trials have investigated the effect of vitamin D supplementation on NFκB activity in vivo in humans. 

AIMS: 
We conducted a double-blind randomized placebo-controlled trial to investigate whether vitamin D supplementation, provided in a sufficient dose and duration to vitamin D-deficient individuals, would improve plasma inflammatory markers as well as reduce NFκB activity in peripheral blood mononuclear cells (PBMCs), compared to placebo.

METHODS: 
Sixty-five overweight or obese (body mass index (BMI)≥ 25 kg/m2), vitamin D-deficient (25-hydroxyvitamin D (25(OH)D)≤ 50 nmol/l) adults were randomized to either a bolus oral dose of 100,000 IU followed by 4,000 IU daily of cholecalciferol, or matching placebo for 16 weeks. Before and after intervention, we measured anthropometry: BMI, waist-to-hip ratio (WHR) and % body fat by dual energy X-ray absorptiometry; serum 25-hydroxyvitamin D (25(OH)D) concentrations (chemiluminescent immunoassays); plasma inflammatory markers: high sensitivity C-reactive protein (hsCRP; rate turbidimetry), tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukins (IL)-1β, -6, -8, -10, -12, -18, -23 and -33 (multiplex assay; flow cytometry); and NFκB activity in PBMCs (DNA-binding assays). Questionnaires were used to collect data on sun exposure habits and dietary vitamin D intake (3-day food record).

RESULTS: Fifty-four participants completed the study (35 males/ 19 females; age= 31.9 ± 8.5 years; BMI= 30.9 ± 4.4 kg/m2 (mean ± SD)). There were no differences in demographic, anthropometric, or biochemical parameters between vitamin D and placebo groups at baseline. Serum 25(OH)D concentrations increased with vitamin D supplementation compared with placebo (57.0 ± 21.3 versus 1.9 ± 15.1 nmol/l, p<0.001). There were no differences between vitamin D and placebo groups in changes in hsCRP, TNF- α, MCP-1, or any of the interleukins. Change in NFκB activity also did not differ between vitamin D and placebo groups. In multivariable models, differences in change in inflammatory markers and NFκB activity between groups remained non-significant after adjustment for baseline values, age, sex, and % body fat, and after further adjustment for season, sun exposure, and dietary vitamin D intake.

CONCLUSIONS: Although in-vitro studies suggest that vitamin D improves inflammation via inhibiting NFκB activity, our novel data from a randomized controlled trial suggest that vitamin D has no effect on inflammatory markers or in vivo NFκB activity in vitamin D-deficient and overweight or obese, but otherwise healthy adults. Further studies are needed to clarify whether vitamin D supplementation may improve inflammation in other populations, including those with existing chronic or inflammatory diseases such as type 2 diabetes.

Effect of vitamin D supplementation on inflammation and nuclear factor kappa-B activity in overweight or obese adults