Abstract
In-vitro studies suggest that vitamin D reduces inflammation by inhibiting nuclear factor kappa-B (NFκB) activity. Yet, no trials have examined the effects of vitamin D supplementation on NFκB activity in-vivo in humans. We conducted a double-blind randomized trial (RCT) examining effects of vitamin D supplementation on inflammatory markers and NFκB activity in peripheral blood mononuclear cells (PBMCs). Sixty-five overweight/obese, vitamin D-deficient (25-hydroxyvitamin D [25(OH)D] ≤ 50 nmol/L) adults were randomized to a single 100,000 IU bolus followed by 4,000 IU daily cholecalciferol or matching placebo for 16 weeks. We measured BMI, % body fat, serum 25(OH)D, high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor (TNF), monocyte chemoattractant protein-1 (MCP-1), interferon-gamma (IFN-γ), several interleukins, and NFκB activity in PBMCs. Fifty-four participants completed the study. Serum 25(OH)D concentrations increased with vitamin D supplementation compared to placebo (p < 0.001). Vitamin D and placebo groups did not differ in any inflammatory markers or NFκB activity (all p > 0.05). Results remained non-significant after adjustment for age, sex, and % body fat, and after further adjustment for sun exposure, physical activity, and dietary vitamin D intake. Although in-vitro studies report anti-inflammatory effects of vitamin D, our RCT data show no effect of vitamin D supplementation on inflammatory markers or NFκB activity in-vivo in humans.
Highlights
Chronic low-grade inflammation is common in obesity and plays an important role in the etiology of many chronic diseases including type 2 diabetes and cardiovascular disease[1]
Changes in inflammatory markers and NFκB activity did not differ between vitamin D and placebo groups in subgroups of participants with high C-reactive protein (CRP) (≥2.0 mg/L), IL-6 (≥21.0 pg/ml), tumor necrosis factor (TNF) (≥28.0 pg/ml) or NFκB activity (≥37.0 pg/μg protein). We compared those in the vitamin D group who reached a 25(OH)D concentration >70 nmol/L (n = 23) or >75 nmol/L (n = 18) at follow up with the placebo group (n = 23 with 25(OH)D < 50 nmol/L at follow up) and found no differences in any of the parameters measured. This randomized placebo-controlled trial examined the effect of oral cholecalciferol (100,000 IU bolus followed by 4,000 IU daily) supplementation for 16 weeks on pro- and anti-inflammatory markers and NFκB activity in overweight or obese but otherwise healthy individuals with vitamin D deficiency (25(OH)D ≤ 50 nmol/L)
Despite a significant increase in 25(OH)D concentration in the vitamin D group, we found no differences between vitamin D and placebo groups in any of the pro- or anti- inflammatory markers measured, including high-sensitivity C-reactive protein (hsCRP), TNF, monocyte chemoattractant protein-1 (MCP-1), IFN-α, and IL-1β, -6, -8, -10, -12, -18, -23, and -33, as well as no difference in NFκB activity in peripheral blood mononuclear cells (PBMCs)
Summary
Chronic low-grade inflammation is common in obesity and plays an important role in the etiology of many chronic diseases including type 2 diabetes and cardiovascular disease[1]. A recent systematic review of RCTs in overweight and obese individuals highlighted important limitations in existing trials including low supplementation doses, variability in participants’ vitamin D status, lack of assessment of lifestyle factors (diet, exercise, sun exposure), and the use of co-interventions including calcium and/or weight reduction programs in most trials[26]. These limitations have made it difficult to interpret findings
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