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Eur J Clin Nutr. 2017 Aug;71(8):931-943. doi: 10.1038/ejcn.2017.67. Epub 2017 May 10.

The impact of cholecalciferol supplementation on the systemic inflammatory profile: a systematic review and meta-analysis of high-quality randomized controlled trials.

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Food, Nutrition &Health, School of Public Health, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia.
School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia.
Occupation and the Environment, School of Public Health, Curtin University, Perth, WA, Australia.


Causal links between vitamin D status [25(OH)D] and systemic inflammation were examined through a systematic review of randomized controlled trials (RCTs). Selected RCTs were ⩾12 weeks, conducted in adults free of acute inflammatory disease, and of high-quality (Jadad score ⩾3). Of 14 studies that met our criteria, 9 studies (15 study arms) permitted extraction of data. There was no effect on the weighted mean difference (WMD) of IL-6 (WMD (95% confidence interval)=0.1, (-0.166, 0.366) pg/ml, P=0.462) or C-reactive protein (CRP) (WMD=-0.324, (-1.007, 0.359) mg/l, P=0.352). Subgroup analyses of trials achieving ⩾80 nmol/l indicated a trend for lower CRP (WMD=-0.834, (-1.726, 0.058) mg/l, P=0.067), however heterogeneity was significant (I2=66.7%, P=0.017). Studies employing a low dose (<1000 IU/d) showed increased CRP (WMD=0.615, (0.132, 1.098), P=0.013). In contrast, ⩾1000 IU/d had a favourable effect on CRP (WMD=-0.939, (-1.805, -0.073), P=0.034) but heterogeneity was significant (I2=61.3%, P=0.017). Meta-regression indicated that older age predicted a significant decrease in IL-6 (β=-0.02, (-0.034, -0.006) pg/ml, P=0.013) and CRP (β=-0.06, (-0.103, -0.017), P=0.01), whereas a greater percentage of females (β=0.027, (0.011, 0.044), P=0.004) and longer study duration independently predicted a higher WMD for CRP (β=0.049, (0.018, 0.079), P=0.005). Available high-quality RCTs did not support a beneficial effect of cholecalciferol on systemic IL-6 and CRP. Future studies should consider the confounding effects of age, gender and study duration, while possibly targeting an achieved 25(OH)D ⩾80 nmol/l.

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