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

European Journal of Clinical Nutrition volume 71, pages 931–943 (2017)Cite this article

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Abstract

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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Acknowledgements

We would like to thank Drs Seth Sokol, Claudia Calderon, Geraldine Horigan, Maria Mulhern, Nasrin Sharifi and Louise Wamberg for generously providing us with additional information from their trials. Funding and sponsorship: This study was supported by strategic intramural funds from School of Public Health and School of Biomedical Sciences, Curtin University. EKC is the recipient of a PhD scholarship (APA) from the Australian Government.

Author contributions

EKC, KNK, MJS and PN designed the research; EKC, KNK and MJS conducted the research; YZ designed the data extraction sheet, planned and performed all statistical analyses; EKC, MJS and KNK wrote the paper; EKC and MJS had primary responsibility for final content. All authors have approved and contributed to the final written manuscript.

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  1. Food, Nutrition & Health, School of Public Health, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia

    E K Calton & M J Soares

  2. School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia

    K N Keane & P Newsholme

  3. Occupation and the Environment, School of Public Health, Curtin University, Perth, WA, Australia

    Y Zhao

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Calton, E., Keane, K., Newsholme, P. et al. The impact of cholecalciferol supplementation on the systemic inflammatory profile: a systematic review and meta-analysis of high-quality randomized controlled trials. Eur J Clin Nutr 71, 931–943 (2017). https://doi.org/10.1038/ejcn.2017.67

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