1. 2016;19;415-427Effect of Vitamin D Supplementation on Pain: A Systematic Review and Meta-analysis
   Systematic Review
   Carlene MM Lawes, MD, PhD, Robert Scragg, MD, PhD, Alistair W Stewart, BSc, Zhenqiang Wu, MSc, and Zarintaj Malihi, MSc.

BACKGROUND: There is conflicting evidence from previous qualitative reviews on the effect of vitamin D supplementation on pain.

OBJECTIVE: To determine with quantitative methods if vitamin D supplementation lowers pain levels.

STUDY DESIGN: Quantitative meta-analysis of published randomized controlled trials (RCTs).

SETTING: This meta-analysis examined all studies involving the effect of vitamin D supplementation on pain score.

Method: Electronic sources (Medline, Embase, Cochrane Central Register of Controlled Trials, clinical trials website, and Google scholar) were systematically searched for RCTs of vitamin D supplementation and pain from inception of each database to October 2015.

RESULTS: Nineteen RCTs with 3,436 participants (1,780 on vitamin D supplementation and 1,656 on placebo) were included in the meta-analysis. For the primary outcome (mean change in pain score from baseline to final follow-up), 8 trials with 1,222 participants on vitamin D and 1,235 on placebo reported a significantly greater mean decrease in pain score for the vitamin D group compared to placebo (mean difference -0.57, 95% CI: -1.00 to -0.15, P = 0.007). The effect from vitamin D was greater in patients recruited with pre-existing pain (P-value for interaction = 0.03). Fourteen studies (1,548 on vitamin D, 1,430 on placebo) reported the mean pain score at final follow-up outcome, and no statistical difference was observed (mean difference -0.06, 95%CI: -0.44 to 0.33, P = 0.78). In 4 studies which reported pain improvement (209 on vitamin D, 146 on placebo), the effect size although not significant, shows participants in the vitamin D supplementation group were more likely to report pain improvement compared with the placebo group (relative risk 1.38, 95%CI: 0.93 to 2.05, P = 0.11).

LIMITATIONS: Only a few studies reported the mean score change from baseline to final follow-up, and we do not have enough data to determine any modifying effect of baseline vitamin D status and different doses of vitamin D supplementation on pain.

CONCLUSION: A significantly greater mean decrease in pain score (primary outcome) was observed with vitamin D supplementation compared with placebo in people with chronic pain. These results suggest that vitamin D supplementation could have a role in the management of chronic pain.

Key words: Meta-analysis, pain, randomized controlled trials, vitamin D supplementation