Effect of vitamin D supplementation in chronic widespread pain: a systematic review and meta-analysis

Abstract

Chronic non-specific widespread pain (CWP) including fibromyalgia (FMS) is characterized by widespread pain, reduced pain threshold, and multiple tender points on examination, causing disability and decreased quality of life. Vitamin D has been proposed as an associated factor in CWP. This meta-analysis aimed to explore the benefit of vitamin D supplementation in the management of CWP. A comprehensive search of the CENTRAL, MEDLINE, and Embase databases was performed from inception through January 2017. The inclusion criterion was the randomized clinical trials' evaluating the effects of vitamin D treatment in adult subjects with CWP or FMS. CWP was defined as chronic recurrent musculoskeletal pain without secondary causes; FMS patients met the American College of Rheumatology criteria for FMS. Study outcome was assessed using visual analog scale (VAS) of pain intensity. Pooled mean difference (MD) of VAS and 95% confidence interval (CI) were calculated using a random-effect meta-analysis. Meta-regression analysis using a random-effects model was performed to explore the effects of change in vitamin D in the treatment group on difference in the mean of VAS. Sensitivity analysis was performed to evaluate the robustness of results. The between-study heterogeneity of effect size was quantified using the Q statistic and I . Data were extracted from four randomized controlled trials involving 287 subjects. Pooled result demonstrated a significantly lower VAS in CWP patients who received vitamin D treatment compared with those who received placebo (MD = 0.46; 95% CI 0.09-0.89, I = 48%). Meta-regression analysis revealed no significant relationship between the changes of vitamin D and VAS (coefficient = 0.04 (95% CI -0.01 to 0.08), p = 0.10). In this meta-analysis, we conclude that vitamin D supplementation is able to decrease pain scores and improve pain despite no significant change in VAS after increasing serum vitamin D level. Further studies need to be conducted in order to explore the improvement of functional status, quality of life, and the pathophysiological change that improves chronic widespread pain.

The effects of vitamin D supplementation on interictal serum levels of calcitonin gene-related peptide (CGRP) in episodic migraine patients: post hoc analysis of a randomized double-blind placebo-controlled trial

“…In this regard, it is demonstrated that following the trial, mean interictal level of CGRP in patients who received 2000 IU/ d of vitamin D was significantly lower than that of placebo receiving group. These results tie well with most of the previous studies wherein vitamin D supplementation effects were investigated in relation to pain, headache or migraine [8,[29][30][31][32][33].…”

Vitamin D levels in relation to low back pain during adolescence

“…A major Cochrane Database systematic review has also precluded a large beneficial effect of vitamin D supplementation in the treatment of painful conditions (30) . Some recent reviews showed no clear benefit of vitamin D supplementation in treatment of chronic non-specific musculoskeletal pain (50) , while other reviews showed that vitamin D supplementation is effective in reducing the pain score in chronic widespread pain (31,51,52) . Currently, vitamin D supplementation cannot be considered as an independent treatment for chronic pain (53) .…”

“…A recent review of randomised controlled trials that aimed to investigate the impact of vitamin D supplement on non-specific LBP or LBP resulting from osteoporosis showed that vitamin D supplementation is no more effective than placebo (27) and a major Cochrane Database systematic review has precluded a large beneficial effect of vitamin D in the treatment of painful conditions (30) . Despite these findings, a recent review showed that vitamin D supplementation is effective in reducing the pain score in chronic widespread pain (31) .…”

Cholecalciferol (Vitamin D3) Reduces Rat Neuropathic Pain by Modulating Opioid Signaling

“…They all conclude that there is modest level of evidence that vitamin D supplementation is efficient to treat chronic pain. In line, reviews of published randomized controlled trials report that vitamin D induces a significantly greater mean decrease in pain score for patients with chronic pain, compared with placebo [14][15][16], especially when patients display calcidiol [25(OH)D] levels below 30 nmol/L [17].…”