Korean J Pain. 2017 Oct;30(4):250-257. doi: 10.3344/kjp.2017.30.4.250. Epub 2017 Sep 29.
Makrani AH1, Afshari M2, Ghajar M1, Forooghi Z1, Moosazadeh M3.
1 Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
2 Department of Community Medicine, Zabol University of Medical Sciences, Zabol, Iran.
3 Health Science Research Center, Addiction Institute, Mazandaran University of Medical Sciences, Sari, Iran.
Note: 9 of the 12 studies measured a decreased level of Vitamin D for those with Fibro.
Vitamin D is a cofactor responsible for autoimmune disorders. There is no agreement in the studies investigating the association between vitamin D and fibromyalgia. This study aims to combine the conflicting results of the primary studies which compared these patients with control groups regarding the serum concentration of vitamin D. This meta-analysis has been designed based on PRISMA guidelines. Relevant keywords were searched in PubMed, Science direct, Scopus, Cochrane, and Google scholar and primary studies were selected. After screening the eligible studies according to inclusion/exclusion criteria, we investigated the risk of bias in the selected studies and also the heterogeneity between the primary results using Cochrane (Q) and I-squared (I2) indices. The primary results were combined using inverse variance method and Cohen statistics as well as a random effects model. Publication bias was assessed using Egger test. Sensitivity analysis was applied to investigate the influence of each primary study on the final result of the meta-analysis. Suspected factors in the heterogeneity were assessed using meta-regression models.
We entered 12 eligible studies in the meta-analysis including 851 cases compared with 862 controls. The standardized mean difference of Vitamin D between the two groups was -0.56 (95% confidence interval: -1.05, -0.08). Our meta-analysis showed that vitamin D serum levels of patients with fibromyalgia was significantly lower than that of control group.
PMID: 29123619 PMCID: PMC5665736 DOI: 10.3344/kjp.2017.30.4.250
Review of the primary studies selected for meta-analysis showed that most of them found lower levels of vitamin D among FM patients than the control groups. But, four studies indicated that these patients had higher levels of vitamin D than healthy individuals. However, pooled estimates showed that FM patients in comparison with the control groups had, on average, 0.56 units lower concentration of vitamin D. Most of these studies compared age-matched cases/controls and half of these studies investigated only women in the premenopausal stage.
Vitamin D deficiency is common worldwide especially among children, women and the elderly population . Half of the eight studies indicating lower concentrations of vitamin D among patients with FM had been carried out in Turkey. It seems that in such a country patients with FMS had low sunlight exposure due to their limited functional capacity.
Olama et al.  investigated the serum levels of vitamin D in the individuals with and without FM and found lower blood vitamin D levels in patients. They also showed that vitamin D level is correlated with pain (according to the VAS score), Beck Depression score, and lumbar bone mineral density.
Okyay et al.  showed severe vitamin D deficiency among patients with FMS, which was similar to our results as well as those reported by Olama et al. , but was in contrast to the results observed by Okumus et al. , which was conducted among premenopausal women.
Olama et al. , Okyay et al. , Labeeb et al. , Baygutalp et al. , Altindag et al. , and Okumus et al.  reported significant correlations between vitamin D blood level and pain intensity. In addition, significant impacts of vitamin D on the quality of life in patients with FM based on the FIQ (Fibromyalgia Impact Questionnaire) were observed by Okyay et al. , Labeeb et al. , and Altindag et al. , which was in contrast to the results of Baygutlap et al. .
The largest sample size (205 cases and controls) was used in the study conducted by Mateos et al.  while the Baygutalp study  with 19 cases/controls included the smallest sample size. Both of these studies reported lower blood vitamin D levels in FM patients than in controls.
One of the limitations of the current meta-analysis was the considerable heterogeneity between the results of the primary studies and we could not detect the source of this heterogeneity by meta-regression models. However, there were differences in the inclusion/exclusion criteria between the primary studies which might be responsible for a part of this heterogeneity. In addition, some of the studies had considered the season of the study conduction but most of them had not taken it into consideration. This might be another explanation for the observed heterogeneity.
our meta-analysis revealed credible evidence that vitamin D can be a determinant factor for fibromyalgia. It seems that the policymakers should consider vitamin D supplementation among women as a preventive strategy. Moreover, further studies are recommended to investigate the role of other factors such as season, obesity, menopausal status, history of hysterectomy, diabetes mellitus and other metabolic disorders, malignancy, pregnancy, sexual hormone levels, and history of OCP consumption in the heterogeneity of the primary studies.
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