Vitamin D and fibromyalgia: a meta-analysis
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
Discussion (from PDF)
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.
- Olama SM, Senna MK, Elarman MM, Elhawary G. Serum vitamin D level and bone mineral density in premenopausal Egyptian women with fibromyalgia. Rheumatol Int 2013; 33: 185-92.
- Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, et al. The American college of rheumatology 1990 criteria for the classification of fibromyalgia. Report of the multicenter criteria committee. Arthritis Rheum 1990; 33: 160-72.
- Okyay R, Kogyigit B, Gursoy S. Vitamin D levels in women with fibromyalgia and relationship between pain, tender point count and disease activity. Acta Med Mediterr 2016; 32: 243-7.
- Labeeb AA, Al-Sharaki DR. Detection of serum 25(OH)-vitamin D level in the serum of women with fibromyalgia syndrome and its relation to pain severity. Egypt Rheumatol Rehabil 2015; 42: 196-200.
- Baygutalp NK, Baygutalp F, §eferoglu B, Bakan E. The relation between serum vitamin D levels and clinical findings of fibromyalgia syndrome. Dicle Med J 2014; 41: 446-50.
- Abokrysha NT. Vitamin D deficiency in women with fibromyalgia in Saudi Arabia. Pain Med 2012; 13: 452-8.
- Abeles AM, Pillinger MH, Solitar BM, Abeles M. Narrative review: the pathophysiology of fibromyalgia. Ann Intern Med 2007; 146: 726-34.
- Wood PB, Holman AJ, Jones KD. Novel pharmacotherapy for fibromyalgia. Expert Opin Investig Drugs 2007; 16: 829-41.
- Bergman S. Management of musculoskeletal pain. Best Pract Res Clin Rheumatol 2007; 21: 153-66.
- Arnold LM, Clauw DJ, Dunegan LJ, Turk DC; FibroCollaborative. A framework for fibromyalgia management for primary care providers. Mayo Clin Proc 2012; 87: 488-96.
- Bhatty SA, Shaikh NA, Irfan M, Kashif SM, Vaswani AS, Sumbhai A, et al. Vitamin D deficiency in fibromyalgia. J Pak Med Assoc 2010; 60: 949-51.
- Atherton K, Berry DJ, Parsons T, Macfarlane GJ, Power C, Hypponen E. Vitamin D and chronic widespread pain in a white middle-aged British population: evidence from a cross-sectional population survey. Ann Rheum Dis 2009; 68: 817-22.
- Plotnikoff GA, Quigley JM. Prevalence of severe hypo- vitaminosis D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc 2003; 78: 1463-70.
- Altindag O, Ogut E, Gur A, Gursoy S, Gunay M. Serum vitamin D level and its relation with clinical parameters in fibromyalgia as a neuropathic pain. Orthop Muscular Syst 2014; 3: 171.
- Ulusoy H, Sarica N, Arslan S, Ozyurt H, Cetin I, Birgul Ozer E, et al. Serum vitamin D status and bone mineral density in fibromyalgia. Bratisl Lek Listy 2010; 111: 604-9.
- Okumus M, Koybas i M, Tuncay F, Ceceli E, Ayhan F, Yorgancioglu R, et al. Fibromyalgia syndrome: is it related to vitamin D deficiency in premenopausal female patients? Pain Manag Nurs 2013; 14: e 156-63.
- Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009; 62: 1006-12.
- Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977; 33: 159-74.
- Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0 [Internet]. London: The Cochrane Collaboration; 2011 [cited 2011 March 3]. Available at http://handbook.cochrane.org.
- Viswanathan M, Ansari MT, Berkman ND, Chang S, Hartling L, McPheeters M, et al. Assessing the risk of bias of individual studies in systematic reviews of health care interventions [Internet]. Rockville (MD): Agency for Healthcare Research and Quality; 2012 [cited 2012 March 8]. Available at https://www.ncbi.nlm.nih.gov/pubmedhealth/ PMH0077771/.
- Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539-58.
- Al-Allaf AW, Mole PA, Paterson CR, Pullar T. Bone health in patients with fibromyalgia. Rheumatology (Oxford) 2003; 42: 1202-6.
- Maafi AA, Ghavidel-Parsa B, Haghdoost A, Aarabi Y, Hajiabbasi A, Shenavar Masooleh I, et al. Serum vitamin D status in Iranian fibromyalgia patients: according to the symptom severity and illness invalidation. Korean J Pain 2016; 29: 172-8.
- Balkarli A, Balkarl i H, Temel S, Ozhan N, Ozkan U, Cobankara V. AB0656 Serum vitamin D and parathyroid hormone levels in premenopausal women with fibromyalgia syndrome. Ann Rheum Dis 2013; 72: A989.
- Mateos F, Valero C, Olmos JM, Casanueva B, Castillo J, Martinez J, et al. Bone mass and vitamin D levels in women with a diagnosis of fibromyalgia. Osteoporos Int 2014; 25: 525-33.
- Monteiro DM. Evaluation of vitamin D status in a population with fibromyalgia [master thesis]. Coimbra: Univ. of Coimbra, 2011.
- Ozcan DS, Oken 0, Aras M, Koseoglu BF. Vitamin D levels in women with fibromyalgia and relationship between pain, depression, and sleep. Turk J Phys Med Rehabil 2014; 60: 329-34.
- de Rezende Pena C, Grillo LP, das Chagas Medeiros MM. Evaluation of 25-hydroxyvitamin D serum levels in patients with fibromyalgia. J Clin Rheumatol 2010; 16: 365-9.
- Tandeter H, Grynbaum M, Zuili I, Shany S, Shvartzman P. Serum 25-OH vitamin D levels in patients with fibromyalgia. Isr Med Assoc J 2009; 11: 339-42.