Skip to main content

The Role of Vitamin D in Pathophysiology and Treatment of Fibromyalgia

Abstract

Recent studies showed that most cells have receptors and enzymes responsible for metabolism of vitamin D. Several diseases have been linked to vitamin D deficiency, such as hypertension, diabetes, depression, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and chronic pain syndromes such as fibromyalgia. The association between fibromyalgia and vitamin D deficiency is very controversial in the literature with conflicting studies and methodological problems, which leads to more questions than answers. The purpose of this article is to raise questions about the association of hypovitaminosis D with fibromyalgia considering causal relationships, treatment, and pathophysiological explanations.

This is a preview of subscription content, access via your institution.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. • Abokrysha NT. Vitamin D deficiency in women with fibromyalgia in Saudi Arabia. Pain Medicine. 2012;13:452–8. This report consists of the prevalence of vitamin D deficiency among patients with fibromyalgia in a neurology clinic in the Kingdom of Saudi Arabia.

    PubMed  Article  Google Scholar 

  2. Mease P. Fibromyalgia syndrome: review of clinical presentation, pathogenesis, outcome measures, and treatment. J Rheumatol. 2005;75(Suppl):6–21.

    Google Scholar 

  3. • Matthana MH. The relation between vitamin d deficiency and fibromyalgia syndrome in women. Saudi Med J. 2011;32:925–9. This article defines the relationship between vitamin D deficiency and fibromyalgia syndrome and evaluates the effect of replacement with vitamin D.

    PubMed  Google Scholar 

  4. Wolfe F, Ross K, Anderson J, et al. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum. 1995;38:19–28.

    PubMed  Article  CAS  Google Scholar 

  5. Arnson Y, Amital D, Amital H. The diverse world of vitamin D: does it also modulate pain sensation? IMAJ. 2009;11:371–2.

    PubMed  Google Scholar 

  6. Plotnikoff GA, Quigley JM. Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc. 2003;78:1463–70.

    PubMed  Article  Google Scholar 

  7. Mascarenhas R, Mobarhan S. Hypovitaminosis D-induced pain. Nutr Rev. 2004;62:354–9.

    PubMed  Article  Google Scholar 

  8. Gloth III F, Lindsay JM, Zelesnick LB, et al. Can vitamin D deficiency produce an unusual pain syndrome? Arch Intern Med. 1991;151:1662–4.

    PubMed  Article  Google Scholar 

  9. Prabhala A, Garg R, Dandona P. Severe myopathy associated with vitamin D deficiency in Western New York. Arch Intern Med. 2000;160:1199–203.

    PubMed  Article  CAS  Google Scholar 

  10. Benson J, Wilson A, Stocks N, et al. Muscle pain as an indicator of vitamin D deficiency in an urban Australian Aboriginal population. Med J Aust. 2006;185:76–7.

    PubMed  Google Scholar 

  11. Lofti A, Abdel-Nasser AM, Hamdy A, et al. Hypovitaminosis D in female patients with chronic low back pain. Clin Rheumatol. 2007;26:1895–901.

    Article  Google Scholar 

  12. Atherton K, Berry DJ, Parsons T, et al. 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.

    PubMed  Article  CAS  Google Scholar 

  13. Badsha H, Daher M, Kong KO. Myalgias or nonspecific muscle pain in Arab or Indo-Pakistani patients may indicate vitamin D deficiency. Clin Rheumatol. 2009;28:971–3.

    PubMed  Article  Google Scholar 

  14. Schwalfenberg G. Improvement of chronic back pain or failed back surgery with vitamin D repletion: a case series. J Am Board Fam Med. 2009;22:69–74.

    PubMed  Article  Google Scholar 

  15. Saud AF, Khalaf AM. Vitamin D deficiency and chronic low back pain in Saudi Arabia. Spine. 2003;28:177–9.

    Article  Google Scholar 

  16. Shinchuk L, Holick MF. Vitamin D and rehabilitation: improving functional outcomes. Nutr Clin Pract. 2007;22:297–304.

    PubMed  Article  Google Scholar 

  17. Armstrong DJ, Meenagh GK, Bickle I, et al. Vitamin D deficiency is associated with anxiety and depression in fibromyalgia. Clin Rheumatol. 2007;26:551–4.

    PubMed  Article  CAS  Google Scholar 

  18. Mouyis M, Ostor AJK, Crisp AJ, et al. Hypovitaminosis D among rheumatology outpatients in clinical practice. Rheumatology. 2008;47:1348–51.

    PubMed  Article  CAS  Google Scholar 

  19. •• McBeth J, Pye SR, O'Neill TW, et al. Musculoskeletal pain is associated with very low levels of vitamin D in men: results from the European Male Ageing Study. Ann Rheum Dis. 2010;69:1448–52. A study was undertaken to test the hypothesis that musculoskeletal pain is associated with low vitamin D levels but the relationship is explained by physical inactivity and/or other putative confounding factors.

    PubMed  Article  Google Scholar 

  20. •• Heidari B, Shirvani JS, Firouzjahi A, et al. Association between nonspecific skeletal pain and vitamin D deficiency. Int J Rheum Dis. 2010;13:340–6. The results of this study indicate a positive association of vitamin D deficiency with a variety of nonspecific bone pain, particularly in women.

    PubMed  Article  Google Scholar 

  21. • Olama SM, Senna MK, Elarman MM, et al. Serum vitamin D level and bone mineral density in premenopausal Egyptian women with fibromyalgia. Rheumatol Int. 2013;33:185–92.

    PubMed  Article  CAS  Google Scholar 

  22. Holick MF. Vitamin D, deficiency: what a pain it is. Mayo Clin Proc. 2003;78:1457–9.

    PubMed  Article  Google Scholar 

  23. Glerup H, Mikkelsen K, Poulsen L, et al. Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited. J Intern Med. 2000;247:260–8.

    PubMed  Article  CAS  Google Scholar 

  24. Bischoff HA, Stahelin HB, Dick W, et al. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res. 2003;18:343–51.

    PubMed  Article  CAS  Google Scholar 

  25. Al-Allaf AW, Mole PA, Paterson CR, et al. Bone heath in patients with fibromyalgia. Rheumatology. 2003;42:1202–6.

    PubMed  Article  CAS  Google Scholar 

  26. Block SR. Vitamin D, deficiency is not associated with nonspecific musculoskeletal pain syndromes including fibromyalgia. Mayo Clin Proc. 2004;79:1585–91.

    PubMed  Article  Google Scholar 

  27. Tandeter H, Grynbaum M, Zuili I, et al. Serum 25-OH vitamin D levels in patients with fibromyalgia. IMAJ. 2009;11:339–42.

    PubMed  Google Scholar 

  28. Huisman AM, White KP, Algra A. Vitamin D levels in women with systemic lupus erythematosus and fibromyalgia. J Rheumatol. 2001;28:2535–9.

    PubMed  CAS  Google Scholar 

  29. •• Daniel D, Pirotta MV. Fibromyalgia—should we be testing and treating for vitamin D deficiency? Aust Fam Physicia. 2011;40:712–6. This review aims to synthesize the evidence whether general practitioners should be testing and treating these patients for vitamin D deficiency in fibromyalgia.

    Google Scholar 

  30. Warner AE, Arnspiger AS. Diffuse musculoskeletal pain is not associated with low vitamin D levels or improved by treatment with vitamin D. J Clin Rheumatol. 2008;14:12–6.

    PubMed  Article  Google Scholar 

  31. •• De Rezende Pena C, Grillo LP, Das Chagas Medeiros MM. Evaluation of 25-hydroxivitamin D serum levels in patients with fibromyalgia. J Clin Rheumatol. 2010;16:365–9. This study showed that light to moderate deficient and insufficient 25(OH)D levels are not found more commonly in patients with FM.

    PubMed  Google Scholar 

  32. Holick MF. Vitamin D, deficiency. N Engl J Med. 2007;357:266–81.

    PubMed  Article  CAS  Google Scholar 

  33. •• Lewis JM, Coley JLB, Frontrier TH. Fibromyalgia syndrome and vitamin D. J Musculoskeletal Pain. 2011;19:164–6. This article is an updated review on the association of fibromyalgia with hypovitaminosis D.

    Article  Google Scholar 

  34. Martinez-Lavin M. Is fibromyalgia a generalized reflex sympathetic dystrophy? Clin Exp Rheumatol. 2001;19:1–3.

    PubMed  CAS  Google Scholar 

  35. Russell IJ. Fibromyalgia Syndrome. Bonica’s Management of Pain. Ed. Loeser J. Lippincott Williams & Wilkins, Philadelphia, 2001;pp.543–56.

  36. Bayliss DA, Millhorn DE. Central neural mechanisms of progesterone action: application to the respiratory system. J Appl Physiol. 1992;73:393–404.

    PubMed  CAS  Google Scholar 

  37. Schimitt CP, Obry J, Feneberg R, et al. Beta-1 adrenergic blockade augments pulsatile PTH secretion in humans. J Am Soc Nephrol. 2003;14:3245–50.

    Article  Google Scholar 

  38. Mostellar ME, Tuttle EP. Effects of alkalosis on plasma concentration and urinary excretion of inorganic phosphate in man. J Clin Invest. 1964;43:138–49.

    PubMed  Article  CAS  Google Scholar 

  39. Valença MM, Medeiros FL, Martins HA, et al. Neuroendocrine dysfunction in fibromyalgia and migraine. Curr Pain Headache Rep. 2009;13:308–13.

    Article  Google Scholar 

  40. Macedo JA, Hesse J, Turner JD, et al. Glucocorticoid sensitivity in fibromyalgia patients decreased expression of corticosteroid receptors and glucocorticoid-induced leucine zipper. Psychoneuroendocrinology. 2008;33:799–809.

    PubMed  Article  CAS  Google Scholar 

  41. Kuchinaid A, Schweinhardt P, Seminowicz DA, et al. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain? J Neurosci. 2007;27:4004–7.

    Article  Google Scholar 

  42. Papageorgiou AC, Silman AJ, Macfarlane GJ. Chronic widespread pain in the population: a seven year follow-up study. Ann Rheum Dis. 2002;61:1071–4.

    PubMed  Article  CAS  Google Scholar 

  43. Nielsen G, Henriksson KG. Pathophysiological mechanisms in chronic musculoskeletal pain (fibromyalgia): the role of central and peripheral sensitization and pain disinhibition. Best Pract Res Clin Rheumatol. 2007;21:465–80.

    PubMed  Article  Google Scholar 

  44. Eyles DW, Smith S, Kinobe R, et al. Distribution of the vitamin D receptor and 1-alfa-hydroxylase in human brain. J Chem Neuroanat. 2005;29:21–30.

    PubMed  Article  CAS  Google Scholar 

  45. Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, et al. New clues about vitamin D functions in the nervous system. Trends Endocrinol Metabol. 2002;13:100–5.

    Article  CAS  Google Scholar 

  46. Bischoff-Ferrari HA, Thomas Dietrich T, Orav EJ, et al. Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged > 60 years. Am J Clin Nutr. 2004;80:752–8.

    PubMed  CAS  Google Scholar 

  47. Boland R. Role of vitamin D in skeletal muscle function. Endocr Rev. 1986;7:434–47.

    PubMed  Article  CAS  Google Scholar 

  48. Sorensen OH, Lund B, Saltin B, et al. Myopathy in bone loss of ageing: improvement by treatment with 1 alpha-hydroxycholecalciferol and calcium. Clin Sci (Colch). 1979;56:157–61.

    CAS  Google Scholar 

  49. Simpson RU, Thomas GA, Arnold AJ. Identification of 1,25 dihydroxyvitamin D3 receptors and activities in muscle. J Biol Chem. 1985;260:8882–91.

    PubMed  CAS  Google Scholar 

  50. Bischoff HA, Borchers M, Gudat F, et al. In situ detection of 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue. Histochem J. 2001;33:19–24.

    PubMed  Article  CAS  Google Scholar 

  51. • Nimitphong H, Holick MF. Vitamin D, neurocognitive functioning and immunocompetence. Curr Op Clin Nutr Metabol Care. 2011;14:7–14. Low vitamin D status has been linked to poor performance in neurocognitive testing in elderly, depression, schizophrenia, Alzheimer's disease, multiple sclerosis, and a lower motor neuron-induced muscle atrophy.

    Article  CAS  Google Scholar 

  52. Ceglia L. Vitamin D, and skeletal muscle tissue and function. Mol Aspects Med. 2008;29:407–14.

    PubMed  Article  CAS  Google Scholar 

  53. Dawson-Hughes B. Serum 25-hydroxyvitamin D and functional outcomes in the elderly. Am J Clin Nutr. 2008;88:537S–40S.

    PubMed  CAS  Google Scholar 

  54. Zehnder D, Bland R, Williams MC, et al. Extrarenal expression of 25-hydroxyvitam in d(3)-1 alpha-hydroxylase. J Clin Endocrinol Metab. 2001;86:888–94.

    PubMed  Article  CAS  Google Scholar 

  55. Diesel B, Radermacher J, Bureik M, et al. Vitamin D(3) metabolism in humanglioblastoma multiforme: functionality of CYP27B1 splice variants, metabolism of calcidiol, and effect of calcitriol. Clin Cancer Res. 2005;11:5370–80.

    PubMed  Article  CAS  Google Scholar 

  56. McCann JC, Ames BN. Is there convincing biological or behavioral evidence linking vitamin D deficiency to brain dysfunction? FASEB J. 2008;22:982–1001.

    PubMed  Article  CAS  Google Scholar 

  57. Tommaso M, Sardaro M, Serpino C. Fibromyalgia comorbidity in primary headaches. Cephalalgia. 2009;29:453–64.

    PubMed  Article  Google Scholar 

  58. Peres MF, Young WB, Kaup AO, et al. Fibromyalgia is common in patients with transformed migraine. Neurology. 2001;57:1326–8.

    PubMed  Article  CAS  Google Scholar 

  59. Peres MF. Fibromyalgia, fatigue, and headache disorders. Curr Neurol Neurosci Rep. 2003;3:97–103.

    PubMed  Article  Google Scholar 

  60. Centonze V, Bassi A, Cassiano MA, et al. Migraine, daily chronic headache and fibromyalgia in the same patient: an evolutive ‘continuum’ of non organic chronic pain? About 100 clinical cases. Neurol Sci. 2004;25:S291–2.

    PubMed  Article  Google Scholar 

  61. Jesus CAS, Peres MFP. Low Vitamin D levels in migraine [Abstract]. International Headache Congress. Boston, USA. June 27–30, 2013.

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Carlos A S Jesus declares that he has no potential conflicts.

David Feder declares that he has no potential conflicts.

Mario F P Peres serves as a Section Editor for Current Pain and Headache Reports.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Carlos A. S. Jesus.

Additional information

This article is part of the Topical Collection on Fibromyalgia

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Jesus, C.A.S., Feder, D. & Peres, M.F.P. The Role of Vitamin D in Pathophysiology and Treatment of Fibromyalgia. Curr Pain Headache Rep 17, 355 (2013). https://doi.org/10.1007/s11916-013-0355-6

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11916-013-0355-6

Keywords

  • Fibromyalgia
  • Pain
  • Hypovitaminosis D
  • Vitamin D deficiency
  • Pathophysiology