The Role of Vitamin D in Pathophysiology and Treatment of Fibromyalgia

  • Carlos A. S. Jesus
  • David Feder
  • Mario F. P. Peres
Fibromyalgia (M Peres, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Fibromyalgia


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.


Fibromyalgia Pain Hypovitaminosis D Vitamin D deficiency Pathophysiology 


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.


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

  1. 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.PubMedCrossRefGoogle Scholar
  2. 2.
    Mease P. Fibromyalgia syndrome: review of clinical presentation, pathogenesis, outcome measures, and treatment. J Rheumatol. 2005;75(Suppl):6–21.Google Scholar
  3. 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.PubMedGoogle Scholar
  4. 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.PubMedCrossRefGoogle Scholar
  5. 5.
    Arnson Y, Amital D, Amital H. The diverse world of vitamin D: does it also modulate pain sensation? IMAJ. 2009;11:371–2.PubMedGoogle Scholar
  6. 6.
    Plotnikoff GA, Quigley JM. Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc. 2003;78:1463–70.PubMedCrossRefGoogle Scholar
  7. 7.
    Mascarenhas R, Mobarhan S. Hypovitaminosis D-induced pain. Nutr Rev. 2004;62:354–9.PubMedCrossRefGoogle Scholar
  8. 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.PubMedCrossRefGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. 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.PubMedGoogle Scholar
  11. 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.CrossRefGoogle Scholar
  12. 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.PubMedCrossRefGoogle Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. 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.PubMedCrossRefGoogle Scholar
  15. 15.
    Saud AF, Khalaf AM. Vitamin D deficiency and chronic low back pain in Saudi Arabia. Spine. 2003;28:177–9.CrossRefGoogle Scholar
  16. 16.
    Shinchuk L, Holick MF. Vitamin D and rehabilitation: improving functional outcomes. Nutr Clin Pract. 2007;22:297–304.PubMedCrossRefGoogle Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. 18.
    Mouyis M, Ostor AJK, Crisp AJ, et al. Hypovitaminosis D among rheumatology outpatients in clinical practice. Rheumatology. 2008;47:1348–51.PubMedCrossRefGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. 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.PubMedCrossRefGoogle Scholar
  22. 22.
    Holick MF. Vitamin D, deficiency: what a pain it is. Mayo Clin Proc. 2003;78:1457–9.PubMedCrossRefGoogle Scholar
  23. 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.PubMedCrossRefGoogle Scholar
  24. 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.PubMedCrossRefGoogle Scholar
  25. 25.
    Al-Allaf AW, Mole PA, Paterson CR, et al. Bone heath in patients with fibromyalgia. Rheumatology. 2003;42:1202–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Block SR. Vitamin D, deficiency is not associated with nonspecific musculoskeletal pain syndromes including fibromyalgia. Mayo Clin Proc. 2004;79:1585–91.PubMedCrossRefGoogle Scholar
  27. 27.
    Tandeter H, Grynbaum M, Zuili I, et al. Serum 25-OH vitamin D levels in patients with fibromyalgia. IMAJ. 2009;11:339–42.PubMedGoogle Scholar
  28. 28.
    Huisman AM, White KP, Algra A. Vitamin D levels in women with systemic lupus erythematosus and fibromyalgia. J Rheumatol. 2001;28:2535–9.PubMedGoogle Scholar
  29. 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. 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.PubMedCrossRefGoogle Scholar
  31. 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.PubMedGoogle Scholar
  32. 32.
    Holick MF. Vitamin D, deficiency. N Engl J Med. 2007;357:266–81.PubMedCrossRefGoogle Scholar
  33. 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.CrossRefGoogle Scholar
  34. 34.
    Martinez-Lavin M. Is fibromyalgia a generalized reflex sympathetic dystrophy? Clin Exp Rheumatol. 2001;19:1–3.PubMedGoogle Scholar
  35. 35.
    Russell IJ. Fibromyalgia Syndrome. Bonica’s Management of Pain. Ed. Loeser J. Lippincott Williams & Wilkins, Philadelphia, 2001;pp.543–56.Google Scholar
  36. 36.
    Bayliss DA, Millhorn DE. Central neural mechanisms of progesterone action: application to the respiratory system. J Appl Physiol. 1992;73:393–404.PubMedGoogle Scholar
  37. 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.CrossRefGoogle Scholar
  38. 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.PubMedCrossRefGoogle Scholar
  39. 39.
    Valença MM, Medeiros FL, Martins HA, et al. Neuroendocrine dysfunction in fibromyalgia and migraine. Curr Pain Headache Rep. 2009;13:308–13.CrossRefGoogle Scholar
  40. 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.PubMedCrossRefGoogle Scholar
  41. 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.CrossRefGoogle Scholar
  42. 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.PubMedCrossRefGoogle Scholar
  43. 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.PubMedCrossRefGoogle Scholar
  44. 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.PubMedCrossRefGoogle Scholar
  45. 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.CrossRefGoogle Scholar
  46. 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.PubMedGoogle Scholar
  47. 47.
    Boland R. Role of vitamin D in skeletal muscle function. Endocr Rev. 1986;7:434–47.PubMedCrossRefGoogle Scholar
  48. 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.Google Scholar
  49. 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.PubMedGoogle Scholar
  50. 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.PubMedCrossRefGoogle Scholar
  51. 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.CrossRefGoogle Scholar
  52. 52.
    Ceglia L. Vitamin D, and skeletal muscle tissue and function. Mol Aspects Med. 2008;29:407–14.PubMedCrossRefGoogle Scholar
  53. 53.
    Dawson-Hughes B. Serum 25-hydroxyvitamin D and functional outcomes in the elderly. Am J Clin Nutr. 2008;88:537S–40S.PubMedGoogle Scholar
  54. 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.PubMedCrossRefGoogle Scholar
  55. 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.PubMedCrossRefGoogle Scholar
  56. 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.PubMedCrossRefGoogle Scholar
  57. 57.
    Tommaso M, Sardaro M, Serpino C. Fibromyalgia comorbidity in primary headaches. Cephalalgia. 2009;29:453–64.PubMedCrossRefGoogle Scholar
  58. 58.
    Peres MF, Young WB, Kaup AO, et al. Fibromyalgia is common in patients with transformed migraine. Neurology. 2001;57:1326–8.PubMedCrossRefGoogle Scholar
  59. 59.
    Peres MF. Fibromyalgia, fatigue, and headache disorders. Curr Neurol Neurosci Rep. 2003;3:97–103.PubMedCrossRefGoogle Scholar
  60. 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.PubMedCrossRefGoogle Scholar
  61. 61.
    Jesus CAS, Peres MFP. Low Vitamin D levels in migraine [Abstract]. International Headache Congress. Boston, USA. June 27–30, 2013.Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Carlos A. S. Jesus
    • 1
  • David Feder
    • 2
  • Mario F. P. Peres
    • 1
  1. 1.Department of Neurology and NeurosurgeryUNIFESPSão PauloBrazil
  2. 2.Pharmacology DepartmentFaculdade de Medicina do ABCSanto AndreBrazil

Personalised recommendations