Skip to content
2000
Volume 21, Issue 4
  • ISSN: 1573-3971
  • E-ISSN: 1875-6360

Abstract

Objective

The aim of this study is to investigate the effect of a high oral dose of omega-3 on serum magnesium (Mg) and calcium (Ca) levels and their effects on clinical measures of pain threshold.

Methods

One hundred twenty patients were recruited and randomized 1:1 to omega-3 or placebo and blinded to their treatment group. At baseline and after 8 weeks of treatment, the Widespread Pain Index (WPI), the Symptom Severity Scale (SSS), the Visual Analogue Scale (VAS), and the FM Impact Questionnaire (FIQ) were completed. In addition, serum was taken for Ca and Mg analysis at the same time point.

Results

The WPI, SSS, VAS, and FIQ scores improved significantly in the omega-3 group compared to the placebo group ( < 0.001). Serum Ca levels were negatively correlated with WPI (r = -0.308), SSS (r = -0.28), VAS (r = -0.311) and FIQ (r = -0.348) scores after 8 weeks of treatment ( < 0.001), while serum Mg levels were negatively correlated with SSS (r = -0.212) and VAS (r = -0.231) scores after 8 weeks of treatment.

Conclusion

The results of this study showed that a high dose of omega-3 could have a positive effect on the relief of FM pain, which could be due to an increase in serum Mg and Ca levels.

Clinical Trial Registration Number

Research4877#.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/crr/10.2174/0115733971314334240930043717
2024-10-07
2025-10-18

  • From This Site

    /content/journals/crr/10.2174/0115733971314334240930043717
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. BairM.J. KrebsE.E. Fibromyalgia.Ann. Intern. Med.20201725ITC33ITC4810.7326/AITC20200303032120395
     [Google Scholar]
  2. HäuserW. FitzcharlesM.A. Facts and myths pertaining to fibromyalgia.Dialogues Clin. Neurosci.2018201536210.31887/DCNS.2018.20.1/whauser29946212
     [Google Scholar]
  3. BjørklundG. DadarM. ChirumboloS. AasethJ. Fibromyalgia and nutrition: Therapeutic possibilities?Biomed. Pharmacother.201810353153810.1016/j.biopha.2018.04.05629677539
     [Google Scholar]
  4. MuñozL.C. Reyes G.A. FernándezM.J. MontoroC.I. Fibromyalgia syndrome and cognitive decline: The role of body mass index and clinical symptoms.J. Clin. Med.20221112340410.3390/jcm1112340435743474
     [Google Scholar]
  5. MelegerA.L. FroudeC.K. WalkerJ.III Nutrition and eating behavior in patients with chronic pain receiving long-term opioid therapy.PMR201461712.e110.1016/j.pmrj.2013.08.59723973502
     [Google Scholar]
  6. KimY.S. KimK.M. LeeD.J. KimB.T. ParkS.B. ChoD.Y. SuhC.H. KimH.A. ParkR.W. JooN.S. Women with fibromyalgia have lower levels of calcium, magnesium, iron and manganese in hair mineral analysis.J. Korean Med. Sci.201126101253125710.3346/jkms.2011.26.10.125322022174
     [Google Scholar]
  7. SendurO.F. TastabanE. TuranY. UlmanC. The relationship between serum trace element levels and clinical parameters in patients with fibromyalgia.Rheumatol. Int.200828111117112110.1007/s00296‑008‑0593‑918496697
     [Google Scholar]
  8. BeckerS. SchweinhardtP. Dysfunctional neurotransmitter systems in fibromyalgia, their role in central stress circuitry and pharmacological actions on these systems.Pain Res. Treat.2012201211010.1155/2012/74174622110944
     [Google Scholar]
  9. MartinS.L. PowerA. BoyleY. AndersonI.M. SilverdaleM.A. JonesA.K.P. 5-HT modulation of pain perception in humans.Psychopharmacology (Berl.)2017234192929293910.1007/s00213‑017‑4686‑628798976
     [Google Scholar]
  10. Healy-StoffelM. LevantB. N-3 (Omega-3) fatty acids: Effects on brain dopamine systems and potential role in the etiology and treatment of neuropsychiatric disorders.CNS Neurol. Disord. Drug Targets201817321623210.2174/187152731766618041215361229651972
     [Google Scholar]
  11. GrossoG. GalvanoF. MarventanoS. MalaguarneraM. BucoloC. DragoF. CaraciF. Omega-3 fatty acids and depression: Scientific evidence and biological mechanisms.Oxid. Med. Cell. Longev.2014201411610.1155/2014/31357024757497
     [Google Scholar]
  12. OzgocmenS. OzyurtH. SogutS. AkyolO. ArdicogluO. YildizhanH. Antioxidant status, lipid peroxidation and nitric oxide in fibromyalgia: Etiologic and therapeutic concerns.Rheumatol. Int.200626759860310.1007/s00296‑005‑0079‑y16283318
     [Google Scholar]
  13. EisingerJ. PlantamuraA. MarieP.A. AyavouT. Selenium and magnesium status in fibromyalgia.Magnes. Res.199473-42852887786692
     [Google Scholar]
  14. ParkS.B. ChoiS.W. NamA.Y. Hair tissue mineral analysis and metabolic syndrome.Biol. Trace Elem. Res.2009130321822810.1007/s12011‑009‑8336‑719221698
     [Google Scholar]
  15. NgS.Y. Hair calcium and magnesium levels in patients with fibromyalgia: A case center study.J. Manipulative Physiol. Ther.199922958659310.1016/S0161‑4754(99)70019‑910626702
     [Google Scholar]
  16. Sánchez-DomínguezB. BullónP. Román-MaloL. Marín-AguilarF. Alcocer-GómezE. CarriónA.M. Sánchez-AlcazarJ.A. CorderoM.D. Oxidative stress, mitochondrial dysfunction and, inflammation common events in skin of patients with fibromyalgia.Mitochondrion201521697510.1016/j.mito.2015.01.01025662535
     [Google Scholar]
  17. CorderoM.D. De MiguelM. MorenoA.M. Carmona LópezI.M. Garrido MaraverJ. CotánD. Gómez IzquierdoL. BonalP. CampaF. BullonP. NavasP. Sánchez AlcázarJ.A. Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: Implications in the pathogenesis of the disease.Arthritis Res. Ther.2010121R1710.1186/ar291820109177
     [Google Scholar]
  18. CorderoM.D. Moreno-FernándezA.M. deMiguelM. BonalP. CampaF. Jiménez-JiménezL.M. Ruiz-LosadaA. Sánchez-DomínguezB. Sánchez AlcázarJ.A. SalviatiL. NavasP. Coenzyme Q10 distribution in blood is altered in patients with Fibromyalgia.Clin. Biochem.2009427-873273510.1016/j.clinbiochem.2008.12.01019133251
     [Google Scholar]
  19. LevineB. YuanJ. Autophagy in cell death: An innocent convict?J. Clin. Invest.2005115102679268810.1172/JCI2639016200202
     [Google Scholar]
  20. Martínez-LaraA. Moreno-FernándezA.M. Jiménez-GuerreroM. Díaz-LópezC. De-MiguelM. CotánD. Sánchez-AlcázarJ.A. Mitochondrial imbalance as a new approach to the study of fibromyalgia.Open Access Rheumatol.20201217518510.2147/OARRR.S25747032922097
     [Google Scholar]
  21. NakahiraK. CloonanS.M. MizumuraK. ChoiA.M.K. RyterS.W. Autophagy: A crucial moderator of redox balance, inflammation, and apoptosis in lung disease.Antioxid. Redox Signal.201420347449410.1089/ars.2013.537323879400
     [Google Scholar]
  22. SiracusaR. PaolaR.D. CuzzocreaS. ImpellizzeriD. Fibromyalgia: Pathogenesis, mechanisms, diagnosis and treatment options update.Int. J. Mol. Sci.2021228389110.3390/ijms2208389133918736
     [Google Scholar]
  23. LeeK.H. ChaM. LeeB.H. Neuroprotective effect of antioxidants in the brain.Int. J. Mol. Sci.20202119715210.3390/ijms2119715232998277
     [Google Scholar]
  24. EsterbauerH. CheesemanK.H. Determination of aldehydic lipid peroxidation products: Malonaldehyde and 4-hydroxynonenal.Methods Enzymol.199018640721
     [Google Scholar]
  25. ShuklaV. DasS.K. MahdiA.A. AgarwalS. KhandpurS. Nitric oxide, lipid peroxidation products, and antioxidants in primary fibromyalgia and correlation with disease severity.J. Med. Biochem.202039216510.2478/jomb‑2019‑003333033448
     [Google Scholar]
  26. BennettR.M. FriendR. JonesK.D. WardR. HanB.K. RossR.L. The revised fibromyalgia impact questionnaire (FIQR): Validation and psychometric properties.Arthritis Res. Ther.2009114R12010.1186/ar278319664287
     [Google Scholar]
  27. AssavarittirongC. SamborskiW. Grygiel-GórniakB. Oxidative stress in fibromyalgia: From pathology to treatment.Oxid. Med. Cell. Longev.2022202211110.1155/2022/158243236246401
     [Google Scholar]
  28. Fernández-AraqueA. VerdeZ. Torres-OrtegaC. Sainz-GilM. Velasco-GonzalezV. González-BernalJ.J. Mielgo-AyusoJ. Effects of antioxidants on pain perception in patients with fibromyalgia—a systematic review.J. Clin. Med.2022119246210.3390/jcm1109246235566585
     [Google Scholar]
  29. GutteridgeJ.M. Lipid peroxidation and antioxidants as biomarkers of tissue damage.Clin. Chem.199541121819182810.1093/clinchem/41.12.18197497639
     [Google Scholar]
  30. OrricoF. LauranceS. LopezA.C. LefevreS.D. ThomsonL. MöllerM.N. OstuniM.A. Oxidative stress in healthy and pathological red blood cells.Biomolecules2023138126210.3390/biom1308126237627327
     [Google Scholar]
  31. Martínez-RamírezM.J. PalmaS. Martínez-GonzálezM.A. Delgado-MartínezA.D. de la FuenteC. Delgado-RodríguezM. Dietary fat intake and the risk of osteoporotic fractures in the elderly.Eur. J. Clin. Nutr.20076191114112010.1038/sj.ejcn.160262417299494
     [Google Scholar]
  32. ZivkovicA.M. TelisN. GermanJ.B. HammockB.D. Dietary omega-3 fatty acids aid in the modulation of inflammation and metabolic health.Calif. Agric.201165310611110.3733/ca.v065n03p10624860193
     [Google Scholar]
  33. BatistaE.D. AndrettaA. de MirandaR.C. NehringJ. dos Santos PaivaE. SchieferdeckerM.E.M. Food intake assessment and quality of life in women with fibromyalgia.Rev. Bras. Reumatol. Engl. Ed.201656210511010.1016/j.rbre.2015.08.01527267522
     [Google Scholar]
  34. JoustraM.L. MinovicI. JanssensK.A.M. BakkerS.J.L. RosmalenJ.G.M. Vitamin and mineral status in chronic fatigue syndrome and fibromyalgia syndrome: A systematic review and meta-analysis.PLoS One2017124e017663110.1371/journal.pone.017663128453534
     [Google Scholar]
  35. SchwalfenbergG.K. GenuisS.J. The importance of magnesium in clinical healthcare.Scientifica (Cairo)2017201711410.1155/2017/417932629093983
     [Google Scholar]
  36. SakaryaS.T. AkyolY. BedirA. CanturkF. The relationship between serum antioxidant vitamins, magnesium levels, and clinical parameters in patients with primary fibromyalgia syndrome.Clin. Rheumatol.20113081039104310.1007/s10067‑011‑1697‑221347604
     [Google Scholar]
  37. ChouM.H. YangY.K. WangJ.D. LinC.Y. LinS.H. Elevated c-reactive protein levels modify the effect of magnesium on depressive symptoms: A population-based study.Nutrients2023157156010.3390/nu1507156037049401
     [Google Scholar]
  38. RosanoffA. WeaverC.M. RudeR.K. Suboptimal magnesium status in the United States: Are the health consequences underestimated?Nutr. Rev.201270315316410.1111/j.1753‑4887.2011.00465.x22364157
     [Google Scholar]
  39. BoulisM. BoulisM. ClauwD. Magnesium and fibromyalgia: A literature review.J. Prim. Care Community Health2021122150132721103843310.1177/2150132721103843334392734
     [Google Scholar]
  40. NeeckG. RiedelW. Thyroid function in patients with fibromyalgia syndrome.J. Rheumatol.1992197112011221512769
     [Google Scholar]
  41. BurnashevN. SchoepferR. MonyerH. RuppersbergJ.P. GüntherW. SeeburgP.H. SakmannB. Control by asparagine residues of calcium permeability and magnesium blockade in the NMDA receptor.Science199225750751415141910.1126/science.13823141382314
     [Google Scholar]
  42. GuerreraM.P. VolpeS.L. MaoJ.J. Therapeutic uses of magnesium.Am. Fam. Physician200980215716219621856
     [Google Scholar]
  43. BagisS. KarabiberM. Asİ. TamerL. ErdoganC. AtalayA. Is magnesium citrate treatment effective on pain, clinical parameters and functional status in patients with fibromyalgia?Rheumatol. Int.201333116717210.1007/s00296‑011‑2334‑822271372
     [Google Scholar]
  44. MazidiM. RezaieP. BanachM. Effect of magnesium supplements on serum C-reactive protein: A systematic review and meta-analysis.Arch. Med. Sci.201814470771610.5114/aoms.2018.7571930002686
     [Google Scholar]
  45. LiuM. DudleyS.C.Jr Beyond ion homeostasis: Hypomagnesemia, transient receptor potential melastatin channel 7, mitochondrial function, and inflammation.Nutrients20231518392010.3390/nu1518392037764704
     [Google Scholar]
  46. OrchardT.S. PanX. CheekF. IngS.W. JacksonR.D. A systematic review of omega-3 fatty acids and osteoporosis.Br. J. Nutr.2012107Suppl. 2S253S26010.1017/S000711451200163822591899
     [Google Scholar]
  47. WolfeF. ClauwD.J. FitzcharlesM.A. GoldenbergD.L. KatzR.S. MeaseP. RussellA.S. RussellI.J. WinfieldJ.B. YunusM.B. The american college of rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity.Arthritis Care Res. (Hoboken)201062560061010.1002/acr.2014020461783
     [Google Scholar]
  48. KoG.D. NowackiN.B. ArseneauL. EitelM. HumA. Omega-3 fatty acids for neuropathic pain: Case series.Clin. J. Pain201026216817210.1097/AJP.0b013e3181bb853320090445
     [Google Scholar]
  49. LingH.Q. ChenZ.H. HeL. FengF. WengC.G. ChengS.J. RongL.M. XieP.G. Comparative efficacy and safety of 11 drugs as therapies for adults with neuropathic pain after spinal cord injury: A bayesian network analysis based on 20 randomized controlled trials.Front. Neurol.20221381852210.3389/fneur.2022.81852235386408
     [Google Scholar]
  50. PreussC.V. KalavaA. KingK.C. Prescription of controlled substances: Benefits and risks.StatPearlsStatPearls Publishing LLC.: Treasure Island (FL)2023
     [Google Scholar]
  51. AllenR. SharmaU. BarlasS. Clinical experience with desvenlafaxine in treatment of patients with fibromyalgia syndrome.Clin. Pharmacol. Drug Dev.20176322423310.1002/cpdd.27127139158
     [Google Scholar]
  52. BoomershineC. Pregabalin for the management of fibromyalgia syndrome.J. Pain Res.20103818810.2147/JPR.S788421197312
     [Google Scholar]
  53. KvaelL.A.H. LøchtingI. MolinM. Use of dietary supplements and perceived knowledge among adults living with fibromyalgia in Norway: A cross-sectional study.Nutrients2021141510.3390/nu1401000535010882
     [Google Scholar]
  54. LowryE. MarleyJ. McVeighJ.G. McSorleyE. AllsoppP. KerrD. Dietary interventions in the management of fibromyalgia: A systematic review and best-evidence synthesis.Nutrients2020129266410.3390/nu1209266432878326
     [Google Scholar]
  55. NakanoM. YamamotoT. OkamuraH. TsudaA. KowatariY. Effects of oral supplementation with pyrroloquinoline quinone on stress, fatigue, and sleep.Funct. Food Health Dis.20122830732410.31989/ffhd.v2i8.81
     [Google Scholar]
  56. OjiriY. EndohH. OkumotoT. AtsutaK. YoshinariO. MoriyamaH. Randomized, double-blind, placebo-controlled, crossover study to evaluate the effects of beta-1,3/1,6 glucan on stress associated with daily lifestyle in healthy subjects.Funct. Food Health Dis.20155514515410.31989/ffhd.v5i5.179
     [Google Scholar]
  57. TakaraT. YamamotoK. SuzukiN. ShimodaH. Seaberry extract with ursolic acid improves anxiety about urinary dysfunction in Japanese adults.Funct. Food Health Dis.201771290192210.31989/ffhd.v7i12.385
     [Google Scholar]
  58. WalittB. KloseP. FitzcharlesM.A. PhillipsT. HäuserW. Cannabinoids for fibromyalgia.Cochrane Libr.201677CD01169410.1002/14651858.CD011694.pub227428009
     [Google Scholar]
  59. OzgocmenS. CatalS.A. ArdicogluO. KamanliA. Effect of omega-3 fatty acids in the management of fibromyalgia syndrome.Int. J. Clin. Pharmacol. Ther.200038736236310.5414/CPP3836210919346
     [Google Scholar]
  60. GuerinC. AttliB. CooleyK. HassanS. SarebanhaS. SadrolsadotP. ChungC. An assessment of naturopathic treatments, health concerns, and common comorbid conditions in fibromyalgia patients: A retrospective medical record review.J. Integr. Complement. Med.202228436337210.1089/jicm.2021.023135100049
     [Google Scholar]
  61. DuránA.M. BeesonW.L. FirekA. Cordero-MacIntyreZ. De LeónM. Dietary omega-3 polyunsaturated fatty-acid supplementation upregulates protective cellular pathways in patients with type 2 diabetes exhibiting improvement in painful diabetic neuropathy.Nutrients202214476110.3390/nu1404076135215418
     [Google Scholar]
  62. HeshmatiJ. MorvaridzadehM. MaroufizadehS. AkbariA. YavariM. AmirinejadA. Maleki-HajiaghaA. SepidarkishM. Omega-3 fatty acids supplementation and oxidative stress parameters: A systematic review and meta-analysis of clinical trials.Pharmacol. Res.201914910446210.1016/j.phrs.2019.10446231563611
     [Google Scholar]
  63. PattenA.R. BrocardoP.S. ChristieB.R. Omega-3 supplementation can restore glutathione levels and prevent oxidative damage caused by prenatal ethanol exposure.J. Nutr. Biochem.201324576076910.1016/j.jnutbio.2012.04.00322841392
     [Google Scholar]
  64. GarrelC. AlessandriJ.M. GuesnetP. Al-GuboryK.H. Omega-3 fatty acids enhance mitochondrial superoxide dismutase activity in rat organs during post-natal development.Int. J. Biochem. Cell Biol.201244112313110.1016/j.biocel.2011.10.00722062949
     [Google Scholar]
  65. ZararsizI. MeydanS. SarsilmazM. SongurA. OzenO.A. SogutS. Protective effects of omega-3 essential fatty acids against formaldehyde-induced cerebellar damage in rats.Toxicol. Ind. Health201127648949510.1177/074823371038985221444354
     [Google Scholar]
  66. SundströmB. StålnackeK. HagforsL. JohanssonG. Supplementation of omega-3 fatty acids in patients with ankylosing spondylitis.Scand. J. Rheumatol.200635535936210.1080/0300974060084435717062435
     [Google Scholar]
  67. MagaldiM. MoltoniL. BiasiG. MarcolongoR. Changes in intracellular calcium and magnesium ions in the physiopathology of the fybromyalgia syndrome.Minerva Med.2000917-813714011155461
     [Google Scholar]
  68. AndrettaA. DiasE. MadalozzoM.E. RasmussenR. BoguszewskiC.L. dos SantosE. Relation between magnesium and calcium and parameters of pain, quality of life and depression in women with fibromyalgia.Adv. Rheumatol.20195915510.1186/s42358‑019‑0095‑331829290
     [Google Scholar]
  69. DiNicolantonioJ.J. LiuJ. O’KeefeJ.H. Magnesium for the prevention and treatment of cardiovascular disease.Open Heart201852e00077510.1136/openhrt‑2018‑00077530018772
     [Google Scholar]
  70. NielsenF.H. Dietary fatty acid composition alters magnesium metabolism, distribution, and marginal deficiency response in rats.Magnes. Res.200922428028810.1684/mrh.2009.018820228007
     [Google Scholar]
  71. ChaudharyD.P. BoparaiR.K. BansalD.D. Implications of oxidative stress in high sucrose low magnesium diet fed rats.Eur. J. Nutr.200746738339010.1007/s00394‑007‑0677‑417823763
     [Google Scholar]
  72. SaviniI. CataniM. EvangelistaD. GasperiV. AviglianoL. Obesity-associated oxidative stress: strategies finalized to improve redox state.Int. J. Mol. Sci.2013145104971053810.3390/ijms14051049723698776
     [Google Scholar]
  73. Al-Hashemi HM. Effect of high doses of omega-3 fatty acids on the metabolism of bones in adult females rats.Rafidain J Sci201324172610.33899/rjs.2013.74502
     [Google Scholar]
  74. VirgoliciB. PopescuL.A. VirgoliciH.M. StefanC.D. MohoraM. TimneaO. Effects of omega-3 fatty acids associated with antioxidant vitamins in overweight and obese children.Acta Endocrinol. (Bucur.)202319222122710.4183/aeb.2023.22137908888
     [Google Scholar]
  75. UwitonzeA.M. RazzaqueM.S. Role of magnesium in vitamin D activation and function.J. Am. Osteopath. Assoc.2018118318118910.7556/jaoa.2018.03729480918
     [Google Scholar]
/content/journals/crr/10.2174/0115733971314334240930043717
Loading
High-dose Omega-3 Alters Serum Magnesium and Calcium Levels and Affects Fibromyalgia Symptoms: A Randomized, Double-blind, Placebo-Control Study
Curr. Rheumatol. Rev. 21, 446 (2025); https://doi.org/10.2174/0115733971314334240930043717
/content/journals/crr/10.2174/0115733971314334240930043717
/content/journals/crr/10.2174/0115733971314334240930043717
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): calcium; fibromyalgia; magnesium; omega-3; pain; Randomized clinical trial

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test