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Supplements for Fibromyalgia: What the Trials Show for Pain, Sleep and Fatigue

No supplement replaces fibromyalgia treatment: regular exercise has the best evidence (grade B), alongside talking therapy and prescribed medicines. Vitamin D, magnesium, 5-HTP, CoQ10 and SAMe have only small or mixed trials (grade C). Never add 5-HTP, SAMe or tryptophan to duloxetine, milnacipran, amitriptyline, an SSRI or tramadol without your prescriber, because serotonin syndrome can be life-threatening. Keep magnesium from supplements at or below 350 mg a day.

Published How we grade evidenceEditorial policy

Fibromyalgia causes long-term pain across the body, with tiredness and poor sleep. The first treatments are an exercise programme, physical therapy and stress relief; duloxetine, pregabalin and milnacipran are approved for it, and amitriptyline and tramadol are also used (MedlinePlus). Supplements are small add-ons at best; this guide covers adults.

The short version

  • Exercise comes first: it was the only treatment the European rheumatology guideline recommended strongly, and aerobic exercise cut pain by about 11 points on a 100-point scale in 6 trials. Grade B (Macfarlane 2017; Bidonde 2017).
  • Vitamin D: two pooled analyses of placebo trials found better daily-function (FIQ) scores but no change in pain, from small pools that lean on a trial where everyone also took the antidepressant trazodone and include people without fibromyalgia. Of the two cleanest placebo trials, one in 30 women with low levels helped pain and one in 80 women did not. Grade C, mixed (Qu 2022; Yang 2023; Wepner 2014; Lozano-Plata 2021).
  • Magnesium: small trials of three different forms, mixed results, and none compared forms. Grade C, mixed (Macian 2022; Ferreira 2019).
  • 5-HTP: in one small 1990 trial, its authors reported that every measure studied improved with 5-HTP, but the study did not say how large any difference from placebo was. Never take it with an antidepressant (an SSRI, an SNRI such as duloxetine or milnacipran, or amitriptyline) or with tramadol without your prescriber: serotonin syndrome can be life-threatening. Grade C (Caruso 1990; duloxetine label).
  • CoQ10, SAMe, acetyl-L-carnitine and melatonin: each has one or two small trials that reported less pain (the carnitine trial began with 2 weeks of injections). Grade C (Cordero 2013; Jacobsen 1991; Rossini 2007; Hemati 2020).
  • Creatine and probiotics: creatine built strength but not less pain, and the largest probiotic trial found no benefit. Grade C (Alves 2013; Calandre 2021).
Option (who, compared with what)What trials foundSize of effectGrade
Aerobic exercise (6 trials vs no exercise)Less painAbout 11 points out of 100B
Vitamin D (placebo trials)Pain: better in 30 women with low levels, no change in 80 womenPooled placebo trials: better FIQ, pain unchanged; small, mixed groupsC, mixed
Magnesium (chloride, citrate, or with malic acid)Mixed; no form compared with anotherNone on main outcomes; small subgroup changesC, mixed
5-HTP (50 people, placebo-controlled, 1990)Authors reported improvement with 5-HTPThe study did not say how it compared with placeboC
CoQ10 (20 people, 40 days, vs placebo)Less pain and fatigueOne small trialC
SAMe (44 people, 6 weeks, vs placebo)Less pain and fatigueOne trialC
Creatine (16 weeks, vs placebo)Stronger muscles; pain unchangedOne trialC

What helps fibromyalgia most?

Grade B for exercise. The 2016 European (EULAR) recommendations rated exercise the only "strong" treatment (Macfarlane 2017). In a Cochrane review, aerobic exercise lowered pain about 11 points out of 100, on low-quality evidence (Bidonde 2017). Medicines such as SNRIs (duloxetine) and gabapentinoids (pregabalin) may help some people, but no drug's average effect on pain reached a level judged clinically important (Zeraatkar 2026).

Does vitamin D help fibromyalgia?

Grade C, mixed: the cleanest trials disagree.

  • Placebo trials: in 30 women with fibromyalgia and low blood levels, raising vitamin D for 20 weeks lowered pain compared with placebo (Wepner 2014). In 80 women given 50,000 IU once a week for 12 weeks, pain and daily-function (FIQ) scores did not differ from placebo (Lozano-Plata 2021). In 50 people with widespread muscle pain (not always fibromyalgia) and low levels, vitamin D did no better than placebo (Warner 2008). In 74 people with low levels who all took trazodone, adding vitamin D improved quality-of-life (SF-36) scores more than placebo (Mirzaei 2018).
  • Pooled analyses: two pooled analyses of placebo trials found better FIQ scores but no change in pain: a 2022 pooling of 5 trials (315 people) that, judging by its references and size, included the trazodone trial and two trials not limited to fibromyalgia (Qu 2022), and a 2023 analysis whose FIQ and pain pools were 4 placebo trials each, some not limited to fibromyalgia (Yang 2023). A 2025 analysis also found lower pain and FIQ scores, but some comparisons were with the same patients before treatment (two of four pain studies, one of four FIQ studies), and its FIQ result lost significance when either of two trials was left out (Ilari 2025). Its studies included two before-and-after studies, one not limited to fibromyalgia (Dogru 2017; Yilmaz 2016), and an age-group comparison during rehabilitation (Scaturro 2022).

A low level on a blood test is worth correcting with your clinician, fibromyalgia or not. Weekly 50,000 IU averages about 7,000 IU a day, over the 4,000 IU daily upper limit for adults; too much vitamin D raises blood calcium, which can cause nausea, vomiting and kidney damage, so take high doses only with medical advice (NIH ODS).

What is the best form of magnesium for fibromyalgia?

Grade C, mixed, and these trials can't settle the "best form" question: each used a different form, and none compared one with another.

  • Magnesium chloride: in 75 people, taking 100 mg daily for 4 weeks left stress, the main goal, no lower than on placebo. In those with mild or moderate stress, stress and pain severity were lower than on placebo; sleep, fatigue and quality of life were not. Minor stomach upset hit 30% on magnesium and 31% on placebo (Macian 2022).
  • Magnesium citrate: 60 women took 300 mg a day (under the upper limit), the antidepressant amitriptyline, or both, for 8 weeks, with no placebo group; tender points, daily-function and depression scores improved from baseline on magnesium (Bagis 2013).
  • Magnesium with malic acid (a blend): in a 24-person crossover trial, tablets giving 300 mg of magnesium and 1,200 mg of malic acid a day matched placebo over 4-week courses; pain eased later on doses up to twice that, above the upper limit, but without a placebo (Russell 1995). A 2019 summary of 7 reviews (11 studies, only one randomized, in all likelihood the trial above) concluded the blend makes little or no difference to pain and depression (Ferreira 2019).

Supplements should give adults no more than 350 mg of magnesium a day (the upper limit); more can cause diarrhea, nausea and cramps (NIH ODS). Our fibromyalgia page shows magnesium at grade B, but that letter comes from blood-vessel stiffness trials, not fibromyalgia. Magnesium can cut the absorption of some antibiotics and osteoporosis pills (NIH ODS); for thyroid medicine, see can I take magnesium with levothyroxine?

Does 5-HTP help fibromyalgia, and is it safe with antidepressants?

Grade C: one small 1990 trial. In a 1990 double-blind, placebo-controlled trial of 50 people, its authors reported that every measure they studied improved significantly with 5-HTP and that side effects were mild and short-lived, but the study did not say how large any difference from placebo was, and the authors called for more controlled studies (Caruso 1990). In a 90-day open study by the same group, symptoms improved from baseline in 50 people with no comparison group; 30% had side effects (Sarzi Puttini 1992).

The bigger issue is safety. 5-HTP is the step between tryptophan and serotonin (Das 2004). The labels for duloxetine, milnacipran and amitriptyline warn that taking them with other serotonin drugs, naming tryptophan and St John's wort, raises the risk of serotonin syndrome, which can be life-threatening (duloxetine label; milnacipran label; amitriptyline label), and the tramadol label warns of it with SSRIs, SNRIs and tricyclics (tramadol label). Don't add 5-HTP to any of them without your prescriber. See can I take 5-HTP with SSRIs? and supplements and antidepressants. One 5-HTP product with an impurity was linked to eosinophilia-myalgia syndrome, a severe muscle-pain illness, in a family (Michelson 1994), though a later review found no confirmed toxic contaminants in tested products (Das 2004).

Do CoQ10, SAMe, acetyl-L-carnitine or melatonin help?

Grade C for each: small trials, several against medicines rather than placebo.

  • CoQ10: in 20 people, 300 mg a day for 40 days lowered pain, fatigue and tender points more than placebo (Cordero 2013), and in an 11-person crossover with pregabalin, adding it eased pain more than placebo (Sawaddiruk 2019). A review counted 15 fibromyalgia studies, most reporting benefit, many being case reports or small trials by one group, and some testing blends or children (Freire de Carvalho 2024). A blend of CoQ10, tryptophan and magnesium did not ease fatigue, its main goal, more than placebo in 89 people (Rosselló Aubach 2025). CoQ10 has no set upper limit; side effects are mild, such as insomnia or stomach upset, and it may interact with warfarin and insulin (NCCIH).
  • SAMe: in 44 people, 800 mg a day by mouth for 6 weeks eased pain, fatigue and morning stiffness more than placebo; tender points and depression scores did not differ (Jacobsen 1991). It has no set upper limit; side effects are uncommon and usually stomach upset, but it may interact with antidepressants, tryptophan and St John's wort, and it can worsen mania in bipolar disorder (NCCIH).
  • Acetyl-L-carnitine: in 102 people, capsules plus a muscle injection for the first 2 weeks, then 1,500 mg a day in capsules, gave less pain and depression than placebo by week 10 (Rossini 2007); against duloxetine, both groups improved (Leombruni 2015). There is no set upper limit, but about 3 g a day of carnitine can cause nausea, diarrhea and a fishy body odor, and seizures in people with seizure disorders (NIH ODS).
  • Melatonin: a review of 4 studies (98 people) found all reported benefit, but they varied widely and not all had a control group (Hemati 2020). In one trial, melatonin eased pain more than amitriptyline alone (de Zanette 2014). Melatonin has no set upper limit; short-term use seems safe for most adults, but it can cause daytime drowsiness, especially in older people, and needs medical supervision with blood thinners or epilepsy (NCCIH).

Do creatine, probiotics or fish oil help?

  • Creatine, grade C: over 16 weeks, creatine raised muscle strength more than placebo, but pain, sleep and quality of life did not change; no side effects were seen (Alves 2013).
  • Probiotics, grade C, mixed: in 110 people, a multi-strain probiotic for 12 weeks was no better than a matching placebo for gut symptoms or overall severity (Calandre 2021). In a three-arm trial of 53 women, the 18 on a probiotic had lower pain scores after 8 weeks than the 18 on placebo (Aslan Çin 2024).
  • Fish oil (omega-3), grade C: in one trial of 120 people, high-dose omega-3 for 8 weeks improved pain and daily-function scores more than placebo (Fattah 2025). In heart trials, fish oil pills made atrial fibrillation (an irregular heartbeat) 25% more likely, and more so above 1 g a day (Gencer 2021); the FDA considers up to 5 g a day of EPA and DHA from supplements safe (NIH ODS).

What we'd skip

  • 5-HTP, SAMe or tryptophan with duloxetine, milnacipran, amitriptyline, an SSRI or tramadol, unless your prescriber agrees, because of serotonin syndrome.
  • DHEA: in 52 women, 50 mg a day for 3 months tripled hormone levels without easing pain, fatigue or mood, and brought more greasy skin, acne and body hair (Finckh 2005).
  • D-ribose: tested in fibromyalgia only in an open pilot study with no control group (Teitelbaum 2006).

Safety and interactions

  • Serotonin syndrome: the labels list agitation, hallucinations, a fast heartbeat, sweating, a high temperature, shaking, stiff or twitching muscles, nausea and diarrhea as signs (duloxetine label). Blends can hide tryptophan: the CoQ10 blend above contained it (Rosselló Aubach 2025).
  • Upper limits: vitamin D 4,000 IU a day (high blood calcium) and magnesium 350 mg a day from supplements (diarrhea) (NIH ODS; NIH ODS). CoQ10, SAMe, carnitine and melatonin have none set. Check my stack if you combine products.
  • Blood thinners: CoQ10 may interact with warfarin, melatonin needs supervision with blood thinners, and fish oil can slow clotting at high doses (NCCIH; NIH ODS); see can I take fish oil with Eliquis?
  • Pregnancy: use supplements only as advised by your midwife or obstetric team; the vitamin D and magnesium limits above still apply (NIH ODS; NIH ODS).
  • Breastfeeding? Ask your midwife, doctor or a lactation specialist, who can check what passes into breast milk.
  • Teenagers and children with fibromyalgia: ask your child's doctor.

When to see a doctor

  • Emergency care for signs of serotonin syndrome (listed above) after adding a supplement to an antidepressant or tramadol (duloxetine label).
  • Thoughts of suicide or self-harm: in the US, call or text 988 now. The duloxetine label warns of suicidal thoughts in children, teenagers and young adults on antidepressants, and asks for close watching in the first months and when a dose changes (duloxetine label).
  • Severe new muscle pain while taking 5-HTP: stop it and get checked, since a contaminated product was linked to eosinophilia-myalgia syndrome (Michelson 1994).

Don't stop a prescribed medicine on your own; ask the prescriber or pharmacist. If pregnant, let your midwife or obstetric team guide you; anyone under 18 should ask a clinician first.

FAQ

Does 5-HTP help fibromyalgia? In one small 1990 trial, its authors reported improvement with 5-HTP, but the study did not say how large any difference from placebo was (grade C). It must not be combined with duloxetine, milnacipran, amitriptyline, an SSRI or tramadol unless your prescriber agrees, because of serotonin syndrome.

What is the best form of magnesium for fibromyalgia? The trials each tested one form (chloride, citrate, or magnesium with malic acid), none against another, and all were small and mixed (grade C). Keep supplements to 350 mg a day of magnesium unless your clinician advises more.

Does vitamin D help fibromyalgia? The placebo trials split: one in women with low levels found less pain, a larger one found no change (grade C, mixed). If a test shows you are low, treat that with your clinician.

Sources

  1. Macfarlane GJ, et al. EULAR revised recommendations for the management of fibromyalgia. Ann Rheum Dis. 2017. PubMed 27377815 · doi:10.1136/annrheumdis-2016-209724
  2. Bidonde J, et al. Aerobic exercise training for adults with fibromyalgia. Cochrane Database Syst Rev. 2017. PubMed 28636204 · doi:10.1002/14651858.CD012700
  3. Ilari S, et al. Does Vitamin D Supplementation Impact Fibromyalgia-Related Pain? A Systematic Review and Meta-Analysis. Nutrients. 2025. PubMed 41156485 · doi:10.3390/nu17203232
  4. Wepner F, et al. Effects of vitamin D on patients with fibromyalgia syndrome: a randomized placebo-controlled trial. Pain. 2014. PubMed 24438771 · doi:10.1016/j.pain.2013.10.002
  5. Lozano-Plata LI, et al. Efficacy and safety of weekly vitamin D(3) in patients with fibromyalgia: 12-week, double-blind, randomized, controlled placebo trial. Clin Rheumatol. 2021. PubMed 33570701 · doi:10.1007/s10067-021-05640-8
  6. Macian N, et al. Short-Term Magnesium Therapy Alleviates Moderate Stress in Patients with Fibromyalgia: A Randomized Double-Blind Clinical Trial. Nutrients. 2022. PubMed 35631229 · doi:10.3390/nu14102088
  7. Ferreira I, et al. Magnesium and malic acid supplement for fibromyalgia. Medwave. 2019. PubMed 31150373 · doi:10.5867/medwave.2019.04.7632
  8. Caruso I, et al. Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome. J Int Med Res. 1990. PubMed 2193835 · doi:10.1177/030006059001800304
  9. Cordero MD, et al. Can coenzyme q10 improve clinical and molecular parameters in fibromyalgia?. Antioxid Redox Signal. 2013. PubMed 23458405 · doi:10.1089/ars.2013.5260
  10. Jacobsen S, et al. Oral S-adenosylmethionine in primary fibromyalgia. Double-blind clinical evaluation. Scand J Rheumatol. 1991. PubMed 1925418 · doi:10.3109/03009749109096803
  11. Rossini M, et al. Double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia patients. Clin Exp Rheumatol. 2007. PubMed 17543140
  12. Hemati K, et al. Melatonin in the treatment of fibromyalgia symptoms: A systematic review. Complement Ther Clin Pract. 2020. PubMed 31783341 · doi:10.1016/j.ctcp.2019.101072
  13. Alves CR, et al. Creatine supplementation in fibromyalgia: a randomized, double-blind, placebo-controlled trial. Arthritis Care Res (Hoboken). 2013. PubMed 23554283 · doi:10.1002/acr.22020
  14. Calandre EP, et al. The Probiotic VSL#3(®) Does Not Seem to Be Efficacious for the Treatment of Gastrointestinal Symptomatology of Patients with Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Pharmaceuticals (Basel). 2021. PubMed 34681287 · doi:10.3390/ph14101063
  15. Zeraatkar D, et al. Drug treatments for fibromyalgia: systematic review and network meta-analysis of randomised trials. BMJ Med. 2026. PubMed 42851751 · doi:10.1136/bmjmed-2026-002902
  16. Warner AE, et al. Diffuse musculoskeletal pain is not associated with low vitamin D levels or improved by treatment with vitamin D. J Clin Rheumatol. 2008. PubMed 18431091 · doi:10.1097/RHU.0b013e31816356a9
  17. Mirzaei A, et al. Effects of vitamin D optimization on quality of life of patients with fibromyalgia: A randomized controlled trial. Med J Islam Repub Iran. 2018. PubMed 30159280 · doi:10.14196/mjiri.32.29
  18. Dogru A, et al. Effects of Vitamin D Therapy on Quality of Life in Patients with Fibromyalgia. Eurasian J Med. 2017. PubMed 28638253 · doi:10.5152/eurasianjmed.2017.16283
  19. Yilmaz R, et al. Efficacy of vitamin D replacement therapy on patients with chronic nonspecific widespread musculoskeletal pain with vitamin D deficiency. Int J Rheum Dis. 2016. PubMed 27860257 · doi:10.1111/1756-185X.12960
  20. Scaturro D, et al. Can the Combination of Rehabilitation and Vitamin D Supplementation Improve Fibromyalgia Symptoms at All Ages?. J Funct Morphol Kinesiol. 2022. PubMed 35736022 · doi:10.3390/jfmk7020051
  21. Qu K, et al. The efficacy of vitamin D in treatment of fibromyalgia: a meta-analysis of randomized controlled studies and systematic review. Expert Rev Clin Pharmacol. 2022. PubMed 35596576 · doi:10.1080/17512433.2022.2081151
  22. Yang CC, et al. Psychological Outcomes and Quality of Life of Fibromyalgia Patients with Vitamin D Supplementation-A Meta-Analysis. J Clin Med. 2023. PubMed 37048833 · doi:10.3390/jcm12072750
  23. Bagis S, et al. Is magnesium citrate treatment effective on pain, clinical parameters and functional status in patients with fibromyalgia?. Rheumatol Int. 2013. PubMed 22271372 · doi:10.1007/s00296-011-2334-8
  24. Russell IJ, et al. Treatment of fibromyalgia syndrome with Super Malic: a randomized, double blind, placebo controlled, crossover pilot study. J Rheumatol. 1995. PubMed 8587088
  25. Sarzi Puttini P, et al. Primary fibromyalgia syndrome and 5-hydroxy-L-tryptophan: a 90-day open study. J Int Med Res. 1992. PubMed 1521674 · doi:10.1177/030006059202000210
  26. Das YT, et al. Safety of 5-hydroxy-L-tryptophan. Toxicol Lett. 2004. PubMed 15068828 · doi:10.1016/j.toxlet.2003.12.070
  27. Michelson D, et al. An eosinophilia-myalgia syndrome related disorder associated with exposure to L-5-hydroxytryptophan. J Rheumatol. 1994. PubMed 7699627
  28. Sawaddiruk P, et al. Coenzyme Q10 supplementation alleviates pain in pregabalin-treated fibromyalgia patients via reducing brain activity and mitochondrial dysfunction. Free Radic Res. 2019. PubMed 31387429 · doi:10.1080/10715762.2019.1645955
  29. Freire de Carvalho J, et al. Coenzyme Q10 supplementation in rheumatic diseases: A systematic review. Clin Nutr ESPEN. 2024. PubMed 38220408 · doi:10.1016/j.clnesp.2023.11.016
  30. Rosselló Aubach L, et al. Effects of Coenzyme Q10, Tryptophan, and Magnesium Supplementation on Fatigue in Patients with Fibromyalgia - A Randomized Trial. J Diet Suppl. 2025. PubMed 40151031 · doi:10.1080/19390211.2025.2483269
  31. Leombruni P, et al. A randomised controlled trial comparing duloxetine and acetyl L-carnitine in fibromyalgic patients: preliminary data. Clin Exp Rheumatol. 2015. PubMed 25786048
  32. de Zanette SA, et al. Melatonin analgesia is associated with improvement of the descending endogenous pain-modulating system in fibromyalgia: a phase II, randomized, double-dummy, controlled trial. BMC Pharmacol Toxicol. 2014. PubMed 25052847 · doi:10.1186/2050-6511-15-40
  33. Aslan Çİn NN, et al. Effect of prebiotic and probiotic supplementation on reduced pain in patients with fibromyalgia syndrome: a double-blind, placebo-controlled randomized clinical trial. Psychol Health Med. 2024. PubMed 37224267 · doi:10.1080/13548506.2023.2216464
  34. Fattah MAA, et al. High-dose Omega-3 Alters Serum Magnesium and Calcium Levels and Affects Fibromyalgia Symptoms: A Randomized, Double-blind, Placebo-Control Study. Curr Rheumatol Rev. 2025. PubMed 39377412 · doi:10.2174/0115733971314334240930043717
  35. Gencer B, et al. Effect of Long-Term Marine ɷ-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis. Circulation. 2021. PubMed 34612056 · doi:10.1161/CIRCULATIONAHA.121.055654
  36. Finckh A, et al. A randomized controlled trial of dehydroepiandrosterone in postmenopausal women with fibromyalgia. J Rheumatol. 2005. PubMed 15996074
  37. Teitelbaum JE, et al. The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study. J Altern Complement Med. 2006. PubMed 17109576 · doi:10.1089/acm.2006.12.857