Antioxidant Treatments for Fibromyalgia
Abstract
1. Introduction
2. Methods
3. Micronutrients
3.1. Vitamins and Minerals—Combined Studies
3.2. Vitamin B12
3.3. Vitamin D
3.4. Iron
4. Melatonin
5. Coenzyme Q (CoQ)
6. Alpha-Lipoic Acid (ALA)
7. Palmitoylethanolamide (PEA)
Antioxidant Category | Dosage and Duration | Sample | Key Measures and Results | Proposed Mechanisms * | Citation |
---|---|---|---|---|---|
Mygrium® nutritional supplement: blend of polyphenols and vitamins B1, B2, B3, B5, B6, and C | 3 capsules/day for 60 days Contents per capsule: 300 mg polyphenol, 60 mg VitC, 1.1 mg VitB1, 1.4 mg VitB2, 16 mgVitB3, 6 mg VitB5, and 1.4 mg VitB6 or placebo (maltodextrins) | 40 adult females with FM | Reduced levels of malondialdehyde and improved scores on the QoL questionnaire. No difference in FIQR scores. | Increased cortisol may reduce pain perception; decreased lipid peroxidation and inflammation; upregulation of proteins that may be related to exosomes involved in pain pathology | [38] |
Vitamin B12 | 1000 mcg/day for 50 days (no placebo) | 28 adult females with FM | Improved total FIQR scores, FIQR function domain, and FIQR symptom domain. Reduced anxiety based on the Hospital Anxiety and Depression Scale but no improvements in depression scores. No improvements in pain using Pain-VAS. | Vit B12 may modulate pain neurobiology and integrated psychological processes. Potential reduction in homocysteine levels, improved brain plasticity via upregulation of brain-derived neurotrophic factor, and reduced inflammation via interaction with cyclooxygenase enzymes. | [46] |
Vitamin D (25-hydroxyvitamin D) | 50,000 IU/week for 3 months (no placebo) | 11 adult females with FM | Reduced perceived pain based on VAS and reduction in tender point count. | Pilot study—none proposed. | [56] |
Vitamin D3 (cholecalciferol) | 50,000 IU/week for 3 months (no placebo) | 180 adult females with FM | FIQ and VAS score Improvement. | Preventing Vit D3 deficiency may reduce the initiation of inflammatory processes that can lead to chronic pain and sensitization. | [57] |
Vitamin D Ϯ | 50,000 IU/week with 25 mg Trazodone or 25 mg Trazodone with placebo for 8 weeks | 74 adult females with FM | Improved FIQ scores and SF-36 scores for physical function, fatigue, emotional well-being, pain, and general health | Potential synergistic effect of Vit D combined with antidepressants for improved physical and psychological state. | [58] |
Vitamin D3 (cholecalciferol) | 50,000 IU/week for 12 weeks (no placebo) | 135 females (70 FM and 65 HC) | Improved quality of life based on FIQ scores and pain based on VAS scores. No sleep improvement. | Since Vit D is needed for normal development and function of the musculoskeletal system, restoring Vit D can reduce bone and muscle pain. | [60] |
Vitamin D3 (cholecalciferol) | 50,000 IU/week for 3 months (no placebo) | 80 adults with FM (74 female and 6 male) | Based on FIQ, NRS, and SF-12 scores, patients >50 years old had improved quality of life and pain. Patients < 50 years old showed improvement in short-term musculoskeletal pain and long-term functional capacity. | Vit D is a steroid hormone that regulates the immune system and reduces pro-inflammatory cytokines that can impact muscle pain and function. | [61] |
Vitamin D3 (cholecalciferol) | 50,000 IU/week or placebo for 12 weeks | 80 adult females with FM | No significant improvement in FIQ or VAS scores. | Skeletal muscles have a Vit D receptor and may require sufficient Vit D for optimal function. | [62] |
Iron | Not available | 7332 adults with IDA | Survey participants with IDA had a lower hazard ratio for developing FM when receiving iron supplementation with or without blood transfusion therapy. | Iron deficiency may impact cognitive function. Reduced oxygen transport and mitochondrial function in muscle can trigger fatigue associated with FM. Deficient iron can also impair the analgesic effect of dopamine. | [65] |
Iron ferric carboxymaltose | Intravenous ferric carboxymaltose (15 mg/kg) or placebo received 2x (day 0 and 5) | 81 adults with FM and iron deficiency (80 female and 1 male) | Improved FIQR, BPI, and FVNS scores. MOSSS scores were not improved and some improvements decreased weeks after receiving the last dose. | Intravenous iron treatment provides a more rapid method to restore iron compared to oral administration. | [69] |
Melatonin and Palmitoylethanolamide PEATONIDE® | Fixed combination of 1200 mg of PEA and 0.2 mg of melatonin: 1 orosoluble stick/day at bedtime for 3 months. (no placebo) | 50 adults with FM 38 female and 12 male | Improved VAS, Insomnia Severity Index, and HAQ scores. Reduced tender points. | Analgesic and anti-inflammatory properties through various signaling pathways. Synergistic effect between PEA and melatonin—both have inhibitor effects on mast cell activation. The activation of mast cells in the thalamus may contribute to the pathophysiology of FM. | [71] |
Melatonin | Increasing doses of oral melatonin (3, 6, 9, 12, and 15 mg) each night for 10 days each with 10 days of placebo before treatment and 10 days placebo between doses (washout period). 110 days total | 33 adult females with FM | Improved sleep quality assessed by actigraphy and PSQI scores and increased serum and urine total antioxidant capacity with higher melatonin doses. | Increased antioxidant capacity from melatonin supplementation may reduce FM symptoms. Melatonin is involved in signaling pathways related to sleep and pain. | [75] |
Melatonin | Increasing doses of oral melatonin (3, 6, 9, 12, and 15 mg) each night for 10 days each with 10 days of placebo before treatment and 10 days placebo between doses (washout period). 110 days total | 33 adult females with FM | Improved mood and quality of life, decreased anxiety, and reduced pain with higher doses of melatonin as assessed by FIQ, STAT, VAS, NPS, and SF-36. Reduced urinary cortisol with 9, 12, or 15 mg/day dose. | Melatonin exerts an inhibitory effect on the secretion of cortisol, improving hormonal balance and circadian rhythm. Both melatonin and cortisol are involved in mood regulation, pain modulation, and anxiety. | [76] |
Coenzyme Q DDM Chinone® | 200 mg/2x daily Group 1—3 months CoQ and 3mo placebo Group 2—3 months placebo and 3 mo CoQ (6 months total) | 22 adult females with FM | Reduced pain, fatigue, and sleep disturbance based on VAS, SF-36, PSQI, ZAS, and ZDS. | Pilot study—none proposed. | [79] |
Coenzyme Q (combined with pregabalin) | 300 mg/day CoQ + 150 mg/day pregabalin or placebo + pregabalin for 40 days (80 days total) | 11 adults with FM; (9 female and 2 male) | Reduced pain and anxiety based on FIQ, VAS, PPT, and HDS. Increased mitochondrial function. Increased plasma SOD and reduced form of glutathione. | Reduced pain may be based on improved mitochondrial function, increased antioxidant status, and reduced inflammation. | [80] |
Coenzyme Q | 300 mg/day for 40 days (divided into 3 daily doses) or placebo | 20 adults with FM (10 CoQ and 10 control) Gender not specified | Improved scores for interpersonal sensitivity, depression, anxiety, hostility, and psychoticism based on the Symptom Checklist-90-R’. | CoQ may improve mitochondrial function and acts as a radical scavenger, reducing oxidative stress. Since mitochondrial dysfunction can lead to decreased energy and depression, CoQ supplementation may reduce FM symptoms. | [81] |
Coenzyme Q (combined with Mg and tryptophan) | 30-day treatment/ 1-month washout/ 30 days placebo Dosage not given | 20 adult females with FM | Well tolerated and some improvement in fatigue, sleep quality, and physical functioning based on the CISF questionnaire, but not statistically significant. | Pilot study—none proposed. | [82] |
Alpha-lipoic acid (ALA) | 300 mg/capsule Week 1: 600 mg Week 2: 1200 mg Week 3&4: 1800 mg Week 5: washout Or placebo for 4 weeks (10 weeks total) | 27 adults with FM (22 female and 5 male) | ALA was well tolerated. No major improvements in FM symptoms based on FIQ, BPI, and SF-36. Gender subgroup analysis revealed a potential sex effect of ALA on pain, showing reduced pain for men but not women. | The antioxidant properties of ALA may reduce oxidative stress and provide an analgesic to reduce pain associated with FM. | [85] |
Alpha-lipoic acid (ALA alone or combined with pregabalin) | Flexible dose titration up to 1800 mg/day ALA and 450 mg/day pregabalin (FM = fibromyalgia) | 41 adults with FM (37 female and 4 male) | No significant reduction in pain or other FM symptoms based on FIQ, SF-36, BDI, and MOSSS. | ALA’s potential inhibition of nociceptive T-type calcium channels that differ from those inhibited by pregabalin provided a strategy to reduce neuropathic pain. | [86] |
Alpha-lipoic acid Migratens ® nutritional supplement: blend of ALA; CoQ10; Mg; vitamins B2, B3, and D; and tryptophan | 2 sachets/day for 12 weeks. Contents per 2 sachets: 800 mg ALA, 450 mg Mg, 300 mg tryptophan, 150 mg CoQ, 25 mg VitB3, 2.4 mg VitB2, and 20 mcg VitD | 21 adult females with FM | Pain, based on VAS, was reduced after 1 month and 3 months of treatment compared to baseline. No differences in FIQR scores or FSS scores. | ALA has both direct and indirect antioxidant roles that may reduce FM symptoms. ALA may reduce pain and inflammation by inhibiting the activation of NF-κB pathways. | [87] |
Palmitoylethanolamide (PEA) with duloxetine and pregabalin | Ultra-micronized 600 mg/2x/day for 30 days, and then micronized 300 mg/2x/day for 2 months | 35 adults with FM 30 female and 5 male | PEA combined with duloxetine and pregabalin improved tender point count and pain scores based on VAS compared to duloxetine and pregabalin alone. No side effects. | PEA exerts anti-inflammatory, analgesic, and pain-relieving effects. PEA may down-modulate mast cell degranulation and release of pro-inflammatory mediators. | [95] |
Palmitoylethanolamide ultra-micronized | Ultra-micronized PEA tablets 600 mg/3x/day for 10 days, then 600 mg/2x/day for 20 days, and then 600 mg/1x/day for 15 months | 407 adults with FM 378 female and 29 male | Improved pain based on VAS and quality of life based on FIQ scores after 1 month. Some adverse effects based on gastrointestinal issues. | PEA may act as an agonist of PPAR-α nuclear receptors, increasing the transcription of pro-inflammatory factors, and resulting in reduced pain. PEA may indirectly inhibit fatty acid amide hydrolase, an enzyme that degrades endogenous cannabinoid anandamide, thus increasing activation of cannabinoid receptors 1 and 2. | [96] |
8. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ALA | Alpha-lipoic acid |
CoQ | Coenzyme Q |
FIQ | Fibromyalgia Impact Questionnaire |
FIQR | Fibromyalgia Impact Questionnaire Revised |
IDA | Iron deficiency anemia |
NF-κB | nuclear factor kappa-light chain enhancer of activated B cells |
Nr2F | nuclear factor erythroid 2-related factor 2 |
PON-1 | Paraoxonase |
ROS | Reactive oxygen species |
SF-36 | Short-Form Health Survey |
VAS | Visual Analog Scale |
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Totten, M.S.; Wondzi, P.K. Antioxidant Treatments for Fibromyalgia. Oxygen 2025, 5, 9. https://doi.org/10.3390/oxygen5030009
Totten MS, Wondzi PK. Antioxidant Treatments for Fibromyalgia. Oxygen. 2025; 5(3):9. https://doi.org/10.3390/oxygen5030009
Chicago/Turabian StyleTotten, Melissa S., and Precious K. Wondzi. 2025. "Antioxidant Treatments for Fibromyalgia" Oxygen 5, no. 3: 9. https://doi.org/10.3390/oxygen5030009
APA StyleTotten, M. S., & Wondzi, P. K. (2025). Antioxidant Treatments for Fibromyalgia. Oxygen, 5(3), 9. https://doi.org/10.3390/oxygen5030009