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Review

Antioxidant Treatments for Fibromyalgia

by
Melissa S. Totten
* and
Precious K. Wondzi
Chemistry, Biochemistry, and Nutrition Program, Salem College, Winston-Salem, NC 27101, USA
*
Author to whom correspondence should be addressed.
Submission received: 27 March 2025 / Revised: 19 June 2025 / Accepted: 20 June 2025 / Published: 23 June 2025

Abstract

Fibromyalgia is a syndrome that causes chronic musculoskeletal pain accompanied by symptoms such as fatigue, sleep disorders, headaches, anxiety, and depression. People diagnosed with fibromyalgia usually have higher levels of reactive oxygen species and lower antioxidant capacity compared to healthy individuals. This condition can contribute to elevated oxidative stress in the body, especially within the lipid-rich nervous system. Treatment with antioxidants through diet or supplements is one method being investigated to reduce the symptoms of fibromyalgia. This narrative review focuses on the latest research, specifically peer-reviewed publications within the last 10 years, on potential antioxidant treatments for patients with fibromyalgia. Relevant micronutrients, such as vitamin B12, vitamin D, and iron, and supplements such as melatonin, coenzyme Q, alpha-lipoic acid, and palmitoylethanolamide are discussed. Based on the current evidence, many of these antioxidants show potential for the management of fibromyalgia symptoms as standalone treatments or in combination with other antioxidants or pharmacological agents. More clinical research is required to understand the long-term efficacy and safety of these micronutrients and supplements, as well as their overall health impact.

1. Introduction

Fibromyalgia is a complex syndrome that causes chronic musculoskeletal pain and stiffness [1]. It is characterized by a wide spectrum of symptoms that may include fatigue, sleep disorders, headaches, anxiety, and depression. The severity of these symptoms can vary significantly. Fibromyalgia is considered the third most common musculoskeletal condition, estimated to affect 2–3% of the population worldwide. Women are more likely to be diagnosed with the syndrome compared to men. Although fibromyalgia can occur at all stages of life, it is more common in adulthood and often initiates between 30 and 35 years of age. Currently, the cause is unknown and there is no cure. The Fibromyalgia Impact Questionnaire (FIQ) and the updated Fibromyalgia Impact Questionnaire Revised (FIQR) are common tools used to assess fibromyalgia symptom severity and impact on quality of life [2]. Pain is frequently assessed using the Visual Analogue Scale (VAS). For these assessments, higher scores refer to higher levels of pain and fibromyalgia symptoms. The wide range of risk factors or triggers for fibromyalgia may include genetics, illness, repeated injury, traumatic events, or emotional stress. No specific biomarkers have been established, making the diagnosis of this syndrome a challenge [1,3]. A tentative diagnosis can be made by assessing many factors, such as pain, sleep, fatigue, anxiety, ability to concentrate, functional status, sensitivity, and stiffness. The extensive variability of causes, symptoms, and severity requires a multidisciplinary, patient-centered approach with a tailored treatment plan that may include a combination of pharmacological agents, non-pharmacological methods, antioxidants, and diet [1,3,4,5]. Some antioxidant compounds that have been studied in the context of fibromyalgia include melatonin, coenzyme Q, vitamin D, vitamin E, and palmitoylethanolamide [3]. Combining different treatment methods is frequently reported to be more effective than a single treatment method for the alleviation of fibromyalgia symptoms. Alternative treatments using hyperbaric oxygen [6,7,8,9,10] and ozone therapy [11,12,13] are also being investigated.
People diagnosed with fibromyalgia usually have higher levels of reactive oxygen species (ROS) and lower antioxidant capacity compared to healthy individuals [3,14]. This can contribute to elevated oxidative stress in the body, especially within the lipid-rich nervous system. Fibromyalgia patients have higher levels of serum pro-oxidant indicators such as total oxidant status and thiol–disulfide levels and lower levels of antioxidant indicators such as total antioxidant capacity, native thiols, and total thiols [15]. Furthermore, a negative correlation between the native thiol/total thiol ratio with FIQ scores and a positive correlation between disulfide and FIQ scores has been reported in female fibromyalgia patients, showing potential connections between oxidative stress and fibromyalgia symptoms [16]. Women with fibromyalgia were found to have higher plasma lipid peroxides and protein carbonyls, two oxidative damage biomarkers that are often associated with fibromyalgia [14]. Oxidative stress due to mitochondrial dysfunction is also a contributing factor in the pathogenesis of this syndrome [17,18]. Coenzyme Q deficiency within the mitochondria results in higher superoxide activity and lipid peroxidation product synthesis, promoting excessive cell autophagy and cell injury [17]. These elevated oxidative processes manifest as increased pain in fibromyalgia patients. It has also been shown that lipid peroxidation product concentration is positively correlated with fibromyalgia severity as assessed by the FIQR [19]. The reduced function of endogenous antioxidant enzymes superoxide dismutase, catalase, and nicotinamide adenine dinucleotide phosphate oxidase has been correlated with pain and fatigue severity in fibromyalgia patients [20]. For example, one study evaluating 47 fibromyalgia patients in Brazil found a significant negative association between plasma superoxide dismutase levels and muscle pain [21]. Furthermore, catalase, glutathione reductase, and glutathione peroxidase have been found to be negatively correlated with fibromyalgia symptoms such as pain, psychological distress, and sleep disorders [14,19]. In a recent study assessing oxidative stress parameters related to fibromyalgia, it was reported that serum paraoxonase (PON-1) and nitric oxide were significantly reduced in female patients with fibromyalgia compared to a control group [22]. PON-1 is an antioxidant enzyme that hydrolyzes lipid peroxides and has the potential to lower the oxidation of low-density lipoprotein, reducing the risk of cardiovascular damage. Nitric oxide is a small molecule that may have a role in reducing fibromyalgia-associated pain through vasodilation. This study also found that serum malondialdehyde levels were significantly higher in fibromyalgia patients, indicating higher rates of lipid peroxidation and oxidative stress. Furthermore, PON-1 was negatively correlated with FIQ scores, disease duration, tender point count, and malondialdehyde concentration. In a 12-week exercise program study comparing female fibromyalgia patients with an age-matched control group, it was found that oxidative stress parameters such as protein carbonyls, nitric oxide, and thiobarbituric acid reactive substances were significantly higher in blood samples of fibromyalgia patients while antioxidant parameters such as catalase and thiols were lower in the patients before the program began [23]. After the exercise program was completed, the fibromyalgia patients showed significantly decreased oxidative stress parameters and increased antioxidant parameters. Taken together, these studies provide evidence that oxidative stress may be a key contributing factor of fibromyalgia etiology and pathophysiology.
Treatment with antioxidants through diet or supplements is one method being investigated to reduce the symptoms of fibromyalgia [4,24,25,26,27]. A recent cross-sectional study in females found that oxidative stress can be reduced in patients with fibromyalgia by increasing dietary antioxidant intake [5]. Plant-based diets and the Mediterranean diet are high in phytochemicals with antioxidant properties and are recommended to reduce oxidative stress, inflammation, and musculoskeletal pain [24,25,28]. The interplay between antioxidants and anti-inflammatory compounds found in plants is important to note. Oxidative stress can trigger inflammation, and vice versa [29]. Thus, incorporating a variety of plants in the diet with both antioxidant and anti-inflammatory properties is a good strategy for improved health. In some animal models, curcumin was found to reduce oxidative stress and suppress cell signaling pathways such as nuclear factor kappa-light chain enhancer of activated B cells (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) [30]. The activated NF-κB pathway triggers the release of inflammatory mediators, which in turn cause the sensitization to pain signals, promoting the development of fibromyalgia. Polyphenols in plants, herbs, and spices, such as capsaicin, curcumin, and quercetin, have a potential role in pain management due to their combined anti-inflammatory and antioxidant properties. Since women with fibromyalgia are more sensitive to the suppressive effect of nitric oxide on oxidative phosphorylation, which can lead to the buildup of glycolytic products in exercising muscle, plant-based diets are recommended to restore normal nitric oxide levels, thus reducing fibromyalgia-related muscle pain [27]. Fruits such as blueberries, strawberries, and pomegranates that are high in antioxidants have been shown to reduce musculoskeletal pain [25]. Microminerals such as zinc, selenium, and iron have antioxidant properties and have shown the potential to reduce fibromyalgia symptoms [17]. Nutrient therapy also shows promise for relieving fatigue, a common symptom of fibromyalgia. For example, the oral or parenteral administration of micronutrients and cofactors such as vitamins B, C and D, zinc, coenzyme Q10, L-carnitine, methionine, nicotinamide adenine dinucleotide (NAD) can significantly reduce pain in both healthy individuals and patients with fibromyalgia [31]. This narrative review will focus on the latest research, specifically publications within the last 10 years, on potential antioxidant treatments for patients with fibromyalgia. Relevant micronutrients and supplements such as melatonin, coenzyme Q, alpha-lipoic acid, and palmitoylethanolamide will be discussed. These specific antioxidants were selected based on the available clinical data within the review time frame. Bioactive compounds with antioxidant capacity, such as curcumin and quercetin, were not included in our review due to limited clinical studies in fibromyalgia patients. However, for readers interested in this topic, recent reviews related to the potential therapeutic effects of bioactive compounds are available [24,32,33].

2. Methods

The research question for this narrative review was to determine if new antioxidant treatments had been discovered for patients with fibromyalgia over the last decade. For the literature search, peer-reviewed articles were retrieved from PubMed and Proquest Central in January 2025. Articles from the past 10 years (January 2015–January 2025) were assessed for suitability based on relation to the main topic. Animal and cell studies were excluded in most cases but may be mentioned briefly. Published protocols were also excluded. Search terms included the following: “fibromyalgia and antioxidants”, “fibromyalgia and vitamins”, “fibromyalgia and minerals”, “fibromyalgia and selenium”, “fibromyalgia and iron”, “fibromyalgia and zinc”, “fibromyalgia and copper”, “fibromyalgia and manganese”, “fibromyalgia and melatonin”, “fibromyalgia and coenzyme Q”, “fibromyalgia and alpha-lipoic acid”, and “fibromyalgia and palmitoylethanolamide”. Since the majority of articles we found regarding bioactive compounds were based on animal models, we did not include this category in our review. Based on the results of the overall search and the number of articles within each category, we narrowed our focus on antioxidants to the following: vitamins (mainly vitamin B12 and vitamin D), iron, melatonin, coenzyme Q, alpha-lipoic acid, and palmitoylethanolamide. Key results were extracted from each article and summarized into antioxidant categories to provide an organized synopsis of the latest antioxidant treatment strategies for fibromyalgia.

3. Micronutrients

3.1. Vitamins and Minerals—Combined Studies

Micronutrients with antioxidant capacity have the potential to improve various symptoms of fibromyalgia based on current evidence [27,31,34]. However, inconsistencies across various studies do exist [17,35]. A cross-sectional study including 92 female fibromyalgia patients and 96 female control participants evaluated potential associations between dietary intake and fibromyalgia symptoms. FIQR scores correlated negatively with iron (r = −0.320, p = 0.002), zinc (r = −0.238, p = 0.023), vitamin B1 (r = −0.218, p = 0.038), vitamin B6 (r = −0.123, p = 0.012), folic acid (r = −0.250, p = 0.017), and vitamin C (r = −0.217, p = 0.039). There was also a statistically significant negative correlation between pain and vitamin B6 intake assessed using the VAS (r = −0.322, p = 0.002). Other vitamins with antioxidant capacity, such as vitamins A and E, did not show statistically significant correlations with fibromyalgia symptoms [36]. This report provides preliminary information about how micronutrients consumed in the diet, a controllable factor for patients, may impact fibromyalgia symptoms.
In a cross-sectional observational study, dietary consumption of vitamins A, E, B12, and folate was found to be lower in female fibromyalgia patients compared to a control group. Low levels of vitamin E were moderately correlated with lower quality of life based on FIQ scores (r = −0.303, p = 0.048). Dietary selenium and calcium were also lower in the fibromyalgia patients compared to the control group; however, zinc levels were comparable. It is important to note that these results were based on a 3-day food registry and not biochemical parameters [37]. A randomized double-blind placebo-controlled intervention trial assessed the nutritional supplement Mygrium® on the impact on fibromyalgia patients. Mygrium® is an olive extract containing a blend of polyphenols, vitamin C, and several B vitamins such as thiamin (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), and pyridoxine (B6). Participants included 40 adult females with fibromyalgia split into a treatment group (20) and a control group (20). The nutritional supplement or placebo was taken three times daily. The treatment group had significantly reduced levels of malondialdehyde (p ≤ 0.01) and improved scores on the quality of life questionnaire under the physical dimension (p ≤ 0.01); however, there were no significant differences in FIQR scores [38]. The clinical significance of this nutritional supplement and other fibromyalgia antioxidant treatments described in this review are summarized in Table 1.
Specific vitamins and minerals are involved in glutamatergic neurotransmission and may impact pain perception in fibromyalgia [39]. Patients with fibromyalgia have been shown to have higher levels of glutamate in the brain and cerebral spinal fluid. Glutamate, an amino acid found in free form and protein-bound form, is a common nutrient in the diet. It acts as an excitatory neurotransmitter and can increase pain severity when glutamate levels are higher than normal. NMDA is a glutamate receptor that is linked to pain and depression. Magnesium blocks N-methyl D-aspartate (NMDA) receptors and prevents excitation; thus, magnesium deficiency can lead to higher excitation levels and increased pain, headaches, and depression, all symptoms associated with fibromyalgia. Zinc can also modulate this excitatory response, making zinc a key mineral that may help reduce fibromyalgia symptoms. Furthermore, excess neurotransmission via glutamate can increase oxidative stress through the production of ROS [40], highlighting the critical need to consume sufficient dietary antioxidants. Vitamin B6 can also reduce neuroexcitation since it acts as a coenzyme for glutamate decarboxylase, an enzyme that converts glutamate to gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter [39]. Therefore, a vitamin B6 deficiency could lead to a buildup of glutamate and reduction in GABA, leading to more neurotransmission and pain. Based on these neurobiological mechanisms, future studies involving magnesium, zinc, and vitamin B6 should be investigated to understand the relationship between micronutrient status and pain in fibromyalgia patients.

3.2. Vitamin B12

Vitamin B12, or cobalamin, can serve as an antioxidant in several ways, such as the neutralization of superoxide and hydroxyl radicals through direct scavenging, enhanced glutathione synthesis, and regulation of antioxidant enzymes such as superoxide dismutase and catalase [41,42,43]. In a retrospective study with 2142 fibromyalgia patients (91.3% women), 42.4% of these patients had low vitamin B12 levels (<400 ng/L). The patients with lower levels of vitamin B12 (<350 ng/L) had significantly higher levels of fatigue (p = 0.01). After adjusting for patients with low vitamin D, low levels of B12 were still associated with fatigue (p = 0.004). Interestingly, patients with <400 ng/L vitamin B12 also trended toward statistical significance for greater memory loss (p = 0.058) [44]. Another study with 58 female fibromyalgia patients and 58 healthy control participants found that the fibromyalgia patients had significantly lower serum vitamin B12 compared to the control group (p < 0.001). Within the patient group, there were also significant negative correlations between vitamin B12 and tender points (r = −0.312, p < 0.001), FIQ scores (r = −0.309, p = 0.018), and fatigue-VAS (r = −0.308, p = 0.018) [45]. An open-label, pre-post study with 28 female fibromyalgia patients showed improved symptom severity and reduced anxiety after a daily dose of 1000 mcg of vitamin B12 for 50 days. After the sublingual vitamin B12 treatment, there was a statistically significant improvement in the total FIQR scores (p < 0.01), FIQR function domain (p = 0.01), and FIRQ symptom domain (p < 0.01). Based on the Hospital Anxiety and Depression Scale, anxiety was significantly reduced (p < 0.01); however, there were no improvements in depression scores, nor were there improvements in pain as assessed with the Pain-VAS [46]. The current evidence suggests that vitamin B12 may be effective for reducing some symptoms of fibromyalgia, such as fatigue and anxiety, but may be less effective for the treatment of pain or depression. More clinical trials should be conducted in order to make a more conclusive recommendation for vitamin B12.

3.3. Vitamin D

Although the role of vitamin D as an antioxidant may be controversial [47], there is some evidence that vitamin D can reduce oxidative stress through various mechanisms such as the modulation of Nrf2, enhanced antioxidant gene expression, and maintenance of normal mitochondrial function [48,49]. The outcomes of these mechanisms lead to increased glutathione and total antioxidant capacity, as well as reduced levels of malondialdehyde and lipid peroxidation.
Vitamin D deficiency is widespread throughout the global population [50] and is common in patients with fibromyalgia [51]. Although the association between vitamin D status and fibromyalgia may be inconsistent between studies, several recent investigations have shown that patients with fibromyalgia are frequently found to have low levels of vitamin D. A meta-analysis comparing 851 cases of females with fibromyalgia compared to 862 controls revealed a significant trend of lower Vit D blood levels in fibromyalgia patients [52]. In a study comparing 58 female fibromyalgia patients to 58 healthy controls, the fibromyalgia patients had significantly lower vitamin D levels compared to the control group (p = 0.013). There was also a significant negative correlation between vitamin D and tender points (r = −0.234, p = 0.012) and FIQ scores (r = −0.346, p = 0.008) within the patient group [45]. A pilot study divided pre-menopausal women with non-specific musculoskeletal symptoms into a low serum 25-hydroxyvitamin D3 group and a control 25-hydroxyvitamin D3 group to compare the prevalence of fibromyalgia syndrome, pain levels, and depression. They found that pain and fibromyalgia syndrome prevalence was higher in the low vitamin D group; however, no differences were found in depression scores [53]. A study in Italy assessed the relationship between blood levels of 25-hydroxyvitamin D, Vitamin B12, magnesium, iron, and ferritin with FIQ scores in 20 female patients with fibromyalgia with an age-matched female control group. The patient group showed a moderate negative correlation between vitamin D and physical functioning (r = −0.561, p = 0.008) and magnesium with stiffness (r = −0.518, p = 0.016). The other vitamins and minerals evaluated in this study did not have a significant relationship with any FIQ scores. Although there were statistically significant relationships found between vitamin D and magnesium with some FIQ scores, there was no statistically significant difference between blood levels of these micronutrients between the fibromyalgia group and the control group [34]. In a prospective questionnaire study with 593 adult fibromyalgia patients in the United States, 20.6% of the participants were found to have low vitamin D status (≤ 25 ng/mL). An adjusted regression analysis revealed a statistically significant association (p = 0.04) between low vitamin D status and total FIQR scores compared to the group with adequate vitamin D status [50]. Based on this evidence, vitamin D deficiency may be a risk factor for worse fibromyalgia symptom severity.
In contrast to these results, other reports have shown that vitamin D status is not associated with fibromyalgia. For example, a cross-sectional study in Saudi Arabia with 40 male and female adult fibromyalgia patients found a significant correlation between fibromyalgia and serum serotonin, but no correlation between fibromyalgia and vitamin D status based on FIQR scores [54]. A cross-sectional study in Brazil found no significant difference in vitamin D status when comparing fibromyalgia patients to an age and gender-matched control group. However, there was a correlation (p = 0.018) between serum vitamin D concentration and disease severity. Although only 4.8% of all the participants were vitamin D deficient, all the deficiencies were found in fibromyalgia patients [55].
Vitamin D supplementation shows promise for some patients with fibromyalgia (Table 1). In a pilot study that included 11 female fibromyalgia patients, vitamin D supplementation (50,000 IU) once per week for three months resulted in reduced perceived pain, evaluated by VAS scores (p = 0.002). There was also a significant reduction in tender point count after the three-month treatment (p = 0.07) [56]. A study with 180 adult female fibromyalgia patients found that vitamin D3 supplementation (50,000 IU) administered for 12 weeks resulted in significant FIQ score improvement (p < 0.05) and VAS score improvement (p < 0.01). Of these patients, 65.6% had deficiency or severe deficiency of vitamin D levels and 12.2% had vitamin D insufficiency before treatment began [57]. In a randomized controlled trial with 74 adult female patients with fibromyalgia and low vitamin D levels, the combination of 25 mg Trazodone, a low-dose antidepressant, with 50,000 IU vitamin D supplementation given weekly for eight weeks at bedtime resulted in improved FIQ scores (p = 0.002) and several improved indices of the Short-Form Health Survey (SF-36), including physical function, fatigue, emotional well-being, pain, and general health (p = 0.0001) [58]. A meta-analysis using five randomized controlled trials with 315 participants found vitamin D supplementation to be effective in reducing FIQ scores in fibromyalgia patients compared to the placebo group (p < 0.001) but found no statistically significant difference in VAS scores between the groups [59]. In a prospective study with 70 premenopausal female fibromyalgia patients and 65 healthy age- and sex-matched control participants, it was found that vitamin D replacement therapy significantly improved the quality of life for female fibromyalgia patients based on FIQ scores (p = 0.001) and pain based on VAS scores (p = 0.001). However, vitamin D did not show improvement in sleep scores [60]. A single-center observational study with 80 fibromyalgia patients (74 female and 6 male) supplemented for 3 months with 50,000 IU of cholecalciferol in combination with planned physical activity found that patients in the older group (>50 years old) experienced an improvement in quality of life and pain. The younger group showed improvement in short-term musculoskeletal pain and long-term functional capacity. These results were based on scores from the FIQ, Numerical Rating Scale (pain level assessment), and 12-Item Short-Form Survey (quality of life assessment) [61]. In contrast to these studies, a randomized, placebo-controlled, double-blind clinical trial with 80 female fibromyalgia patients found no significant improvement in FIQ or VAS scores after taking capsules of 50,000 IU vitamin D3 weekly for 12 weeks [62]. Taken together, these recent investigations show a trend of improved fibromyalgia symptoms when patients are supplemented with vitamin D, although not all studies reported improvements. Vitamin D reduced pain only in some patients. Since the dose of vitamin D in most studies has been similar (50,000 IU), it is possible that various populations are responding to vitamin D in opposing ways due to differences in genetics or age.

3.4. Iron

Iron deficiency or general iron dysregulation has been reported as a potential risk factor for fibromyalgia [63]. However, the precise mechanism of how iron may be associated with the etiology or pathophysiology of fibromyalgia is unknown. In the context of antioxidants, iron is known to be a key structural component of the endogenous scavenging enzyme catalase [64]. Iron is also a key cofactor for enzymes involved in neurotransmitter synthesis, such as tryptophan hydroxylase for the production of serotonin and tyrosine hydroxylase for the synthesis of dopamine and norepinephrine [65]. These neurotransmitters act as modulators for pain signals and have a role in pain perception [66,67,68]. Decreased ferritin, the storage protein for iron, has been associated with fibromyalgia and related muscle pain in humans [27]. In a study comparing 58 female fibromyalgia patients to 58 healthy control participants, the patients had significantly lower serum ferritin compared to the control group (p = 0.009). Within the patient group, there were significant negative correlations between ferritin and tender points (r = −0.202, p = 0.029), FIQ scores (r = −0.517, p < 0.001), fatigue (r = −0.378, p =0.003), and sleep quality based on the Pittsburgh Sleep Quality Scale (r = −0.263, p =0.046) [45]. A population-based retrospective cohort study using data from the Taiwan National Health Insurance Research Database that included 13,381 adult participants (74.2% female and 25.8% male) with newly diagnosed iron-deficiency anemia (IDA) had a significantly higher incidence of fibromyalgia compared to an age- and sex-matched non-IDA cohort (p < 0.001). Furthermore, iron supplementation in 7332 IDA patients was associated with a reduced incidence of fibromyalgia [65]. A blinded randomized control trial in the United States evaluated the efficacy and safety of intravenous ferric carboxymaltose (15 mg/kg) in adults with both fibromyalgia and iron deficiency (based on low ferritin and transferrin levels) compared to control participants. It was found that the ferric carboxymaltose treatment group had increased serum ferritin and transferrin saturation (p < 0.001), improved FIQR scores at day 14 (p ≤ 0.015), improved Brief Pain Inventory scores (p ≤ 0.022), and improved Fatigue Visual Numeric Scale scores (p ≤ 0.005). The Medical Outcomes Study Sleep Scale scores were not significantly different after treatment, and some improvements were diminished several weeks after receiving the last dose of ferric carboxymaltose. The safety of intravenous ferric carboxy maltose was also determined to be safe and well tolerated [69]. More research is needed to determine if iron supplementation is a feasible treatment strategy for fibromyalgia patients.

4. Melatonin

Melatonin can act as an antioxidant directly by quenching ROS and reactive nitrogen species, or indirectly by upregulating the synthesis of glutathione or by stimulating glutathione peroxidase and glutathione reductase antioxidant enzymes [70]. Melatonin is also a hormone that improves sleep quality and increases pain threshold [17]. Low levels of melatonin at night can increase the sensation of pain. The relationship between pain and sleep is widely acknowledged. Pain not only interrupts sleep patterns but initiates a negative feedback loop where shorter or disrupted sleep lowers the pain threshold, further amplifying spontaneous pain. A recent study revealed that non-restorative sleep, which is common in patients with fibromyalgia, exacerbates pain the following day and a more painful day precedes a night of reduced sleep quality [71]. Accumulating data indicates that sleep is a more dependable signal of chronic pain than the reverse [72]. The strength ratio of each direction of the pain–sleep correlation is still being investigated [73].
It has been hypothesized that many fibromyalgia-related symptoms are connected to an impaired pattern of endogenous melatonin [74]. An open-label study conducted in 2024 examined the impact of 0.2 mg of melatonin paired with 1200 mg of palmitoylethanolamide on the pain, sleep, and overall well-being of fibromyalgia patients (Table 1) [71]. A group of 50 adults (38 female and 12 male) were treated and assessed at multiple time points (1 month, 3 months, and 4 months) from June 2023 to March 2024. The treatment resulted in a reduction in tender points at one and three months, which was maintained in the fourth month. These patients reflected significant progress in the VAS, Insomnia Severity Index, and Health Assessment Questionnaire scores compared to their baseline scores. This study brought to attention the prospects of melatonin combined with palmitoylethanolamide for alleviating pain and enhancing the sleep quality of fibromyalgia patients.
Based on a review of several preliminary clinical studies, it has been postulated that total antioxidant capacity, 6-sulfatoxymelatonin, urinary cortisol levels, and other biological parameters improved upon oral supplementation with melatonin [74]. A longitudinal placebo-controlled study evaluated the effect of melatonin (3, 6, 9, 12, and 15 mg/day) on sleep quality and total antioxidant capacity in 33 female adults with fibromyalgia. Each dose was administered for 10 days followed by a placebo washout period of 10 days. Sleep quality was improved compared to baseline and placebo using higher doses of melatonin as assessed by actigraphic monitoring and the Pittsburg Sleep Quality Index. Both serum and urinary total antioxidant capacity increased with higher doses of melatonin treatment [75]. A related study from the same sample of 33 female patients with fibromyalgia used multiple psychological measures, such as the Numerical Pain Scale, the State–Trait Anxiety Inventory, VAS, FIQ, the Short-Form-36 Health Survey, and analysis of urinary cortisol levels to evaluate the impact of increasing doses of melatonin on mood. Higher doses of melatonin treatment were found to improve fibromyalgia-related symptoms, such as low mood state, increased anxiety levels, high pain levels, and impaired quality of life. Urinary cortisol levels were also reduced with higher doses of melatonin. The combination of increased melatonin with decreased cortisol may improve hormone balance and circadian rhythm, thus improving sleep, mood, and pain perception [76].
Though promising, the current research on melatonin’s effects on fibromyalgia is insufficient to make broad conclusions. There is a need for further investigation to determine a more precise dosage and management strategy for fibromyalgia patients. More clinical trials need to be conducted to validate the existing findings regarding melatonin as an integral part of fibromyalgia management.

5. Coenzyme Q (CoQ)

Patients with fibromyalgia are often found to have lower levels of coenzyme Q (CoQ), leading to mitochondrial dysfunction and increased oxidative stress [17]. CoQ10, also known as ubiquinone, is an endogenous antioxidant that plays a critical role in mitochondrial ATP production [77]. Current research studies make a compelling case for the link between reduced antioxidant capacity and fibromyalgia symptoms, emphasizing the oxidative stress observed in patients with fibromyalgia [77,78]. Several medical practitioners prescribe CoQ, an over-the-counter food supplement, for diseases like myopathy, hypertension, diabetes, neurological disorders, and fibromyalgia [78].
A randomized crossover pilot study involving 22 female participants diagnosed with fibromyalgia assessed the effects of administering CoQ10 (DDM Chinone®) at a dose of 200 mg twice daily for three months compared to a placebo. After the first three months, the treatment and placebo groups were reversed (Table 1). The findings indicated that CoQ10 significantly improved most pain-related outcomes by 24–37% (p < 0.05) and led to reductions in fatigue, anxiety, depression, and sleep disturbance after both the three-month and six-month evaluations (p < 0.05) [79].
CoQ10 supplementation was also shown to be beneficial in fibromyalgia patients treated with pregabalin. In a double-blind randomized placebo-controlled crossover trial, 300 mg/day of CoQ10 plus 150 mg/day of pregabalin or placebo plus pregabalin was administered for 40 days in 9 females and 2 males. After the first 40 days, the treatment protocols were reversed and continued for an additional 40 days. Pain and anxiety were assessed using the FIQ, VAS, pain pressure threshold, and the Hamilton Depression Rating Scale anxiety questionnaire. The results showed that CoQ10 supplementation led to a statistically significant reduction in pain and anxiety (p < 0.05) while also lowering mitochondrial oxidative stress (p < 0.05) relative to the control group that received pregabalin and a placebo. Patients taking the CoQ supplement also showed increased levels of plasma superoxide dismutase and increased levels of reduced glutathione (p < 0.05) [80].
A double-blinded placebo-controlled clinical control trial evaluated the effect of CoQ10 soft gel capsules (300 mg/day for 40 days) on psychopathological symptoms in 20 adult fibromyalgia patients. Based on the Symptom Checklist-90-R’, a multidimensional psychological screening tool, a statistically significant improvement was found for interpersonal sensitivity, depression, anxiety, hostility, and psychoticism (p < 0.001) in the CoQ-treated patients compared to the placebo group [81]. This preliminary study demonstrates the potential of CoQ treatment for common psychological symptoms in fibromyalgia patients.
CoQ combined with magnesium and tryptophan administered for 30 days was well tolerated and showed a slight improvement in fatigue, sleep quality, and physical functioning in female fibromyalgia patients in another pilot study, although these changes were not statistically significant. Additionally, the treatment did not have any effect on emotional factors such as depression and anxiety, despite the use of coping strategies and mood-enhancing components [82].
In summary, CoQ still shows potential as a supplement for alleviating fibromyalgia symptoms, particularly in reducing pain and fatigue, and improving mitochondrial function. Despite these optimistic findings from multiple studies, the small sample sizes and methodological constraints underscore the need for more thorough research to validate its efficacy and fully understand its mechanisms. In the meantime, while CoQ may provide relief for some patients, more evidence is needed before it can be endorsed for general use.

6. Alpha-Lipoic Acid (ALA)

Fibromyalgia often occurs alongside other conditions such as migraines, irritable bowel syndrome, and diabetic neuropathy. In diabetic neuropathy, alpha-lipoic acid (ALA) improves nerve blood flow and provides antioxidant protection against further neural damage [83].
The similarities between fibromyalgia and neuropathic pain suggest that they may share common underlying mechanisms, which could lead to similar treatment approaches. One such treatment is the use of antioxidants, which has been shown in current research to help alleviate pain. ALA, a caprylic acid-derived antioxidant with a dithiol functional group [80], is one of the most studied for its potential analgesic effects in humans [84]. ALA not only reduces pain but also alleviates numbness and tingling [4]. Based on these findings, it is reasonable to hypothesize that ALA could be effective in treating fibromyalgia symptoms. However, a recent randomized placebo-controlled crossover trial evaluating ALA for fibromyalgia found no evidence to support its effectiveness [85]. Patients with fibromyalgia (22 females and 5 males) received either placebo lactose capsules or 600 mg of ALA in week 1, 1200 mg in week 2, and up to 1800 mg ALA in weeks 3 and 4, followed by a 1-week washout period before crossover (Table 1). Although the ALA treatment was well tolerated, the analysis of pain showed no significant difference between ALA and placebo using various surveys, including the FIQ, Brief Pain Inventory, and SF-36. For most items on the Brief Pain Inventory, there were no significant differences, except for a slight improvement in social relations for the ALA group (p = 0.01). Interestingly, a gender subgroup analysis revealed a significant pain reduction in men with ALA, but not in women. Although the sample size of this pilot study was small, the potential influence of biological sex on the effectiveness of ALA warrants further investigation.
Combining various supplements or medications for their potential synergistic effects is a common approach to treating disease symptoms. In this context, one study examined the combination of ALA with pregabalin, a medication for neuropathic pain relief, to assess its efficacy in alleviating fibromyalgia pain. In this randomized, double-blind crossover study, the combination of pregabalin and ALA was compared to their respective monotherapies for the treatment of fibromyalgia in 41 adults (37 female and 4 male) [86]. Pregabalin, a sedative anticonvulsant, has been shown to be efficient in the treatment of fibromyalgia and neuropathy pain. Still, this trial provided no empirical support for combining ALA and pregabalin to soothe fibromyalgia pain based on the FIQ and SF-36. Although the combination treatment resulted in a reduction in average pain intensity compared to ALA monotherapy, no such improvement was observed when compared to pregabalin monotherapy. It is also important to note that the combined treatment and pregabalin monotherapy were both superior to ALA monotherapy for measures of mood and sleep affect according to Beck Depression Inventory-II scores and the Medical Outcomes Study Sleep Scale, respectively.
A randomized control trial in Italy evaluated a supplement containing ALA for the potential treatment of symptoms in 21 female fibromyalgia patients. The Migratens® supplement, containing a combination of ALA; CoQ10; vitamins B2, B3, and D; magnesium; and tryptophan, was taken twice daily for 12 weeks. Pain, based on VAS, was significantly reduced after one month (p = 0.025) and three months of treatment (p = 0.012) compared to baseline. However, at a six-month follow-up (three months since the last treatment dose), there was no difference in pain scores. There were no differences in FIQR scores nor Fibromyalgia Severity Scale scores at any of the time points. Nevertheless, the ALA-containing Migratens® supplement shows potential as an antioxidant blend for reduction in fibromyalgia symptoms [87], but should be assessed over a longer duration.
It has been demonstrated in a rodent model for neuropathic pain that the subcutaneous administration of R-lipoic acid effectively reduced pain sensitivity [83]. Most clinical studies generally do not specify the exact composition of R and S isomers included in ALA. Generally, the term alpha-lipoic acid refers to a mixture of the R and S isomers, unless otherwise specified, while the R-isomer alone is often referred to as lipoic acid or R-alpha-lipoic acid [88]. Given that the R-isomer may be the more bioactive form, future investigations may yield more significant outcomes if they combine pregabalin with R-alpha-lipoic acid instead of R/S-alpha-lipoic acid.

7. Palmitoylethanolamide (PEA)

Palmitoylethanolamide (PEA) is an endogenous endocannabinoid mediator [30] and a fatty acid amide known for its anti-inflammatory and analgesic properties. [89]. Recent studies show that PEA can also behave as an antioxidant by reducing plasma lipid peroxidation induced by copper or 2-azo-bis (2-aminidinopropane) dihydrochloride and by reducing oxidative stress when PON-1 levels are diminished due to elevated ROS [90]. PEA may serve as a biomarker for chronic musculoskeletal pain and indicate systemic inflammation [91]. It has many useful properties but has some disadvantages when consumed orally. One issue is that it is highly lipophilic in nature [92], and has a large particle size, making it difficult for the body to absorb [93]. Moreover, PEA has poor water solubility, which hinders its absorption when taken orally. This leads to its short-lived effects in the body, as it reaches peak concentration in blood within just two hours. The efficacy of micron-size PEA formulations appears to be time-dependent [94]. To overcome these challenges, PEA is typically used in a micronized form that the body can absorb easily. Also, it is usually combined with other substances that enhance its absorption and reinforce its effectiveness in reducing inflammation.
Several recent studies have examined the use of micronized PEA formulations, which are more readily absorbed by the body, as supported by clinical trials [92]. In a prospective observational study, 35 adult fibromyalgia patients (30 female and 5 male) were administered an ultra-micronized PEA supplement (600 mg twice daily) for 30 days, and then a lower dose of micronized PEA (300 mg twice daily) for two months, coupled with their routine medications (duloxetine and pregabalin). This brought forth a substantial improvement in tender point scores and pain as assessed with VAS (p < 0.0001) compared to those only taking duloxetine and pregabalin (Table 1). None of the participants suffered any side effects from this treatment [95]. In a retrospective observational study, 407 fibromyalgia patients (378 female and 29 male) prescribed oral ultra-micronized PEA tablets were assessed for potential symptom improvement. The prescribed dosage was 1800 mg/day for 10 days, then 1200 mg/day for 20 days, followed by a maintenance period of 600 mg/day for 15 months (Table 1). Quality of life FIQ scores and pain VAS scores were both significantly improved (p < 0.001) after 1 month of treatment. Some participants reported adverse effects, mainly based on gastrointestinal issues [96].
Based on the current evidence, micronized PEA shows potential for alleviating fibromyalgia symptoms, particularly due to its pain-relieving effects. Though the existing research is promising, additional studies are essential to fully assess its long-term effects.
Table 1. Clinical studies using antioxidants to treat fibromyalgia symptoms from January 2015–January 2025.
Table 1. Clinical studies using antioxidants to treat fibromyalgia symptoms from January 2015–January 2025.
Antioxidant
Category
Dosage and
Duration
SampleKey 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 B121000 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 FMReduced 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 FMFIQ 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 Ϯ50,000 IU/week with 25 mg Trazodone or 25 mg Trazodone with placebo for 8 weeks 74 adult females with FMImproved 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 FMNo significant improvement in FIQ or VAS scores.Skeletal muscles have a Vit D receptor and may require sufficient Vit D for optimal function.[62]
IronNot available7332 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]
MelatoninIncreasing 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 FMImproved 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]
MelatoninIncreasing 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 FMImproved 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 FMReduced 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 Q300 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 FMWell 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 FMPain, 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]
* Potential mechanisms proposed by the authors of each study. Ϯ Type of vitamin D (D2 vs. D3) not specified. Abbreviations: ALA = alpha-lipoic acid; BDI = Beck Depression Inventory; BPI = Brief Pain Inventory; CISF = Combined Index Severity of Fibromyalgia; FIQ = Fibromyalgia Impact Questionnaire; FIQR = Fibromyalgia Impact Questionnaire Revised; FM = fibromyalgia; FSS = Fibromyalgia Severity Scale; FVNS = Fatigue Visual Numeric Scale; HAQ = Health Assessment Questionnaire; HC = healthy control; HDS = Hamilton Depression Rating Scale; IDA = Iron Deficiency Anemia; Mg = magnesium; MOSSS = Medical Outcomes Study Sleep Scale; NPS = Numerical Pain Scale; NRS = Numerical Rating Scale (for pain); PEA = palmitoylethanolamide; PPT = pain pressure threshold; PSQI = Pittsburg Sleep Quality Index; QoL = quality of life; SF-36 = Short-Form Health Survey; SF-12 = 12-Item Short-Form Survey (physical and mental health); SOD = superoxide dismutase; STAT = State–Trait Anxiety Test; VAS = Visual Analog Scale; ZAS = Zung Self-Rating Anxiety Scale; ZDS = Zung Self-Rating Depression Scale.

8. Conclusions

Antioxidant treatments for improvement in various fibromyalgia symptoms show potential based on the evidence presented in peer-reviewed scientific publications over the last 10 years. Future studies involving magnesium, zinc, and vitamin B6 should be investigated to understand the relationship between micronutrient status and pain in fibromyalgia patients based on neurobiological mechanisms that involve these cofactors. Vitamin D supplementation shows promise for some patients with fibromyalgia by improving quality of life and reducing FIQ scores. However, the impact of vitamin D on pain has been inconsistent. More investigation is required to understand why the effect of vitamin D treatment varies within different populations. Vitamin B12 may be effective for reducing symptoms such as fatigue and anxiety, but may be less effective for the treatment of pain or depression. Although preliminary studies show that iron supplementation may reduce fibromyalgia symptoms in patients with iron deficiency, more research is required to determine the correct form and dose of iron supplementation. Recent evidence also shows that antioxidant supplements such as melatonin, CoQ, ALA, and PEA are potential treatments when administered alone or in combination with other antioxidants or medications for reduction in fibromyalgia symptoms. Since many of these studies were based on small sample sizes or pilot studies, more clinical research is required to understand the efficacy and safety of these supplements, as well as the long-term health impact. In summary, vitamin B12, vitamin D, iron, melatonin, CoQ, ALA, and PEA all show potential for the management of fibromyalgia symptoms as standalone treatments or in combination with other antioxidants or pharmacological agents.

Author Contributions

Conceptualization, M.S.T. and P.K.W.; methodology, M.S.T. and P.K.W.; software, P.K.W.; validation, M.S.T.; formal analysis, M.S.T. and P.K.W.; investigation, M.S.T. and P.K.W.; resources, M.S.T. and P.K.W.; data curation, M.S.T. and P.K.W.; writing—original draft preparation, M.S.T. and P.K.W.; writing—review and editing, M.S.T. and P.K.W.; visualization, M.S.T. and P.K.W.; supervision, M.S.T.; project administration, M.S.T.; funding acquisition, not applicable. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Acknowledgments

We would like to acknowledge the Chemistry, Biochemistry and Nutrition Program at Salem College for supporting our time to write this article. We also thank the Salem College library staff for their assistance with obtaining full-text peer-reviewed articles and technical assistance with Zotero.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
ALAAlpha-lipoic acid
CoQCoenzyme Q
FIQFibromyalgia Impact Questionnaire
FIQRFibromyalgia Impact Questionnaire Revised
IDAIron deficiency anemia
NF-κBnuclear factor kappa-light chain enhancer of activated B cells
Nr2Fnuclear factor erythroid 2-related factor 2
PON-1Paraoxonase
ROSReactive oxygen species
SF-36Short-Form Health Survey
VASVisual 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

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Totten MS, Wondzi PK. Antioxidant Treatments for Fibromyalgia. Oxygen. 2025; 5(3):9. https://doi.org/10.3390/oxygen5030009

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Totten, Melissa S., and Precious K. Wondzi. 2025. "Antioxidant Treatments for Fibromyalgia" Oxygen 5, no. 3: 9. https://doi.org/10.3390/oxygen5030009

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Totten, M. S., & Wondzi, P. K. (2025). Antioxidant Treatments for Fibromyalgia. Oxygen, 5(3), 9. https://doi.org/10.3390/oxygen5030009

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