Fibromyalgia is a condition marked by chronic widespread pain of varying severity in the absence of obvious tissue damage.^1,2 People with fibromyalgia also experience multiple other symptoms, particularly fatigue, sleep disturbance, cognitive challenges (sometimes called “fibro fog”), and frequently a range of other concerns such as tender points, muscle stiffness, other types of pain, and mood disorders. Fibromyalgia is associated with significant emotional distress and functional disability and often leads to social isolation and stigmatization.^1,3 It affects an estimated 2–5% of the U.S. population, mostly women.^1,3,4

Historically, many people with fibromyalgia had their symptoms dismissed as psychosomatic, leading to stigma, invalidation, and delays in care. This is changing as the medical community increasingly recognizes fibromyalgia as a pain disorder rooted in altered pain processing, with supportive evidence from neuroimaging, quantitative sensory testing, and, in some patients, small-fiber pathology (damage or dysfunction involving small nerve fibers). Professional guidelines and clinician education now emphasize validating patients’ experiences, timely diagnosis, and multi-faceted treatment based on underlying mechanisms. As a result, care is shifting toward compassionate, evidence-informed management that addresses both symptom burden and quality of life.^1,2,4-6

The exact causes of fibromyalgia are not completely understood. Fibromyalgia does not meet the definition of an inflammatory or autoimmune condition, as there are no tissue changes clearly and directly caused by either of those mechanisms. However, newer research has shown that both inflammation and autoimmunity appear to play some role in fibromyalgia.^1,7-9

There is general agreement, however, that abnormal processing of pain signals in the brain (central sensitization) and heightened sensitivity along peripheral pain pathways are key mechanisms underlying fibromyalgia.^1,7

Disordered neurotransmitter levels and altered brain structure have been seen in fibromyalgia patients and may contribute to central and peripheral sensitization, as may neuroinflammation. Studies in people with fibromyalgia have also shown abnormal patterns of nerve density in skin.^1,2

In addition, psychological and social factors are believed to play a role in the onset of fibromyalgia.¹⁰ Observational studies have linked traumatic life events, greater exposure to stress, and higher levels of emotional distress with increased risk of fibromyalgia, though it is unclear if these are causative factors.^1,10 Fibromyalgia patients often have sleep and mood disturbances, cognitive impairment, and certain personality trait profiles.^1,2 Dysregulated stress signaling and neuroinflammation are common underlying features of stress, depression, and anxiety, as well as fibromyalgia and other chronic pain syndromes, and may connect these conditions.^1,11

Overall, fibromyalgia is a complex and poorly understood condition that is difficult to treat and can have devastating effects on quality of life.¹ An individualized, multifaceted treatment plan offers the best chance for symptom relief and improved well-being. This Life Extension Protocol summarizes the symptoms of fibromyalgia; the diagnostic process; current understanding of underlying mechanisms; drug therapies; and a range of dietary, lifestyle, nutrient supplementation, and other non-pharmacologic treatment approaches. Specifically, magnesium, coenzyme Q10 (CoQ10), vitamin D, and melatonin have demonstrated promising effects in reducing pain, improving other symptoms, and restoring quality of life in fibromyalgia patients.

The primary symptom of fibromyalgia is widespread pain, primarily in the musculoskeletal system, that cannot be attributed to obvious tissue injury.^1,3 A range of other symptoms often accompany the pain, including fatigue, sleep disturbance, tenderness, stiffness, depressed or anxious mood, and cognitive difficulties such as trouble concentrating, forgetfulness, and disorganized thinking.¹² It is a chronic condition, persisting for at least three months and often for years or decades, that significantly impairs physical, emotional, and social functioning.^1,13

Fibromyalgia pain is widespread, occurring in nearly any region of the body, though specific areas such as the back or neck may be particularly painful in some individuals.¹⁴ The pain associated with fibromyalgia varies substantially and unpredictably over time, but may be made worse by inactivity, humid or cold conditions, stress, and fatigue.^13,15 The quality of pain is described variably from dull, deep, or aching, to burning, stabbing, or tingling.^1,3 General sensitivity is a common feature, with frequent reports of hypersensitivity to painful stimuli and pain from normally non-painful stimuli such as touch.^1,3

Sleep problems are also common among those with fibromyalgia. Sleep difficulties often worsen with increased fibromyalgia severity and duration.¹⁶ Sleep studies that include electroencephalogram (EEG, brain electrical wave monitoring) have shown fibromyalgia patients experience shorter sleep duration, more awakenings during sleep, longer light sleep phases, and shorter deep restorative sleep phases. In addition, self-reported sleep quality has been shown to be poor in subjects with fibromyalgia.^13,17

Pain can be a reason for sleep loss, and sleep disturbance aggravates pain sensitivity. This leads to a cycle of pain and poor sleep linked to increased fatigue, cognitive dysfunction, and emotional distress.^18-20 As a result of its impact on quality of life, some people with fibromyalgia report feeling that poor sleep is the worst symptom of their condition.²⁰

The following factors have been associated with increased fibromyalgia risk^13,21-23:

• Female sex. Women are far more likely to develop fibromyalgia than men.
• Age. Fibromyalgia can affect people at any age but most commonly has its onset in middle age.
• Family history. Although the genetic heritability of fibromyalgia is not well understood, having a family member with fibromyalgia greatly increases risk, suggesting a genetic contribution to susceptibility.
• Chronic pain. People with other chronic pain conditions such as headaches, back pain, arthritis, and other rheumatologic diseases have an increased risk of fibromyalgia.
• Irritable bowel syndrome (IBS). Like fibromyalgia, IBS is a functional disorder marked by increased tissue sensitivity; these conditions often co-occur (30–70% of cases).^13,24
• Mental health disorders. Anxiety and depressive disorders are associated with higher fibromyalgia risk.
• Sleep disorders. Chronic insomnia has been linked to fibromyalgia risk.
• Psychological trauma. A history of traumatic events, even from childhood, increases fibromyalgia risk.
• Physical trauma. Physically traumatizing events such as car accidents can be a trigger for fibromyalgia onset.
• Smoking
• Having other medical conditions

Dysregulated pain signal processing and hypersensitization is a common feature among many of these inter-related conditions.¹³ The co-occurrence of conditions with overlapping symptoms can complicate diagnosis and treatment.¹⁵ Examples of conditions associated with fibromyalgia are:

• Sleep disorders, such as chronic insomnia, obstructive sleep apnea, and restless leg syndrome, which affect a majority of people with fibromyalgia.^13,15
• Migraines and other types of headaches, which occur in approximately half of fibromyalgia sufferers.¹³
• Mood disorders (depression and anxiety), which are present in roughly one in three people with fibromyalgia.¹³
• Myalgic encephalomyelitis/Chronic fatigue syndrome^13,25
• Post-infection syndromes (eg, following a viral infection or Lyme disease)²⁵
• Lower urinary tract symptoms (LUTS), including symptoms of interstitial cystitis, overactive bladder, and stress urinary incontinence; one observational study found 37% of fibromyalgia patients had diagnoses associated with LUTS, often in addition to IBS and/or generalized anxiety disorder.^15,26
• Female genital pain (vulvodynia)⁴
• Chronic pelvic pain^4,27
• Chronic low back pain⁴
• Arthritis, including osteoarthritis, rheumatoid arthritis, and gout¹⁵
• Temporomandibular disorder⁴
• Sexual dysfunction¹³
• Cognitive disorders¹³

In addition, fibromyalgia has a bi-directional relationship with cardiometabolic conditions, including coronary artery disease, hypertension, type 2 diabetes, and obesity.¹⁵

Accurate diagnosis of fibromyalgia is complicated by several factors, including a lack of objective markers on physical exam, blood tests, or imaging studies, as well as the high frequency of co-occurring conditions, often with symptoms that overlap with fibromyalgia. For these reasons, diagnosis has historically relied on exclusion of other possible causes. Almost 75% of fibromyalgia cases are undiagnosed, while many other cases are wrongly diagnosed.^13,28 In fact, the average time between seeking care and getting a fibromyalgia diagnosis has been reported to be 2.7 years.¹⁵

The American College of Rheumatology reviewed and revised its diagnostic criteria for fibromyalgia in 2016. To diagnose fibromyalgia, the following are required:

• The presence of generalized pain, for which there is no other explanation, lasting at least three months and affecting at least four of five established body regions: the left upper, right upper, left lower, right lower, and axial (encompassing the head, neck, chest, and back) regions.
• A minimum score of 7 on the 19-point Widespread Pain Index (WPI), which measures how diffuse the pain is.
• A minimum score of 5 on the 12-point Symptom Severity Scale (SSS), which combines two measures: 1) severity of fatigue, poor sleep, and cognitive symptoms, and 2) severity of physical symptoms.
• Alternatively, scores of 4–6 on the WPI and at least 9 on the SSS are sufficient for diagnosis.

Along with these criteria, the College states, “A diagnosis of fibromyalgia is valid irrespective of other diagnoses and does not exclude the presence of other illnesses.”²⁸

An alternative set of diagnostic criteria was introduced by AAPT (Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society Pain Taxonomy) in 2019. This simpler system requires the following for a diagnosis of fibromyalgia⁴:

• · Pain in at least six of the following body regions:
  • Head
  • Left arm
  • Right arm
  • Chest
  • Abdomen
  • Upper back and spine
  • Lower spine including buttocks
  • Left leg
  • Right leg
• Moderate to severe sleep problems or fatigue
• Symptoms present for at least three months

Although there is no lab test for fibromyalgia, several blood tests may be useful to rule out alternative diagnoses, identify co-occurring conditions, and screen for health problems that might influence treatment. These tests may include²⁵:

• Complete blood count (CBC) to screen for anemia and conditions affecting red or white blood cells or platelets
• Comprehensive metabolic panel to check kidney function and general health status
• Erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) to screen for inflammatory disorders
• Thyroid stimulating hormone (TSH) to rule out thyroid disease
• 25-hydroxy vitamin D to identify cases of deficiency
• Ferritin to assess iron status, especially in those with fatigue, cognitive dysfunction, restless leg syndrome, or a high risk of deficiency
• Vitamin B12 to test for deficiency, especially in cases involving cognitive dysfunction

Various additional blood tests may be ordered when indicated to rule out other suspected diagnoses, such as autoimmune diseases, muscle diseases, neurologic disorders, and infections.²⁵

Although they are not diagnosed through blood tests, it is also important to rule out or identify conditions such as sleep disorders, psychiatric disorders, and autonomic nervous system dysfunction, which are frequently present in patients being evaluated for fibromyalgia.²⁵

The causes of fibromyalgia are still not completely understood, but are likely to involve multiple physiologic, social, and psychological factors. Changes in genetic sequence and/or expression appear to influence susceptibility.²⁸ Co-occurring conditions like anxiety, depression, stress, and sleep disorders can be contributors, while disturbances that are difficult to diagnose, such as dysregulated stress reactivity, neurotransmitter imbalance, inflammation, mitochondrial dysfunction, free radical damage, hormonal imbalance, and metabolic disturbance, as well as crosstalk between these factors, may also play a role. Altogether, this mix of factors makes for a complex condition with highly variable expression among individuals.^29,30

Pain Hypersensitivity

Dysregulation of pain processing networks is thought to be a key underlying mechanism that contributes to chronic pain in fibromyalgia. This dysfunction occurs at the central level, involving the brain, and the peripheral level, involving non-spinal nerves throughout the body, and may be aggravated by crosstalk between the nervous system and immune cells. This type of pain, which does not arise from tissue damage and inflammation, is known by the relatively new term nociplastic pain.²⁸

Pain sensitization lowers the pain threshold, resulting in two pain responses that are characteristic of fibromyalgia:

• Allodynia, which is heightened sensitivity to stimuli that are not normally painful, and
• Hyperalgesia, which is increased sensitivity to painful stimuli such as heat or pressure.¹²

Brain imaging studies have shown central sensitization in fibromyalgia patients is associated with alterations in brain structure, neurotransmitter function, and patterns of brain activity at rest and when exposed to experimental pain.³¹ Although it is unclear how or why pain sensitization develops, researchers have identified several possible theories, some of which are detailed below.²⁸

Stress and Autonomic Nervous System Dysfunction

Stressful life events have been consistently correlated with fibromyalgia risk, and stress is frequently cited as a trigger for fibromyalgia onset and flare-ups.²⁸ One study in 88 women with fibromyalgia found traumatic events, including emotional, physical, and sexual abuse, especially in childhood and early adolescence, were commonly reported; in fact, more than 71% of participants met the criteria for a diagnosis of post-traumatic stress disorder (PTSD).³² Other evidence suggests childhood adversity, often defined by a history of abuse, trauma, neglect, or maltreatment, may be associated with fibromyalgia.³³ Trauma and chronic stress can induce epigenetic changes, altered neurotransmitter activity, and inflammatory signaling that disrupt normal nervous system control over stress reactivity.^11,34,35

Abnormal functioning of the autonomic nervous system, a key regulator of the stress response, is thought to be an important underlying mechanism in fibromyalgia.^36,37 People with fibromyalgia have been shown to have increased sympathetic (“fight or flight”) and decreased parasympathetic (relaxed) signaling in the autonomic system while at rest; on the other hand, the normal rise in sympathetic activation in response to acute stress is blunted.^37,38

Sympathetic signaling activates the hypothalamic-pituitary-adrenal (HPA) axis, a network that connects the nervous system to the adrenal glands and controls their release of the body’s primary stress hormone, cortisol.^11,38 Cortisol levels appear to be generally lower in fibromyalgia patients, but both high and low levels have been reported.^11,39 Some evidence indicates higher cortisol concentrations may be related to more intense symptoms while lower cortisol concentrations may be correlated with longer duration of fibromyalgia.⁴⁰

Sympathetic dominance (ie, excessive fight-or-flight activation relative to resting nervous system activity) and the inability to mount a normal adaptive response to stress promote multiple symptoms, including pain, cognitive dysfunction, and feelings of stress.^34,37,38

Growth hormone is also released during a normal stress response. Individuals with fibromyalgia have been shown to have lower blood levels of growth hormone, as well as a blunted rise in growth hormone in response to exercise, compared with healthy individuals.⁴¹ Low growth hormone levels appear to increase pain hypersensitivity. Fibromyalgia patients with growth hormone deficiency plus low levels of insulin-like growth factor-1 (IGF-1, a peptide hormone released by the liver in response to growth hormone) have been found to benefit from growth hormone replacement therapy in clinical trials.⁴² In addition, exercise therapy can improve growth hormone responsiveness and quality of life in fibromyalgia patients.⁴³

Neuroendocrine Dysfunction

Neurotransmitter and hormonal imbalances have been proposed as contributing factors underlying fibromyalgia. Some, but not all, studies have noted altered levels or activities of neurotransmitters that affect pain signaling (eg, serotonin and dopamine) in fibromyalgia patients.^44,45 Estrogen appears to modulate pain perception in multiple ways, including through effects on nerve pathways and neurotransmitter function, influencing serotonin, dopamine, epinephrine, and endogenous opioid signaling.⁴⁶ Progesterone may also be a factor in fibromyalgia pain, with women in a small clinical study reporting greater fibromyalgia pain severity on days when their progesterone levels were lower.⁴⁷ Disrupted neuroendocrine pathways may be one reason people with fibromyalgia are more likely to also suffer from depression, irritable bowel syndrome (IBS), migraines, and other types of headaches.^44,48

An imbalance in excitatory versus inhibitory neurotransmitters has also been associated with fibromyalgia and other chronic pain conditions.^49,50 Glutamate is the main neurotransmitter for increasing nerve excitability, while gamma-aminobutyric acid (GABA) is the main inhibitor of nerve signal transmission. Glutamate and GABA are important modulators of pain signaling and processing.⁵¹ In subjects with fibromyalgia, altered glutamate and GABA levels and receptor densities have been found in specific regions of the brain where pain signal processing occurs.^49,51,52 In addition, imbalanced glutamate and GABA activity may contribute to a link between depression and chronic pain.⁵³

Fluctuating hormone levels, in particular, have been correlated with increased pain sensitivity. For example, in reproductive-aged women, pain thresholds are lowest when estrogen drops after ovulation, but are also decreased at the mid-cycle peak in estrogen levels.⁴⁶ Because middle-aged women, aged 40–65 years, have the highest risk of developing fibromyalgia, hormone fluctuations that occur in the menopause transition have been proposed as a possible trigger.⁵⁴ More support for this connection comes from a clinical trial in which 69 menopausal women, 32 of whom had fibromyalgia, experienced improvements in sleep, quality of life, and fibromyalgia symptoms after 12 weeks of hormone therapy using bioidentical transdermal estrogen and oral progesterone.⁵⁵

Inflammation & Immune Dysfunction

The relationship between fibromyalgia and inflammation is complex and an area of active investigation. Although signs of inflammatory tissue damage are absent in fibromyalgia, current evidence suggests inflammation is a primary driver in fibromyalgia onset and persistence.⁸ There is ample evidence that systemic inflammatory marker levels are elevated in fibromyalgia patients.^56-59 Some researchers have proposed a role for chronic inflammation and neuroinflammation in triggering sensitization of central and peripheral pain pathways, contributing to fibromyalgia symptoms.^8,60,61 Thus, individuals with fibromyalgia may benefit from periodic blood testing to assess various inflammatory biomarkers to monitor the course of their illness and response to treatment.

Table 1: Serum Inflammatory Markers that May be Useful in Fibromyalgia

Fibromyalgia patients have been shown to have higher levels of C-reactive protein (CRP, a non-specific marker of systemic inflammation) and imbalanced cytokine levels, generally favoring inflammatory over anti-inflammatory immune activity, relative to healthy individuals.^56-59 Inflammatory cytokines associated with fibromyalgia, such as interleukin (IL)-6 and IL-8, can cross the blood–brain barrier and trigger neuroinflammation, which may contribute to changes in pain processing and may also link fibromyalgia to depression.^48,61

Fibromyalgia has been associated with higher serum levels of tumor necrosis factor (TNF)-alpha, substance P, and corticotropin-releasing hormone (CRH), all of which play a role in mediating inflammation.^57,69 Substance P is a neuropeptide activated by tissue injury or inflammation that causes transmission of pain signals to the brain.⁷⁰ In addition, substance P accelerates inflammatory signaling and is of considerable research interest in chronic pain as well as psychological conditions including depression, anxiety, and PTSD.^65,67 Corticotropin-releasing hormone activates the stress response by stimulating pituitary secretion of adrenocorticotropic hormone (ACTH), which in turn stimulates cortisol release from the adrenal glands.⁶⁷

A growing body of evidence indicates an important role of mast cells in fibromyalgia and other inflammatory and painful conditions.^1,69 People with fibromyalgia have been found to have higher concentrations of mast cells in the skin.^69,71 These mast cells, as well as mast cells in the brain, can be activated by CRH, substance P, and various cytokines; they then exacerbate inflammation and pain by releasing IL-6, TNF-alpha, substance P, CRH, and other signaling molecules.^1,69,71

Neutrophils (white blood cells with a key role in the innate immune response) have also been implicated as contributors to fibromyalgia pain. Some studies have reported finding increased neutrophil-to-lymphocyte ratios in fibromyalgia sufferers.^59,72,73 One study in pain-sensitized mice found neutrophils invaded peripheral sensory nerves and increased their pain signaling, whereas neutrophil depletion prevented the mice from developing chronic widespread pain.⁶⁸

Mitochondrial Dysfunction

Some researchers have hypothesized that mitochondrial dysfunction may contribute to fibromyalgia.⁷⁴ Mitochondria are intracellular organelles that use oxygen and electron carriers to convert pyruvate (a byproduct of glucose metabolism) into energy in the form of adenosine triphosphate (ATP). They also help regulate fundamental cell processes such as cell signaling, apoptosis (normal cell death), and senescence (age-related gradual cessation of function).⁷⁵ Mitochondrial dysfunction is characterized by decreased ATP and increased oxygen free radical production and is a common underlying feature of chronic and age-related conditions.⁷⁶

Mitochondrial dysfunction has been correlated with pain and fatigue in subjects with fibromyalgia.⁷⁴ This is thought to be due to lower muscle cell energy production, leading to fatigue, and lactate and pyruvate build-up due to poor oxygen utilization in muscle tissue, leading to pain.^74,77 A study in fibromyalgia patients showed their muscle oxygen use was lower, a possible sign of reduced mitochondrial energy production, and did not increase during exercise.⁷⁴ In another study, ATP levels were lower, pyruvate levels were higher (indicating reduced mitochondrial uptake for conversion into energy), and blood flow was reduced in some back muscles of fibromyalgia patients; these factors were associated with increased pain levels.⁷⁷ Findings from animal studies indicate mitochondrial dysfunction in nerve cells may play a role in dysregulated chronic pain signaling.⁷⁸

A study in which 609 participants underwent mitochondrial deoxyribonucleic acid (DNA) analysis found the presence of a single nucleotide polymorphism that appears to be related to lower mitochondrial capacity was associated with increased fibromyalgia risk.⁷⁹ Immune cells from people with fibromyalgia have demonstrated signs of mitochondrial dysfunction including low CoQ10 levels, increased oxidative stress, reduced mitochondrial capacity to generate energy, and increased removal of dysfunctional mitochondria.⁸⁰ Furthermore, mitochondria in immune cells from fibromyalgia patients were found to have structural abnormalities and the number of affected mitochondria corresponded with severity of pain.⁸¹ These observations suggest supporting healthy mitochondrial function with targeted nutrients such as CoQ10 and melatonin may be helpful in treating fibromyalgia.^82,83

Oxidative Stress

Oxidative stress is an imbalance between antioxidant capacity and free radicals, favoring free radicals and leading to molecular, cellular, and tissue damage. Inflammation and mitochondrial dysfunction are proposed underlying features of fibromyalgia that contribute to oxidative stress by increasing free radical production. High levels of free radicals increase excitability of both central (brain and spinal) and peripheral nerves and reduce pain thresholds, potentially leading to chronic hypersensitization.^84,85 Higher oxidative stress, in conjunction with mitochondrial dysfunction and inflammation, was demonstrated in skin samples from fibromyalgia patients and was correlated with pain.⁸⁶ Other research has shown subjects with fibromyalgia had increased blood levels of free radicals and lower antioxidant status. This increased oxidative stress may contribute to soreness and symptom severity.^87-89

Metabolic Dysfunction & Impaired Glucose Metabolism

Metabolic dysfunction has been hypothesized to be a driver of certain chronic pain conditions, and it is possible that similar mechanisms are involved in fibromyalgia. Research in subjects with some other types of pain conditions shows insulin resistance activates inflammatory pathways that may contribute to chronic pain and may also impair metabolic function of brain cells, possibly affecting brain regions involved in pain processing.^90,91

Women with fibromyalgia were reported to be at nearly four times higher risk of metabolic syndrome than healthy women, and co-occurrence was correlated with increased fibromyalgia severity in a study with 138 participants.⁹² In another observational study, the prevalence of diabetes was 21% (13 out of 62) in subjects with fibromyalgia compared with less than 8% (315 out of 4,093) in a general population. The study also found fibromyalgia was associated with a greater likelihood of having high blood pressure, being treated for hypertension and high cholesterol levels, and having a history of a cardiovascular event such as atrial fibrillation or heart attack.⁹³ A study that measured hemoglobin A1C (HbA1C) values to assess long-term blood glucose control, stratified by age, found higher values (indicating poorer long-term blood glucose control) among 33 subjects with fibromyalgia than in healthy population groups from two large observational studies (the National Health and Nutrition Examination Survey and the Framingham Offspring Study).⁹⁴

Obesity is another metabolic disorder that has been associated with fibromyalgia. Observational evidence has indicated women with overweight and obesity are more likely to report having fibromyalgia.⁹⁵ Some studies have found fibromyalgia patients who also had overweight or obesity experienced more severe fibromyalgia symptoms and greater disease-related disability.^96-98 However, a meta-analysis of findings from 41 studies found that the association between obesity and symptom patterns in fibromyalgia patients was weak and inconsistent.⁹⁹

More information related to understanding and overcoming metabolic disorders are detailed in Life Extension’s Protocols on Diabetes and Glucose Control and Weight Management.

There is broad expert agreement that optimal management of fibromyalgia involves first-line non-pharmacologic interventions, prioritizing lifestyle interventions (eg, diet, exercise, and sleep improvement) as well as patient education, psychotherapy, and mindfulness or other stress management practices.

Many fibromyalgia patients also receive medications as part of their treatment.^107,108 Medications are generally recommended for those who do not respond to non-pharmacologic treatments alone. Personalizing therapy to target prominent symptoms and co-occurring conditions is an important aspect of treatment.^109,110

Non-Pharmacological Treatment

Education

Education that strives to enhance the understanding of pain, known as pain neuroscience education (PNE), may play a valuable role in the treatment of chronic pain. Pain neuroscience education involves educating individuals about the neurophysiological and neurobiological underpinnings of pain perception. The goal is to help people with chronic pain move beyond the notion that tissue damage is the sole cause of pain.¹¹¹ Understanding how genetic and epigenetic, neurologic, hormonal, and immune mechanisms contribute to the experience of pain may help patients reconceptualize their condition, feel less anxious, and feel more empowered to make changes that can improve their outcomes.¹¹²

Some clinical trials have found PNE, delivered alone or integrated into a broader approach, may reduce symptom severity in patients with fibromyalgia and other chronic pain disorders; however, findings have been somewhat inconsistent.¹¹³ For example, one meta-analysis that included four randomized controlled trials involving 612 fibromyalgia patients found PNE improved fibromyalgia impact as well as pain intensity, catastrophizing, depression, and anxiety.¹¹⁴ In another meta-analysis that pooled findings from eight randomized controlled trials, PNE was found to moderately reduce pain intensity but did not reduce fibromyalgia impact, catastrophizing, or anxiety; however, evidence from studies that performed post-intervention follow-ups found fibromyalgia impact improved over time in those who had received PNE.¹¹⁵

The effectiveness of PNE may depend on how well it meets an individual’s perceived learning needs and objectives. In an observational study designed similarly to a randomized controlled trial, 450 subjects with fibromyalgia who ranked their need to learn about pain as high attended a two-day PNE program. After the program, they ranked their learning needs again. The educational outcome was categorized as good in those whose learning needs substantially diminished and poor in those whose learning needs did not substantially diminish. The study found only 26.9% of participants experienced a good educational outcome, while 73.1% experienced a poor educational outcome. At a nine-month follow-up, Fibromyalgia Impact Questionnaire scores improved significantly more in those who had good educational outcomes.¹¹⁶

Psychotherapy and Mindfulness

Cognitive behavioral therapy (CBT) is an approach that blends psychotherapy and behavioral changes. It involves recognizing unhelpful thought patterns and incorporates psychological and behavioral strategies for interrupting them. A meta-analysis of data from 29 randomized controlled trials with a combined total of 2,509 participants with fibromyalgia found CBT was more effective than no treatment for improving pain, quality of life, negative mood, disability, and fatigue.¹¹⁷ In a meta-analysis of findings from five randomized controlled trials, CBT specifically targeting insomnia (CBT-I) was found to be effective for improving sleep quality, reducing pain, and decreasing anxiety and depression symptoms in fibromyalgia patients.¹¹⁸ Internet-based delivery of CBT has shown mixed evidence of efficacy for chronic pain and fibromyalgia. One meta-analysis of six randomized controlled trials with a total of 493 participants found internet-based CBT programs improved fibromyalgia-related mood symptoms and disability.¹¹⁹ However, a later systematic review of 32 randomized controlled trials in nearly 5,000 patients with various types of chronic pain, including fibromyalgia, found internet delivered CBT had small benefits for pain and functional disability, but these improvements were not sustained over time.¹²⁰

Mindfulness-based therapies cultivate nonjudgemental awareness of the present moment. This can allow individuals to observe their experiences without the usual reactive biases that potentially alter them.¹²¹ In patients with chronic pain, mindfulness fosters acceptance of pain and modifies beliefs and expectations around pain relief. Clinical trials have indicated a long-term mindfulness practice can increase pain threshold and reduce pain-related distress.¹²² Mindfulness-based interventions have led to promising outcomes in preliminary clinical trials involving people with fibromyalgia.¹²³ Mindfulness practices appear to be especially helpful in reducing sleep difficulties and negative mood symptoms.¹²⁴ Acceptance and commitment therapy (ACT) is a mindfulness-based form of psychotherapy that, like CBT, involves releasing unhelpful thoughts and feelings. Acceptance and commitment therapy has been found to be helpful in treating fibromyalgia and other chronic pain disorders,¹²⁵ though remotely delivered ACT is of uncertain benefit.¹²⁰

Acupuncture

A meta-analysis that included data from 12 controlled trials in fibromyalgia patients found acupuncture reduced pain and improved well-being.¹²⁶ Another meta-analysis included 41 randomized controlled trials investigating acupuncture and related therapies, such as electroacupuncture, abdominal acupuncture, and dry needling, in 2,877 subjects with fibromyalgia. The analysis found acupuncture plus massage therapy and umbilical acupuncture were especially effective for reducing pain, while electroacupuncture and abdominal acupuncture had the strongest benefits on mood and sleep symptoms.¹²⁷ The positive effects of acupuncture may be due to its ability to reduce inflammation, balance autonomic nervous system activity, and regulate pain signaling.¹²⁸

Balneotherapy

Balneotherapy involves immersion in heated natural mineral waters. It is often complemented with mud packs, massage, exercise, or other spa modalities.¹²⁹ Balneotherapy has been used for centuries to treat various rheumatologic conditions, including fibromyalgia. It is thought to work by improving circulation, reducing inflammation, and enhancing metabolism through thermal, chemical, and mechanical properties.^130,131 Meta-analyses of randomized controlled trials have shown balneotherapy can have lasting benefits on pain, disability, and quality of life.^129,132 However, most of the evidence is of low to moderate quality, making it difficult to draw conclusions.^131-133

Massage

Various types of massage therapy may be helpful in relieving fibromyalgia symptoms. A systematic review and meta-analysis of 10 controlled trials found a massage technique called myofascial release reduced pain, depression symptoms, fatigue, and stiffness in fibromyalgia patients. Connective tissue massage, manual lymphatic drainage, and Shiatsu have also shown promising effects in clinical trials.¹³⁴

Tender Point Injection Therapy

Tender point or trigger point injection therapy involves injecting medication into tender or trigger points. It is more frequently performed to treat myofascial pain syndrome, a chronic pain condition usually affecting back muscles.¹³⁵ Numerous medications and other substances have been used in this therapy, including the anesthetic lidocaine, corticosteroid drugs, botulinum toxin A, platelet-rich plasma, sodium bicarbonate, and even sterile saline.^135,136

One study reported on the use of tender point injection therapy in 68 fibromyalgia patients who also had myofascial pain syndrome. After two treatment sessions, tender point injection therapy reduced the number of pain sites, intensity of pain, and fibromyalgia-related pain and tenderness compared with placebo injections. This difference persisted for three weeks after the second treatment.¹³⁷ Another trial involving 28 women with fibromyalgia found back muscle tender point injection using lidocaine decreased pain sensitivity at injection sites as well as at non-injection sites, compared with saline injections.¹³⁸

Light Therapy

Different types of light have been studied for their treatment effects in fibromyalgia. One team of researchers has published two studies on light therapy for fibromyalgia. In a pilot, single-blind, randomized, controlled trial in 10 women with fibromyalgia, six days of treatment with bright light in the morning resulted in reduced pain sensitivity and enhanced function more than the same treatment administered in the evening.¹³⁹ A second trial compared four weeks of morning bright light to dim light exposure in 58 women and two men with fibromyalgia. Both treatments resulted in improvements in a broad range of fibromyalgia-relevant symptoms including pain intensity, physical function, sleep, and depressive symptoms.¹⁴⁰

In a pilot crossover trial, 21 subjects with fibromyalgia underwent 10 weeks of light therapy using white light emitting diodes (LEDs) in 1–2-hour sessions per day and 10 weeks of similar therapy using green LEDs, in random order. Green LED therapy resulted in substantially greater pain relief than white LED therapy.¹⁴¹ In another pilot trial, 45 fibromyalgia patients being treated with opioid pain relievers were assigned to wear different color eyeglasses for at least four hours per day for two weeks. At the end of the study, opioid use decreased by 33% in the green glasses group, with lesser improvements for other glasses.¹⁴²

Low-level laser therapy and infrared light therapy, which are applied through the skin at wavelengths that can penetrate skin and affect deeper tissues, have also been studied and shown some benefits.^143,144

Neurostimulation

Neurostimulation therapies are a non-invasive option for some fibromyalgia patients. The most studied neurostimulation modalities for fibromyalgia are repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and transcranial alternating current stimulation (tACS).^145,146

Repetitive transcranial magnetic stimulation is the most studied form of neurostimulation for fibromyalgia. It involves use of a device placed against the skull that generates changing magnetic fields across specific brain regions. This stimulates electrical current, which alters nerve function and brain electrical activity. After 10 or more sessions, fibromyalgia patients can experience pain relief lasting for weeks, and may also have better sleep, energy level, and overall function.¹⁴⁶ A meta-analysis of findings from seven randomized controlled trials involving 217 fibromyalgia patients found high-frequency (10-Hz) rTMS, typically performed five times per week for two to four weeks, effectively reduced pain and improved quality of life but did not relieve depression symptoms.¹⁴⁷ Other meta-analyses have reached similar conclusions.^148,149

Transcranial direct current stimulation involves use of an external device that applies a small constant electrical current across a target brain region. This affects nerve polarization and modulates neurotransmitter levels, thereby changing nerve excitability.¹⁴⁶ It has shown promise in multiple small clinical trials in fibromyalgia patients.¹⁵⁰ Transcranial alternating current stimulation is similar to tDCS but uses oscillating electrical current.¹⁴⁶ Two clinical trials investigating tACS in fibromyalgia patients have yielded mixed results.^52,151

Pharmacologic Therapies

Pharmacotherapy does not cure fibromyalgia, though it is frequently a component of fibromyalgia treatment. Despite their widespread use, many patients do not derive clear benefits from medications, and inappropriate prescribing and polypharmacy are common.^152,153 Medications for fibromyalgia have been shown to be, at best, moderately effective in fewer than half of patients.⁶ In fact, most fibromyalgia patients stop taking medications after a short time due to lack of effect and/or side effects.¹⁵⁴

Four medications are currently approved by the U.S. Food and Drug Administration (FDA) for treating fibromyalgia^6,154,155:

• Pregabalin (Lyrica) is an anti-seizure drug that is also used to treat chronic pain. Pregabalin has been shown to reduce pain by 30–50% in about 10% of people with moderate-to-severe fibromyalgia. And adverse side effects, such as dizziness, drowsiness, weight gain, and edema in the feet or hands, occurred in 80–90% of users.¹⁵⁶ Importantly, pregabalin can damage the retinal nerve and is therefore contraindicated for those with diabetic retinopathy or glaucoma.¹⁴⁵
• Duloxetine (Cymbalta) and milnacipran (Savella) are serotonin-norepinephrine reuptake inhibitors (SNRIs) that work by altering neurotransmitter balance. These medications have been shown to be more effective than placebo at reducing fibromyalgia pain by at least 30%; however, the proportion of those whose pain was reduced by 50% or more was not significantly different than with placebo. Furthermore, duloxetine and milnacipran have not been found to improve health-related quality of life scores more than placebo. Common side effects of drugs in this class include nausea, dizziness, and sleepiness.¹⁵⁷
• Sublingual cyclobenzaprine (Tonmya) is a skeletal muscle relaxant formulated for use under the tongue, where it is rapidly absorbed, and intended to be taken at bedtime. It was approved for treating fibromyalgia in 2025.¹⁵⁵ The approval was based on findings from two phase III, randomized, controlled trials with a combined total of 960 participants with fibromyalgia. Both trials found sublingual cyclobenzaprine, taken at bedtime for 14 weeks, reduced pain more than placebo. In addition, sublingual cyclobenzaprine improved patient-reported measures of sleep quality and other fibromyalgia symptoms.^158,159 A meta-analysis of four randomized controlled trial in a total of 1,993 fibromyalgia patients found sublingual cyclobenzaprine reduced pain intensity, improved Fibromyalgia Impact Questionnaire scores, and improved self-reported sleep. Its main side effects were sedation, mouth numbness and tingling, and taste disturbance.¹⁶⁰

Despite their lack of FDA approval for fibromyalgia treatment, oral cyclobenzaprine (Flexeril, a skeletal muscle relaxant) and amitriptyline (a tricyclic antidepressant) are widely prescribed for fibromyalgia. Cyclobenzaprine relaxes skeletal muscles by quieting motor neuron signaling in the central nervous system.¹⁶¹ Because it has sedating effects, oral cyclobenzaprine, like other muscle relaxants, is generally recommended for short-term use (2–3 weeks).¹⁶² Furthermore, although it has been shown to improve pain, fatigue, depression, and sleep quality in the short term, long-term cyclobenzaprine has been found to be no more effective than placebo for treating fibromyalgia and other chronic pain conditions.^161,162 Amitriptyline is a tricyclic antidepressant that raises serotonin and norepinephrine availability by inhibiting their reuptake.¹⁶¹ A number of clinical trials have shown amitriptyline can reduce fibromyalgia pain, and some, but not all, have indicated it may improve sleep, fatigue, and quality of life. Unfortunately, despite its long track record of use as a first-line pharmacotherapy for fibromyalgia, the evidence supporting its efficacy is considered to be of low quality and therefore inconclusive.^161,163 It can cause adverse side effects such as dry mouth, lethargy, weight gain, and dizziness.¹⁶¹

A variety of other medications from different neurologically targeted drug classes have limited evidence suggesting positive effects. Examples of such medications include the following^154,164:

• Gabapentin (Neurontin), an anti-seizure drug
• Fluoxetine (Prozac), citalopram (Celexa), escitalopram (Lexapro), and paroxetine (Paxil), antidepressants in the selective serotonin reuptake inhibitor (SSRI) class
• Memantine (Namenda), an N-methyl-D-aspartate (NMDA) receptor antagonist
• Sodium oxybate (Xyrem), an anti-anxiety and sedative
• Tramadol (Ultram), an opioid pain reliever and SNRI

Although over-the-counter analgesics and anti-inflammatory drugs, such as acetaminophen (Tylenol), ibuprofen (Advil), and naproxen (Aleve), are frequently used, these medications have not demonstrated efficacy for reducing fibromyalgia pain in clinical trials.¹⁶⁵

Hormone Therapies

Estrogen fluctuations appear to coincide with times of increased pain sensitivity in women, but little is known about the role of estrogen and progesterone therapy in treating fibromyalgia.⁴⁶ A randomized placebo-controlled trial in 29 postmenopausal women with fibromyalgia found 50 mcg of transdermal estradiol per day for eight weeks had no effect on pain and tenderness compared with placebo.¹⁶⁶ On the other hand, an observational study involving 32 postmenopausal women with fibromyalgia found transdermal estradiol plus oral micronized progesterone for 12 weeks resulted in reduced fibromyalgia severity, with a 30% reduction in Fibromyalgia Impact Questionnaire scores, as well as improved sleep and quality of life.⁵⁵

Dehydroepiandrosterone (DHEA) is an adrenal hormone that acts as a precursor for other hormones and has independent actions on various tissues in the body. Several studies have indicated levels of DHEA-sulfate (DHEA-S, a stable form of circulating DHEA) are lower in women with fibromyalgia than in healthy women, and low levels are correlated with greater pain sensitivity.^167-169 In a randomized controlled crossover trial in 52 postmenopausal women with fibromyalgia, 50 mg of DHEA per day for three months raised DHEA-S levels from 51.6 to 165.8 mcg/dL; however, pain, fatigue, and other related symptoms improved after both the DHEA and placebo phases of the trial, with no significant differences.¹⁷⁰ More research is needed to determine whether DHEA supplementation and/or achieving specific DHEA-S blood levels can benefit people with fibromyalgia.

Growth hormone is released as part of a normal stress response, and low levels have been reported in people with fibromyalgia.⁴¹ In a randomized, placebo-controlled, crossover trial in 120 fibromyalgia patients receiving standard treatment, pain and other fibromyalgia indices improved more with six months of growth hormone injections than placebo.^171,172 In an older randomized placebo-controlled trial in 45 women with fibromyalgia and low levels of IGF-1 (a peptide made in the liver in response to stimulation by growth hormone), those receiving subcutaneous growth hormone injections for nine months had greater reductions in tender points and fibromyalgia impact scores and were more likely to experience global improvement compared with those receiving placebo.¹⁷³

The use of growth hormone has been associated with numerous side effects including injection site reactions, headaches, muscle and joint pain, digestive upset, and vision changes. In addition, it may increase the risk of developing skin and brain cancers.¹⁷⁴

Emerging Pharmacotherapies

Cannabinoids. Cannabis products containing varying amounts of the cannabinoids tetrahydrocannabinol (THC) and cannabidiol (CBD) are widely used by people with fibromyalgia. Two synthetic THC analogs, nabilone (Cesamet) and dronabinol (Marinol), have been studied in fibromyalgia patients with mixed results.¹⁵⁴ Research into cannabinoid-based medications has shown moderate benefit in managing chronic pain conditions and related symptoms such as sleep problems and anxiety.¹⁷⁵ A systematic review found some evidence that cannabinoids may provide short-term pain relief and improve quality of life measures in fibromyalgia patients. Side effects such as drowsiness, dizziness, nausea and vomiting, dry mouth, drug high, and others were reported in studies included in the systematic review, though none were severe.¹⁷⁶

Low-dose naltrexone. Naltrexone is a type of opioid receptor antagonist that has analgesic effects at low doses. Low-dose naltrexone has attracted interest as a potential therapy for chronic pain conditions, including fibromyalgia.¹⁷⁷ Low-dose naltrexone has been hypothesized to work by reducing neuroinflammation, modulating the body’s own opioid system, and modulating neuroimmune function.^178,179

Multiple systematic reviews of clinical trials and case reports have found that low-dose naltrexone probably reduces pain and improves quality of life in people with fibromyalgia, but can also cause adverse side effects such as insomnia, vivid dreams, and digestive upset.^178-180 However, a meta-analysis of eight clinical trials found low-dose naltrexone slightly reduced pain and symptom severity in patients with fibromyalgia but was not significantly more effective than placebo.¹⁸¹

Ketamine. Ketamine is an intravenous anesthetic that works by inhibiting NMDA receptors. This results in reduced nerve excitability. At lower than anesthetic doses, ketamine appears to suppress pain hypersensitivity.¹⁸² Intravenous infusion of a single low dose of ketamine has been reported to reduce pain intensity for hours to several days in subjects with fibromyalgia.^183-185 Two case reports found that higher doses, administered slowly over several hours and repeated daily for up to 10 days, resulted in long-term pain relief.^186,187 Ketamine can cause adverse side effects including confusion, euphoria, drowsiness, dizziness, and nausea.¹⁸⁸ Ketamine is also known to cause more serious side effects, such as hallucinations, impaired consciousness, cognitive dysfunction, high blood pressure, cystitis (bladder inflammation), and liver and gallbladder dysfunction, and should be used with caution.^189,190

Botulinum toxin. Botulinum toxin (Botox) is used as an intramuscular injection. It blocks the release of acetylcholine by nerves in muscle tissue, resulting in relaxation of muscle tone. Botulinum toxin also appears to have a direct analgesic effect and has been used to treat chronic pain disorders.¹⁹¹ Although evidence is mixed, botulinum toxin use in trigger point injections may be helpful for reducing symptoms in people with myofascial pain syndrome, a condition characterized by localized muscle and connective tissue pain; however, little is known about its effects on fibromyalgia.^192,193 In a small randomized controlled trial, 66 fibromyalgia patients received either botulinum toxin injection therapy in the neck, group problem-solving therapy, or both. Botulinum toxin reduced pain and mood symptoms, while combination therapy reduced suicidal thoughts.¹⁹⁴

A number of nutrients have been found to be beneficial in fibromyalgia treatment. They generally target underlying mechanisms such as sleep disturbance, stress, inflammation, mitochondrial dysfunction, oxidative stress, neurotransmitter imbalance, and dysbiosis.¹⁹⁵ Because fibromyalgia is a complex chronic condition without a clear cause, treatment is challenging and usually involves multiple modalities.

Magnesium

Reported dosage: 100–600 mg per day

Magnesium has been studied for a range of pain conditions. Magnesium’s beneficial effect in painful conditions has been attributed to its antagonism of glutamate receptors known as N-methyl-D-aspartate (NMDA) receptors, thereby inhibiting pain signaling. Magnesium deficiency can increase substance P levels, contributing to increased pain signal transmission.¹⁹⁶

Magnesium insufficiency and deficiency often go undetected, yet even mild magnesium deficits have been linked to a wide range of chronic conditions, including some that are closely associated with fibromyalgia.¹⁹⁷ In fibromyalgia patients, lower magnesium intake and red blood cell magnesium concentrations have been correlated with increased number of tender points, decreased pain threshold, and greater fibromyalgia intensity.^198,199

Increasing dietary magnesium intake may be beneficial for reducing fibromyalgia symptoms. In a randomized controlled trial in 22 women with fibromyalgia, both groups ate a Mediterranean diet— but one group consumed extra walnuts as an added source of magnesium and tryptophan (60 mg of each). Those eating a walnut supplemented diet for 16 weeks experienced decreased anxiety symptoms, mood disturbance, eating disorders, and body image dissatisfaction compared with those consuming a standard Mediterranean diet.²⁰⁰

A randomized placebo-controlled trial involving 75 subjects with fibromyalgia found 100 mg of oral magnesium (as magnesium chloride) once daily for one month improved scores on the Depression Anxiety Stress Scale and reduced pain severity in a subgroup of participants with mild-to-moderate stress, but had no effect on symptom parameters in those with severe-to-extremely severe stress.²⁰¹ In a controlled clinical trial, 60 women with fibromyalgia were treated with 300 mg of magnesium (as magnesium citrate), the antidepressant drug amitriptyline, or both for eight weeks. While magnesium and amitriptyline each improved many of the assessed parameters, the combination of the two was more effective than either alone and significantly improved pain, tender points, depression, anxiety, sleep, and irritability.¹⁹⁹

A randomized placebo-controlled trial in 24 fibromyalgia patients found a magnesium malate supplement providing 150 mg of elemental magnesium and 600 mg of malic acid twice daily for four weeks did not significantly affect pain; however, in a six-month, follow-up, open trial with the same participants, increasing the dose as needed, based on symptom response and side effects, up to a maximum of 300 mg of magnesium and 1,200 mg of malic acid twice daily led to reductions in all measures of pain and tenderness.²⁰² A small pilot trial involving 15 fibromyalgia patients found tender point index scores decreased after an average of eight weeks of supplementation with 300–600 mg of magnesium plus 1,200–2,400 mg of malic acid daily and increased after two weeks of placebo; in six of the participants, pain was significantly reduced within two days of magnesium malate therapy.²⁰³

In an open clinical trial, 24 women with fibromyalgia used topical magnesium chloride spray, applying four sprays on each arm and leg twice daily for four weeks; scores on the Fibromyalgia Impact Questionnaire were significantly reduced at the end of the trial.²⁰⁴

Coenzyme Q10 (CoQ10)

Reported dosage: 100–400 mg daily

Coenzyme Q10 (CoQ10) is a nutrient needed for healthy mitochondrial function and a powerful antioxidant.²⁰⁵ One study found CoQ10 concentrations were lower and oxidative stress levels higher within white blood cells of fibromyalgia patients than those of healthy individuals, while blood CoQ10 levels were higher, suggesting altered CoQ10 metabolism may be associated with this condition.²⁰⁶ A report from another small study indicated both CoQ10 and serotonin levels in platelets from 20 fibromyalgia patients were lower than in platelets from healthy individuals. Furthermore, 100 mg of CoQ10 (as ubiquinone) three times daily for 40 days reduced depression scores better than placebo and increased platelet levels of both CoQ10 and serotonin to levels seen in healthy individuals.²⁰⁷

In a randomized, controlled, crossover trial, the effect of CoQ10 (form not specified) was compared with placebo in 11 fibromyalgia patients being treated with pregabalin. Participants received 300 mg of CoQ10 per day for 40 days and placebo for 40 days, in random order, along with pregabalin. CoQ10 reduced mitochondrial oxidative stress and inflammation and augmented the positive effects of pregabalin on pain and anxiety compared with placebo.²⁰⁸ An open crossover trial in 22 subjects with fibromyalgia found 200 mg of CoQ10 (as ubiquinone) twice daily (in a supplement that also contained vitamins B2, B6, B9, B12, and E) for three months reduced pain, fatigue, and sleep disturbance compared with no treatment.²⁰⁹ In a randomized placebo-controlled trial that included 20 participants with fibromyalgia, 300 mg of CoQ10 (as ubiquinone) daily for 40 days reduced fibromyalgia symptoms, particularly pain, fatigue, and morning tiredness, as well as inflammation and oxidative stress. It also increased generation of new mitochondria and expression of a gene related to cellular metabolism.²¹⁰ A secondary analysis of data from that trial indicated CoQ10 also improved mood and other psychological symptoms.²¹¹ An uncontrolled clinical trial that included 25 volunteers with fibromyalgia found 200 mg of CoQ10 plus 200 mg of Ginkgo biloba extract per day for 12 weeks led to improvement in quality of life scores; in fact, 64% of participants reported feeling better at the end of the trial.²¹²

One randomized, double-blind, placebo-controlled, crossover trial involving 89 participants with fibromyalgia found sleep quality and Fibromyalgia Impact Questionnaire scores improved more following three months of treatment with a supplement providing 100 mg of CoQ10 (as ubiquinone), 592 mg of magnesium, and 300 mg of tryptophan per day than after three months of placebo.²¹³

Vitamin D

Reported dosage: 1,000–2,400 IU (25–60 mcg) per day or 50,000 IU (1,250 mcg) once per week.²¹⁴ Note: Life Extension recommends daily dosing of vitamin D when possible, rather than periodic bolus dosing.

Vitamin D has multiple functions related to musculoskeletal health and helps regulate inflammatory processes.²¹⁵ Although findings have been mixed, vitamin D deficiency appears to be more common in those with fibromyalgia and some other types of chronic pain than in the general population.^216-218 In fibromyalgia patients, vitamin D deficiency has been associated with higher levels of inflammatory cytokines and worse Fibromyalgia Impact Questionnaire scores.²¹⁹

According to reviews of correlational studies and clinical trials, vitamin D supplementation may reduce fibromyalgia-related pain, fatigue, and depression, especially in those with vitamin D deficiency.^216,217,220 A meta-analysis that pooled findings from eight randomized controlled trials involving 649 subjects with fibromyalgia found vitamin D improved physical function, emotional health, social function, and general health, as well as scores on the Fibromyalgia Impact Questionnaire, better than placebo. The dose of vitamin D was 50,000 IU (1,250 mcg) per week in seven of the trials and 1,000 IU (25 mcg) per day in one trial.²²¹ Another meta-analysis of five randomized controlled trials with 315 participants found vitamin D improved Fibromyalgia Impact Questionnaire scores, but did not change pain severity. Four trials in this analysis used a dose of 50,000 IU (1,250 mcg) weekly and one used 2,400 IU (60 mcg) daily of oral vitamin D.²²²

In an uncontrolled trial involving 180 women with fibromyalgia, 65.6% were found to have vitamin D deficiency (<20 ng/mL) and another 12.2% had vitamin D insufficiency (<30 ng/mL), while only 22.2% had adequate (≥30 ng/mL) vitamin D status. Those with deficiency and insufficiency were then treated with 50,000 IU (1,250 mcg) of vitamin D per week for 12 weeks, resulting in improvements in measures of fibromyalgia severity and impact.²²³ In a randomized controlled trial in 30 women with fibromyalgia and vitamin D levels below 32 ng/mL, 1,200 IU (30 mcg) or 2,400 IU (60 mcg) of vitamin D3 daily, depending on baseline levels, for 20 weeks led to marked reduction in symptom severity and improved physical function compared with placebo.²²⁴ Treating vitamin D deficiency may also improve the effectiveness of antidepressant therapy. In a randomized controlled trial in 74 subjects with fibromyalgia and vitamin D deficiency (<20 ng/mL) being treated with trazadone (an antidepressant with sedating effects) at bedtime, 50,000 IU (1,250 mcg) of oral vitamin D weekly was more effective than placebo for improving measures of pain and quality of life.²²⁵

Fibromyalgia patients should have their vitamin D levels checked regularly. Life Extension suggests that a 25-hydroxyvitamin D level of 50–80 ng/mL should be targeted for optimal health among most aging individuals.

Melatonin

Reported dosage: 3–15 mg nightly

Melatonin is a hormone that helps regulate circadian rhythms as well as mood, pain, inflammation, and oxidative stress.²²⁶ Some evidence suggests people with fibromyalgia may have low melatonin levels or disrupted diurnal melatonin cycles compared with healthy individuals.^226-228

A trial in which 36 subjects with fibromyalgia received placebo and increasing doses of melatonin (3 mg, 6 mg, 9 mg, 12 mg, and 15 mg nightly) during alternating 10-day cycles found 9 mg, 12 mg, and 15 mg of melatonin per day decreased scores on the Fibromyalgia Impact Questionnaire, number of tender points, and urinary cortisol levels. In addition, anxiety scores improved relative to placebo with 12 mg and 15 mg nightly.²²⁹ An uncontrolled trial involving 21 subjects with fibromyalgia found 3 mg of melatonin at bedtime for four weeks improved tenderness, pain, sleep, and overall status.²²⁷

Melatonin may be helpful as an adjunct to antidepressant therapy in treating fibromyalgia. In a randomized placebo-controlled trial that included 101 participants with fibromyalgia, those who received 3 mg or 5 mg of melatonin nightly in addition to antidepressant therapy with fluoxetine had improvement on Fibromyalgia Impact Questionnaire scores after eight weeks.²³⁰ A similar trial involving 63 women with fibromyalgia found treatment with the antidepressant amitriptyline plus 10 mg of melatonin nightly for six weeks reduced pain more than either amitriptyline or melatonin alone.²³¹

Acetyl-L-Carnitine

Reported dosage: 1,000–1,500 mg daily

Acetyl-L-carnitine, a form of the amino acid carnitine, is involved in mitochondrial energy production and reducing oxidative stress.²³² Acetyl-L-carnitine is particularly important for nervous system function since it modulates neurotransmitter activity, increases activity of nerve growth factors, and appears to quiet pain signaling and inhibit pain sensitization.²³³

In a randomized controlled trial, 102 people with fibromyalgia received daily treatment with either 500 mg of oral acetyl-L-carnitine twice daily plus 500 mg of intramuscularly injected acetyl-L-carnitine or oral and intramuscular placebos for two weeks. Then, for eight weeks, the carnitine group received 1,500 mg of oral acetyl-L-carnitine while the other group continued receiving placebo. At the end of the 10-week trial, those receiving acetyl-L-carnitine had improvements in depression, musculoskeletal pain, and quality of life scores.²³⁴ Another randomized controlled trial in 65 women with fibromyalgia compared 500 mg of oral acetyl-L-carnitine three times daily to treatment with the antidepressant duloxetine; after 12 weeks, improvements in pain, depressive symptoms, and general clinical status were seen in both groups, but duloxetine improved psychological aspects of quality of life more than acetyl-L-carnitine.²³⁵ In a controlled trial involving 130 fibromyalgia patients being treated with duloxetine plus pregabalin, the addition of 500 mg of acetyl-L-carnitine plus 600 mg of palmitoylethanolamide (PEA) twice daily for 12 weeks improved Widespread Pain Index, Fibromyalgia Impact Questionnaire, and Fibromyalgia Assessment Status scores more than medical treatment alone.²³⁶

Probiotics

Reported dosage: 1–40 billion CFUs of mixed probiotic species per day

Research suggests that intestinal homeostasis may directly affect brain functioning via the gut–brain axis. This has potential therapeutic implications for a range of chronic conditions involving nervous system dysfunction, including fibromyalgia and other chronic pain disorders.^237,238

In a randomized placebo-controlled trial involving 53 women with fibromyalgia, eight weeks of treatment with a daily probiotic formula containing a total of 40 billion colony forming units (CFUs) of Lactobacillus acidophilus, L. rhamnosus, Bifidobacterium longum, and Saccharomyces boulardii improved sleep quality, anxiety, depression, and pain scores, while another group that received 10 grams of the prebiotic inulin had improved pain scores and sleep quality only.²³⁹ In an uncontrolled trial that included 15 women with fibromyalgia, seven of whom had also been diagnosed with chronic fatigue syndrome, treatment with a synbiotic (probiotic/prebiotic combination) for 30 days decreased stress, anxiety, and depression, improved quality of life, and reduced IL-8 levels. More benefits were seen in those without chronic fatigue syndrome. The daily supplement used in this study provided 1 billion CFUs of probiotic strains (B. lactis, L. rhamnosus, and B. longum); 200 mg of the prebiotic fructooligosaccharides; 1.5 mg of zinc; 8.25 mcg of selenium; and 30 IU (0.75 mcg) of vitamin D.²⁴⁰

Palmitoylethanolamide (PEA)

Reported dosage: 600–1,200 mg daily

PEA is an endocannabinoid-like compound naturally produced by the body that has been suggested to have anti-inflammatory, analgesic, and neuroprotective effects.^241,242 Multiple clinical trials and several meta-analyses have found PEA may be an effective treatment for chronic pain.^243-245 An observational study that included data from 359 subjects with fibromyalgia found inclusion of PEA in therapy was associated with reduced pain and improved quality of life scores.²⁴⁶ Another observational study in 35 fibromyalgia patients found that adding a combination of micronized and ultra-micronized PEA to treatment with duloxetine plus pregabalin for three months was associated with further reductions in tender points and pain. In this study, PEA supplement-users took 600 mg of PEA twice daily for the first month followed by 300 mg twice daily for two months.²⁴⁷ In a randomized controlled trial, 130 fibromyalgia patients were treated with duloxetine plus pregabalin for 12 weeks. They were then assigned to receive 600 mg of PEA plus 500 mg of acetyl-L-carnitine twice daily in addition to medical treatment or continue medical treatment alone for another 12 weeks. At the end of the trial, fibromyalgia pain and symptom questionnaire scores improved more in those receiving PEA and acetyl-L-carnitine.²³⁶

Creatine

Reported dosage: 3 grams per day for three weeks or 20 grams per day for five days, followed by 5 grams per day

Creatine is a non–protein-forming amino acid that plays a crucial role in ATP recycling and energy storage in muscle and brain tissue.^248,249 An observational study found 19 fibromyalgia patients had lower muscle concentrations of ATP and phosphocreatine (the most prevalent form of creatine in muscle), higher muscle fat content, and lesser muscle function compared with 14 healthy individuals.²⁵⁰ In addition, another observational study found abnormal brain creatine metabolism in fibromyalgia patients with high stress levels and PTSD.²⁴⁸

In an open-label clinical study in 30 women receiving ongoing medical therapy for fibromyalgia, eight weeks of creatine supplementation, at 3 grams daily for three weeks followed by 5 grams daily for five weeks, improved fibromyalgia severity, quality of life, sleep, disability, and pain.²⁵¹ In a randomized placebo-controlled trial with 28 female participants with fibromyalgia, those who received creatine, at 5 grams four times daily for five days followed by 5 grams daily for the remainder of 16 weeks, had greater increases in muscle phosphocreatine stores and strength than those who received placebo, although no differences in fibromyalgia symptoms were detected.²⁵²

5-Hydroxytryptophan (5-HTP)

Reported dosage: 100 mg three times per day

5-hydroxytryptophan (5-HTP), a metabolite of the amino acid tryptophan, can be used in the body to make serotonin. It is found in many plants and mushrooms and is often extracted commercially from the seeds of Griffonia simplicifolia.²⁵³ 5-HTP has been shown to raise serotonin levels and activity in humans,²⁵⁴ and one study found women with fibromyalgia had lower levels of 5-HTP and serotonin than matched controls.²⁵⁵

Two clinical trials from the early 1990s reported fibromyalgia patients benefited from 5-HTP supplementation. One trial was an open clinical trial involving 50 fibromyalgia patients and found 100 mg of 5-HTP three times daily for 90 days reduced tender point number, anxiety, pain intensity, sleep difficulty, and fatigue. Overall, 50% of participants experienced fair to good treatment response.²⁵⁶ The other was a placebo-controlled trial in 50 fibromyalgia patients and reported similar improvement after 30 days of treatment with the same dose of 5-HTP.²⁵⁷ 5-HTP has also been shown to have positive effects in patients with depression, anxiety, migraines, sleep disorders, and neurodegenerative diseases, which frequently co-occur with fibromyalgia.²⁵³

Ginseng

Reported dosage: 100–400 mg per day

Panax ginseng (also known as Asian, Korean, or red ginseng) has been used for centuries to increase energy and vitality. It is considered an adaptogenic herb because of its ability to improve stress resilience. In an open clinical trial involving 188 subjects with fibromyalgia and chronic fatigue syndrome, more than 60% of participants rated themselves as improved after one month of treatment with 100 mg to 400 mg of a proprietary form of red ginseng extract per day for one month. Specifically, those who felt better reported improvements in energy, well-being, mental clarity, sleep, pain, and stamina.²⁵⁸ A small randomized controlled trial in 38 fibromyalgia patients found 100 mg of ginseng extract daily for 12 weeks led to improvement in pain, fatigue, sleep, number of tender points, and quality of life; however, those receiving amitriptyline or placebo also improved in these parameters, and the differences between groups were not statistically significant for most endpoints.²⁵⁹

S-Adenosyl-L-Methionine (SAMe)

Reported dosage: 400–800 mg per day

S-adenosyl-L-methionine (SAMe) is an amino acid metabolite and a crucial methyl donor that is necessary for many biochemical processes, including hormone and neurotransmitter synthesis. It can be synthesized in the body, and that process is dependent on vitamin B12 and folate.²⁶⁰

Most trials of SAMe for fibromyalgia were conducted in the 1980s or 1990s, and both oral and intramuscular SAMe have been studied. In one placebo-controlled trial in 44 fibromyalgia patients, 800 mg of SAMe per day for six weeks improved some measures of pain, fatigue, stiffness, and mood.²⁶¹ In an uncontrolled trial in 47 subjects with fibromyalgia, 400 mg of oral SAMe twice daily plus 200 mg of intramuscularly injected SAMe once daily for six weeks decreased tenderness, increased general well-being, and improved scores measuring depression, anxiety, and mood.²⁶² A trial involving 30 fibromyalgia patients reported 200 mg of intramuscular plus 400 mg of oral SAMe daily for six weeks was more effective than transcutaneous electrical nerve stimulation (TENS) for reducing tender points, pain and fatigue, and depression and anxiety scores.²⁶³ Other clinical trials have also reported SAMe reduced fibromyalgia pain and depression symptoms.^260,264,265 However, one 10-day trial compared 600 mg intravenous SAMe daily to placebo in 34 fibromyalgia patients and found no significant effect from treatment.²⁶⁶

Iron

Reported dosage: 60–120 mg elemental iron once every other day (as indicated by iron status on lab testing)

One observational study found low levels of iron and other nutrients in people with fibromyalgia.²⁶⁷ Lower blood levels of ferritin (the body’s main storage form of iron)^268,269 and low iron concentration in hair²⁷⁰ have also been found in fibromyalgia patients. Furthermore, individuals with iron deficiency anemia have been found to have an increased risk of fibromyalgia.^271,272 One study found that, while fibromyalgia was associated with a high rate of iron deficiency without anemia, ferritin levels were not associated with a number of characteristic fibromyalgia symptoms.^268,273

In a randomized placebo-controlled trial in 80 fibromyalgia patients with iron deficiency anemia, intravenous iron replacement in two sessions five days apart improved symptom severity over 42 days of monitoring. The amount of elemental iron administered in each session was 15 mg per kg of body weight, up to a maximum of 750 mg.²⁷⁴ Oral iron at doses needed to reverse deficiency (60–120 mg per day) is best taken in a single morning dose every other day with vitamin C to maximize absorption.²⁷⁵

Vitamin B12 (and Other B Vitamins)

Reported dosage: 1,000 mcg of vitamin B12 per day; may be taken as part of a B-complex supplement

B vitamins are important cofactors in a wide spectrum of metabolic pathways. Lower intakes of vitamins B1 (thiamin), B6, and folic acid were correlated with worse Fibromyalgia Impact Questionnaire scores in a study in 92 fibromyalgia patients, and low intake of B6 was also associated with higher pain scores.²⁶⁷ Poor vitamin B12 (cobalamin) status has been proposed to play a role in fibromyalgia onset.²⁶⁸ A study that examined data from 2,142 people with fibromyalgia found more than 42% were deficient in vitamin B12, and fatigue was more common among those with B12 deficiency.²⁷⁶ In an uncontrolled clinical trial in 28 women with fibromyalgia, 1,000 mcg of vitamin B12 daily for 50 days reduced symptom severity and anxiety scores.²⁷⁷ Vitamin B1 may also have therapeutic value in fibromyalgia patients, according to a set of three case reports.²⁷⁸

D-ribose

Reported dosage: 5 grams two to three times per day

D-ribose is a sugar that helps increase cellular energy synthesis in muscle cells. One uncontrolled trial involving 41 participants with fibromyalgia and/or chronic fatigue syndrome found 5 grams of D-ribose three times daily significantly improved energy, sleep, mental clarity, pain intensity, and general well-being.²⁷⁹ In a case-report of a 37-year-old woman with fibromyalgia, 5 grams of D-ribose twice daily, as an addition to an existing treatment plan, led to symptom improvement.²⁸⁰

Diet

Adherence to a healthy diet can have significant benefits in fibromyalgia by supporting a healthy gut microbiome, reducing inflammation, decreasing oxidative stress, and minimizing nutrient deficiency risks.²⁸¹ Several specific dietary interventions have shown promise in reducing fibromyalgia symptoms, including plant-based, Mediterranean, anti-inflammatory, low-FODMAPs (fermentable oligo-, di-, and monosaccharides and polyols), and monosodium glutamate- and aspartame-free diets.^281-283

Diets that emphasize fruits, vegetables, olive oil or other plant oils, and nuts, while limiting red meat intake, have shown the most consistent benefits in people with fibromyalgia.²⁸² Mediterranean, vegetarian, and vegan diets in particular appear to help reduce chronic musculoskeletal pain.²⁸⁴ A systematic review of six studies found vegetarian and vegan diets improved quality of life, pain at rest, sleep quality, and general health status in fibromyalgia patients.²⁸⁵ Diets high in plant foods are a source of polyphenols, plant compounds that are well known for their anti-inflammatory and antioxidant effects and may have a role in fibromyalgia treatment.²⁸⁶ Animal research has highlighted that polyphenols may have pain-relieving effects, including diosmetin (derived from diosmin, found in citrus fruits and olive leaf), quercetin (found in fruits and vegetables), kaempferol (found in tea and many fruits and vegetables), hyperin (found in St. John’s wort [Hypericum perforatum]), fisetin (found in many fruits and vegetables), chlorogenic acid (found in coffee and several foods), and hesperidin and naringenin (found in citrus fruits).²⁸⁷

One randomized controlled trial compared the effects of a Mediterranean diet to a Mediterranean diet enriched with walnuts, providing 60 mg of magnesium and 60 mg of tryptophan, for 16 weeks in 22 women with fibromyalgia. Anxiety symptoms, mood disturbance, eating disorders, and body image dissatisfaction decreased more in those eating the walnut-enhanced diet.²⁰⁰

A low-FODMAPs diet restricts intake of non-digestible carbohydrates found mainly in wheat, legumes, unaged dairy products, and some fruits and vegetables. This diet has been shown to be helpful in managing IBS, a functional condition that frequently co-occurs with fibromyalgia.²⁸⁸ One study examined the effects of a low-FODMAPs diet on fibromyalgia symptoms in 38 participants. After four weeks, all fibromyalgia measures showed improvement, digestive symptoms were reduced, and significant weight loss was seen.^289,290 A controlled trial in 46 women with fibromyalgia found that eating a low-FODMAPs and anti-inflammatory (no gluten, dairy, added sugars, or ultra-processed foods) diet for one month, followed by two months of adherence to the anti-inflammatory practices, resulted in improved pain, symptom severity, sleep, fatigue, and quality of life scores compared with general healthy eating practices.²⁹¹

The prevalence of non-celiac gluten/wheat sensitivity among fibromyalgia patients appears to be similar to that in the general population, and studies investigating the possible role of a gluten-free diet in fibromyalgia treatment have been mixed.^292,293 A clinical trial in 20 women with fibromyalgia and without celiac disease or IBS found pain and symptom severity were reduced after six months on a gluten-free diet.²⁹⁴ However, another trial involving 75 subjects with fibromyalgia found a gluten-free diet was no better than a low-calorie diet for improving fibromyalgia symptoms after 24 weeks.²⁹⁵

Obesity may play a contributing role in fibromyalgia, and weight loss has been associated with reduced pain in people with fibromyalgia.^99,282 In small uncontrolled trials of limited duration, very-low-calorie, very-low-carbohydrate ketogenic, vegetarian, and vegan diets have each been shown to improve aspects of fibromyalgia, effects that did not appear to be fully explained by the weight loss alone.^282,296,297

In a dietary intervention study, 41 women with fibromyalgia were assigned to eat a very-low-carbohydrate ketogenic diet (group 1, less than 10 grams of carbohydrates per day) or a low-glycemic and insulinemic diet (group 2) for 45 days. The low-glycemic and insulinemic diet included 100–150 grams per day of low-glycemic index carbohydrates. Those in the ketogenic diet group received herbal preparations and mineral salts intended to replenish mineral losses expected in ketosis. Both groups experienced improvements in physical and mood symptom scores, but group 1 had more pronounced effects.²⁹⁸ The study continued for another 45 days, during which both groups ate a low-glycemic and insulinemic diet. Symptom scores were stable in both groups during this phase, indicating 45 days of a very-low-carbohydrate ketogenic diet followed by 45 days of a low-glycemic and insulinemic diet had a lasting benefit that could not be achieved by 90 days on a low-glycemic and insulinemic diet. Notably, similar weight loss was seen in the two groups, suggesting symptom improvements were only partly attributable to weight loss.²⁹⁹

Advanced glycation end products (AGEs) are another factor that may contribute to fibromyalgia symptoms. Advanced glycation end products are harmful compounds produced when, usually as a result of high-heat cooking, glucose spontaneously binds to proteins, fats, and nucleic acids (DNA and ribonucleic acid [RNA]), disrupting their ability to function normally.^300,301 They are also generated in the body, particularly when blood glucose levels are chronically elevated.³⁰² Blood levels of the AGEs pentosidine and carboxymethyllysine were found to be higher in 41 subjects with fibromyalgia than in healthy individuals.^303,304 Muscle tissue samples from the fibromyalgia patients also showed increased concentrations of carboxymethyllysine, as well as higher levels of activated nuclear factor-kappa B, an inflammatory signaling protein.³⁰⁴ A study involving blood tests from 33 fibromyalgia patients found all of the participants had evidence of insulin resistance, a condition associated with poor blood glucose control and high risk of type 2 diabetes.⁹⁴ These findings suggest a low-AGE diet may have a role in treating fibromyalgia.

Other dietary additives may also be involved in inducing fibromyalgia pain. For example, monosodium glutamate (MSG) and aspartame are food additives that can cause excessive stimulation of nerve fibers, possibly contributing to increased pain signaling.²⁸³ Several case reports describe patients with fibromyalgia whose symptoms completely resolved or nearly completely resolved after eliminating dietary MSG, aspartame, or both.^305,306

In a study involving 37 participants with fibromyalgia and IBS, 31 reported a reduction in fibromyalgia symptoms after four weeks on an MSG- and aspartame-free diet. Reintroduction of a very high dose of MSG worsened symptoms.³⁰⁷ However, in a randomized controlled trial in 72 women with fibromyalgia, those assigned to MSG and aspartame elimination had no greater decrease in symptoms than those in a control group assigned to a waiting list.³⁰⁸

Exercise

Exercise has been shown to be one of the most effective treatments for fibromyalgia and is recommended as a central component of non-pharmacologic management.¹⁰⁹ In addition to reducing pain, exercise can improve sleep quality, physical and emotional functioning, and quality of life in those with chronic musculoskeletal pain.³⁰⁹ Several mechanisms have been proposed for exercise’s benefits, including³¹⁰:

• Analgesic effects due to increased growth hormone and adrenocorticotrophin hormone
• Better autonomic nervous system balance through reduced sympathetic hyperactivity
• Anti-inflammatory effects with decreased inflammatory cytokine levels
• Better hypothalamic-pituitary-adrenal axis tone
• Increased release of serotonin, dopamine, and nerve growth factors
• Normalized pain signaling through reduced central and peripheral pain hypersensitization

All types of exercise appear to have positive impacts on fibromyalgia, but different types of exercise may affect symptoms differently.^311,312 A meta-analysis of findings from 18 randomized controlled trials involving a combined total of 1,184 participants with fibromyalgia found aerobic exercise, strength training, and stretching exercises all decreased pain perception, improved Fibromyalgia Impact Questionnaire scores, and increased physical and mental health-related quality of life; however, only aerobic exercise significantly reduced depression.³¹² Another meta-analysis showed home-based exercise programs can reduce pain and depression while enhancing quality of life in fibromyalgia patients, but supervised exercise programs may lead to greater improvement.³¹³

Traditional Chinese mind-body exercises, such as Tai Chi and Qigong, have also been found to be beneficial in fibromyalgia patients. A meta-analysis of 15 randomized controlled trials conducted in seven different countries and involving a total of 936 participants with fibromyalgia found traditional Chinese exercise reduced pain and symptom severity, enhanced sleep quality, and decreased anxiety and depression symptoms.³¹⁴ Yoga is another type of mind-body therapy that encompasses activity, posture, meditation, mindfulness, and breathing exercise. A small systematic review included findings from three randomized controlled trials involving 116 women with fibromyalgia. Yoga was found to improve Fibromyalgia Impact Questionnaire scores and reduce pain in all three trials. Specifically, fatigue, depression, anxiety, strength, and coping strategies were significantly improved in fibromyalgia patients treated with yoga therapy, and these improvements were largely sustained at follow-ups after the intervention.³¹⁵

Clinical trials have shown low-, moderate-, and high-intensity aerobic exercises can all have pain relieving effects. Exercise interventions that incorporate multiple types of physical activity, including aerobic, strength, and balance training, targeting not only pain relief but also fitness, strength, posture, coordination, balance, and emotional well-being, are often more effective for treating chronic pain than single-component interventions.³⁰⁹ In a meta-analysis that included findings from 50 randomized controlled trials involving a total of 3,761 fibromyalgia patients, a combination of aerobic plus flexibility training appeared to be the most effective exercise strategy for relieving pain, although variability between trial methods made it difficult to draw conclusions. The analysis also showed pain relief was only sustained if regular exercise was continued.³¹⁶

Fibromyalgia patients may benefit most from beginning gently with light- to moderate-intensity physical activity and gradually progressing to more vigorous exercise, in 30–60-minute sessions several times per week.^309,317

It is important to note that any increase in any form of physical activity may be beneficial. Although symptoms may temporarily worsen when adding or increasing physical activity, a gradual approach can help minimize this effect.⁶ Before beginning any exercise program, or significantly changing your level of physical activity, it is advisable to first consult with your healthcare practitioner.

Sleep Hygiene

Most people with fibromyalgia have sleep difficulties.³¹⁸ Poor sleep quality is described by fibromyalgia patients as a major problem that impacts pain and other symptoms as well as overall health and well-being. Despite its importance, little is known about how to effectively manage fibromyalgia-related sleep problems.³¹⁹

Sleep hygiene is a set of habits and behaviors undertaken to promote better and longer sleep. It is widely recommended as a core non-pharmacologic treatment for fibromyalgia.¹⁰⁹ There is no single definition of sleep hygiene, but most recommendations include³²⁰:

• Avoiding alcohol, caffeine, and tobacco products in the evening
• Not eating or engaging in stimulating activities close to bedtime
• Getting adequate exercise during the day
• Having a wind-down routine before bed
• Adhering to regular sleep and wake times
• Managing the sleep environment for temperature, noise, and darkness
• Ensuring bed and bedding are comfortable

A controlled clinical trial in 70 fibromyalgia patients found sleep hygiene education was more effective than no intervention after one month for reducing pain and depression scores and improving subjective sleep quality.³²¹ Another controlled trial involving 70 fibromyalgia patients found, after three months, those who received sleep hygiene instructions had reduced pain and fatigue, improved subjective sleep quality, and reduced difficulty falling back to sleep after waking in the night.³²² However, in studies comparing sleep hygiene to cognitive behavioral therapy for insomnia (CBT-I) in subjects with fibromyalgia, CBT-I has been found to be more effective than sleep hygiene education.^323,324 Cognitive behavioral therapy for insomnia integrates psychotherapy with behavior changes specifically to promote better sleep. It involves identifying and changing unhelpful thought patterns and incorporates sleep hygiene, stimulus control, relaxation, and sleep restriction.³²⁵

One meta-analysis evaluated treatments specifically addressing sleep in fibromyalgia patients. The analysis included 65 studies, representing 35 distinct treatment categories, with a total of 8,247 participants. Two types of therapy emerged as having the best potential to improve sleep—combined aerobic exercise plus flexibility training and water aerobics. In addition, some evidence showed strength training, sleep-focused psychological and behavioral therapy, electrotherapy/neurostimulation, weight loss, dental splints, and certain medications (antipsychotics and tricyclic antidepressants) had positive effects on sleep, but they were likely to be modest.³¹⁸ In a meta-analysis of 11 randomized controlled trials involving 729 participants that looked exclusively at non-pharmacologic approaches to fibromyalgia-related sleep problems, mindfulness-based therapy had the greatest likelihood of reducing sleep symptoms.³²⁶ Another meta-analysis included 47 randomized controlled trials with 11,094 participants that investigated the effects of either medications or CBT-I on sleep quality in fibromyalgia patients. The analysis found CBT-I moderately improved sleep quality. Pregabalin had a smaller positive effect on sleep quality, while other medications showed no or uncertain effects on sleep, and drug therapies in general were associated with more adverse side effects.³²⁷

More information is available in Life Extension’s Protocol on Insomnia. Also please see the section on Psychotherapy and Mindfulness earlier in this protocol.

What is Fibromyalgia?

Fibromyalgia is a chronic pain syndrome marked by widespread pain without an obvious cause. In addition to pain, people with fibromyalgia usually experience a range of other symptoms, often including fatigue, sleep problems, and cognitive dysfunction.^1,10 There is no specific cure for fibromyalgia. The best approach to treatment is a multifaceted, individualized program incorporating first-line nondrug therapies such as exercise, education, and cognitive behavioral therapy, with the addition of drug therapies as needed. It often takes weeks or months for treatment to have noticeable effects on fibromyalgia symptoms.³²⁸

Which diets may help manage fibromyalgia?

In general, a healthy, nutrient-dense diet may help improve symptoms of fibromyalgia. Several specific diets have shown promise in reducing fibromyalgia symptoms, including Mediterranean, vegetarian and vegan, anti-inflammatory, and low-FODMAPs (fermentable oligo-, di-, and monosaccharides and polyols) diets. For some individuals, gluten-free, ketogenic, and monosodium glutamate- and aspartame-free diets may also be beneficial.^281-283

What nutrients or supplements may ease fibromyalgia symptoms?

• Magnesium. Low magnesium levels may be associated with the development and severity of fibromyalgia. Supplementation has been shown to improve symptoms.
• Coenzyme Q10 (CoQ10). Coenzyme Q10 (CoQ10) metabolism may be altered in fibromyalgia patients, and supplementation has been shown to improve symptoms.
• Vitamin D. Many patients with fibromyalgia have vitamin D deficiency. Supplementation has been shown to reduce fibromyalgia-related pain, fatigue, and depression, especially in those with deficiency.
• Melatonin. Fibromyalgia patients may have low levels of melatonin or release less at night than healthy individuals. Clinical trials suggest melatonin supplementation can reduce fibromyalgia impact and anxiety, improve sleep, and decrease tenderness.
• Acetyl-L-carnitine. Acetyl-L-carnitine use has been shown to improve depression, pain, and quality of life in fibromyalgia, and may enhance the effects of medical treatment.
• Probiotics. Clinical evidence shows supplementing with probiotics may reduce stress, anxiety, depression, sleep problems, and pain and increase quality of life in fibromyalgia patients.
• Palmitoylethanolamide (PEA). Palmitoylethanolamide (PEA) supplementation has been found to reduce fibromyalgia pain and improve quality of life. It may also have a supportive role in fibromyalgia patients receiving medical treatment.
• Other supplements that have demonstrated promising effects in fibromyalgia patients include creatine, 5-hydroxytryptophan (5-HTP), B vitamins, S-adenosyl-L-methionine (SAMe), iron, and D-ribose.

What diet & lifestyle changes can improve fibromyalgia symptoms?

• Regular physical activity, which may include aerobic, flexibility, strengthening, and mind-body exercise
• Eating a healthy diet, typified by plant-based, Mediterranean, and anti-inflammatory dietary patterns
• Sleep hygiene practices
• Mindfulness-based practices
• Quitting smoking

What types of exercise are most effective for fibromyalgia?

The best exercise routine may involve multiple types of physical activity (aerobic, strength, flexibility, and balance training). Because introducing physical activity can temporarily aggravate fibromyalgia, it is best to begin with gentle or light- to moderate-intensity physical activity and gradually progress to more vigorous exercise, eventually reaching 30–60-minute sessions several times per week.^309,317 Aerobic exercise and yoga have been found to reduce pain and improve functioning in daily life while other mind-body exercises, such as Tai Chi and Qigong, have been shown to improve sleep quality and decrease anxiety and depression symptoms.^314,315,329 Importantly, even small increases in daily physical activity may be beneficial.⁶

How much exercise should someone with fibromyalgia do?

Research shows a minimum of 50 minutes of exercise per week is needed to reduce symptoms of fibromyalgia. Optimal benefits from exercise appear to require 150 minutes per week and may take as long as 20 weeks to be fully realized.³²⁹

How can sleep quality be improved for fibromyalgia sufferers?

People with fibromyalgia may be able to improve their sleep quality by incorporating habits and behaviors considered to be good sleep hygiene. Cognitive behavioral treatment for insomnia, which incorporates aspects of sleep hygiene, has been shown to improve sleep in fibromyalgia sufferers.^321,324

Can fibromyalgia be caused by stress?

Stress may contribute to some aspects of fibromyalgia by altering nervous system functioning. Studies have shown the chance of developing fibromyalgia is higher in those with traumatic life events, greater exposure to stress, and higher levels of emotional distress. Abnormal stress signaling has been noted in patients with fibromyalgia and other chronic pain disorders.^1,10 Stress is also reported to be a common trigger of fibromyalgia flare-ups.²⁸

What strategies help during fibromyalgia flare-ups?

Since inactivity, stress, and fatigue can trigger worsening of fibromyalgia symptoms, strategies to cope with flare-ups might include gentle and restorative physical activities, management of stress and anxiety, relaxation techniques, and addressing sleep issues.^28,330

What are Risk Factors for Fibromyalgia?

• Being female
• Being middle-aged
• Having a family member with fibromyalgia
• Other chronic pain conditions
• Irritable bowel syndrome (IBS)
• Anxiety and depressive disorders
• Sleep disorders
• Psychological trauma
• Physical trauma
• Smoking
• Any medical illness

What are the Signs and Symptoms of Fibromyalgia?

• Widespread chronic pain
• Fatigue
• Sleep disturbance
• Cognitive difficulties
• Anxiety and depressive symptoms
• Tender points
• Stiffness
• Other types of pain

How is Fibromyalgia Treated?

Education, psychotherapy, and exercise interventions are first-line fibromyalgia treatments. Light therapy, neurostimulation techniques, and complementary therapies such as acupuncture and massage may be added to the treatment plan to help reduce pain and improve other symptoms.³²⁸ It is important to note that treatment for such a complex disorder can take time to be effective.

The only medications currently approved for use in fibromyalgia treatment are pregabalin (Lyrica, an anti-seizure drug), duloxetine (Cymbalta, an antidepressant), milnacipran (Savella, an antidepressant), and sublingual cyclobenzaprine (Tonmya, a skeletal muscle relaxant). Other medications that may be prescribed include³²⁸:

• Other antidepressants
• Other muscle relaxants
• Other anti-seizure drugs
• N-methyl-D-aspartate (NMDA) receptor antagonists
• Anti-anxiety and sedative drugs
• Serotonin modulators
• Opioid pain relievers