What Causes Fibromyalgia?

What Causes Fibromyalgia? A Functional Medicine Perspective

Fibromyalgia is a complex and often misunderstood condition characterised by widespread chronic pain, fatigue, cognitive disturbances (“fibro fog”), and sleep issues. While traditional medicine focuses on managing symptoms, functional medicine aims to uncover and address the root causes of fibromyalgia. This approach considers how different systems in the body—hormonal, immune, digestive, and neurological—interact to influence health.

In this article, we’ll explore potential causes of fibromyalgia from a functional medicine perspective, focusing on hormonal imbalances, gut health, infections, autoimmunity, toxins, nutrient deficiencies, stress and trauma, mast cells, and oxidative stress.

What Is Fibromyalgia?

Fibromyalgia (FM) is a multifactorial syndrome characterised by chronic widespread pain, as defined by the International Association for the Study of Pain as pain in at least 4 of 5 body regions (in at least 3 or 4 body quadrants)”. Although pain is the main symptom among patients with Fibromyalgia, patients may also experience functional and cognitive disorders, including fatigue, sleep and mood disorders, and cognitive impairment.

Given its estimated global prevalence of almost 3%, fibromyalgia is considered a significant medical issue. It primarily affects women during their fifth decade of life, but it can occur at any age and may be associated with various conditions, including chronic fatigue syndrome, anxiety, irritable bowel syndrome, and most of musculoskeletal rheumatic diseases.

Hormonal Imbalances

Hormones play a critical role in regulating energy, mood, and pain perception. In people with fibromyalgia, imbalances in the following hormones have been observed:

• Cortisol (the stress hormone): Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis can result in abnormal cortisol levels, leading to fatigue, sleep disturbances, and increased pain sensitivity (source, source).
• Thyroid Hormones: Hypothyroidism or subclinical thyroid dysfunction can mimic fibromyalgia symptoms, including fatigue, depression, and muscle pain. In fact some research has discussed a connection between thyroid autoimmunity and fibromyalgia (source, source, source).
• Sex Hormones: Low levels of estrogen and testosterone have been linked to increased pain perception, which may explain why fibromyalgia is more common in women (source, source, source, source).

Functional Medicine Approach:

• Testing adrenal, sex hormone, and thyroid hormones (when felt appropriate).
• Addressing chronic stress.
• Balancing sex hormones through diet, lifestyle changes, supplements and, if necessary, bioidentical hormone therapy.

Gut Health: Dysbiosis, SIBO, and Leaky Gut

The gut plays a significant role in immune regulation, inflammation, and even mood—factors closely linked to fibromyalgia. Research has explored the connection between the gut microbiome and fibromyalgia (source).

• Dysbiosis: An imbalance in gut bacteria can trigger systemic inflammation and affect neurotransmitter production, contributing to fatigue, depression, and pain (source).
• Small Intestinal Bacterial Overgrowth (SIBO): A subset of people with fibromyalgia also have SIBO (source), which causes bloating, gas, and IBS-like symptoms. In fact symptom severity correlates with the degree of abnormality in the SIBO breath test (source).
• Leaky Gut (Intestinal Permeability): When the gut lining becomes compromised, toxins and undigested food particles can enter the bloodstream, triggering inflammation and immune responses that exacerbate fibromyalgia symptoms (source, source). You can test for leaky gut by doing a Ultimate Gut Health Test.
• Alterations in the gut-brain axis may also affect the production of neurotrasmitters such as serotonin and dopamine, which play a role in pain modulation and mood regulation. Dysregulation of these neurotransmitters may contribute to the development of FM symptoms (source).

To demonstrate the importance of gut health, a study published in 2024 found that probiotic supplementation significantly improved sleep quality, depression, anxiety, and pain scores compared to those at baseline in fibromyalgia patients, while prebiotic supplementation significantly improved pain scores and sleep quality (source).

Functional Medicine Approach:

• SIBO, and comprehensive stool testing, like our Ultimate Gut Health Test to assess gut microbiome health.
• Treating any microbial imbalances with dietary changes and targeted pre-, pro- and postbiotics, as well as potentially with antimicrobial herbs.
• Repairing gut lining with nutrients like L-glutamine, zinc, and probiotics.

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Chronic Infections

Hidden or chronic infections can contribute fibromyalgia (source, source), potentially by causing ongoing inflammation, immune dysfunction. In fact a study published in 2024 concluded that FM patients had a significantly higher incidence of infectious diseases than the general population (source).

• Viral Infections: Epstein-Barr virus (EBV), cytomegalovirus (CMV), and other herpes viruses have been linked to fibromyalgia (source).
• Bacterial Infections: Lyme disease, caused by Borrelia burgdorferi, can trigger fibromyalgia-like symptoms (source).

Functional Medicine Approach:

• Identifying hidden infections with advanced testing.
• Supporting immune health through lifestyle, diet, and supplements.
• Using antiviral, antibacterial, or anti-fungal treatments as needed.

Autoimmunity

Some of the strongest evidence suggesting that fibromyalgia (FM) might be an autoimmune disorder comes from the presence of anti-G protein-coupled receptor (GPCR) antibodies and the condition known as Small Fiber Neuropathy (SFN) (source).

• Anti-GPCR antibodies are autoantibodies that mistakenly target receptors in the autonomic nervous system (the system that controls functions like heart rate and digestion). These antibodies have been found in the blood of people with fibromyalgia, and their levels seem to be linked to the severity of symptoms.
• Interestingly, these same antibodies are also present in people with other conditions that often occur alongside fibromyalgia.

According to scientific criteria for diagnosing autoimmune diseases (developed by Ernst Witebsky and Noel Rose), if these autoantibodies are truly causing fibromyalgia, transferring them to animals should trigger the same symptoms. In fact, when researchers transferred IgG antibodies from fibromyalgia patients to mice, the mice developed symptoms similar to fibromyalgia, including signs of Small Fiber Neuropathy—a condition that affects small nerve fibers, leading to pain and sensory issues.

This research strengthens the theory that fibromyalgia could have an autoimmune component (source).

Functional Medicine Approach:

• Testing for autoimmune markers (ANA, RF, thyroid antibodies)
• Reducing inflammation through anti-inflammatory diets and appropriate lifestyle changes.
• Supporting immune regulation with supplements like omega-3s, and vitamin D.

 Toxin Exposure

Environmental toxins, including heavy metals (mercury, lead), can contribute to mitochondrial dysfunction, oxidative stress, and chronic inflammation—all common features in fibromyalgia (source, source, source). While there is no published research around this yet, many practitioners will agree that mould and mycotoxins (metabolites of mould) may also contribute to fibromyalgia.

Functional Medicine Approach:

• Assessing toxin exposure through specialised lab tests.
• Supporting detoxification pathways with nutrients like glutathione, N-acetylcysteine (NAC), and supporting gut health.
• Reducing exposure to environmental toxins in food, water, and personal care products.

Nutrient Deficiencies

Deficiencies in key nutrients can affect muscle function, nerve health, and energy production:

• Magnesium: Evidence is mixed in regards to the benefit of supplementing magnesium (source).
• Vitamin D: Deficiency can worsen pain and fatigue and deficiency is common in patients with fibromyalgia (source).
• B Vitamins: Crucial for nerve health and energy production. Vitamin B12 has been shown to be helpful (source).

CoQ10: Research has shown that people with fibromyalgia (FM) often have low levels of Coenzyme Q10 (CoQ10), an important nutrient that helps produce energy in the body. This discovery has led to the idea of using CoQ10 supplements to help manage FM symptoms. Over time, more studies have been conducted to test how effective CoQ10 is for fibromyalgia. The results suggest that taking CoQ10 supplements can help reduce symptoms, especially fatigue, which is one of the most common and challenging issues for people with FM. In general, the more consistent the supplementation, the better the improvement in energy levels and overall well-being (source).

Functional Medicine Approach:

• Testing for nutrient deficiencies. This can be via blood or urine generally.
• Personalised supplementation plans.
• Nutrient-dense, anti-inflammatory diets.

Stress and Trauma

Psychological stress and past trauma (emotional, physical, or sexual) are significant risk factors for fibromyalgia (source). Chronic stress disrupts the HPA axis, increases inflammation, and can even change the way the brain processes pain.

Functional Medicine Approach:

• Mind-body therapies such as mindfulness meditation, yoga, and cognitive behavioural therapy (CBT).
• Stress management techniques like deep breathing, vagus nerve stimulation, and biofeedback.
• Addressing past trauma through therapy and somatic experiencing.

Oxidative Stress

Researchers believe that oxidative stress—an imbalance between harmful molecules (free radicals) and the body’s ability to fight them with antioxidants—might play an important role in the development of FM (source).

How Oxidative Stress Contributes to Fibromyalgia (source):

• Increased levels of harmful molecules like nitric oxide and products of lipid peroxidation (damage to cell membranes) may lead to increased sensitivity to pain.
• Mitophagy, the process of removing damaged mitochondria (the energy producers in our cells), when not properly regulated, results in fatigue and pain.

Can Antioxidants Help with Fibromyalgia?

Many studies suggest that treatments targeting oxidative stress—by boosting the body’s natural antioxidant defences—may help reduce pain, fatigue, and other FM symptoms (source).

Potential Antioxidant-Based Therapies (source):

• Hyperbaric Oxygen Therapy (HBOT): Involves breathing pure oxygen in a pressurized room, which may reduce oxidative stress and improve symptoms.
• Dietary Changes: A diet rich in antioxidants (found in fruits, vegetables, nuts, and seeds) can help combat oxidative damage.
• Physical Activity: Regular exercise has antioxidant effects, reducing inflammation and improving energy levels and mood.

While there’s still no definitive cure for fibromyalgia, addressing oxidative stress through lifestyle changes and targeted therapies offers hope for managing symptoms and improving quality of life. Ongoing research continues to explore the best ways to reduce pain, fatigue, and mental health challenges associated with FM.

Mast cells

Mast cells are a type of immune cell that play a key role in inflammation and allergic reactions. Recent research suggests they may also be involved in the development of fibromyalgia (FM), particularly in how the body processes pain. Here’s how mast cells might contribute to FM symptoms (source):

Mast Cells and Pain

Studies have shown that blocking mast cells can reduce pain in experimental models, suggesting that these cells may play a role in triggering or worsening pain in FM.

Inflammation in the Nervous System

Mast cells release inflammatory chemicals called interleukins, such as IL-17, IL-6, and TGF-β, which can cause inflammation in the central nervous system (CNS)—the brain and spinal cord. This type of inflammation can increase sensitivity to pain.

They also produce IL-1, another inflammatory molecule, especially after being activated by signals from infections or allergic reactions. IL-1 has been found in the skin of people with fibromyalgia, suggesting it plays a role in their symptoms.

The Role of Inflammasomes

IL-1 is activated by structures in the body called inflammasomes, which are like “molecular alarm systems” that trigger inflammation. Targeting inflammasomes could be a future treatment option for FM, as it may help reduce IL-1-related pain.

Infections as a Trigger

Certain bacterial and viral infections are linked to the onset of fibromyalgia. Mast cells respond to infections by releasing inflammatory substances like IL-1, which could help explain why some people develop FM after an illness.

Increased Mast Cells in FM Patients

Research shows that people with fibromyalgia have about three times more mast cells in their skin compared to healthy individuals. This could contribute to the widespread pain and skin sensitivity often reported by FM patients.

Mast Cells and the Brain

Mast cells can disrupt the blood-brain barrier, which normally protects the brain from harmful substances. When this barrier is weakened, inflammatory chemicals can enter the brain, potentially worsening pain and other neurological symptoms.

The Vicious Cycle with Substance P

People with FM often have high levels of a pain-related chemical called Substance P. This chemical can stimulate mast cells, causing them to release even more inflammatory substances. This creates a vicious cycle where mast cells and the nervous system continuously activate each other, worsening symptoms.

Interaction with Microglia

Mast cells interact with microglia, the brain’s immune cells. And when mast cells activate microglia, they release additional pro-inflammatory substances like histamine and tryptase, which can lead to chronic pain.

All this evidence suggests that mast cells are deeply involved in the development of fibromyalgia. They contribute to inflammation, pain signalling, and interactions with the nervous system. Understanding this connection opens new possibilities for treating FM by targeting mast cells, inflammatory pathways, and their effects on the brain and immune system.

Other Potential Triggers

• Mitochondrial Dysfunction: Impaired energy production at the cellular level may contribute to fatigue and muscle pain (source, source, source).
• Genetic Predisposition: Variations in genes related to serotonin metabolism and pain perception may increase susceptibility.
• Sleep Disorders: Conditions like sleep apnea or restless leg syndrome can worsen fibromyalgia symptoms.

Conclusion: What Causes Fibromyalgia?

Fibromyalgia is not caused by a single factor. It is caused by a complex interplay of biological, psychological, and environmental factors. The functional medicine approach seeks to identify and address these root causes through personalised assessments, advanced lab testing, and holistic treatment strategies.

By looking beyond symptom management and addressing factors like hormonal imbalances, gut health, infections, toxins, and stress, individuals with fibromyalgia can find lasting relief and improve their quality of life.