Fibromyalgia & ME/CFS: The Functional Medicine Approach

Two Conditions, One Shattered Terrain

Fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are among the most misunderstood conditions in modern medicine. Patients are often told their labs are normal, their symptoms are psychosomatic, or they simply need to exercise more. This is a catastrophic failure of the conventional model. These are real, measurable, physiological conditions — and functional medicine has the tools to address them.

They overlap substantially but are distinct. Fibromyalgia is defined by widespread pain and central sensitization. ME/CFS is defined by post-exertional malaise — a pathological crash after physical or cognitive exertion that can last days or weeks. Many patients have both. The treatment must respect the differences.

Diagnostic Criteria

Fibromyalgia (ACR 2010/2016 criteria): Widespread pain index (WPI) score plus symptom severity scale (SSS) covering fatigue, waking unrefreshed, and cognitive symptoms. The old tender-point examination has been replaced by these validated questionnaires, though tender points remain clinically useful.

ME/CFS (IOM 2015 criteria, now called SEID): Three required symptoms — substantial reduction in activity lasting >6 months, post-exertional malaise (PEM), and unrefreshing sleep. Plus at least one of: cognitive impairment or orthostatic intolerance. PEM is the cardinal feature — if a patient can exercise vigorously without crashing, it is not ME/CFS.

Root Causes: Mapping the IFM Matrix

These conditions are not caused by one thing. They represent a collapse of multiple systems simultaneously — which is exactly why they are invisible to the specialist model that examines one organ at a time.

Mitochondrial Dysfunction

The energy production system is broken. Sarah Myhill’s 2009 ATP profile study demonstrated that mitochondrial function directly correlates with disability level in ME/CFS patients. Complex I, III, and IV of the electron transport chain are impaired. The cells cannot produce adequate ATP, so every system that requires energy (which is every system) degrades.

Think of it this way: your body runs on ATP the way a city runs on electricity. When the power grid drops to 40% capacity, everything still technically functions — but poorly. Lights dim, trains slow, hospitals ration. That is ME/CFS.

HPA Axis Dysfunction

Not “adrenal fatigue” (a term that oversimplifies), but measurable HPA axis dysregulation. The cortisol awakening response is blunted. DHEA is often low. The diurnal cortisol curve flattens. The stress response system has been running at maximum for so long that it has downregulated — like a smoke alarm that stopped beeping because the battery died, not because the fire went out.

Neuroinflammation

Jarred Younger’s 2014 PET imaging study using a TSPO ligand showed activated microglia (the brain’s immune cells) in fibromyalgia patients, concentrated in regions corresponding to pain processing. Substance P — a pain neurotransmitter — is elevated 3-fold in the cerebrospinal fluid of fibromyalgia patients. The pain is not imagined. The brain’s immune system is on fire.

Central sensitization means the volume knob on the pain system has been turned up. Normal stimuli register as painful (allodynia). Mildly painful stimuli become excruciating (hyperalgesia). The dorsal horn neurons in the spinal cord are firing at a lower threshold.

Gut Dysbiosis

Mark Pimentel’s research found that 100% of fibromyalgia patients in his study had small intestinal bacterial overgrowth (SIBO). One hundred percent. ME/CFS research has identified a distinct microbiome signature — reduced diversity, loss of butyrate-producing species, increased inflammatory organisms. The gut-brain axis is a superhighway, and in these conditions, the traffic is all going the wrong direction.

Infections

Many cases of ME/CFS begin with an acute infection that never fully resolves:

• EBV reactivation: The most common trigger. Not a new infection but reactivation of latent Epstein-Barr virus. Elevated early antigen (EA) IgG indicates reactivation.
• HHV-6: Human herpesvirus 6 — neurotropic, can cause encephalitis, commonly reactivates in immune-compromised states
• Mycoplasma pneumoniae: Cell-wall-deficient bacteria that evade immune detection
• Lyme and co-infections: Borrelia, Babesia, Bartonella — significant overlap with fibro/ME/CFS symptom profiles
• Coxsackie virus: Enteroviruses found in stomach biopsies of ME/CFS patients (Chia 2008)

Environmental Toxins

Mold and mycotoxin exposure (chronic inflammatory response syndrome — CIRS) produces a clinical picture nearly identical to ME/CFS. Heavy metals (mercury, lead, arsenic) impair mitochondrial function and drive neuroinflammation. Every fibro/ME/CFS patient deserves environmental exposure screening.

Autonomic Dysfunction

Postural orthostatic tachycardia syndrome (POTS) and orthostatic intolerance are present in up to 70% of ME/CFS patients. Heart rate increases >30 bpm on standing (or >40 bpm in ages 12-19). Blood volume is reduced by up to 20%. The vagus nerve — the body’s primary parasympathetic brake — has impaired tone.

Sleep Architecture Disruption

Harvey Moldofsky’s landmark research identified alpha-wave intrusion during delta (deep) sleep in fibromyalgia — the brain is producing wakefulness signals during what should be the deepest, most restorative phase of sleep. The patient sleeps 8-10 hours and wakes exhausted. This is not insomnia. This is corrupted sleep architecture.

Structural Considerations

An often-overlooked cause: craniocervical instability (CCI), Chiari malformation, or cervical stenosis — especially in patients with concurrent hypermobility/Ehlers-Danlos syndrome. Mechanical compression of the brainstem can produce the full ME/CFS picture. Upright MRI with flexion-extension views may be needed.

Testing

A comprehensive workup for fibro/ME/CFS includes:

Metabolic and Nutrient:

• CBC, CMP, hs-CRP, ESR
• Ferritin (target >50 for energy, >70 for hair)
• B12 and methylmalonic acid (MMA — functional B12 deficiency)
• Vitamin D (25-OH)
• Magnesium RBC (serum magnesium is useless — only 1% of body magnesium is in serum)
• Omega-3 index

Mitochondrial:

• Organic Acids Test (OAT) — look at mitochondrial markers: suberic, adipic, ethylmalonic acids; citric acid cycle intermediates
• CoQ10 level
• Lactate/pyruvate ratio

Hormonal:

• DUTCH test (dried urine): Full cortisol pattern (diurnal curve), cortisol metabolites, DHEA, melatonin
• Full thyroid panel (TSH, free T4, free T3, reverse T3, TPO and TG antibodies)

Immune/Infectious:

• ANA (autoimmune screen)
• EBV panel: VCA IgG, VCA IgM, EBNA IgG, EA IgG (EA IgG positive = reactivation)
• HHV-6 IgG
• Mycoplasma IgG/IgM

Gut:

• GI-MAP (comprehensive stool with PCR pathogen detection, zonulin for permeability, calprotectin for inflammation)
• SIBO breath test (lactulose — 3-hour with both hydrogen and methane)

Environmental:

• Mycotoxin urine testing (RealTime Labs or Great Plains GPL-MycoTOX)
• Heavy metals (provoked or unprovoked urine, or blood metals panel)

Autonomic:

• Tilt table test or NASA lean test for POTS/orthostatic intolerance
• Heart rate variability (HRV) analysis

Treatment Protocol: Phased and Gentle

These patients are exquisitely sensitive. What helps a healthy person can devastate someone with ME/CFS. Start low, go slow. The principle is stabilize first, repair second, rebuild third.

Phase 1: Foundations (Months 1-2)

Sleep optimization — nothing heals without sleep:

• Magnesium glycinate 400mg before bed
• Melatonin 0.5-3mg (start low)
• If needed (physician-guided): low-dose trazodone 25-50mg, gabapentin 100-300mg, or low-dose amitriptyline 10-25mg for alpha-wave intrusion
• Sleep hygiene: completely dark room, consistent sleep-wake time, no screens 1 hour before bed, cool temperature (65-68F)

Nervous system calming — the sympathetic nervous system is stuck in overdrive:

• Vagal toning: gargling, cold water face immersion, humming, singing, slow exhale breathing (4 counts in, 7 counts out)
• Pacing: the most important behavioral intervention. Activity must stay within the energy envelope. No boom-and-bust cycling. Use a heart rate monitor to avoid exceeding the aerobic threshold.
• Gentle yoga nidra or body scan meditation

Basic nutrient repletion:

• Vitamin D3: 5000 IU/day (with K2 100mcg)
• B12: Methylcobalamin or hydroxocobalamin 5000mcg sublingual
• Magnesium glycinate: 400mg/day
• CoQ10 (ubiquinol form): 200mg/day as starting dose
• Omega-3: 2-3g/day EPA+DHA

Phase 2: Mitochondrial Repair (Months 2-4)

The full mitochondrial support stack:

• CoQ10 (ubiquinol): Increase to 400mg/day — essential electron carrier in Complex III
• D-ribose: 5g 3x/day — the sugar backbone of ATP. Jacob Teitelbaum’s SHINE protocol study showed 61% improvement in energy, sleep, cognitive function, and pain with D-ribose supplementation. Patients often feel this within days.
• Acetyl-L-carnitine (ALCAR): 1g 2x/day — shuttles fatty acids into mitochondria for beta-oxidation
• PQQ (pyrroloquinoline quinone): 20mg/day — stimulates mitochondrial biogenesis (makes new mitochondria)
• NAD+ precursors: NMN 500mg/day or NR 300mg 2x/day — NAD+ is essential for Complex I function and declines with age and illness
• Alpha-lipoic acid: 300-600mg/day — mitochondrial antioxidant, regenerates other antioxidants

Immune modulation:

• LDN (low-dose naltrexone): 1.5-4.5mg at bedtime. Start at 0.5mg, increase by 0.5mg weekly. Jarred Younger’s 2013 crossover trial in fibromyalgia showed 30% reduction in pain scores. Mechanism: transient endorphin blockade upregulates endogenous opioid production and modulates microglial activation. This is one of the most promising interventions for both conditions.
• For EBV reactivation: L-lysine 3g/day (inhibits viral replication), monolaurin 1800mg/day (disrupts lipid-enveloped viruses), high-dose vitamin C 3-5g/day

Phase 3: Gut and Detox (Months 3-6)

SIBO treatment if positive:

• Rifaximin 550mg 3x/day for 14 days (hydrogen-dominant)
• Add neomycin or metronidazole for methane-dominant
• Or herbal alternative: Allicin (stabilized garlic) + berberine + oregano oil for 4-6 weeks (Johns Hopkins study showed herbal protocols equivalent to rifaximin)

Gut healing 5R protocol:

• Remove: pathogens, food triggers (guided by elimination diet or testing)
• Replace: HCl if low (Heidelberg test), digestive enzymes
• Reinoculate: Spore-based probiotics (MegaSporeBiotic), Saccharomyces boulardii, targeted Lactobacillus/Bifidobacterium strains
• Repair: L-glutamine 5g 2x/day, zinc carnosine 75mg 2x/day, colostrum, butyrate
• Rebalance: stress management, sleep, movement

Mold/mycotoxin protocol if testing is positive:

• Environmental remediation first (cannot treat while still exposed)
• Binders: Cholestyramine (Rx) or activated charcoal, bentonite clay, chlorella — rotate
• Glutathione support: liposomal glutathione 500mg, NAC 1200mg/day
• Infrared sauna 20-30 min 3-4x/week (start at 10 min — some patients are sauna-intolerant)

Phase 4: Gradual Reconditioning

Only when energy is measurably stabilizing. Never before. Premature exercise is the most harmful prescription in ME/CFS.

• Workwell Foundation protocol: Establish anaerobic threshold via CPET (cardiopulmonary exercise testing). Stay below that heart rate during all activity.
• Start with 5-minute walks. If no PEM in 48 hours, maintain for 1-2 weeks before increasing by 2 minutes.
• Recumbent exercises first if POTS is present (recumbent bike, swimming)
• Never push into PEM. If a crash occurs, the activity level was too high. Drop back and stabilize.

Special Considerations

Advanced therapies (evidence emerging, access varies):

• IV NAD+: 250-750mg infusion over 2-4 hours. Directly replenishes cellular NAD+. Many patients report significant cognitive and energy improvements. Start low — can cause intense niacin flush and temporary symptom flare.
• IV Myers’ cocktail: Magnesium, calcium, B-vitamins, vitamin C. Weekly for 4-8 weeks. Bypass GI absorption issues common in these patients.
• HBOT (hyperbaric oxygen therapy): 1.3-1.5 ATA, 60-minute sessions, 20-40 sessions. Reduces neuroinflammation, supports mitochondrial function, enhances neuroplasticity.
• FSM (frequency-specific microcurrent): Specific frequencies targeting inflammation, vagal tone, and tissue repair. Carolyn McMakin’s protocols show promising results for fibromyalgia pain.
• Limbic system retraining: DNRS (Dynamic Neural Retraining System) or Gupta Programme. The limbic system and insula can become stuck in a threat-detection loop that perpetuates symptoms. These programs use neuroplasticity to reset the pattern. Not a psychological treatment — a neurological one.

The Clinical Truth

Fibromyalgia and ME/CFS are not mysteries. They are complex, multi-system conditions with identifiable drivers: broken mitochondria, inflamed nervous systems, dysbiotic guts, reactivated viruses, disrupted autonomic function, and toxic exposures. The conventional model fails because it looks for one cause and one drug. Functional medicine succeeds because it maps the entire terrain and addresses each contributor systematically.

These patients have been gaslit by medicine for decades. The first therapeutic act is believing them.