What Actually Causes Fibromyalgia? The Mitochondrial, Mast Cell, and Small Fiber Neuropathy Mechanisms Standard Treatment Misses — The four mechanistic drivers of fibromyalgia

Driver 1: Mitochondrial dysfunction in muscle and nerve tissue The fibromyalgia muscle is bioenergetically compromised. This is one of the most consistent findings in the research literature, supported by work from Cordero and colleagues, Sánchez-Domínguez and colleagues, and others. Patients with fibromyalgia have reduced coenzyme Q10 levels in mononuclear cells, increased oxidative stress markers, reduced ATP production capacity in muscle biopsies, and increased lactate-to-pyruvate ratios suggesting impaired mitochondrial function. The mechanism connects to the broader Host Capacity Model framework. The CD38-NAD+-SIRT3 cascade described in the dedicated article operates in fibromyalgia as it does in other chronic inflammatory states. CD38 is induced by inflammation. NAD+ is depleted. SIRT3 activity falls. Mitochondrial proteome regulation fails. ATP output falls in cells throughout the body, but particularly in tissues with high bioenergetic demand: muscle, nerve, brain. The clinical consequence in muscle is sustained low-grade compromise of contractile function and slowed recovery from exertion. This is the mechanism behind post-exertional malaise in fibromyalgia, where exercise that should be tolerated produces disproportionate worsening. The muscle has the structures, has the substrates, but cannot generate the ATP at the rate the work demands. The patient experiences this