Table 1_Depleted before the dose: the mitochondrial vulnerability threshold hypothesis for fluoroquinolone-associated multisystem toxicity.pdf

We propose the Mitochondrial Vulnerability Threshold (MVT) hypothesis: that whether a standard therapeutic FQ dose produces clinically significant toxicity may depend substantially on the patient’s pre-existing mitochondrial reserve capacity rather than on fixed pharmacological properties alone.

Although this toxicity was first recognized through musculoskeletal injury—particularly tendinopathy and tendon rupture—the reported syndrome extends to peripheral nerve, autonomic, central nervous system, and other tissues; we therefore use the term fluoroquinolone-associated multisystem toxicity (FQMT), with musculoskeletal (tendon) injury as its prototypical and best-characterized manifestation. We hypothesize that converging iatrogenic, nutritional, infectious, lifestyle, and environmental stressors—statin-associated CoQ10 depletion, proton-pump-inhibitor magnesium and B12 malabsorption, metformin-associated B12 depletion with genetically stratifiable risk, physical inactivity, metabolic syndrome, post-COVID-19 mitochondrial injury, antibiotic-induced dysbiosis, and environmental toxin burden—may contribute to higher apparent vulnerability in contemporary prescribing populations.