Micronutrition as a Therapeutic Strategy for Mitochondrial Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue...

Fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are chronic multisystem disorders characterized by persistent fatigue, pain, cognitive dysfunction, sleep disturbances, and reduced quality of life. Increasing evidence implicates mitochondrial dysfunction, oxidative and nitrosative stress, immune dysregulation, and altered redox and nicotinamide adenine dinucleotide (NAD⁺) metabolism as interconnected mechanisms contributing to fatigue, although the strength of evidence varies across these pathways. Micronutrients are essential components of mitochondrial bioenergetics, antioxidant defense, and immune-metabolic regulation. This narrative review critically examines the mechanistic and clinical evidence supporting mitochondrial-oriented micronutritional interventions in fibromyalgia and ME/CFS, including NAD⁺ precursors, B-complex vitamins, magnesium, coenzyme Q10, alpha-lipoic acid, GlyNAC, L-carnitine, pyrroloquinoline quinone, taurine, and creatine. Mechanistic plausibility is distinguished from clinical efficacy, as disease-specific randomized controlled evidence remains limited for several interventions. We further discuss biomarkers, metabolic phenotyping, and precision nutrition within a systems-based micronutrition framework. Finally, we present the rationale for a future randomized, double-blind, placebo-controlled trial in fibromyalgia patients with clinically significant fatigue, which is planned for 2027, subject to ethics approval and prospective registration, as a strategy for future clinical validation.