Mechanism of Action and Therapeutic Potential of Sulforaphane in Skeletal Muscle Diseases: Molecular Pathways and Precision Medicine.

Sulforaphane (SFN), a bioactive isothiocyanate abundant in cruciferous vegetables, has attracted growing interest as a potential nutraceutical intervention for skeletal muscle disorders. This narrative review synthesizes preclinical and early clinical evidence on the mechanisms and therapeutic applicability of SFN in ICU-acquired weakness, diabetic myopathy, sarcopenia, and exercise-induced muscle damage. SFN modulates skeletal muscle pathophysiology through four interconnected axes: regulation of protein homeostasis via mTOR-associated signaling and suppression of ubiquitin-proteasome-mediated catabolism; upregulation of oxidative stress defenses through Nrf2-driven antioxidant enzyme induction; attenuation of inflammatory networks via NF-κB inhibition and promotion of M2 macrophage polarization; and metabolic reprogramming through AMPK-mediated mitochondrial biogenesis and enhanced insulin sensitivity. Preclinical data suggest preliminary protective effects on respiratory and locomotor muscle; however, clinical translation remains uncertain. Several randomized controlled trials have failed to demonstrate significant effects on Nrf2 target genes or metabolic stress biomarkers, and bioavailability varies markedly across formulations and individuals. Heterogeneous responses across muscle fiber types, an undefined therapeutic window, and interindividual variability in gut microbiota-mediated conversion further complicate clinical application. To address these challenges, we propose a conceptual "Sulforaphane Precision Medicine Framework" integrating molecular biomarkers, gut microbiome profiling, and dynamic delivery systems to guide personalized intervention. While SFN shows promise as an adjunctive therapy, standardized formulations, refined patient stratification, and rigorous phase III trials are essential before routine clinical adoption can be recommended.