Dietary organosulfur compounds and the H₂S-polysulfide redox axis: Current evidence and limitations

Dietary organosulfur compounds (OSCs) are a structurally diverse class of sulfur-containing food-derived molecules increasingly recognized for their potential interactions with endogenous sulfur and redox metabolism. Emerging evidence, largely from chemical, cellular, and preclinical studies, suggests that OSCs derived from Allium and Brassicaceae vegetables, as well as sulfur-containing amino acids, may influence hydrogen sulfide (H₂S) and reactive polysulfide biology, key components of reactive sulfur species (RSS)-mediated signaling. This review synthesizes current findings on the chemical diversity, dietary sources, processing sensitivity, and bioavailability of nutritional OSCs, with emphasis on how gastrointestinal metabolism, microbial transformation, and thiol-dependent reactions shape their biological fate. We examine proposed biochemical routes linking OSC intake to endogenous H₂S and polysulfide generation, including non-enzymatic sulfur transfer reactions and enzymatic pathways involving cystathionine β-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfurtransferase. Particular attention is given to protein persulfidation, mitochondrial redox regulation, and redox-sensitive transcriptional responses such as Nrf2 signaling, while acknowledging ongoing methodological and conceptual challenges in reactive sulfur species detection and interpretation. The potential implications of OSC-mediated modulation of sulfur signaling for oxidative stress responses, metabolic regulation, vascular function, neurobiology, and immune homeostasis are discussed, alongside current limitations in human evidence and key priorities for future research in nutrition-redox biology.