Dietary Reactive Oxygen Species and Oxidative Stress: Pathogenic Mechanisms Linking Food and Feed Exposure to Disease in Humans and Companion Animals.

Oxidative stress, arising from an imbalance between reactive oxygen species (ROS) and antioxidant defenses, is a shared pathogenic mechanism underlying numerous chronic diseases in humans and, increasingly, in companion animals that consume structurally similar processed diets. This narrative review synthesizes current evidence on dietary and feed-derived sources of ROS, spanning intrinsic pro-oxidant systems in unprocessed foods (lipid hydroperoxides, heme iron, and polyphenol autoxidation) and heat processing-generated toxicants (advanced glycation end products, acrylamide, heterocyclic aromatic amines, and lipid oxidation products), and examines the molecular mechanisms that link these compounds to organ-specific and systemic disease, including receptor-mediated signaling, cytochrome P450 activation, mitochondrial dysfunction, and antioxidant depletion. Comparative analysis across humans, dogs, and cats reveals parallel disease burdens in metabolic syndrome, chronic kidney disease, inflammatory bowel disease, and cancer, alongside instructive species-specific divergences in atherosclerosis and neurodegenerative disease driven by differences in lipoprotein metabolism and toxicokinetics. The review further reassesses canonical dietary antioxidants, including polyphenols and omega-3 polyunsaturated fatty acids, as context-dependent redox modulators capable of both cytoprotective and pro-oxidant activity. Collectively, these findings position dietary and feed processing as an under-recognized, modifiable contributor to chronic disease across species. In this context, companion animals emerge as valuable naturalistic translational models for studying diet-induced oxidative pathology. Priority research needs include standardized dose-response and biomarker frameworks, characterization of gut microbiome-mediated effects, and assessment of combinatorial pro-oxidant exposures.