Abstract

Chronic diseases such as cardiovascular disease, diabetes mellitus, chronic kidney disease, neurodegenerative 
disorders, and chronic inflammatory conditions share a common pathological thread: systemic redox imbalance. 
This imbalance reflects a disruption between the generation of reactive oxygen and nitrogen species (ROS/RNS) 
and the body’s antioxidant defenses, resulting in sustained oxidative stress that drives cellular dysfunction, 
inflammation, and tissue injury across multiple organs. While ROS act as essential mediators of physiological 
signaling, excessive ROS accumulation overwhelms endogenous antioxidant systems, contributing to 
mitochondrial dysfunction, endothelial damage, immune dysregulation, genomic instability, and metabolic 
disturbances. Recent research has increasingly focused on whether augmenting antioxidant capacity, either 
through dietary, pharmacological, or novel molecular approaches, can mitigate oxidative damage and confer 
multiorgan protection. Clinical and preclinical studies suggest that enhancing antioxidant defense may bolster 
tissue resilience and reduce complications in chronic disease. However, clinical trials have yielded mixed results, 
and unresolved questions remain regarding optimal antioxidant types, dosing strategies, bioavailability, timing of 
intervention, and organ-specific targeting. This review synthesizes current understanding of systemic redox 
imbalance in chronic disease, critically examines the role of antioxidants in modulating redox homeostasis, and 
explores future directions for integrating antioxidant strategies into multiorgan protection paradigms.