Dietary Antioxidants in Human Physiology and Pathogenesis: Molecular Pathways, Therapeutic Applications, and Clinical Translational Challenges in Redox-Based Interventions for Chronic Disease Management

The "antioxidant" buzzword has infested public health literature, more often than not with huff and hyperbole. This review surpasses broad-brush claims to present a critical appraisal of the fine chemical mechanisms underlying the activity of key dietary antioxidants: vitamins C and E, the glutathione system, and polyphenols. We begin by outlining their targets and the reactive oxygen species (ROS) they assail, emphasizing their unique redox chemistry, including hydrogen atom transfer (HAT) and single electron transfer (SET) activity. The review then evaluates the multifaceted roles these compounds play in combating oxidative stress within the pathophysiological context of atherosclerosis and liver disease, two diseases wherein oxidative damage is a major driving force. We synthesize 2020-2024 new in vitro, animal, and human evidence, emphasizing conditions under which antioxidant interventions work and where they have failed. Close examination reveals that the biological effectiveness of antioxidants is not solely a function of concentration but is increasingly modulated by their bioavailability, the cell redox state, and by their complex interaction with cellular signaling. The conclusion stresses that a comprehensive, mechanism-centered comprehension is needed to tailor effective nutritional and therapeutic interventions, moving beyond the reductionist notion of antioxidants as an overall panacea and towards their targeted application in precision nutrition and medicine.