Nutritional redox reprogramming in cardiometabolic diseases: alpha-lipoic acid, urolithin A, and ergothioneine as modulators of the ferroptosis-mitophagy axis and mitochondrial metabolic remodeling.

Cardiometabolic disorders, encompassing atherosclerosis, myocardial ischemia, and myocardial infarction, persist as predominant contributors to morbidity and mortality on a global scale. An expanding corpus of research delineates redox imbalance, ferroptosis, compromised mitophagy, and mitochondrial metabolic dysfunction as pivotal determinants of cardiovascular pathophysiology. The paradigm of nutritional redox reprogramming has emerged as a potentially effective approach to modulate these interrelated pathways through the utilization of bioactive dietary compounds. This review emphasizes three novel nutraceutical modulators such as alpha-lipoic acid (ALA), urolithin A (UA), ergothioneine (EGT), and their respective functions in the regulation of ferroptosis, mitochondrial quality control, and cardiac bioenergetics. ALA exhibits multifaceted cardioprotective properties by diminishing oxidative stress, inhibiting lipid peroxidation, enhancing endothelial function, and restoring mitochondrial metabolism in the contexts of atherosclerosis and ischemic injury. UA, a metabolite derived from gut microbiota, primarily promotes mitophagy and mitochondrial biogenesis, thereby augmenting metabolic flexibility and enhancing resistance to ischemic stress. EGT, a thiol antioxidant derived from dietary sources and transported through the OCTN1 transporter, exhibits nascent potential in mitigating oxidative stress and maintaining mitochondrial homeostasis, although the mechanistic insights remain sparse. Collectively, these compounds signify promising candidates for the targeted modulation of redox status in cardiometabolic pathologies. Elucidating their common and unique molecular mechanisms may enhance the formulation of precision nutritional interventions aimed at preventing and mitigating the progression of cardiovascular diseases.