Fundamentals of Reductive Stress

Abstract

Reductive stress is a cellular insult stemming from the overgeneration of reducing equivalents and heightened antioxidant potential within the body. Maintaining redox homeostasis necessitates a delicate balance between oxidant and antioxidant production. Key indicators of this balance include ratios such as Reduced glutathione (GSH) to Oxidized glutathione (GSSG), Nicotinamide adenine dinucleotide phosphate (NADP) to Reduced nicotinamide adenine dinucleotide phosphate (NADPH), and Nicotinamide adenine dinucleotide (NAD⁺) to Reduced nicotinamide adenine dinucleotide (NADH). Glutathione, an endogenous antioxidant, can also be supplemented through natural food sources such as okra, spinach, broccoli, and sweet potatoes among others. These reducing equivalents primarily stem from cellular metabolic processes such as the Krebs cycle and glycolysis. When present in excess, they can modulate signaling pathways, disrupt transcriptional activity, and reduce cellular metabolism, paving the way for various diseases. Conditions associated with reductive stress include cancer, protein aggregation cardiomyopathy, muscular dystrophy, and Alzheimers disease, among others. Moreover, prolonged use of antioxidant supplements like Vitamins and/or flavonoids may have pro-oxidant effects, disturbing cellular redox balance, inducing reductive stress, and potentially shortening life expectancy. Therefore, the consumption of antioxidant supplements should be moderate and appropriate, as excessive or haphazard intake can be detrimental to overall health.