The antioxidant paradox in diabetes mellitus.
There is ample empiric evidence to indicate that oxidative stress contributes to the pathogenesis of coronary artery disease and has a key role in the onset and progression of diabetes and its complications. Diabetes leads to depletion of the cellular antioxidant defense system and is associated with an increase in the production of free radicals. Oxidative stress can be the result of multiple pathways. Some of these are related to substrate-driven overproduction of mitochondrial reactive oxygen species, advanced glycation end product formation, glucose autoxidation, and depletion of micronutrients and cellular elements with antioxidative properties. There are numerous observational studies in the literature showing a beneficial outcome of the consumption of antioxidant vitamins. However, the interventional trials portray a different picture. The divide between the robust experimental evidence of the pathogenetic role of increased oxidative load in diabetes and the overwhelming failure of antioxidants to show any health benefits in clinical trials may well be characterized as the "antioxidant paradox."