The Antioxidant Paradox in Diabetes Mellitus

Abstract

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."

Expression of mitochondrial superoxide dismutase in polymorphonuclear leukocytes from patients with type 1 diabetes with and without microvascular complications

“…Nevertheless, our results show that impairment of functional antioxidant defense could be one of the reasons for the development and progress of chronic complications in type 1 diabetes, which is in line with studies showing a relation between the enhanced level of oxidative stress and development of chronic complications in patients with diabetes. 30,36 In a study assessing the relationship of retinal neuron apoptosis with MnSOD activity at an early phase of diabetic retinopathy, a decreased activity of MnSOD was observed with extended course of the disease in the retinas obtained from diabetic rats. It suggests that the longer the course of diabetes, the worse the oxidative damage of the retina and the lower the antioxidative capacity of MnSOD.…”

Impact of Extracellular Calcium Along With Ascorbic Acid on Cellular Reactivation and Insulin Secretion in Diabetic Min6 Cells

“…Another studies concluded that excessive consumption of vitamin supplements is related to various adverse effects and posseses no health benefits 15,16 . In an investigation, antioxidant activity of chitooligosaccharides (COS) showed that COSs can prohibit the apoptosis of pancreatic islet cells in streptozotocin-induced diabetes in rats 17 .…”

Shifting the Paradigm in Radiation Safety

“…Application of this idea in humans has however been problematic. Antioxidant therapies have failed to reduce diabetes (Sheikh-Ali et al, 2011), cardiovascular disease (Kris-Etherton et al, 2004) and stroke (Schurks et al, 2010) in controlled clinical trials, though oxidative damage has been identified as playing a key role in these. Bioavailability of the antioxidants in the relevant organs may be a factor, as the administered antioxidants are distributed throughout the body.…”