Abstract
Overfeeding, an increased intake of saturated fatty acids, and sugary foods are key dietary changes that have occurred in recent decades in addition to the emergence of the obesity epidemic. In addition to an increase in energy storage as fat, these dietary changes are accompanied by an increase in mitochondrial macronutrient oxidation, leading to an excessive free radical production and, hence, oxidative stress. The latter has long been considered a central mechanism linking nutrient overload, insulin resistance, the metabolic syndrome, and diabetes. However, food, through fruit and vegetable consumption, also can be a great source of antioxidants that protect the body against oxidative damage and insulin resistance and thus help cope with the metabolic backlash of the energy-dense Westernized diet. Experimental data are in favor of the beneficial role conveyed by antioxidants in glucose metabolism, but clinical data in humans remain controversial. This review therefore aimed to sort out any underlying discrepancies and provide an overall clear view of the role of antioxidants in the ongoing fight against abnormal glucose metabolism. Ó 2012 Elsevier Inc. All rights reserved. Introduction The obesogenic dietary changes of recent decades, the key aspects of which are increased fatty and sugary food intake in parallel to a decrease in fruit and vegetable consumption, have been proposed to play essential roles in the growing epidemic of chronic diseases afflicting developed and developing countries. These dietary changes combined with a sedentary lifestyle force the body to manage excess energy that must be metabolized. One of the expected actions is increased energy storage as fat, and other macronutrients undergo oxidation in the mitochon-dria, favoring an increased production of free radicals and oxidative stress, which has long been proposed as a unifying mechanism linking excessive nutrient intake, insulin resistance (IR), the metabolic syndrome, and diabetes. Beyond the quantitative aspects of food ingestion, quality is just as important in the development of oxidative stress; for example, different types of fatty acids have variable effects on the production of free radicals. Moreover, nutrition is a potent tool in regulating glucose metabolism, and it has been reported that food rich in antioxidants such as food in the Mediterranean diet might be protective [1,2]. We recently summarized the data linking oxidative stress to diet and to IR and the preventive role of antioxidants against these metabolic alterations [3]. In the present review, we present an update of recent discoveries in this rapidly evolving field, try to sort out any underlying controversies, and supply a global recapitulative view of the role of antioxidants in the ongoing fight against an abnormal glucose metabolism. Oxidative stress and insulin resistance Reactive oxygen species (ROS), or free radicals, are atoms or molecules characterized by an unpaired electron that allows the atoms or molecules to react with various molecules present at their site of formation (Table 1). They are produced within the cell by different mechanisms; the main source of superoxide anions is mitochondrial by the electron transport chain. Other precursors of endogenous superoxides include reduced nicotinamide adenine dinucleotide phosphate oxidase, xanthine oxidase, nitrite oxide synthase, the endoplasmic reticulum, an unfolded