Insulin resistance is a likely driver of weight gain. Insulin resistance is characterised by a deterioration of the strength of the signal elicited by insulin on the cell, and as a result the insulin signal becomes less efficient at stimulating the transport of glucose from the blood into the cell. This causes fasting blood glucose levels to rise, a condition known as hyperglycaemia. In response to the higher than normal fasting blood glucose levels, the body's homeostatic mechanisms, controlled by the hypothalamus, increase the release of insulin to counter the effects of too much glucose in the blood. The pancreas therefore releases more insulin and this raises fasting insulin levels, a condition known as hyperinsulinemia. It these changes to the insulin system that need to be reversed in order to cause successful long term fat loss, as body fat levels cannot be brought under control with raised levels of insulin. This is because insulin stimulates the fat accumulation pathways inhibits the fat breakdown pathways.
The role of oxidative stress in insulin resistance has be suspected for some time based on the observation that antioxidant nutrients improve insulin sensitivity. Oxidative stress is a condition that describes a state in cells and tissues whereby free radical activity is chronically increased above normal physiological levels. Free radicals are chemicals with unpaired electrons, and these unpaired electrons cause the molecules to be very reactive. Free radicals therefore react with components in the body, and this causes these components themselves to become free radicals, setting up a chain reaction that damages tissues and cells and leads to disease. Free radicals are generated naturally by metabolic activity, but they are kept in check at manageable levels by a network of antioxidants, some of which are vitamins and some of which are naturally produced in the body. Possibly the most important exogenous antioxidants are vitamin C and vitamin E and the most important endogenous antioxidant is glutathione.
Overproduction of free radicals leads to oxidative stress, and this may cause interference with the insulin signal cascade, the metabolic steps that describe the transfer of the insulin signal from the membrane to the interior of the cell. Alternatively the oxidative stress may disrupt the membrane structure and interfere with the binding of insulin to its receptor. Oxidative stress can result from either an increase in free radical production or from a depletion of the antioxidants that normally prevent oxidative stress. Sources of free radicals include pollution, food components, inflammatory, stress and intense physical activity. All of these factors contribute to the production of oxidative stress. In such a circumstance, an increase in antioxidants will be required to prevent the metabolic damage from the increased free radical generation. Antioxidant vitamins and plant antioxidants have therefore been shown to be beneficial at improving insulin sensitivity through their inhibitory effects on cellular oxidative stress.