Vitamin C is a key compound in the body's antioxidant network, a chain of synergistic, inextricability linked, well-studied antioxidants that includes glutathione (GSH) and vitamin E. When vitamin E uses its antioxidant function in neutralizing free radicals, it also loses this antioxidant function. Vitamin C can change this status; it can regenerate vitamin E back to its native form, and is thought to spare glutathione in the body as well. Importantly, when ascorbate donates an electron and becomes itself oxidized, or consumed, the ascorbate radical is relatively harmless. In a double-blind, placebo-controlled study in which blood GSH was measured in healthy subjects at several stages, 500 mg of vitamin C taken daily for 2 weeks significantly raised erythrocyte (red blood cell) glutathione levels. The researchers concluded that vitamin C supplementation at that level can benefit the overall antioxidant capacity of the blood. In another study of similar design, 1000 mg of vitamin C taken daily for 4 weeks bolstered vitamin E and glutathione content in erythrocyte cell membranes, compared with placebo. The highest concentrations of vitamin C in the body are found in the central nervous system (in neurons of the brain & spinal cord) and the adrenal glands. Although the presence of ascorbate in neurons is in part explained by its neuromodulatory enzyme activity, its high concentration suggests that vitamin C is so greatly retained by neurons in order to address the higher rates of oxidative metabolism experienced by the brain. This has led to the conclusion that under normal conditions, vitamin C helps safeguard the integrity of neurons (and therefore the brain), largely through neutralization of the free radicals of reactive oxygen species (ROS). Low levels of blood vitamin C and the resulting accumulation of ROS are thought to be detrimental--especially to aging populations.