Effects of vitamin E and glutathione on glucose metabolism - Role of magnesium

Vitamin E is an antioxidant that has been demonstrated to improve insulin a ction. Glutathione, another natural antioxidant, may also be important in b lood pressure and glucose homeostasis, consistent with the involvement of f ree radicals in both essential hypertension and diabetes mellitus. Our grou p has recently suggested that the effects of reduced glutathione on glucose metabolism may be mediated, at least in part, by intracellular magnesium l evels (Mg-[i]). Recent evidence suggests that vitamin E enhances glutathion e levels and may play a protective role in magnesium deficiency-induced car diac lesions. To directly investigate the effects of vitamin E supplementat ion on insulin sensitivity in hypertension, in relation to the effects on c irculating levels of reduced (GSH) and oxidized (GSSG) glutathione and on M g-[i], we performed a 4-week, double-blind, randomized study of vitamin E a dministration (600 mg/d) versus placebo in 24 hypertensive patients and mea sured whole-body glucose disposal (WBGD) by euglycemic glucose clamp, GSH/G SSG ratios, and Mg-[i] before and after intervention. Thr relationships amo ng WBGD, GSH/GSSG, and Mg-[i] in both groups were evaluated. In hypertensiv e subjects;, vitamin E administration significantly increased WBGD (25.56+/ -0.61 to 31.75+/-0.53 mu mol/kg of fat-free mass per minute; P<0.01), GSH/G SSG ratio (1.10+/-0.07 to 1.65+/-0.11; P<0.01), and Mg-[i] (1.71+/-0.042 to 1.99+/-0.049 mmol/L; P<0.01), In basal conditions, WBGD was significantly related to both GSH/GSSG ratios (r =0.58, P=0.047) and Mg-[i] (r=0.78, P=0. 003), These data show a clinical link between vitamin E administration, cel lular magnesium, GSH/GSSG ratio, and tissue glucose metabolism. Further stu dies are needed to explore the cellular mechanism(s) of this association.