Noninvasive quantification of human brain antioxidant concentrations after an intravenous bolus of vitamin C

Abstract

Until now, the lack of a means to detect a deficiency or to measure the pharmacologic effect in the human brain in situ has been a hindrance to the development of antioxidant-based prevention and treatment of dementia. In this study, a recently developed (1) H MRS approach was applied to quantify key human brain antioxidant concentrations throughout the course of an aggressive antioxidant-based intervention. The concentrations of the two most abundant central nervous system chemical antioxidants, vitamin C and glutathione, were quantified noninvasively in the human occipital cortex prior to and throughout 24 h after bolus intravenous delivery of 3 g of vitamin C. Although the kinetics of the sodium-dependent vitamin C transporter and physiologic blood vitamin C concentrations predict theoretically that brain vitamin C concentration will not increase above its homeostatically maintained level, this theory has never been tested experimentally in the living human brain. Therefore, human brain vitamin C and glutathione concentrations were quantified noninvasively using MEGA-PRESS double-edited (1) H MRS and LCModel. Healthy subjects (age, 19-63 years) with typical dietary consumption, who did not take vitamin supplements, fasted overnight and then reported for the measurement of baseline antioxidant concentrations. They then began controlled feeding which they adhered to until after vitamin C and glutathione concentrations had been measured at 2, 6, 10 and 24 h after receiving intravenous vitamin C. Two of the twelve studies were sham controls in which no vitamin C was administered. The main finding was that human brain vitamin C and glutathione concentrations remained constant throughout the protocol, even though blood serum vitamin C concentrations spanned from the low end of the normal range to very high.