Background Glutathione is an endogenous antioxidant found in oxidized (GSSG) and reduced (GSH) forms. Glutathione depletion is indicative of oxidative stress and occurs in various pathological conditions and following extreme exercise activity. Raising blood glutathione concentration has potential to attenuate and prevent chronic disease and also to improve recovery from exercise. There are a number of challenges to achieving this through traditional dietary supplements, and thus there is a need to develop optimized delivery methods to improve blood glutathione status. This study evaluated the effect of a novel glutathione formulation on blood glutathione parameters in healthy individuals. Methods 15 (8 male) healthy individuals (25±5y old, 78.0±14.6kg) participated in a single-blinded randomized placebo-controlled crossover study, with a minimum one-week washout period between treatments. Participants were overnight fasted and administered 1mL of a non-liposomal nano-size glutathione solution (NLNG) containing 200mg of glutathione or 1mL of placebo lacking glutathione. The solution was held in the mouth for 90 seconds before the remainder was swallowed. Blood was collected at baseline, 5, 10, 30, 60 and 120 minutes post-treatment. Protein-bound plasma and erythrocyte lysate concentrations of GSH and GSSG were measured at all time points using previously validated procedures. Linear mixed effects models were used to compare differences between baseline and post-treatment glutathione concentrations between NLNG and placebo for each parameter. Results There was a significant main effect for treatment type, such that increases in GSH concentration in erythrocyte lysate were greater following NLNG than placebo (p = 0.001). Similar significant main effects for treatment were also found for total (protein bound + erythrocyte lysate) GSH (p = 0.015) and GSSG (p = 0.037) concentration, as well as total blood glutathione pool (GSH+GSSG, p = 0.006). Discussion NLNG increased multiple blood glutathione parameters compared to placebo. Future research should examine whether NLNG can attenuate oxidative stress.

No abstract

Intro: Glutathione is endogenous within human plasma, erythrocyte lysate and is also bound to the protein within plasma. Glutathione mediates redox chemistry and prevents oxidative damage within and around cellular components via reduction of reactive species (e.g. reactive oxygen, nitrogen, or sulfur species). Polyphenols and antioxidants have been shown to improve NO bioavailability which may reduce long term incidence of endothelial dysfunction. Less is known about whether changes in antioxidant capacity augments the risk of developing hypertension. Hypothesis: We hypothesized that acute glutathione supplementation would decrease arterial stiffness and reduce both brachial (bBP) and central blood pressure (cBP) in healthy male and female volunteers. Methods: Six males and six females (25 ± 3 and 22 ± 1 years, respectively) participated in a randomized, double blind, placebo controlled, crossover protocol. On two visits separated by 1 week, following a 12-hour fast, participants consumed either a placebo or glutathione (negligible and 200 mg, respectively) supplement via 90 second sublingual absorption which was then swallowed. Concentrations of oxidized (GSSG) and reduced glutathione (GSH) were spectrophotometrically measured in plasma (protein-bound) and erythrocyte lysate using a kinetic, enzymatic assay. Arterial stiffness was measured via pulse wave velocity (PWV) using applanation tonometry, and cBP was determined non-invasively using pulse wave analysis. All data were recorded before supplementation (baseline) and at 10, 30, 60 and 120 minutes post-consumption. Results: Linear mixed effect models revealed a significant (p<0.01) increase in total glutathione (GSH+GSSG) in the supplement group compared to placebo across all post-supplementation time points with the greatest increase occurring at 120 minutes (mean 99.0; 95%CI: 7.9,190.1). At 120 minutes post-consumption, no difference was present between glutathione and placebo groups for PWV (5.86 ± 1.19 and 6.08 ± 1.25 m/s, respectively; p=0.43), resting heart rate (52.95 ± 3.55 and 55.83 ± 6.36, respectively; p=0.16), systolic bBP (123.05 ± 12.75 and 123.13 ± 14.52 mmHg; p=0.22), diastolic bBP (71.81 ± 7.87 and 74.21 ± 6.53; p=0.48), systolic cBP (108.05 ± 10.45 and 108.68 ± 11.14 mmHg, respectively; p=0.11) and diastolic cBP (72.03 ± 7.82 and 74.94 ± 6.42 mmHg, respectively; p=0.46). Conclusion: Young healthy males and females experienced an increase in circulating humoral antioxidants in response to glutathione supplementation. However, supplementation had minimal effects on resting hemodynamics. Future research should examine glutathione supplementation’s effect in participants with decreased antioxidant capacity and increased oxidative stress including patients with known disease such as hypertension or peripheral artery disease.