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PLoS One. 2019 Apr 30;14(4):e0215815. doi: 10.1371/journal.pone.0215815. eCollection 2019.

The absorptive effects of orobuccal non-liposomal nano-sized glutathione on blood glutathione parameters in healthy individuals: A pilot study.

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Department of Chemistry, High Point University, High Point, North Carolina, United States of America.
Department of Biology, High Point University, High Point, North Carolina, United States of America.
Department of Exercise Science, High Point University, High Point, North Carolina, United States of America.
Department of Physical Therapy, High Point University, High Point, North Carolina, United States of America.



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.


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.


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).


NLNG increased multiple blood glutathione parameters compared to placebo. Future research should examine whether NLNG can attenuate oxidative stress.

Conflict of interest statement

J.M. Smoliga, A.J. Wommack, and C.R. Carriker all received funding from Pelame, LLC to perform this study. This funding does not alter our adherence to PLOS ONE policies on sharing data and materials. The authors have no other conflicts of interest to disclose.

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