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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption, Physiological*
  • Adult
  • Glutathione / administration & dosage
  • Glutathione / blood*
  • Humans
  • Liposomes
  • Male
  • Mouth / metabolism*
  • Nanoparticles / chemistry*
  • Particle Size*
  • Pilot Projects


  • Liposomes
  • Glutathione

Grants and funding

Funding for this study was provided by Pelame, LLC. JMS, CRC, and AJW received the funding. The sponsor provided NLNG and placebo solutions and recommended the administration protocol. Pelame, LLC provided minor revisions to the study design. Pelame, LLC did not have any role in the decision to publish this research, but did provide minor revisions to the manuscript draft prior to submission. Pelame, LLC did not have any role in the data collection and analysis.