Eight weeks of resistance training in conjunction with glutathione and L-Citrulline supplementation increases lean mass and has no adverse effects on blood clinical safety markers in resistance-trained males

J Int Soc Sports Nutr. 2018 Jun 27;15(1):30. doi: 10.1186/s12970-018-0235-x.


Background: Supplementation of combined glutathione (GSH) with L-citrulline in response to a single bout of resistance exercise has been shown to increase plasma nitric oxide metabolites, nitrite and nitrate and cyclic guanosine monophosphate (cGMP), which may play a role in muscle protein synthesis. As a result, in response to resistance training (RT) these responses may establish a role for GSH + L-citrulline to increase muscle mass. This study attempted to determine the effects of an 8-week RT program in conjunction with GSH (Setria®) + L-citrulline, L-citrulline-malate, or placebo supplementation on lean mass and its association with muscle strength. The secondary purpose was to assess the safety of such supplementation protocol by assessing clinical chemistry markers.

Methods: In a randomized, double-blind, placebo-controlled design, 75 resistance-trained males were randomly assigned to ingest GSH + L-citrulline (GSH + CIT), L-citrulline-malate, or cellulose placebo daily while also participating in 8 weeks of RT. The full dose of each supplement was delivered in capsules that were identical in weight, size, shape, and color. Participants completed testing sessions for body composition and muscle strength before and after 4 and 8 weeks of RT and supplementation. Venous blood samples were obtained before and after 8 weeks.

Results: Leg press was increased with RT but was not significantly different between groups (p > 0.05); however, bench press strength was not increased with RT (p > 0.05). There were no significant changes in total body mass, fat mass, or total body water during 8 weeks of RT and supplementation. Lean mass increased in both GSH + CIT when compared to PLC; however, the increase was significant only after 4 weeks. Lean mass and strength were positively correlated (p < 0.05) in GSH + CIT, but not CIT-malate or PLC. Neither RT nor supplementation had any significant effects on blood clinical chemistry variables (p > 0.05).

Conclusion: Compared to PLC, supplementation of GSH + CIT during resistance training increased lean mass after 4 weeks of RT and was positively associated with muscle strength. However, after 8 weeks of RT there were no significant differences in any of the measured variables.

Keywords: Body composition; Glutathione; L-citrulline; Muscle strength; Resistance training.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Biomarkers / blood
  • Body Composition
  • Citrulline / analogs & derivatives
  • Citrulline / pharmacology*
  • Diet
  • Dietary Supplements*
  • Double-Blind Method
  • Glutathione / pharmacology*
  • Humans
  • Malates
  • Male
  • Muscle Strength / drug effects*
  • Resistance Training*
  • Sports Nutritional Physiological Phenomena
  • Young Adult


  • Biomarkers
  • Malates
  • Citrulline
  • Glutathione
  • citrulline malate