Combination Setria® Glutathione and L-Citrulline Supplementation Proven to Increase Post-Exercise Benefits

Study Participants Showed Increased and Longer-Lasting Level of Nitric Oxide After Only Seven Days

A new randomized, double-blind, placebo-controlled, human clinical trial published in the Journal of the International Society of Sports Nutrition found, for the first time, that one week of daily oral supplementation with 200 mg of Setria® Glutathione and 2 grams of L-citrulline enhanced nitric oxide (NO) levels.1 Setria® Glutathione led to longer lasting levels of NO by preventing its oxidative reaction when ingested in combination with L-citrulline.1

The study, led by Dr. Darryn Willoughby of Baylor University, was designed to determine the effectiveness of Glutathione and L-citrulline on improving exercise performance, based on markers of nitric oxide (NO) synthesis.1 L-citrulline is known to impact NO levels as it’s converted to L-arginine, which synthesizes NO when ingested. However, L-citrulline supplementation alone has shown conflicting results in reference to improving exercise performance. Previous studies have indicated that Glutathione stimulates L-arginine turnover and increases nitric oxide synthase (NOS). These results suggest that it may play a role in preventing oxidative reaction and sustaining the release of NO, however; its effectiveness, particularly in combination with L-citrulline, had not been determined prior to this study.

Results from the study found that after seven days of oral supplementation, levels of nitric oxide and NOx in the L-citrulline and Glutathione group showed a measured increase 30 minutes post exercise when compared to the placebo group.1 Participants of the study included 60 healthy, resistance-trained males aged 18 – 30, with a body mass index between 18.5 – 30 kg/m2, divided into four groups that received either a placebo, Setria® Glutathione (1 gram), L-citrulline (2 grams), or a combination of Setria® Glutathione (200mg) and L-citrulline (2 grams) for one week.1 To measure the impact of supplementation or placebo during the seven day study period, the groups were evaluated after completing resistance exercise sessions, including three sets of 15 repetitions at 70 – 75 percent of the estimated 1-RM involving the elbow flexors.1 Participants were assessed on their maximum muscular strength at the beginning of the study, prior to supplementation and following three sets of fifteen repetitions of the elbow flexion exercise.1

“In this study, we were able to determine that combining Setria® Glutathione with L-citrulline not only increased blood levels of nitrite and NOx, but sustained the increases for a longer period of time, compared to placebo,” said Dr. Willoughby, Baylor University, associate professor, Health, Human Performance, and Recreation, director, Exercise and Biochemical Nutritional Lab. “The results of this first-of-its kind study indicate that Setria® Glutathione and L-citrulline may play a role in muscle protein synthesis and muscle performance when combined with resistance exercise.”

“In addition to its immune health benefits, Setria® Glutathione is known to work in the body to eliminate toxic chemicals, maintain cell proteins and act as an antioxidant,” said Danielle Citrolo, registered pharmacist and manager of technical services for Kyowa Hakko USA. “With its reputation as the ‘master antioxidant,’ due in part to its role in combatting oxidative stress, it’s encouraging to see the benefits of Setria® Glutathione supplementation extended to slowing the release of and sustaining the body’s levels of NO with L-citrulline. These results give consumers a research-backed approach to increasing the effectiveness of resistance training with regular intake of L-citrulline and Setria® Glutathione oral supplements.”

In the same paper, similar results were seen in phase one in-vitro (cell culture) and phase two rodent studies. These results combined with the human clinical trial data shows that the combination of Setria® Glutathione and L-citrulline has the same positive, long lasting benefit of enhancing nitric oxide across a variety of subjects, as well as blood levels of NOx.

About Setria® Glutathione

Setria® Glutathione, manufactured by KYOWA HAKKO BIO CO., LTD. is a clinically studied form of glutathione that, when taken orally, has been shown to replenish the body's reserves, which may be depleted as a result of poor lifestyle choices, stress or natural aging. Called the "master antioxidant," glutathione helps protect cells in the body from the damaging effects of oxidative stress and toxins. Setria® Glutathione is manufactured through a patented fermentation and patent pending for increasing natural killer (NK) cell activity, is pure, vegetarian and allergen-free.

About L-Citrulline

L-Citrulline is an amino acid that plays an important role in nitric oxide metabolism and regulation. L-Citrulline is converted to L-Arginine in the body, leading to sustained increases in both L-Arginine and nitric oxide. An ingredient with application in the areas of heart health and sports nutrition, L-Citrulline is preservative-free, allergen-free, and contains no artificial flavors or colors. It’s non-hygroscopic, highly stable, and mild taste makes it suitable for use in a variety of formulations. This pure, vegetarian ingredient is also self-affirmed GRAS. Manufactured in the U.S. using a proprietary fermentation process, L-Citrulline is an ultra-pure amino acid that carries the Kyowa Quality logo, ensuring the ingredient is backed by our commitment to the highest manufacturing standards. For more information, visit


KYOWA HAKKO USA, INC. is the North American sales office for KYOWA HAKKO BIO CO., LTD., an international health ingredients manufacturer and world leader in the development, manufacturing and marketing of pharmaceuticals, nutraceuticals and food products. Kyowa is the maker of branded ingredients including Cognizin® Citicoline, Pantesin® Pantethine, Setria® Glutathione, as well as Sustamine® L-Alanyl-L-Glutamine. For more information, visit


  1. McKinley S, Andrew T, Morita M, Willoughby D. Combined L-Citrulline and Glutathione Supplementation Increases the Concentration of Markers Indicative of Nitric Oxide Synthesis. Journal of the International Society of Sports Nutrition. 2015 x. [Epub ahead of print] PubMed PMID: xx.

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