title: Combined L-citrulline and glutathione supplementation increases the concentration of markers indicative of nitric oxide synthesis.
abstract: BACKGROUND
  Nitric oxide (NO) is endogenously synthesized from L-arginine and L-citrulline. Due to its effects on nitric oxide synthase (NOS), reduced glutathione (GSH) may protect against the oxidative reduction of NO. The present study determined the effectiveness of L-citrulline and/or GSH on markers indicative of NO synthesis in in vivo conditions with rodents and humans and also in an in vitro condition.
  
  
  METHODS
  In phase one, human umbilical vein endothelial cells (HUVECs) were treated with either 0.3 mM L-citrulline, 1 mM GSH (Setria®) or a combination of each at 0.3 mM. In phase two, Sprague-Dawley rats (8 weeks old) were randomly assigned to 3 groups and received either purified water, L-citrulline (500 mg/kg/day), or a combination of L-citrulline (500 mg/kg/day) and GSH (50 mg/kg/day) by oral gavage for 3 days. Blood samples were collected and plasma NOx (nitrite + nitrate) assessed. In phase three, resistance-trained males were randomly assigned to orally ingest either cellulose placebo (2.52 g/day), L-citrulline (2 g/day), GSH (1 g/day), or L-citrulline (2 g/day) + GSH (200 mg/day) for 7 days, and then perform a resistance exercise session involving 3 sets of 10-RM involving the elbow flexors. Venous blood was obtained and used to assess plasma cGMP, nitrite, and NOx.
  
  
  RESULTS
  In phase one, nitrite levels in cells treated with L-citrulline and GSH were significantly greater than control (p < 0.05). In phase two, plasma NOx with L-citrulline + GSH was significantly greater than control and L-citrulline (p < 0.05). In phase three, plasma cGMP was increased, but not significantly (p > 0.05). However, nitrite and NOx for L-citrulline + GSH were significantly greater at 30 min post-exercise when compared to placebo (p < 0.05).
  
  
  CONCLUSIONS
  Combining L-citrulline with GSH augments increases in nitrite and NOx levels during in vitro and in vivo conditions.
authors.affiliation: Department of Health, Human Performance, and Recreation, Baylor University, Exercise and Biochemical Nutritional Lab, 76798 Waco, TX USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: McKinley-Barnard
authors.affiliation: Department of Health, Human Performance, and Recreation, Baylor University, Exercise and Biochemical Nutritional Lab, 76798 Waco, TX USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Andre
authors.affiliation: Function Research Group, Healthcare Products Development Center, KYOWA HAKKO BIO CO., LTD., 2, Miyukigaoka, 305-0841 Tsukuba, Ibaraki Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Morita
authors.affiliation: Department of Health, Human Performance, and Recreation, Baylor University, Exercise and Biochemical Nutritional Lab, 76798 Waco, TX USA.
authors.forename: Darryn S
authors.initials: DS
authors.lastname: Willoughby
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001120:Arginine; D015415:Biomarkers / Q000097:blood*; D015992:Body Mass Index; D002956:Citrulline / Q000008:administration & dosage* / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D019587:Dietary Supplements; D004311:Double-Blind Method; D005978:Glutathione / Q000008:administration & dosage* / Q000097:blood; D064368:Healthy Volunteers; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000097:blood; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D051381:Rats; D055070:Resistance Training; D055815:Young Adult
chemical_list: D015415:Biomarkers; D009566:Nitrates; D009573:Nitrites; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D005978:Glutathione; D006152:Cyclic GMP
keywords: Glutathione; L-arginine; L-citrulline; Nitric oxide; Resistance exercise