title: High doses of dietary arginine during repletion impair weight gain and increase infectious mortality in protein-malnourished mice.
abstract: There is considerable evidence for the beneficial effects of dietary arginine, a conditionally-essential amino acid that enhances anabolism and T-cell function. However, the safety and efficacy of higher doses of arginine supplementation following infection have not been investigated completely. These issues were explored therefore, in a murine model of malnutrition and infection. Severe protein malnutrition was induced by feeding mice for 6 weeks on an isoenergetic diet containing only 10 g protein/kg. Mice were then allowed to consume diets with normal amounts of protein (200 g/kg) with 50 g/kg provided as amino acid mixtures of glycine and arginine in which the arginine content ranged from 0 to 50 g/kg. During the repletion period a significant weight gain was noted in the groups fed on diets with either 10 or 20 g arginine/kg, but not in the group fed on the diet with 50 g arginine/kg, compared with the diet with 0 g arginine/kg. Mortality rates after infection with Salmonella typhimurium were not decreased by the addition of 10 or 20 g arginine/kg to the diet, and were in fact worsened by supplementation with 50 g arginine/kg. The results of the present study showed that not only are the beneficial effects of arginine supplementation after infection lost when high doses are administered, but also that these high doses become toxic. Mice fed on higher doses showed significant impairment of weight gain and an increase in mortality rates.
authors.affiliation: Department of Surgery, University of Miami School of Medicine, Florida 33101, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Peck
authors.forename: G F
authors.initials: GF
authors.lastname: Babcock
authors.forename: J W
authors.initials: JW
authors.lastname: Alexander
authors.forename: T
authors.initials: T
authors.lastname: Billiar
authors.forename: J
authors.initials: J
authors.lastname: Ochoa
mesh_terms: D000818:Animals; D001120:Arginine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D011502:Protein-Energy Malnutrition / Q000188:drug therapy* / Q000401:mortality; D012481:Salmonella Infections, Animal / Q000401:mortality*; D012486:Salmonella typhimurium; D015430:Weight Gain / Q000187:drug effects
chemical_list: D001120:Arginine