HIGH-DOSES OF DIETARY ARGININE DURING REPLETION IMPAIR WEIGHT-GAIN AND INCREASE INFECTIOUS MORTALITY IN PROTEIN-MALNOURISHED MICE

There is considerable evidence for the beneficial effects of dietary a rginine, 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 investig ated completely, These issues were explored therefore, in a murine mod el of malnutrition and infection, Severe protein malnutrition was indu ced by feeding mice for 6 weeks on an isoenergetic diet containing onl y 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 mix tures of glycine and arginine in which the arginine content ranged fro m 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/k g, but not in the group fed on the diet with 50 g arginine/kg, compare d with the diet with 0 g arginine/kg. Mortality rates after infection with Salmonella typhimurium were not decreased by the addition of 10 o r 20 g arginine/kg to the diet, and were in fact worsened by supplemen tation with 50 g arginine/kg, The results of the present study showed that not only are the beneficial effects of arginine supplementation a fter infection lost when high doses are administered, but also that th ese high doses become toxic, Mice fed on higher doses showed significa nt impairment of weight gain and an increase in mortality rates.