Dietary arginine availability and creatine accretion: Is creatine supplementation necessary for the newborn?

De novo arginine synthesis in neonatal piglets and humans occurs in the small intestinal mucosa during first-pass metabolism, predominantly from dietary proline. Arginine is one of the precursor amino acids required for creatine bio-synthesis. Creatine rapidly accrues in growing neonates. Availability of arginine may become limited with intestinal injury or when intravenous feeding is necessary; thus, creatine bio-synthesis may be compromised secondary to reduced arginine synthesis. We investigated for the first time, whether creatine supplementation to IV nutrition (TPN) affects normal creatine accretion and tissue specific fractional protein synthesis in the growing neonatal piglets. Creatine supplementation to TPN down-regulated enzyme involved in the first step of the creatine biosynthetic pathway, and enhanced tissue creatine accretion. In a second study, we used stable isotope kinetics to specifically quantify the partitioning of dietary arginine into guanidinoacetic acid (GAA, the intermediate metabolite in creatine biosynthesis) and into creatine. Piglets were fed intra-gastric diets with an adequate amount of arginine or inadequate arginine provided with creatine or GAA. Briefly, the concentration of arginine in the diet did alter conversion rates to GAA and creatine, suggesting that high dietary arginine, or creatine supplementation, is necessary in the diets of neonates.