Creatine Supplementation of TPN and Sparing of Amino Acids in Neonatal Piglets

Arginine and methionine are indispensable amino acids in the neonates and have a metabolic role in the synthesis of creatine, phosphatidylcholine (PC) as well as protein synthesis. Creatine synthesis consumes significant amounts of dietary arginine and methionine, while PC requires methionine for its synthesis. Total parenteral nutrition (TPN) is typically marginal in the amino acids arginine, and methionine, and devoid in creatine. Moreover, gut atrophy from TPN feeding further limits arginine synthesis in neonates. Our group set out to find if creatine or its precursor guanidinoacetic acid (GAA) can spare methionine for other functions during TPN in neonates. Yucatan miniature-piglets (6-10 d old; n=31) were fed 1 of 5 elemental PN diets: 1) low arginine and low methionine (Base), 2) low arginine and methionine plus GAA (Base+GAA), 3) low arginine and methionine plus creatine (Base+Creatine), 4) high arginine and high methionine (High Arg & Met), or 5) low arginine with high methionine plus GAA (High Met & GAA). After 7 d of feeding, a primed, constant infusion of [3H-methyl]-methionine was intravenously infused for 6 h and label incorporation into transmethylation products creatine, PC and protein were measured. We found that supplementation with creatine, but not GAA, increased protein synthesis suggesting methionine was spared. Furthermore, arginine or GAA is need to adequately synthesize creatine in TPN-fed piglets, but only when sufficient methionine is fed to provide methyl groups. These data suggest that creatine should be further investigated as a supplement for TPN.