Parenteral nutrition supplemented with arginine and citrulline to improve systemic creatine availability
Brett Farewell, Applied Physiology, Nutrition, and Metabolism, Vol. 46, No. 4 (Suppl. 1): S11
Creatine is a key nutrient during infancy, as the creatine phosphate
energy system is relied upon by the brain to rapidly restore energy
pools and promote neurological development. In neonates, the vast
majority of accrued creatine is endogenously synthesized from arginine, a conditionally essential amino acid dependent on gut metabolism. However, newborns with intestinal dysfunction may not
tolerate oral feeding and must be fed total parenteral nutrition
(TPN). Since TPN bypasses the gut, the infants are prone to gut
atrophy which diminishes arginine synthesis, placing a strain on
arginine and creatine availability. Unfortunately, supplemental arginine is rapidly catabolized by the liver and not available for the
first step in creatine synthesis—arginine to guanidinoacetate in the
kidney. However, supplemental citrulline, an arginine precursor,
bypasses liver extraction and may lead to increased arginine availability to the kidney. The study's objective was to investigate supplemental citrulline's ability to increase creatine availability in
TPN-fed neonates. We hypothesize that citrulline supplementation
will facilitate creatine synthesis and availability to a greater extent
than arginine supplementation during TPN. Yucatan miniature piglets (7-10 d old) were fed control TPN or TPN supplemented with arginine or citrulline. After 7 d on TPN, creatine concentration was
measured by HPLC in portal, renal, and jugular veins, and the carotid
artery to assess organ creatine balance across the small intestine,
kidney and brain. Citrulline TPN reduced creatine levels in the carotid artery compared to other treatments (p<0.0007). Further, supplemental arginine resulted in higher creatine levels in the portal
vein compared to the control treatment (p=0.0135), suggesting the
gut can extract arterial arginine to make creatine. A net positive
creatine balance across the gut and kidney was observed in the
control and arginine treatment. Conversely, the citrulline treatment resulted in a net negative balance in the gut, suggesting citrulline is not an effective precursor for creatine synthesis by the
gut. Creatine and guanidinoacetate status will also be assessed in
the liver, kidney and brain to further understand creatine metabolism. Overall, it appears that citrulline is not an effective precursor for gut creatine synthesis when supplemented to TPN.
