Arginine and Citrulline in Parenteral Nutrition

Parenteral nutrition is a means by which nutrients are delivered directly to the blood via intravenous infusion and is necessary when infants cannot tolerate oral feedings. Although lifesaving, prolonged parenteral nutrition reduces blood flow to the gut, gut atrophy and reduced protein synthesis. The atrophied gut reduces the intestinal synthesis of arginine, a key amino acid required for the regulation of blood flow via nitric oxide (NO) production, protein synthesis and creatine synthesis. Supplemental arginine can increase arginine availability, thus enhancing nutrient delivery and blood flow to the gut, thereby preventing gut atrophy and increasing protein synthesis and growth. However, supplemental arginine is rapidly broken down by the liver and not available to the rest of the body. Therefore, we propose to use supplemental citrulline, the precursor to arginine, as an alternative means of increasing arginine availability. Unlike arginine, citrulline bypasses breakdown by the liver, thereby enhancing arginine availability to a greater extent than arginine supplementation. The objective of the study is to improve arginine availability via supplemental citrulline, a novel ingredient for parenteral nutrition solutions. We hypothesize that citrulline supplementation will enhance arginine availability and increase blood flow to the gut and increase protein and creatine synthesis more effectively than arginine supplementation alone. Yucatan piglets received one of three nutritional interventions: control TPN, arginine supplemented TPN, or citrulline supplemented TPN for six days. Creatine concentration was assessed in the portal, renal, and jugular veins, along with the carotid artery, to assess the cross-organ creatine balance of the gut, kidneys and brain. Arterial blood flow to the gut reduced over the course of the study but did not differ between treatment groups, thus indicating that supplemental arginine or citrulline did not increase arginine availability for NO synthesis. Daily growth rate and gut parameters did not differ, indicating that supplemental arginine and citrulline did not influence piglet growth or gut morphology. Interestingly, arginine supplementation led to greater duodenal villus height, but intestinal protein synthesis did not differ, suggesting an alternate mechanism for the longer villi. Citrulline supplementation resulted in greater intestinal protein synthesis but not villus height. Lastly, the control and supplemental arginine groups elicited a net positive creatine balance across the gut and kidneys; however, the supplemental citrulline yielded a net negative balance in the gut and a near net-zero balance across the kidneys. Overall, these data suggest that citrulline and arginine supplementation to PN solutions have differential effects, and more research is needed before recommending supplementation.