Citrulline possesses a highly specific metabolism that bypasses splanchnic extraction because it is not used by the intestine or taken up by the liver. The administration of
citrulline may be used to deliver available
nitrogen for protein homeostasis in peripheral tissues and as an
arginine precursor synthesized de novo in the kidneys and endothelial and immune cells. Fresh research has shown that
citrulline is efficiently transported across the intestinal
luminal membrane by a set of transporters belonging to the B⁰,⁺, L, and b⁰,⁺ systems. Several pharmacokinetic studies have confirmed that
citrulline is efficiently absorbed when administered orally. Oral
citrulline could be used to deliver
arginine to the systemic circulation or as a
protein anabolic agent in specific clinical situations, because recent data have suggested that
citrulline, although not a component of
proteins, stimulates
protein synthesis in skeletal muscle through the
mammalian target of rapamycin signaling pathway. Hence,
citrulline could play a pivotal role in maintaining protein homeostasis and is a promising pharmaconutrient in
nutritional support strategies for malnourished patients, especially in aging and
sarcopenia.