Leucine and Citrulline: Two Major Regulators of Protein Turnover

Abstract

Both leucine and citrulline stimulate muscle protein synthesis, in part through a common mechanism of action mediated by the mTOR signaling pathway. Both leucine- and citrulline-enriched diets improve nutritional status in various experimental models of injury. However, in the context of intensive care unit (ICU) patients, there is conflicting data on leucine and no data at all on citrulline. Therefore, beyond a strong rationale, large clinical studies are required before any reliable recommendations can be issued on the use of leucine- or citrulline-enriched diets in ICU patients.

Innate Immunity in the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome and Its Implications for Therapy

“…In a prospective randomized trial, the use of BCAA-fortified parenteral nutrition in surgical patients improved several nutritional and immunological parameters such as nitrogen balance, prealbumin levels, and lymphocyte counts ( 249 ). Moreover, recent studies demonstrated that leucine supplementation improves muscle protein synthesis in the elderly and in cancer patients by stimulating the mammalian target of rapamycin (mTOR) pathway ( 250 , 251 ). Thus, leucine or BCAA supplementation may be beneficial in PICS.…”

An increased need for dietary cysteine in support of glutathione synthesis may underlie the increased risk for mortality associated with low protein intake in the elderly

“…This anabolic effect is clearest in the context of underfeeding and reflects an increased rate of synthesis of muscle myofibrillar proteins and glycolytic enzymes (Osowska et al 2006;Faure et al 2013). Data are inconsistent as to whether muscle-specific activation of mTORC1 activity plays a role in this effect; it is also unknown whether this effect is mediated by arginine or NO (Moinard et al 2015;Cynober et al 2013) In healthy human volunteers fed a low-protein diet, postabsorptive administration of citrulline, in comparison to equal intakes of a mixture of non-essential amino acids, increases the fractional synthesis rate of mixed muscle protein (Jourdan et al 2015). Whether citrulline supplementation can aid control of sarcopenia in humans remains to be determined, and, as citrulline is not a constituent of proteins, this phenomenon cannot explain the favorable impact of higher protein intake on mortality in the elderly.…”

Nutrition Support for Persistent Inflammation, Immunosuppression, and Catabolism Syndrome

“…Unfortunately, this PRT and others failed to demonstrate improved mortality or other major clinical outcome parameters, and because BCAA PNs were expensive, interest in their use faded. However, with more recent understanding of the intracellular regulation of protein synthesis, there has been renewed interest in leucine because it has been shown to be a potent stimulator of protein synthesis via the mammalian target of rapamycin (mTOR) complex pathway 33 . Consistent with the idea that leucine supplementation should stimulate protein synthesis, it has recently been shown to be effective in elderly subjects 34 .…”