Although citrulline does not appear to be an activator of mTOR, like leucine, (mTOR activation, via S6K, induces muscle protein synthesis), citrulline does appear to restore muscle protein synthesis rates[1][2] and muscular function after food restriction,[3] and this positive effect on muscle protein synthesis is abolished by rapamycin and is thus mediated by the mTORc1 pathway.[4][5]
Citrulline does not activate the p44/42 MAPK pathway or the ERK1/2 pathway in skeletal muscle,[1] whereas leucine itself can activate ERK1/2 and induce 4E-BP1 (downstream of mTOR) to a much larger degree than citrulline.[1]
Citrulline positively influences the mTOR pathway but does not appear to occur through direct activation, as with leucine. At minimum, citrulline normalizes suppressed mTOR signaling.
In human studies, supplementation with 0.18 g/kg of citrulline per day for one week did not significantly modify leucine oxidation rates or whole-body protein synthesis,[6] but elsewhere, at the same dosage, it has been noted to improve nitrogen balance in humans in the fed state.[7] Oral doses of citrulline between 2 and15 grams do not appear to acutely affect urinary nitrogen in the fasted state.[8]
Mixed evidence as to whether citrulline supplementation can help with muscle protein synthesis
References
- ^Le Plénier S, Walrand S, Noirt R, Cynober L, Moinard CEffects of leucine and citrulline versus non-essential amino acids on muscle protein synthesis in fasted rat: a common activation pathway?Amino Acids.(2012-Sep)
- ^Osowska S, Duchemann T, Walrand S, Paillard A, Boirie Y, Cynober L, Moinard CCitrulline modulates muscle protein metabolism in old malnourished rats.Am J Physiol Endocrinol Metab.(2006-Sep)
- ^Faure C, Raynaud-Simon A, Ferry A, Daugé V, Cynober L, Aussel C, Moinard CLeucine and citrulline modulate muscle function in malnourished aged rats.Amino Acids.(2012-Apr)
- ^Direct action of citrulline on muscle protein synthesis: role of the mTORC1 pathway
- ^Cynober L, de Bandt JP, Moinard CLeucine and citrulline: two major regulators of protein turnover.World Rev Nutr Diet.(2013)
- ^Thibault R, Flet L, Vavasseur F, Lemerle M, Ferchaud-Roucher V, Picot D, Darmaun DOral citrulline does not affect whole body protein metabolism in healthy human volunteers: results of a prospective, randomized, double-blind, cross-over studyClin Nutr.(2011 Dec)
- ^Rougé C, Des Robert C, Robins A, Le Bacquer O, Volteau C, De La Cochetière MF, Darmaun DManipulation of citrulline availability in humansAm J Physiol Gastrointest Liver Physiol.(2007 Nov)
- ^C Moinard, I Nicolis, N Neveux, S Darquy, S Bénazeth, L CynoberDose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic studyBr J Nutr.(2008 Apr)