Citrulline does not enhance blood flow, microvascular circulation, or myofibrillar protein synthesis in elderly men at rest or following exercise

Am J Physiol Endocrinol Metab. 2014 Jul 1;307(1):E71-83. doi: 10.1152/ajpendo.00096.2014. Epub 2014 May 13.

Abstract

Aging is associated with anabolic resistance, a reduced sensitivity of myofibrillar protein synthesis (MPS) to postprandial hyperaminoacidemia, particularly with low protein doses. Impairments in postprandial skeletal muscle blood flow and/or microvascular perfusion with hyperaminoacidemia and hyperinsulinemia may contribute to anabolic resistance. We examined whether providing citrulline, a precursor for arginine and nitric oxide synthesis, would increase arterial blood flow, skeletal muscle microvascular perfusion, MPS, and signaling through mTORC1. Twenty-one elderly males (65-80 yr) completed acute unilateral resistance exercise prior to being assigned to ingest a high dose (45 g) of whey protein (WHEY) or a low dose (15 g) of whey protein with 10 g of citrulline (WHEY + CIT) or with 10 g of nonessential amino acids (WHEY + NEAA). A primed, continuous infusion of L-[ring-(13)C6] phenylalanine with serial muscle biopsies was used to measure MPS and protein phosphorylation, whereas ultrasound was used to measure microvascular circulation under basal and postprandial conditions in both a rested (FED) and exercised (EX-FED) leg. Argininemia was greater in WHEY + CIT vs. WHEY and WHEY + NEAA from 30 to 300 min postexercise (P < 0.001), but there were no treatment differences in blood flow or microvascular perfusion (all P > 0.05). Phosphorylation of p70S6K-Thr(389) was greater in WHEY vs. WHEY + NEAA (P = 0.02). Postprandial MPS was greater in WHEY vs. WHEY + CIT and WHEY + NEAA under both FED (WHEY: ~128%; WHEY + CIT: ~56%; WHEY + NEAA: ~38%) and EX-FED (WHEY: ~251%; WHEY + CIT: ~124%; WHEY + NEAA: ~108%) conditions (P = 0.003). Citrulline coingestion with a low quantity of protein was ineffective in augmenting the anabolic properties of protein compared with nonessential amino acids.

Keywords: citrulline; elderly; myofibrillar protein synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anabolic Agents / pharmacology
  • Blood Flow Velocity / drug effects
  • Blood Flow Velocity / physiology
  • Citrulline / pharmacology*
  • Exercise / physiology*
  • Humans
  • Male
  • Microcirculation / drug effects
  • Microcirculation / physiology*
  • Muscle Proteins / biosynthesis*
  • Muscle, Skeletal / blood supply
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / physiology*
  • Myofibrils / drug effects
  • Myofibrils / metabolism*
  • Postprandial Period / drug effects
  • Postprandial Period / physiology
  • Protein Biosynthesis / drug effects
  • Rest / physiology*

Substances

  • Anabolic Agents
  • Muscle Proteins
  • Citrulline