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

Abstract

Churchward-Venne TA, Cotie LM, MacDonald MJ, Mitchell CJ, Prior T, Baker SK, Phillips SM. 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 307: E71-E83, 2014. First published May 13, 2014; doi:10.1152/ajpendo.00096.2014.-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. Twentyone 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 ϩ CIT) or with 10 g of nonessential amino acids (WHEY ϩ 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 ϩ CIT vs. WHEY and WHEY ϩ NEAA from 30 to 300 min postexercise (P Ͻ 0.001), but there were no treatment differences in blood flow or microvascular perfusion (all P Ͼ 0.05). Phosphorylation of p70S6K-Thr 389 was greater in WHEY vs. WHEY ϩ NEAA (P ϭ 0.02). Postprandial MPS was greater in WHEY vs. WHEY ϩ CIT and WHEY ϩ NEAA under both FED (WHEY: ϳ128%; WHEY ϩ CIT: ϳ56%; WHEY ϩ NEAA: ϳ38%) and EX-FED (WHEY: ϳ251%; WHEY ϩ CIT: ϳ124%; WHEY ϩ NEAA: ϳ108%) conditions (P ϭ 0.003). Citrulline coingestion with a low quantity of protein was ineffective in augmenting the anabolic properties of protein compared with nonessential amino acids. citrulline; myofibrillar protein synthesis; elderly DECLINES IN MUSCLE MASS WITH AGING are due to rates of myofibrillar protein synthesis (MPS) being less than the net rate of muscle protein breakdown (37). Aminoacidemia and physical exercise are potent anabolic stimuli that elicit the synthesis of new muscle proteins; however, aging is associated with a reduced MPS response following both hyperaminoacidemia (54) and resistance exercise (28), a phenomenon termed "anabolic resistance" (for review, see Ref. 10). Although the mechanisms underlying anabolic resistance are not fully understood, age-related impairments in blood flow may be involved (31,48,50).Aminoacidemia and insulinemia increase MPS (54), arterial blood flow (54), and muscle microvascular perfusion (52) in the young; however, these responses are blunted in the elderly (48, 54). Age-related impairments in vascular function may be...

Sodium nitrate co-ingestion with protein does not augment postprandial muscle protein synthesis rates in older, type 2 diabetes patients

“…The plasma phenylalanine and tyrosine 13 C and 2 H enrichments were determined using selective ion monitoring at m/z 336, 337, and 341 for unlabeled and labeled (1-13 C and ring-2 H5) phenylalanine, respectively, and m/z 466, 467, 468, and 470 for unlabeled and labeled (1-13 C, ring-3,5-2 H2, and ring-2 H4) tyrosine, respectively. For L-[1-…”

“…Standard regression curves were applied from a series of known standard enrichment values against the measured values to assess the linearity of the mass spectrometer and to account for any isotope fractionation that may have occurred during the analysis. Phenylalanine and tyrosine enrichments were corrected for the presence of the 13 …”

“…In support of this notion, pharmacological strategies utilizing NO donors (i.e., sodium nitroprusside or methacholine) have been shown to effectively increase blood flow and microvascular perfusion and augment the muscle protein synthetic response to amino acid administration (17,44). However, practical dietary interventions providing precursors for endothelial NOS-mediated NO synthesis, such as citrulline (13) and/or arginine (41) co-ingested with protein, have not been effective in increasing the postprandial rise in muscle protein synthesis rates. In the present study, dietary NO 3 Ϫ was provided as a practical nutritional strategy to increase NO availability through a separate pathway that does not require endothelial NOS.…”

“…These data are the first to demonstrate that acute NO 3 Ϫ supplementation does not represent an effective nutritional strategy to enhance postprandial protein handling in vivo in humans. As acute dietary interventions to restore vascular function do not appear to increase postprandial muscle protein synthesis rates (13,37,41), longer-term intervention studies involving chronic supplementation of NO substrates may be necessary to enhance vascular function and augment the anabolic response to protein ingestion (30,48,59 …”

Exceptional body composition changes attributed to collagen peptide supplementation and resistance training in older sarcopenic men

“…In addition, 1·7 g of arginine would not have affected blood flow (6,7) . In their study, Zdzieblik et al (1) proposed that the provision of collagen peptides could enhance creatine synthesis.…”