Effects of leucine-enriched essential amino acid and whey protein bolus dosing upon skeletal muscle protein synthesis at rest and after exercise in older women

Daniel J Wilkinson, Syed S I Bukhari, Bethan E Phillips, Marie C Limb, Jessica Cegielski, Matthew S Brook, Debbie Rankin, William K Mitchell, Hisamine Kobayashi, John P Williams, Jonathan Lund, Paul L Greenhaff, Kenneth Smith, Philip J Atherton, Daniel J Wilkinson, Syed S I Bukhari, Bethan E Phillips, Marie C Limb, Jessica Cegielski, Matthew S Brook, Debbie Rankin, William K Mitchell, Hisamine Kobayashi, John P Williams, Jonathan Lund, Paul L Greenhaff, Kenneth Smith, Philip J Atherton

Abstract

Background & aims: Impaired anabolic responses to nutrition and exercise contribute to loss of skeletal muscle mass with ageing (sarcopenia). Here, we tested responses of muscle protein synthesis (MPS), in the under represented group of older women, to leucine-enriched essential amino acids (EAA) in comparison to a large bolus of whey protein (WP).

Methods: Twenty-four older women (65 ± 1 y) received (N = 8/group) 1.5 g leucine-enriched EAA supplements (LEAA_1.5), 6 g LEAA (LEAA_6) in comparison to 40 g WP. A primed constant I.V infusion of 13C6-phenylalanine was used to determine MPS at baseline and in response to feeding (FED) and feeding-plus-exercise (FED-EX; 6 × 8 unilateral leg extensions; 75%1-RM). We quantified plasma insulin/AA concentrations, leg femoral blood flow (LBF)/muscle microvascular blood flow (MBF), and anabolic signalling via immunoblotting.

Results: Plasma insulineamia and EAAemia were greater and more prolonged with WP than LEAA, although LEAA_6 peaked at similar levels to WP. Neither LEAA or WP modified LBF or MBF. FED increased MPS similarly in the LEAA_1.5, LEAA_6 and WP (P < 0.05) groups over 0-2 h, with MPS significantly higher than basal in the LEAA_6 and WP groups only over 0-4 h. However, FED-EX increased MPS similarly across all the groups from 0 to 4 h (P < 0.05). Only p-p70S6K1 increased with WP at 2 h in FED (P < 0.05), and at 2/4 h in FED-EX (P < 0.05).

Conclusions: In conclusion, LEAA_1.5, despite only providing 0.6 g of leucine, robustly (perhaps maximally) stimulated MPS, with negligible trophic advantage of greater doses of LEAA or even to 40 g WP. Highlighting that composition of EAA, in particular the presence of leucine rather than amount is most crucial for anabolism.

Keywords: Ageing; Exercise; Human metabolism; Leucine; Low dose amino acid supplementation; Muscle protein synthesis.

Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1
Fig. 1
Study protocol: effects of leucine-enriched amino acids (LEAA) and whey protein (WP) at rest and after resistance exercise (RE) in older women. 1-RM, 1-repetition maximum; CEUS, contrast-enhanced ultrasound.
Fig. 2
Fig. 2
Time course effects of 1.5 g, 6 g of LEAA or 40 g of WP on plasma amino acids (AA) and insulin concentrations: nonessential AA (NEAA; A), essential AA (EAA; B), branched-chain AA (BCAA; C), leucine (D), insulin (E), and insulin AUC (F). a: significantly different vs. basal (P < 0.05). b: significantly different between groups (P < 0.05).
Fig. 3
Fig. 3
The effect of 1.5 g, 6 g of LEAA or 40 g of WP in skeletal muscle of older women on leg blood flow (LBF: A, C & E) and microvascular blood flow (MBF: B, D & F) responses in the rest and exercise legs.
Fig. 4
Fig. 4
The effects of 1.5 g, 6 g of LEAA or 40 g WP on skeletal muscle myofibrillar protein synthesis in A) FED and B) FED + EX. a: significantly different vs. basal (P < 0.05).
Fig. 5
Fig. 5
The effects of 1.5 g, 6 g of LEAA or 40 g WP on muscle signalling responses to FED and FED-EX. Responses were log transformed and normalized to the basal-fasted biopsy (represented by dotted line). a: significantly different vs. basal (P < 0.05).
Fig. 6
Fig. 6
Summary dose–response relationship between MPS and AA feeding (±RE) in older women (including data from Bukhari et al. [27]). Over 0–2 h, feeding increased MPS with little enhancement with RE (A). Over the entire 4 h (B) postprandial measurement period, MPS was elevated although diminished with feeding, whilst RE sustained elevated MPS. All groups displayed similar MPS in response to feeding (±resistance exercise) suggesting only a small dose of leucine and/or EAA are required in combination with exercise to maintain elevations in MPS post nutrition, at least over the first 4 h. Left Y axis shows FSR for each feed (open circles FED, open squares FED + RE) whilst dotted lines show average FSR of all groups for baseline, FED and FED + RE. Right Y axis shows total AA load and content of leucine, EAA and NEAA.

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