The impact of leucine‐enriched essential amino acid and whey protein dosing upon skeletal muscle protein synthesis in older women at rest and after exercise
Authors: Phillips Bethan E , Wilkinson Daniel J , Bukhari Syed S , Limb Marie C , Williams John P , Kobayashi Hisamine , Smith Kenneth , Atherton Philip J 
Published: November 2023

Loss of skeletal muscle mass with ageing (sarcopenia) is a problem for which anabolic neutraceutical interventions could hold therapeutic promise. Older women are understudied with recommendations based on studies in older men inappropriate given that women exhibit distinct protein metabolism (i.e. reduced responses to feeding).We previously showed that increases in muscle protein synthesis (MPS) were identical in older women fed 3 g of 40% leucine‐enriched essential amino acids (LEAA) vs. 20 g whey protein (WP). Here we tested whether lower or higher doses of LEAA and WP modified this response.We recruited 24 older women (64±0.7 y) who received (N=8/group) 1.5 g LEAA, 6 g LEAA or 40 g WP while undergoing a primed constant I.V infusion of 13C6 phenylalanine. Using a unilateral resistance exercise model (6×8 leg extensions; 75% 1‐RM) we determined the effects of feeding (FED) and feeding‐plus‐exercise (FED‐EX) over a 2 and 4 h period upon MPS, microvascular blood flow (MBF) and plasma insulin. Muscle biopsies were taken from the vastus lateralis at baseline, 2.5 h later (BASAL) and then at 2 and 4 h in both the rest and exercised legs. MPS was determined by mass spectrometry, MBF by contrast‐enhanced ultrasound (CEUS) and plasma insulin by ELISA. Data were analyzed by 2‐way repeated measures ANOVA with Bonferroni post‐hoc testing; a P‐value of <0.05 was considered significant.We found that FED increased MPS similarly in response to 1.5 g LEAA (0.061±0.003 vs. 0.086±0.005 %/h, P<0.05), 6 g LEAA (0.066±0.006 vs. 0.090±0.007 %/h, P<0.05) and 40 g WP (0.056±0.004 vs. 0.084±0.011 %/h, P<0.01) over 0–2 h, whereas at 2–4 h this was not significantly different to baseline under each condition. Only 40g WP maintained FED responses at 0–4 h.At 0–2 h FED‐EX increased MPS only in response to 40 g WP (0.056±0.004 vs. 0.089±0.017 %/h, P<0.05), however over 0–4 h increases in MPS were similar across the groups (1.5 g, 0.061±0.003 vs. 0.091±0.007 %/h, P<0.01; 6 g, 0.066±0.006 vs. 0.097±0.007 %/h, P<0.01 and 40 g WP, 0.56±0.004 vs. 0.104±0.011 %/h, P<0.001).No significant increases in MBF were evident in response to FED, whilst only WP elicited increases with FED‐EX (0.13±0.04 vs. 0.31±0.09 AU, P<0.05). Plasma insulin increased in response to 1.5 g LEAA (peak: 11.50±1.83 uU/mL), 6 g LEAA (peak: 12.76±1.61 uU/mL) and 40 g WP (peak: 21.03±3.62 uU/mL, all P<0.01). However, both the peak and area under the curve (AUC: 74.62±11.8 vs. 45.6±10.4 (1.5 g LEAA), 33.79±3.0 (6 g LEAA), P<0.05) was markedly greater in response to WP.We conclude there does not exist a bona fide dose‐response of MPS to FED in older women as 1.5 g of LEAA (equating to 0.6 g leucine and 0.9 g other EAA) maximally stimulated MPS in relation to 40 g WP. Similar was true following FED‐EX. The lack of increase in MBF is consistent with reports in older men while the heightened insulin response to WP vs. LEAA would not be expected to modify MPS given the permissive role of insulin in MPS. We conclude LEAA strategies have anabolic potential in older women; nonetheless longer‐term studies are needed to determine how “one‐off” MPS responses reflect myo‐anabolic and functional outcomes.Support or Funding InformationThis work was funded by Ajinomoto Company Incorporation