Resistance training, but not leucine, increased basal muscle protein synthesis and reversed frailty in older women consuming optimized protein intake

Frailty, often linked to sarcopenia, involves reduced muscle strength and mass. While sarcopenia has multiple causes, impaired muscle protein synthesis may contribute. Leucine and resistance training (RT) are anabolic stimuli, but the long-term effects of leucine combined with RT in pre/frail older women remain unclear. This double-blind, placebo-controlled study aimed to assess their impact on muscle anabolism and characteristics in women consuming adequate protein. Pre/frail elderly women (n = 19, 77.5 ± 1.3 y, BMI: 25.1 ± 0.9 kg/m²), underwent 12 weeks of RT with protein-optimized diet (1.2 g⋅kg BW^-1⋅d^-1) and were randomized to 7.5 g/d of leucine (Leu) or placebo 5.1 g/d alanine (Ala). The primary outcome was myofibrillar fractional synthesis rate (MyoFSR) in the postabsorptive and postprandial states. Secondary outcomes are changes in protein content and expression, 1-repetition maximum, body composition (DXA), and myofiber profiles were investigated. Overall MyoFSR increased by 47%, with a concomitant increase in type 1 and 2a myofiber cross sectional area (CSA) (16% and 28%, respectively), and total lean mass (2%). Total AKT, S6, and AMPKα levels were unchanged. However, AKT and S6 phosphorylation increased postprandially before RT, with no change following RT. The number of Frailty Criteria was reduced by 64%, with improvements in physical function and strength. Leucine had no added anabolic benefit. RT with optimal protein intake significantly improved the Frailty Phenotype and increased basal MyoFSR along with type 1 and 2a myofiber CSA and total lean mass, with no added benefit of leucine supplementation.