RESUMO
Background: Frailty is a clinical condition associated with loss of muscle mass and strength (sarcopenia). Mitochondria are centrally implicated in frailty and sarcopenia. Leucine (Leu) can alter mitochondrial content in myocytes, while resistance training (RT) is the strongest stimulus to counteract sarcopenia and may enhance mitochondrial biogenesis. Objective: We determined the effects of Leu supplementation and RT on mitochondrial content and function in pre/frail elderly women in a randomized double-blinded placebo-controlled study. Methods: Nineteen pre/frail elderly women (77.5 ± 1.3 y, BMI: 25.1 ± 0.9 kg/m2), based on the Frailty Phenotype, underwent 3-months of RT 3×/week with protein-optimized diet and were randomized to 7.5 g/d of Leu supplementation or placebo alanine (Ala). Pre/post-intervention mitochondrial respiration, reactive oxygen species (ROS) production, calcium retention capacity (CRC), time to permeability transition pore (mPTP) opening, mitochondrial voltage-dependent anion channel (VDAC) protein content, leg press 1-repetition maximum (1RM), and 6-min walk test (6MWT) were measured. Results: No time, supplementation, or interaction effects were observed for respiration, ROS, time to mPTP opening, and CRC. VDAC levels significantly increased in the Leu group post-intervention (p = 0.012). Both groups significantly increased leg press 1RM and 6MWT, with no effect of supplementation. Discussion: Leu supplementation with 3 months of RT increased mitochondrial content. Future studies should investigate if there is an increase in mitochondrial turnover or a shift in quality control (mitophagy) in leucine supplemented pre/frail elderly women who undergo 12 weeks of RT. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT01922167.
RESUMO
BACKGROUND: Frailty is a clinical condition associated with loss of muscle mass and strength (sarcopenia). Although sarcopenia has multifactorial causes, it might be partly attributed to a blunted response to anabolic stimuli. Leucine acutely increases muscle protein synthesis, and resistance training (RT) is the strongest stimuli to counteract sarcopenia and was recently shown to improve insulin sensitivity (IS) in frail older women. Discrepancies exist regarding whether chronic supplementation of leucine in conjunction with RT can improve muscle mass and IS. OBJECTIVE: The aim of this double-blinded placebo-controlled study was to determine the effects of leucine supplementation and RT on IS in prefrail and frail older women. METHODS: Using the Fried criteria, 19 nondiabetic prefrail (1-2 criteria) and frail (≥3 criteria) older women (77.5 ± 1.3 y; body mass index (kg/m2): 25.1 ± 0.9) underwent a 3-mo intervention of RT 3 times/wk with protein-optimized diet of 1.2 g·kg-1·d-1 and 7.5 g·d-1 of l-leucine supplementation compared with placebo l-alanine. Pre-/postintervention primary outcomes were fasting plasma glucose, serum insulin, and 4-h responses to a standard meal of complete liquid formula. Secondary outcomes of resting energy expenditure using indirect calorimetry and body composition using dual-energy X-ray absorptiometry were obtained. Paired t tests analyzed pooled data, and 2-factor repeated-measures ANOVA determined supplementation, training, and interaction effects. RESULTS: No significant time, group, or interaction effects were observed for postprandial areas under the curve of serum insulin or plasma glucose or for resting energy expenditure in l-leucine compared with l-alanine. Total lean body mass increased and percentage body fat decreased significantly for both groups postintervention (0.76 ± 0.13 and -0.92 ± 0.33 kg, respectively; time effect: P < 0.01). CONCLUSIONS: IS was not affected by RT and leucine supplementation in nondiabetic prefrail and frail older women. Therefore, leucine supplementation does not appear to influence IS under these conditions. This trial was registered at clinicaltrials.gov as NCT01922167.