Supplement-based nutritional strategies to tackle frailty: A multifactorial, double-blind, randomized placebo-controlled trial.

BACKGROUND: Sarcopenia plays a central role in the development of frailty syndrome. Nutrition and exercise are cornerstone strategies to mitigate the transition to frailty; however, there is a paucity of evidence for which dietary and exercise strategies are effective. OBJECTIVE: This large, multifactorial trial investigated the efficacy of different dietary strategies to enhance the adaptations to resistance training in pre-frail and frail elderly. METHODS: This was a single-site 16-week, double-blind, randomized, placebo-controlled trial conducted at the Clinical Hospital, School of Medicine - University of São Paulo, Sao Paulo, Brazil. Four integrated, sub-investigations were conducted to compare: 1) leucine vs. placebo; 2) whey vs. soy vs. placebo; 3) creatine vs. whey vs. creatine plus whey vs. placebo; 4) women vs. men in response to whey. Sub-investigations 1 to 3 were conducted in women, only. Two-hundred participants (154 women/46 men, mean age 72 ± 6 years) underwent a twice-a-week, resistance training program. The main outcomes were muscle function (assessed by dynamic and isometric strength and functional tests) and lean mass (assessed by DXA). Muscle cross-sectional area, health-related quality of life, bone and fat mass, and biochemical markers were also assessed. RESULTS: We observed that leucine supplementation was ineffective to improve muscle mass and function. Supplementation with whey and soy failed to enhance resistance-training effects. Similarly, supplementation with neither whey nor creatine potentiated the adaptations to resistance training. Finally, no sex-based differences were found in response to whey supplementation. Resistance exercise per se increased muscle mass and function in all sub-investigations. There were no adverse effects. CONCLUSION: Neither protein (whey and soy), leucine, nor creatine supplementation enhanced resistance training-induced adaptations in pre-frail and frail elderly, regardless of sex. These findings do not support the notion that some widely used supplement-based interventions can add to the already potent effects of resistance exercise to counteract frailty-related muscle wasting and dynapenia. CLINICAL TRIAL REGISTRY: NCT01890382; https://clinicaltrials.gov/ct2/show/NCT01890382. DATA SHARING: Data described in the manuscript will be made available upon request pending application.

Number of high-protein containing meals correlates with muscle mass in pre-frail and frail elderly.

BACKGROUND: Aging is accompanied by the inability to optimally respond to anabolic stimulus of nutrition, with consequent loss of muscle mass and functionality. It has been speculated that not only total protein intake, but also the per meal protein dose may have important implications to protein balance and, hence, muscle mass in middle-aged and older adults, but evidence is lacking in a more vulnerable population such as the frail elderly. The aim was to investigate possible associations between total protein intake and its per meal dose with multiple measures of muscle mass, strength, and functionality in a cohort of pre-frail and frail elderly individuals. METHODS: One-hundred-and-fifty-seven pre-frail and frail elderly individuals were assessed for total and per meal protein intake (food diaries), total and appendicular lean mass (DXA), vastus lateralis cross-sectional area [(CSA) B-mode ultrasound], and muscle function [leg-press and bench press 1-RM, timed-stands test, timed-up-and-go test, handgrip, and risk of falls (Biodex Balance System®)]. RESULTS: Protein intake and number of meals with either ≥20 g or ≥30 g of protein were significantly associated (after controlling for confounding factors) with greater total and appendicular lean mass and vastus lateralis CSA. CONCLUSIONS: We found that not only total protein intake but also the number of high-protein containing meals are associated with muscle mass in frail and pre-frail elderly.

Beta-alanine supplementation improves isometric, but not isotonic or isokinetic strength endurance in recreationally strength-trained young men.

ß-Alanine (BA) supplementation may be ergogenic during high-intensity exercise, primarily due to the buffering of hydrogen cations, although the effects of beta-alanine supplementation on strength endurance are equivocal. The aim of the study was to determine the effects of 4 weeks of beta-alanine supplementation on skeletal muscle endurance using a battery of performance tests. This study employed a parallel group, repeated measures, randomised, double-blinded and placebo-controlled design. Twenty recreationally strength-trained healthy males completed tests of isotonic strength endurance (repeated bench and leg press), along with tests of isometric and isokinetic endurance conducted using an isokinetic dynamometer. Tests were performed before and after a 4 week intervention, comprising an intake of 6.4 g day-1 of BA (n = 9) or placebo (maltodextrin, n = 11). Time-to-exhaustion during the isometric endurance test improved by ~ 17% in the BA group (p < 0.01), while PL remained unchanged. No significant within-group differences (p > 0.1) were shown for any of the performance variables in the isokinetic test (peak torque, fatigue index, total work) nor for the total number of repetitions performed in the isotonic endurance tests (leg or bench press). Four weeks of BA supplementation (6.4 g day-1) improved isometric, but not isokinetic or isotonic endurance performance.

Different protein and derivatives supplementation strategies combined with resistance training in pre-frail and frail elderly: Rationale and protocol for the "Pro-Elderly" Study.

BACKGROUND: Frailty is a multifactorial geriatric syndrome characterized by progressive decline in health and associated with decreased muscle mass, strength, and functional capacity. Resistance training (RT) combined with protein or amino acids supplementation has been shown to be promising for mitigating age-related impairments. AIM: To investigate the chronic effects of different strategies of protein and derivatives supplementation in association with RT on selected health-related parameters in pre-frail and frail elderly. METHODS: This is a series of double-blind, randomized, placebo-controlled, parallel-group clinical trials. Volunteers will be divided into nine groups, comprising four different sub-studies evaluating the effects of: isolated leucine supplementation (study 1); protein source (whey vs. soy - study 2); combination of whey protein and creatine (study 3); and sexual dimorphism on the response to protein intake and RT (males vs. females - study 4). Muscle cross-sectional area, fiber cross-sectional area, body composition, lower-limb maximal dynamic and isometric strength, functionality, lipid profile, biochemical parameters, renal function, quality of life, and nutritional status will be assessed before and after a 16-week intervention period. Data will be tested for normality and a mixed-model for repeated measures will be conducted to assess within- and between-group effects of the intervention on the dependent variables. Confidence intervals (95%), effect sizes, and relative changes will also be determined, with significance set at p < 0.05.

Leucine supplementation improves adiponectin and total cholesterol concentrations despite the lack of changes in adiposity or glucose homeostasis in rats previously exposed to a high-fat diet.

BACKGROUND: Studies suggest that leucine supplementation (LS) has a therapeutic potential to prevent obesity and to promote glucose homeostasis. Furthermore, regular physical exercise is a widely accepted strategy for body weight maintenance and also for the prevention of obesity. The aim of this study was to determine the effect of chronic LS alone or combined with endurance training (ET) as potential approaches for reversing the insulin resistance and obesity induced by a high-fat diet (HFD) in rats. METHODS: Forty-seven rats were randomly divided into two groups. Animals were fed a control diet-low fat (n = 10) or HFD (n = 37). After 15 weeks on HFD, all rats received the control diet-low fat and were randomly divided according to treatment: reference (REF), LS, ET, and LS+ET (n = 7-8 rats per group). After 6 weeks of treatment, the animals were sacrificed and body composition, fat cell volume, and serum concentrations of total cholesterol, HDL-cholesterol, triacylglycerol, glucose, adiponectin, leptin and tumor necrosis factor-alpha (TNF-α) were analyzed. RESULTS: At the end of the sixth week of treatment, there was no significant difference in body weight between the REF, LS, ET and LS+ET groups. However, ET increased lean body mass in rats (P = 0.019). In addition, ET was more effective than LS in reducing adiposity (P = 0.019), serum insulin (P = 0.022) and TNF-α (P = 0.044). Conversely, LS increased serum adiponectin (P = 0.021) levels and reduced serum total cholesterol concentration (P = 0.042). CONCLUSIONS: The results showed that LS had no beneficial effects on insulin sensitivity or adiposity in previously obese rats. On the other hand, LS was effective in increasing adiponectin levels and in reducing total cholesterol concentration.