Targeting the Gut Microbiota to Improve Dietary Protein Efficacy to Mitigate Sarcopenia

Sarcopenia is characterised by the presence of diminished skeletal muscle mass and strength. It is relatively common in older adults as ageing is associated with anabolic resistance (a blunted muscle protein synthesis response to dietary protein consumption and resistance exercise). Therefore, interventions to counteract anabolic resistance may benefit sarcopenia prevention and are of utmost importance in the present ageing population. There is growing speculation that the gut microbiota may contribute to sarcopenia, as ageing is also associated with [1) dysbiosis, whereby the gut microbiota becomes less diverse, lacking in healthy butyrate-producing microorganisms and higher in pathogenic bacteria, and [2) loss of epithelial tight junction integrity in the lining of the gut, leading to increased gut permeability and higher metabolic endotoxemia. Animal data suggest that both elements may impact muscle physiology, but human data corroborating the causality of the association between gut microbiota and muscle mass and strength are lacking. Mechanisms wherein the gut microbiota may alter anabolic resistance include an attenuation of gut-derived low-grade inflammation and/or the increased digestibility of protein-containing foods and consequent higher aminoacidemia, both in favour of muscle protein synthesis. This review focuses on the putative links between the gut microbiota and skeletal muscle in the context of sarcopenia. We also address the issue of plant protein digestibility because plant proteins are increasingly important from an environmental sustainability perspective, yet they are less efficient at stimulating muscle protein synthesis than animal proteins

Mobility and strength training with and without protein supplements for pre-frail or frail older adults with low protein intake: the Maximising Mobility and Strength Training (MMoST) feasibility randomised controlled trial protocol

Background Frailty is a common syndrome affecting older people and puts them at risk of hospitalisation, needing care or death. First signs of frailty include reduced muscle strength and mobility decline. A key cause of mobility decline as we age is sarcopenia (age related reduction in muscle strength and mass). Poor nutrition contributes to sarcopenia. A shortfall in protein is associated with reduced muscle mass and strength. This may be due to inadequate intake but also because older people have higher protein needs, especially those with multimorbidity. We need to develop effective treatment to reduce or slow the onset of frailty and mobility decline. Exercise is a recommended treatment. Protein supplements to address the shortfall in protein have the potential to enhance the benefit of regular exercise in frail or pre-frail older adults. This has yet to be definitively demonstrated. Aim To establish the feasibility of conducting an RCT evaluating mobility and strength training with or without protein supplements for people over 60 years old who are frail or pre-frail with a low protein intake. Methods A multicentre, parallel, 2-group, feasibility RCT. Participants (recruitment target = 50) with problems walking, low protein intake and classified as frail or pre-frail will be recruited from four NHS Physiotherapy community services. Participants will be randomised (secure computer-generated: 1:1) to receive 24 weeks of mobility and strength training (delivered in 16 group sessions plus home exercises) or 24 weeks of mobility and strength training with daily protein supplements. Primary feasibility objectives are to estimate 1) ability to screen and recruit eligible participants, 2) intervention fidelity, adherence, and tolerance and 3) retention of participants at follow up. Secondary objectives are to 1) test data collection procedures, 2) assess data completeness and 3) confirm sample size calculation for a definitive RCT. Registration ISRCTN Registry (ISRCTN30405954; 18/10/2022)

Exercise energy expenditure and postprandial lipemia in girls

Purpose: This study aimed to examine the effect of 30 and 60 min of moderate-intensity treadmill walking on postprandial triacylglycerol concentrations ([TAG]) in healthy girls. Methods: Eighteen 10- to 14-yr-old girls (mean ± SD; body mass = 48 ± 11 kg, body fat = 19.0 T 4.6%, peak oxygen uptake [VO2] = 47 ± 6 mL·kg -1min-1) completed three 2-d trials in a counterbalanced crossover design, each separated by 14 d. On day 1, they rested (CON) or completed 30 min (EX30) or 60 min (EX60) of intermittent treadmill exercise at 56% peak VO2, inducing energy expenditures of 777 and 1536 kJ (186 and 367 kcal), respectively. On day 2, after a 12-h fast, a capillary blood sample was taken for fasting [TAG] before a high-fat milkshake (80 kJ·kg-1 body mass) was consumed. Further blood samples were taken hourly over a 6-h postprandial rest period for [TAG]. ANOVA and Student's t-tests were used to analyze the data. Results: Fasting [TAG] was lower in EX60 than CON (95% confidence interval [CI] = -0.36 to 0.04, effect size (ES) = 0.41) and EX30 (95% CI = -0.47 to 0.04, ES = 0.46); all group mean concentrations were low (≤0.90 mmol·L-1). The main effect for condition revealed differences in postprandial [TAG] over time (ES = 0.36). The EX60 total area under the [TAG] versus time curve was lower than CON (95% CI = -2.66 to -0.04, ES 0.40) and EX30 (95%CI = -2.11 to 0.15, ES = 0.30); CON and EX30 were similar (95%CI = -1.44 to 0.71, ES = 0.10). Conclusion: This study demonstrates that 60 min but not 30 min of moderate treadmill exercise, with a gross energy expenditure of 1536 kJ (367 kcal), attenuated postprandial [TAG] in girls. Copyright © 2013 by the American College of Sports Medicine

Plasma lutein and zeaxanthin concentrations associated with musculoskeletal health and incident frailty in The Irish Longitudinal Study on Ageing (TILDA)

peer-reviewedIntroduction Lutein and zeaxanthin are diet-derived carotenoids that are proposed to help mitigate frailty risk and age-related declines in musculoskeletal health via their anti-oxidant and anti-inflammatory properties. Therefore, this study aimed to investigate the association between lutein and zeaxanthin status and indices of musculoskeletal health and incident frailty among community-dwelling adults aged ≥50 years in the Irish Longitudinal Study on Ageing (TILDA). Methods Cross-sectional analyses (n = 4513) of plasma lutein and zeaxanthin concentrations and grip strength, usual gait speed, timed up-and-go (TUG), probable sarcopenia (defined as grip strength <27 kg in men, <16 kg in women), and bone mass (assessed using calcaneal broadband ultrasound stiffness index) were performed at Wave 1 (2009–2011; baseline). In the longitudinal analyses (n = 1425–3100), changes in usual gait speed (at Wave 3, 2014–2015), grip strength (Wave 4, 2016) and TUG (at Wave 5, 2018), incident probable sarcopenia (at Wave 4) and incident frailty (Fried's phenotype, Frailty Index, FRAIL Scale, Clinical Frailty Scale-classification tree, at Wave 5) were determined. Data were analysed using linear and ordinal logistic regression, adjusted for confounders. Results Cross-sectionally, plasma lutein and zeaxanthin concentrations were positively associated with usual gait speed (B [95 % CI] per 100-nmol/L higher concentration: Lutein 0.59 [0.18, 1.00], Zeaxanthin 1.46 [0.37, 2.55] cm/s) and inversely associated with TUG time (Lutein −0.07 [−0.11, −0.03], Zeaxanthin −0.14 [−0.25, −0.04] s; all p 0.05). Plasma lutein concentration was positively associated with bone stiffness index (0.54 [0.15, 0.93], p 0.05). Conclusion Higher plasma lutein and zeaxanthin concentrations at baseline were associated with a reduced likelihood of incident frailty after ~8 years of follow up. Baseline plasma lutein and zeaxanthin concentrations were also positively associated with several indices of musculoskeletal health cross-sectionally but were not predictive of longitudinal changes in these outcomes over 4–8 years.Horizon 2020 Marie Skłodowska-Curie ActionsThis work was supported by the Teagasc Research Leaders 2025 programme co-funded by Teagasc and the European Union's Horizon 2020 - Research and Innovation Framework Programme under the H2020 Marie Skłodowska-Curie Actions grant agreement number 754380. TILDA is funded by Atlantic Philanthropies, the Irish Department of Health and Irish Life. Roman Romero-Ortuno is funded by a grant from Science Foundation Ireland under grant number 18/FRL/6188

Dietary Factors May Be Associated With Measures of Ultrasound-derived Skeletal Muscle Echo Intensity

Skeletal muscle echo intensity (EI) is affected by ageing and physical activity; however, the effects of nutrition are less understood. The aim of this study was to explore whether habitual nutrient intake may be associated with ultrasound-derived EI. Partial least squares regression (PLSR) models were trained on an initial sample (n=100, M=45; F=55; 38±15 years) to predict EI of two quadriceps muscles from 19 variables, using the ‘jack-knife’ function within the ‘pls’ package (RStudio), which was then tested in an additional dataset (n= 30, M=13; F=17; 38±16 years). EI was determined using B-mode ultrasonography of the rectus femoris (RF) and vastus lateralis (VL) and nutritional intake determined via three-day weighed food diaries. Mean daily intake of specific nutrients were included as predictor variables with age, sex and self-reported physical activity. PLSR training model 1 explained ~52% and model 2 ~46% of the variance in RF and VL EI, respectively. Model 1 also explained ~35% and model 2 ~30% of the variance in RF and VL EI in the additional testing dataset. Age and biological sex were associated with EI in both models (P<0.025). Dietary protein (RF: β=-7.617,VL: β=-7.480), and selenium (RF: β=-7.144,VL: β=-4.775) were associated with EI in both muscles (P<0.05), whereas fibre intake (RF: β=-5.215) was associated with RF EI only and omega-3 fatty acids (n-3/ω-3 FAs, RF: β=3.145) with VL EI only (P<0.05). Therefore, absolute protein, selenium, fibre and n-3 FAs may be associated with skeletal muscle EI, although further mechanistic work is required before claiming causal inference

Does supplementation with leucine-enriched protein alone and in combination with fish-oil-derived n–3 PUFA affect muscle mass, strength, physical performance, and muscle protein synthesis in well-nourished older adults? A randomized, double-blind, placebo-controlled trial

peer-reviewedBackground Leucine-enriched protein (LEU-PRO) and long-chain (LC) n–3 (ω–3) PUFAs have each been proposed to improve muscle mass and function in older adults, whereas their combination may be more effective than either alone. Objective The impact of LEU-PRO supplementation alone and combined with LC n–3 PUFAs on appendicular lean mass, strength, physical performance and myofibrillar protein synthesis (MyoPS) was investigated in older adults at risk of sarcopenia. Methods This 24-wk, 3-arm parallel, randomized, double-blind, placebo-controlled trial was conducted in 107 men and women aged ≥65 y with low muscle mass and/or strength. Twice daily, participants consumed a supplement containing either LEU-PRO (3 g leucine, 10 g protein; n = 38), LEU-PRO plus LC n–3 PUFAs (0.8 g EPA, 1.1 g DHA; LEU-PRO+n–3; n = 38), or an isoenergetic control (CON; n = 31). Appendicular lean mass, handgrip strength, leg strength, physical performance, and circulating metabolic and renal function markers were measured pre-, mid-, and postintervention. Integrated rates of MyoPS were assessed in a subcohort (n = 28). Results Neither LEU-PRO nor LEU-PRO+n–3 supplementation affected appendicular lean mass, handgrip strength, knee extension strength, physical performance or MyoPS. However, isometric knee flexion peak torque (treatment effect: −7.1 Nm; 95% CI: −12.5, −1.8 Nm; P < 0.01) was lower postsupplementation in LEU-PRO+n–3 compared with CON. Serum triacylglycerol and total adiponectin concentrations were lower, and HOMA-IR was higher, in LEU-PRO+n–3 compared with CON postsupplementation (all P < 0.05). Estimated glomerular filtration rate was higher and cystatin c was lower in LEU-PRO and LEU-PRO+n–3 postsupplementation compared with CON (all P < 0.05). Conclusions Contrary to our hypothesis, we did not observe a beneficial effect of LEU-PRO supplementation alone or combined with LC n–3 PUFA supplementation on appendicular lean mass, strength, physical performance or MyoPS in older adults at risk of sarcopenia. This trial was registered at clinicaltrials.gov as NCT03429491.Horizon 2020 Framework ProgrammeThis work was supported by the Department of Agriculture, Food and the Marine Food Institutional Research Measure grant entitled NUTRIMAL “Novel Nutritional Solutions for the Prevention of Malnutrition” (grant 14F822), the European Union’s Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie Grant Agreement No. 666010, and a Research Fellowship awarded to CHM by the European Society of Clinical Nutrition and Metabolism (ESPEN). HMR was supported by funding from the Joint Programming Initiative Healthy Diet for a Healthy Life (JPI HDHL) EU Food Biomarkers Alliance “FOODBAll” with Science Foundation Ireland (14/JPHDHL/B3076)

Considerations for protein intake in managing weight loss in athletes

A large body of evidence now shows that higher protein intakes (2–3 times the protein Recommended Dietary Allowance (RDA) of 0.8 g/kg/d) during periods of energy restriction can enhance fat-free mass (FFM) preservation, particularly when combined with exercise. The mechanisms underpinning the FFM-sparing effect of higher protein diets remain to be fully elucidated but may relate to the maintenance of the anabolic sensitivity of skeletal muscle to protein ingestion. From a practical point of view, athletes aiming to reduce fat mass and preserve FFM should be advised to consume protein intakes in the range of ∼1.8–2.7 g kg−1 d−1 (or ∼2.3–3.1 g kg−1 FFM) in combination with a moderate energy deficit (−500 kcal) and the performance of some form of resistance exercise. The target level of protein intake within this recommended range requires consideration of a number of case-specific factors including the athlete's body composition, habitual protein intake and broader nutrition goals. Athletes should focus on consuming high-quality protein sources, aiming to consume protein feedings evenly spaced throughout the day. Post-exercise consumption of 0.25–0.3 g protein meal−1 from protein sources with high leucine content and rapid digestion kinetics (i.e. whey protein) is recommended to optimise exercise-induced muscle protein synthesis. When protein is consumed as part of a mixed macronutrient meal and/or before bed slightly higher protein doses may be optimal

Targeting the Gut Microbiota to Improve Dietary Protein Efficacy to Mitigate Sarcopenia

Sarcopenia is characterised by the presence of diminished skeletal muscle mass and strength. It is relatively common in older adults as ageing is associated with anabolic resistance (a blunted muscle protein synthesis response to dietary protein consumption and resistance exercise). Therefore, interventions to counteract anabolic resistance may benefit sarcopenia prevention and are of utmost importance in the present ageing population. There is growing speculation that the gut microbiota may contribute to sarcopenia, as ageing is also associated with [1) dysbiosis, whereby the gut microbiota becomes less diverse, lacking in healthy butyrate-producing microorganisms and higher in pathogenic bacteria, and [2) loss of epithelial tight junction integrity in the lining of the gut, leading to increased gut permeability and higher metabolic endotoxemia. Animal data suggest that both elements may impact muscle physiology, but human data corroborating the causality of the association between gut microbiota and muscle mass and strength are lacking. Mechanisms wherein the gut microbiota may alter anabolic resistance include an attenuation of gut-derived low-grade inflammation and/or the increased digestibility of protein-containing foods and consequent higher aminoacidemia, both in favour of muscle protein synthesis. This review focuses on the putative links between the gut microbiota and skeletal muscle in the context of sarcopenia. We also address the issue of plant protein digestibility because plant proteins are increasingly important from an environmental sustainability perspective, yet they are less efficient at stimulating muscle protein synthesis than animal proteins

Nutrition strategies to counteract sarcopenia: a focus on protein, LC n-3 PUFA and precision nutrition

Diminished skeletal muscle strength and size, termed sarcopenia, contributes substantially to physical disability, falls, dependence and reduced quality of life among older people. Physical activity and nutrition are the cornerstones of sarcopenia prevention and treatment. The optimal daily protein intake required to preserve muscle mass and function among older adults is a topic of intense scientific debate. Older adults require protein intakes about 67 %higher than their younger counterparts to maximally stimulate postprandial muscle protein synthesis rates. In addition, evidence suggests a possible benefit of increasing protein intake above the population reference intake (0⋅83 g/kg/d) on lean mass and, when combined with exercise training, muscle strength. In addition to protein quantity, protein quality, the pattern of protein intake over the day and specific amino acids (i.e. leucine) represent key considerations. Long-chain n-3 PUFA (LC n-3 PUFA) supplementation has been shown to enhance muscle protein synthesis rates, increase muscle mass and function and augment adaptations to resistance training in older adults. Yet, these effects are not consistent across all studies. Emerging evidence indicates that an older person’s dietary, phenotypic and behavioural characteristics may modulate the efficacy of protein and LC n-3 PUFA interventions for promoting improvements in muscle mass and function, highlighting the potential inadequacy of a ‘one-size-fits-all’ approach. The application of personalised or precision nutrition to sarcopenia represents an exciting and highly novel field of research with the potential to help resolve inconsistencies in the literature and improve the efficacy of dietary interventions for sarcopeni

Per meal dose and frequency of protein consumption is associated with lean mass and muscle performance

Background It has been hypothesized that for older adults evenly distributing consumption of protein at 30–40 g per meal throughout the day may result in more favorable retention of lean mass and muscular strength. Such a thesis has not, to our knowledge, been tested outside of short-term studies or acute measures of muscle protein synthesis. Aims To examine whether the number of times an individual consumed a minimum of 30 g of protein at a meal is associated with leg lean mass and knee extensor strength. Methods Data from the 1999–2002 NHANES were used, with 1081 adults (50–85 y) constituting the analytic sample. A “multiple pass” 24-h dietary interview format was used to collect detailed information about the participants' dietary intake. Knee extensor strength was assessed objectively using the Kin Com MP dynamometer. Leg lean mass was estimated from whole-body dual-energy X-ray absorptiometry (DXA) scans. Results Participants with 1 vs. 0 (βadjusted = 23.6, p = 0.002) and 2 vs. 0 (βadjusted = 51.1, p = 0.001) meals of ≥30 g protein/meal had greater strength and leg lean mass (1 vs. 0, βadjusted = 1160, p < 0.05 and 2 vs. 0, βadjusted = 2389, p < 0.05). The association of protein frequency with leg lean mass and strength plateaued at ∼45 g protein/meal for those consuming 2 vs. 0 meals above the evaluated protein/meal threshold. However, for those with only 1 meal at or above the evaluated threshold, the response plateaued at 30 g/meal. Leg lean mass mediated the relationship between protein frequency and strength, with the proportion of the total effect mediated being 64%. Conclusions We found that more frequent consumption of meals containing between 30 and 45 g protein/meal produced the greatest association with leg lean mass and strength. Thus, the consumption of 1–2 daily meals with protein content from 30 to 45 g may be an important strategy for increasing and/or maintaining lean body mass and muscle strength with aging