Effect of 1-year daily protein supplementation and physical exercise on muscle protein synthesis rate and muscle metabolome in healthy older Danes: a randomized controlled trial.

BACKGROUND: The skeletal muscle mass decreases with age and the responsiveness of aging muscles' protein synthesis rate (MPS) to protein intake seems to deteriorate. OBJECTIVE: This study investigated the impact of 12 months of protein supplementation with or without physical exercise training on the basal and postprandial MPS and the skeletal muscle metabolome of healthy older Danes (> 65 years, 29 females/37 males). METHODS: Subjects were randomized to follow one of five intervention groups: (1) carbohydrate, (2) collagen protein, (3) whey protein, (4) home-based light resistance training with whey protein, and (5) center-based heavy-load resistance training with whey protein. Before and after the intervention, a tracer infusion trial was conducted to measure basal and postprandial MPS in response to intake of a cocktail consisting of 20 g whey hydrolysate + 10 g glucose. In addition, the skeletal muscle metabolome was measured using gas chromatography-mass spectrometry (GC-MS) at basal state and 4 h after the intake of the cocktail. RESULTS: One year of daily protein or carbohydrate supplementation did not alter the basal and protein-stimulated postprandial muscle protein synthesis rate or the muscle metabolome of healthy older Danes. Basal MPS (%/h) at baseline for all subjects were 0.0034 ± 0,011 (mean ± SD). In contrast to previous studies, no difference was observed in basal MPS between males and females (p = 0.75). With the developed untargeted GC-MS methodology, it was possible to detect and tentatively annotate > 70 metabolites from the human skeletal muscle samples. CONCLUSION: One year of protein supplementation in comparison to an isocaloric-control supplement seems to affect neither the MPS at basal or postprandial state nor the skeletal muscle metabolome. CLINICAL TRIAL REGISTRY: Number: NCT02115698, clinicaltrials.gov/ct2/show/NCT02115698.

Changes in Muscle Mass and Strength During Follow-Up After One-Year Resistance Training Interventions in Older Adults.

ABSTRACT: Mertz, KH, Reitelseder, S, Rasmussen, MA, Bülow, J, Højfeldt, G, Jensen, M, Hjulmand, M, Lindberg, J, Kramer, MU, Bechshøft, R, and Holm, L. Changes in muscle mass and strength during follow-up after one-year resistance training interventions in older adults. J Strength Cond Res 37(10): 2064-2070, 2023-The aim of this study was to investigate if home-based resistance training compared with center-based resistance training was associated with better preservation of muscle mass and strength in older individuals, 6 months after the interventions ended. One hundred four healthy older individuals (>65 years) who had completed 1 year of either home-based light-intensity training with daily whey protein supplementation (LITW), center-based heavy resistance training with whey protein supplementation (HRTW), or daily whey protein supplementation alone (WHEY) returned for follow-up measurement 6 months after the interventions. Measures of muscle mass, strength, and power were assessed at the end of intervention as well as at follow-up. Furthermore, we compared changes in these parameters between subjects who continued resistance training (≥1 weekly training session) during follow-up (CONT) with those who stopped (STOP). Resistance training continuation during follow-up did not differ between HRTW and LITW (41 vs. 41%, P = 1.0) but was higher for both groups compared with WHEY (18%, P = 0.04-0.05). However, no between-group differences were observed between LITW/HRTW/WHEY in changes in muscle mass, strength, or power during follow-up. STOP was associated with a poorer preservation of quadriceps cross-sectional area compared with CONT (-1.7 cm 2 [-0.4 to -3.0], P = 0.01, effect size: 0.79). No effect of training continuation was observed on changes in muscle strength and power. In conclusion, maintenance of muscle mass and strength is not superior after home-based resistance training compared with center-based training. However, training continuation seems crucial for the maintenance of muscle mass, irrespective of the training intervention.

Human Fecal Metabolome Reflects Differences in Body Mass Index, Physical Fitness, and Blood Lipoproteins in Healthy Older Adults.

This study investigated how body mass index (BMI), physical fitness, and blood plasma lipoprotein levels are related to the fecal metabolome in older adults. The fecal metabolome data were acquired using proton nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry on 163 healthy older adults (65-80 years old, 80 females and 83 males). Overweight and obese subjects (BMI ≥ 27) showed higher levels of fecal amino acids (AAs) (valine, alanine, and phenylalanine) compared to normal-weight subjects (BMI ≤ 23.5). Adults classified in the high-fitness group displayed slightly lower concentrations of fecal short-chain fatty acids, propionic acid, and AAs (methionine, leucine, glutamic acid, and threonine) compared to the low-fitness group. Subjects with lower levels of cholesterol in low-density lipoprotein particles (LDLchol, ≤2.6 mmol/L) displayed higher fecal levels of valine, glutamic acid, phenylalanine, and lactic acid, while subjects with a higher level of cholesterol in high-density lipoprotein particles (HDLchol, ≥2.1 mmol/L) showed lower fecal concentration of isovaleric acid. The results from this study suggest that the human fecal metabolome, which primarily represents undigested food waste and metabolites produced by the gut microbiome, carries important information about human health and should be closely integrated to other omics data for a better understanding of the role of the gut microbiome and diet on human health and metabolism.

Effects of Prolonged Whey Protein Supplementation and Resistance Training on Biomarkers of Vitamin B12 Status: A 1-Year Randomized Intervention in Healthy Older Adults (the CALM Study).

We investigated the effect of long-term whey supplementation on biomarkers of B12 status in healthy older adults subjected to different schemes of supplements and exercise. The total study population examined at baseline consisted of 167 healthy older adults (age ≥ 65 year) who were randomized to 1-y intervention with two daily supplements of (1) whey protein (3.1 µg B12/day) (WHEY-ALL), (2) collagen (1.3 µg B12/day) (COLL), or (3) maltodextrin (0.3 µg B12/day) (CARB). WHEY-ALL was comprised of three groups, who performed heavy resistance training (HRTW), light resistance training (LITW), or no training (WHEY). Dietary intake was assessed through 3-d dietary records. For the longitudinal part of the study, we included only the participants (n = 110), who met the criteria of ≥ 50% compliance to the nutritional intervention and ≥ 66% and ≥ 75% compliance to the heavy and light training, respectively. Fasting blood samples collected at baseline and 12 months and non-fasting samples collected at 6 and 18 months were examined for methylmalonic acid, B12 and holotranscobalamin. At baseline, the study population (n = 167) had an overall adequate dietary B12 intake of median (range) 5.3 (0.7-65) µg/day and median B12 biomarker values within reference intervals. The whey intervention (WHEY-ALL) caused an increase in B12 (P < 0.0001) and holotranscobalamin (P < 0.0001). In addition, methylmalonic acid decreased in the LITW group (P = 0.04). No change in B12 biomarkers was observed during the intervention with collagen or carbohydrate, and the training schedules induced no changes. In conclusion, longer-term daily whey intake increased plasma B12 and holotranscobalamin in older individuals. No effect of intervention with collagen or carbohydrate or different training regimes was observed. Interestingly, the biomarkers of B12 status appeared to be affected by fasting vs. non-fasting conditions during sample collection.

Physical fitness in community-dwelling older adults is linked to dietary intake, gut microbiota, and metabolomic signatures.

When humans age, changes in body composition arise along with lifestyle-associated disorders influencing fitness and physical decline. Here we provide a comprehensive view of dietary intake, physical activity, gut microbiota (GM), and host metabolome in relation to physical fitness of 207 community-dwelling subjects aged +65 years. Stratification on anthropometric/body composition/physical performance measurements (ABPm) variables identified two phenotypes (high/low-fitness) clearly linked to dietary intake, physical activity, GM, and host metabolome patterns. Strikingly, despite a higher energy intake high-fitness subjects were characterized by leaner bodies and lower fasting proinsulin-C-peptide/blood glucose levels in a mechanism likely driven by higher dietary fiber intake, physical activity and increased abundance of Bifidobacteriales and Clostridiales species in GM and associated metabolites (i.e., enterolactone). These factors explained 50.1% of the individual variation in physical fitness. We propose that targeting dietary strategies for modulation of GM and host metabolome interactions may allow establishing therapeutic approaches to delay and possibly revert comorbidities of aging.

Lack of muscle fibre hypertrophy, myonuclear addition, and satellite cell pool expansion with resistance training in 83-94-year-old men and women.

AIMS: To examine satellite cell and myonuclear content in very old (≥83 years) individuals, and the response to heavy resistance training. METHODS: A group of very old men and women (Old, 83-94 years, n = 29) was randomized to 12 weeks of heavy resistance training or untrained controls. A group of young men who did not resistance train (Young, 19-27 years, n = 9) were included for comparison. RESULTS: Compared to young men, prior to training the old men had smaller type II fibres (-38%, P < 0.001), lower satellite cell content (-52%, P < 0.001), smaller myonuclear domain (-30%, P < 0.001), and a trend for lower myonuclear content (-13%, P = 0.09). Old women were significantly different from old men for these parameters, except for satellite cell content. Resistance training had no effect on these parameters in these old men and women. Fibre-size specific analysis showed strong correlations between fibre size and myonuclei per fibre and between fibre size and myonuclear domain for both fibre types (r = 0.94-0.99, P < 0.0001). In contrast, muscle fibre perimeter per myonucleus seemed to be constant across the range in fibre size, particularly in type I fibres (r = -0.31, P = 0.17). CONCLUSIONS: The present data demonstrate that type II fibre size, satellite cell content and myonuclear domain is significantly smaller in very old men compared to young men, while myonuclear content is less affected. These parameters were not improved with heavy resistance training at the most advanced stage of ageing.

Investigating Risk of Suboptimal Macro and Micronutrient Intake and Their Determinants in Older Danish Adults with Specific Focus on Protein Intake-A Cross-Sectional Study.

Suboptimal intake of nutrients is associated with adverse health outcomes. The current study investigated the risk of suboptimal macro and micronutrient intake and their potential determinants in a cross-sectional study of community-dwelling older Danish adults (65⁻81 years). Nutrient intake was obtained through a 3-day weighted dietary record and information on personal characteristics and attitudes towards specific foods and dietary habits and nutrition through questionnaires. Dietary Reference Values (DRV) from the Nordic Nutrition Recommendations were used for the assessment. Among 157 participants, 68% and 66% had risk of suboptimal intake of dietary fiber and saturated fatty acids (SFA). For mono-unsaturated fatty acids (MUFA) and poly-unsaturated fatty acids (PUFA), the numbers were 47% and 62%, respectively. Increased risk of suboptimal protein intake was estimated in 3 to 45% of the participants, depending on the criteria used for the DRV and of the mode of expressing protein intake. Fifty percent had intakes of alcohol above the maximum recommended intake. Risk of micronutrient inadequacy was particularly high for vitamin D and thiamine (80 and 45%, respectively). Total energy intake and attitude regarding healthy eating were associated with lower nutrient intake. The current study illustrates that there is room for improvements in the dietary quality of community dwelling older Danish adults.

Development of a Mobility Diet Score (MDS) and Associations With Bone Mineral Density and Muscle Function in Older Adults.

Introduction: Reduced bone mineral density (BMD) and muscle function is associated with increased risk of multiple health related issues. Diet may play a role in sustaining BMD and muscle function throughout old age, but much is still to be learned with regards to which specific food groups and dietary patterns that are important for such outcomes. The aim of the current study was to identify food groups important for both BMD and muscle function. Methods: A narrative review was performed on studies published on dietary patterns and their association with BMD and muscle function, respectively. Based on these findings, two dietary indices were constructed characterizing food groups associated with BMD and muscle function, respectively. Associations between adherence to these indices and BMD and muscle function were then investigated in a population of older community-dwelling Danes. Food groups found to be associated with both BMD and muscle function in our study population were suggested for inclusion into a common dietary index named the Mobility Diet Score. Results: In contrast to previous studies, adherence to a dietary index based on foods previously linked to BMD could not be established as important for BMD in our study population of 184 older individuals (53.3% men). We found that adhering to a dietary index characterized by higher intakes of whole grains, dairy products, fish, legumes, nuts, fruit, and vegetables is associated with faster 400 m walking speeds and an increased number of chair stands measured over a 30 s time period. Since no food group could be established as important for both BMD and muscle function in our study population, a Mobility Diet Score could not be established. However, based on our narrative review, the food groups commonly associated with improved BMD and muscle function are similar. Conclusion: Adherence to a dietary index characterized by high intakes of whole grains, dairy products, fish, legumes, nuts, fruit, and vegetables was not found to be associated with BMD in a group of community-dwelling older Danes. However, our results indicate that the adherence to such foods could be important in sustaining physical function in older individuals.

Improved skeletal muscle mass and strength after heavy strength training in very old individuals.

Age-related loss of muscle mass and function represents personal and socioeconomic challenges. The purpose of this study was to determine the adaptation of skeletal musculature in very old individuals (83+ years) performing 12weeks of heavy resistance training (3×/week) (HRT) compared to a non-training control group (CON). Both groups received similar protein supplementations. We studied 26 participants (86.9±3.2 (SD) (83-94, range) years old) per-protocol. Quadriceps cross-sectional area (CSA) differed between groups at post-test (P<0.05) and increased 1.5±0.7cm2 (3.4%) (P<0.05) in HRT only. The increase in CSA is correlated inversely with the baseline level of CSA (R2=0.43, P<0.02). Thigh muscle isometric strength, isokinetic peak torque and power increased significantly only in HRT by 10-15%, whereas knee extension one-repetition maximum (1 RM) improved by 91%. Physical functional tests, muscle fiber type distribution and size did not differ significantly between groups. We conclude that in protein supplemented very old individuals, heavy resistance training can increase muscle mass and strength, and that the relative improvement in mass is more pronounced when initial muscle mass is low.

Counteracting Age-related Loss of Skeletal Muscle Mass: a clinical and ethnological trial on the role of protein supplementation and training load (CALM Intervention Study): study protocol for a randomized controlled trial.

BACKGROUND: Aging is associated with decreased muscle mass and functional capacity, which in turn decrease quality of life. The number of citizens over the age of 65 years in the Western world will increase by 50 % over the next four decades, and this demographic shift brings forth new challenges at both societal and individual levels. Only a few longitudinal studies have been reported, but whey protein supplementation seems to improve muscle mass and function, and its combination with heavy strength training appears even more effective. However, heavy resistance training may reduce adherence to training, thereby attenuating the overall benefits of training. We hypothesize that light load resistance training is more efficient when both adherence and physical improvement are considered longitudinally. We launched the interdisciplinary project on Counteracting Age-related Loss of Skeletal Muscle Mass (CALM) to investigate the impact of lifestyle changes on physical and functional outcomes as well as everyday practices and habits in a qualitative context. METHODS: We will randomize 205 participants older than 65 years to be given 1 year of two daily nutrient supplements with 10 g of sucrose and 20 g of either collagen protein, carbohydrates, or whey. Further, two groups will perform either heavy progressive resistance training or light load training on top of the whey supplement. DISCUSSION: The primary outcome of the CALM Intervention Study is the change in thigh cross-sectional area. Moreover, we will evaluate changes in physical performance, muscle fiber type and acute anabolic response to whey protein ingestion, sensory adaptation, gut microbiome, and a range of other measures, combined with questionnaires on life quality and qualitative interviews with selected subjects. The CALM Intervention Study will generate scientific evidence and recommendations to counteract age-related loss of skeletal muscle mass in elderly individuals. TRIAL REGISTRATION: ClinicalTrials.gov NCT02034760 . Registered on 10 January 2014. ClinicalTrials.gov NCT02115698 . Registered on 14 April 2014. Danish regional committee of the Capital Region H-4-2013-070. Registered on 4 July 2013. Danish Data Protection Agency 2012-58-0004 - BBH-2015-001 I-Suite 03432. Registered on 9 January 2015.