Physical activity and fiber intake beneficial for muscle mass and strength preservation during aging: A comprehensive cross-sectional study in the UK biobank cohort.

BACKGROUND: Aging triggers intricate physiological changes, particularly in whole-body fat-free mass (FFM) and handgrip strength, affecting overall health and independence. Despite existing research, the broader significance of how muscle health is affected by the intricate interplay of lifestyle factors simultaneously during aging needs more exploration. This study aims to examine how nutrition, physical activity, and sleep impact on FFM and handgrip strength in middle-aged men and women, facilitating future personalized recommendations for preserving muscle health. METHODS: The cross-sectional analysis of the UK Biobank involved 45,984 individuals (54 % women) aged 40-70 years with a complete dataset. Multiple linear regression explored determinants of FFM and handgrip strength, considering traditional, socio-demographics, medication use and smoking as covariates, with sex and age (younger and older than 55 years) stratifications. RESULTS: In older men and women, higher physical activity beneficially affect both FFM (respectively Β = 3.36 × 10-3, p-value = 1.66 × 10-3; Β = 2.52 × 10-3, p-value = 3.57 × 10-4) and handgrip strength (Β = 6.05 × 10-3, p-value = 7.99 × 10-5, Β = 8.98 × 10-3, p-value = 2.95 × 10-15). Similar results were found in fiber intake for FFM in older men and women (respectively B = 3.00 × 10-2, p-value = 2.76 × 10-5; B = 2.68 × 10-2, p-value = 1.78 × 10-9) and handgrip strength (Β = 3.27 × 10-2, p-value = 1.40 × 10-3; Β = 3.12 × 10-2, p-value = 1.34 × 10-5). Other lifestyle factors influence FFM and handgrip strength differently. Key determinants influencing handgrip strength included higher protein intake, lower water intake, higher alcohol intake, and extended sleep duration whereas mainly higher water intake is associated with higher FFM. CONCLUSIONS: In both men and women, the main factors associated with FFM and handgrip strength are physical activity and fiber intake, which may underlie a connection between gut and muscle health. Given the observed complexity of muscle health in the age and sex strata, further longitudinal research is needed to provide personalized lifestyle recommendations.

Adherence to and Efficacy of the Nutritional Intervention in Multimodal Prehabilitation in Colorectal and Esophageal Cancer Patients.

Multimodal prehabilitation programs to improve physical fitness before surgery often include nutritional interventions. This study evaluates the efficacy of and adherence to a nutritional intervention among colorectal and esophageal cancer patients undergoing the multimodal Fit4Surgery prehabilitation program. The intervention aims to achieve an intake of ≥1.5 g of protein/kg body weight (BW) per day through dietary advice and daily nutritional supplementation (30 g whey protein). This study shows 56.3% of patients met this goal after prehabilitation. Mean daily protein intake significantly increased from 1.20 ± 0.39 g/kg BW at baseline to 1.61 ± 0.41 g/kg BW after prehabilitation (p < 0.001), with the main increase during the evening snack. BW, BMI, 5-CST, and protein intake at baseline were associated with adherence to the nutritional intervention. These outcomes suggest that dietary counseling and protein supplementation can significantly improve protein intake in different patient groups undergoing a multimodal prehabilitation program.

Digitally Supported Dietary Protein Counseling Changes Dietary Protein Intake, Sources and Distribution in Community-Dwelling Older Adults.

Digitally supported dietary counselling may be helpful in increasing the protein intake in combined exercise and nutritional interventions in community-dwelling older adults. To study the effect of this approach, 212 older adults (72.2 ± 6.3 years) were randomised in three groups: control, exercise, or exercise plus dietary counselling. The dietary counselling during the 6-month intervention was a blended approach of face-to-face contacts and videoconferencing, and it was discontinued for a 6-month follow-up. Dietary protein intake, sources, product groups, resulting amino acid intake, and intake per eating occasion were assessed by a 3-day dietary record. The dietary counselling group was able to increase the protein intake by 32% at 6 months, and the intake remained 16% increased at 12 months. Protein intake mainly consisted of animal protein sources: dairy products, followed by fish and meat. This resulted in significantly more intake of essential amino acids, including leucine. The protein intake was distributed evenly over the day, resulting in more meals that reached the protein and leucine targets. Digitally supported dietary counselling was effective in increasing protein intake both per meal and per day in a lifestyle intervention in community-dwelling older adults. This was predominantly achieved by consuming more animal protein sources, particularly dairy products, and especially during breakfast and lunch.

The association of objectively measured physical activity and sedentary behavior with skeletal muscle strength and muscle power in older adults: A systematic review and meta-analysis.

BACKGROUND: Engaging in physical activity (PA) and avoiding sedentary behavior (SB) are important for healthy ageing with benefits including the mitigation of disability and mortality. Whether benefits extend to key determinants of disability and mortality, namely muscle strength and muscle power, is unclear. AIMS: This systematic review aimed to describe the association of objective measures of PA and SB with measures of skeletal muscle strength and muscle power in community-dwelling older adults. METHODS: Six databases were searched from their inception to June 21st, 2020 for articles reporting associations between objectively measured PA and SB and upper body or lower body muscle strength or muscle power in community dwelling adults aged 60 years and older. An overview of associations was visualized by effect direction heat maps, standardized effect sizes were estimated with albatross plots and summarized in box plots. Articles reporting adjusted standardized regression coefficients (ß) were included in meta-analyses. RESULTS: A total of 112 articles were included representing 43,796 individuals (range: 21 to 3726 per article) with a mean or median age from 61.0 to 88.0 years (mean 56.4 % female). Higher PA measures and lower SB were associated with better upper body muscle strength (hand grip strength), upper body muscle power (arm curl), lower body muscle strength, and lower body muscle power (chair stand test). Median standardized effect sizes were consistently larger for measures of PA and SB with lower compared to upper body muscle strength and muscle power. The meta-analyses of adjusted ß coefficients confirmed the associations between total PA (TPA), moderate-to-vigorous PA (MVPA) and light PA (LPA) with hand grip strength (ß = 0.041, ß = 0.057, and ß = 0.070, respectively, all p ≤ 0.001), and TPA and MVPA with chair stand test (ß = 0.199 and ß = 0.211, respectively, all p ≤ 0.001). CONCLUSIONS: Higher PA and lower SB are associated with greater skeletal muscle strength and muscle power, particularly with the chair stand test.

Sarcopenia, Low Handgrip Strength, and Low Absolute Muscle Mass Predict Long-Term Mortality in Older Hospitalized Patients: An Observational Inception Cohort Study.

OBJECTIVE: Sarcopenia is highly prevalent in hospitalized older patients and associated with short-term mortality. This study aimed to investigate whether sarcopenia and its measures handgrip strength (HGS) and muscle mass at hospital admission were associated with long-term mortality in a cohort of hospitalized older patients. DESIGN: Observational, prospective, longitudinal inception cohort study. SETTING AND PARTICIPANTS: Academic teaching hospital; patients age ≥70 years admitted to the internal medicine, acute admission, trauma, or orthopedic wards. METHODS: HGS and muscle mass were measured at admission using a hand dynamometer and bioelectrical impedance analysis. Sarcopenia was determined based on the European Working Group on Sarcopenia in Older People definition. HGS and muscle mass (skeletal muscle mass index, appendicular lean mass, relative skeletal muscle mass) were expressed as sex-specific tertiles. The associations of sarcopenia, HGS, and muscle mass with mortality (during a follow-up of 3.4-4.1 years) were analyzed using Cox regression, adjusted for age, sex, comorbidity, and weight or height. Associations of HGS and muscle mass were stratified by sex. RESULTS: Out of 363 patients [mean age: 79.6 years (standard deviation: 6.4), 49.9% female] 49% died. Probable sarcopenia (prevalence of 53.7%) and sarcopenia (prevalence of 20.8%) were significantly associated with long-term mortality [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.08‒2.17 and 1.71 95% CI 1.12‒2.61, respectively]. Low HGS, skeletal muscle mass index, and appendicular lean mass were associated with a higher mortality risk (lowest tertile vs highest tertile: HR 2.660, 95% CI 1.40‒5.05; HR 1.95, 95% CI 1.06‒3.58 and HR 1.99 (95% CI 1.12‒3.53) in male patients. No statistically significant associations of relative muscle mass with mortality were found. CONCLUSIONS AND IMPLICATIONS: Sarcopenia and its measures (low HGS and low absolute muscle mass at admission) predict long-term mortality in older hospitalized patients.

Effect of an Enriched Protein Drink on Muscle Mass and Glycemic Control during Combined Lifestyle Intervention in Older Adults with Obesity and Type 2 Diabetes: A Double-Blind RCT.

BACKGROUND: Weight loss is key to treatment of older adults with obesity and type 2 diabetes, but also a risk for muscle mass loss. This study investigated whether a whey protein drink enriched with leucine and vitamin D could preserve muscle mass and improve glycemic control during combined lifestyle intervention in this population. METHODS: 123 older adults with obesity and type 2 diabetes were randomized into a 13-week lifestyle intervention with dietary advice and exercise, receiving either the enriched protein drink (test) or an isocaloric control (control). Muscle mass was assessed with dual-energy X-ray absorptiometry and glycemic control by oral glucose tolerance test. Statistical analyses were performed using a linear mixed model. RESULTS: There was a nonsignificant increase in leg muscle mass (+0.28 kg; 95% CI, -0.01 to 0.56) and a significant increase in appendicular muscle mass (+0.36 kg; 95% CI, 0.005 to 0.71) and total lean mass (+0.92 kg; 95% CI, 0.19 to 1.65) in test vs. control. Insulin sensitivity (Matsuda index) also increased in test vs. control (+0.52; 95% CI, 0.07 to 0.97). CONCLUSIONS: Use of an enriched protein drink during combined lifestyle intervention shows beneficial effects on muscle mass and glycemic control in older adults with obesity and type 2 diabetes.

Safety and tolerability of 6-month supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink in sarcopenic older adults.

AIMS: Safety and tolerability of prolonged supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink (WP-MND) was evaluated in sarcopenic older adults. METHODS: A 13-week double-blinded, randomized, isocaloric placebo-controlled trial (PROVIDE study; n = 380) was extended with a voluntary 13-week open-label extension (OLE). OLE participants were randomized to receive daily 1 or 2 servings of WP-MND (21 g protein, 3 g leucine, 10 µg vitD and 500 mg calcium per serving). Gastro-intestinal tolerability, kidney function and serum levels of calcidiol, parathyroid hormone (PTH) and calcium were evaluated at week 0, 13 and 26. RESULTS AND DISCUSSION: In response to the high daily protein intake (median1.5; IQR: 1.3, 1.7 g/kg BW/day), the estimated glomerular filtration rate (eGFR) increased in the test group during the RCT (p = 0.013). The same trend was observed for those participants with moderate chronic kidney disease. During OLE no eGFR change was observed in any of the groups. Serum calcidiol and calcium reached a plateau after 13-week WP-MND supplementation. As expected, PTH significantly changed in the opposite direction, decreasing during RCT in the test group (T vs C: p < 0.001) and during OLE in former control groups. During RCT, 20/366 participants with normal baseline calcidiol reached levels ≥ 100 nmol/L (T: n = 18; C: n = 2) and 6 developed albumin-corrected calcium levels > 2.55 mmol/L (T: n = 3; C: n = 3), without associated adverse events. CONCLUSION: A 6 months intervention with up to 2 servings of WP-MND did neither result in kidney function deterioration nor symptoms of vitamin D or calcium toxicity. The product was overall well tolerated.

Malnutrition is associated with dynamic physical performance.

BACKGROUND: Malnutrition and poor physical performance are both conditions that increase in prevalence with age; however, their interrelation in a clinically relevant population has not been thoroughly studied. AIMS: This study aimed to determine the strength of the association between malnutrition and measures of both static and dynamic physical performance in a cohort of geriatric outpatients. METHODS: This cross-sectional study included 286 older adults (mean age 81.8, SD 7.2 years, and 40.6% male) who were referred to geriatric outpatient mobility clinics. The presence of malnutrition was determined using the Short Nutritional Assessment Questionnaire (SNAQ, cut-off ≥ 2 points). Measures of dynamic physical performance included timed up and go (TUG), 4-m walk test, and chair stand test (CST). Static performance encompassed balance tests and hand grip strength (HGS). Physical performance was standardized into sex-specific Z-scores. The association between malnutrition and each individual measure of physical performance was assessed using linear regression analysis. RESULTS: 19.9% of the cohort was identified as malnourished. Malnutrition was most strongly associated with CST and gait speed; less strong but significant associations were found between malnutrition and TUG. There was no significant association between malnutrition and HGS or balance. DISCUSSION: Physical performance was associated with malnutrition, specifically, dynamic rather than static measures. This may reflect muscle power being more impacted by nutritional status than muscle strength; however, this needs to be further addressed. CONCLUSIONS: Malnutrition is associated with dynamic physical performance in geriatric outpatients, which should inform diagnosis and treatment/prevention strategies.

A Vitamin D, Calcium and Leucine-Enriched Whey Protein Nutritional Supplement Improves Measures of Bone Health in Sarcopenic Non-Malnourished Older Adults: The PROVIDE Study.

Alterations in musculoskeletal health with advanced age contribute to sarcopenia and decline in bone mineral density (BMD) and bone strength. This decline may be modifiable via dietary supplementation. To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of bone health. Participants (n 380) were participants of the PROVIDE study, a 13-week, multicenter, randomized, controlled, double-blind, 2 parallel-group study among non-malnourished older participants (≥ 65 years) with sarcopenia [determined by Short Physical Performance Battery (SPPB; 0-12) scores between 4 and 9, and a low skeletal muscle mass index (SMI; skeletal muscle mass/BW × 100) ≤ 37% in men and ≤ 28% in women using bioelectric impedance analysis] Supplementation of a vitamin D, calcium and leucine-enriched whey protein drink that comprises a full range of micronutrients (active; 2/day) was compared with an iso-caloric control. Serum 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), biochemical markers of bone formation (osteocalcin; OC, procollagen type 1 amino-terminal propeptide; P1NP) and resorption (carboxy-terminal collagen crosslinks; CTX), insulin like growth factor 1 (IGF-1) and total-body BMD were analysed pre- and post-intervention. Serum 25(OH)D concentrations increased from 51.1 ± 22.9 nmol/L (mean ± SD) to 78.9 ± 21.1 nmol/L in the active group (p < 0.001 vs. control). Serum PTH showed a significant treatment difference (p < 0.001) with a decline in the active group, and increase in the control group. Serum IGF-1 increased in the active group (p < 0.001 vs. control). Serum CTX showed a greater decline in the active group (p = 0.001 vs. control). There were no significant differences in serum OC or P1NP between groups during the intervention. Total body BMD showed a small (0.02 g/cm2; ~ 2%) but significant increase in the active group after supplementation (p = 0.033 vs. control). Consuming a vitamin D, calcium and leucine-enriched whey protein supplement for 13 weeks improved 25(OH)D, suppressed PTH and had small but positive effects on BMD, indicative of improved bone health, in sarcopenic non-malnourished older adults.

Thirteen weeks of supplementation of vitamin D and leucine-enriched whey protein nutritional supplement attenuates chronic low-grade inflammation in sarcopenic older adults: the PROVIDE study.

BACKGROUND: A chronic low-grade inflammatory profile (CLIP) is associated with sarcopenia in older adults. Protein and Vitamin (Vit)D have immune-modulatory potential, but evidence for effects of nutritional supplementation on CLIP is limited. AIM: To investigate whether 13 weeks of nutritional supplementation of VitD and leucine-enriched whey protein affected CLIP in subjects enrolled in the PROVIDE-study, as a secondary analysis. METHODS: Sarcopenic adults (low skeletal muscle mass) aged ≥ 65 years with mobility limitations (Short Physical Performance Battery 4-9) and a body mass index of 20-30 kg/m2 were randomly allocated to two daily servings of active (n = 137, including 20 g of whey protein, 3 g of leucine and 800 IU VitD) or isocaloric control product (n = 151) for a double-blind period of 13 weeks. At baseline and after 13 weeks, circulating interleukin (IL)-8, IL-1 receptor antagonist (RA), soluble tumor-necrosis-factor receptor (sTNFR)1, IL-6, high-sensitivity C-reactive protein, pre-albumin and 25-hydroxyvitamin(OH)D were measured. Data-analysis included repeated measures analysis of covariance (corrected for dietary VitD intake) and linear regression. RESULTS: IL-6 and IL-1Ra serum levels showed overall increases after 13 weeks (p = 0.006 and p < 0.001, respectively). For IL-6 a significant time × treatment interaction (p = 0.046) was observed, with no significant change over time in the active group (p = 0.155) compared to control (significant increase p = 0.012). IL-8 showed an overall significant decrease (p = 0.03). The change in pre-albumin was a significant predictor for changes in IL-6 after 13 weeks. CONCLUSIONS: We conclude that 13 weeks of nutritional supplementation with VitD and leucine-enriched whey protein may attenuate the progression of CLIP in older sarcopenic persons with mobility limitations.

Acute inflammation is associated with lower muscle strength, muscle mass and functional dependency in male hospitalised older patients.

BACKGROUND: Hospitalisation is associated with adverse health outcomes including loss of muscle strength, muscle mass and functional decline, which might be further aggravated by acute inflammation. This study aimed to determine whether acute inflammation, as denoted by C-reactive protein (CRP), is associated with muscle strength, muscle mass and functional dependency in hospitalised older patients. METHODS: The observational, prospective EMPOWER study included 378 hospitalised patients aged 70 years and older. As part of the hospital assessment, 191 patients (50.5%) had CRP measured. Muscle strength and mass were measured using handheld dynamometry and bioelectrical impedance analysis respectively. Activities of Daily Living (ADL) were assessed using Katz score and Instrumental ADL (IADL) by Lawton and Brody score. Linear regression analyses and logistic regression analyses were performed stratified by sex and adjusted for age and comorbidities. RESULTS: Mean age was 79.7 years (SD 6.4) and 50.8% were males. On admission and discharge, males with elevated CRP had significantly lower handgrip strength and lower absolute muscle mass compared with males with normal CRP and those with no CRP measured. At three months post-discharge, males with elevated CRP were more likely to be ADL dependent than those with normal CRP and with no CRP measured. In females, no associations were found between CRP and muscle strength, muscle mass, ADL or IADL. CONCLUSIONS: Hospitalised older male patients with acute inflammation had lower muscle strength at admission and discharge and lower absolute muscle mass at admission and higher ADL dependency at three months post-discharge.

Prevalence of sarcopenia in inpatients 70 years and older using different diagnostic criteria.

AIM: To compare prevalence rates of sarcopenia applying multiple diagnostic criteria in hospitalized older patients. DESIGN: Observational, longitudinal EMPOWER study. METHODS: A total of 378 hospitalized inpatients aged 70 years and older were recruited. Muscle mass and strength were measured using bioelectrical impedance analysis and handheld dynamometer respectively. Nine commonly used diagnostic criteria for sarcopenia were applied. Analyses were stratified for sex. RESULTS: Mean age was 79.7 years (SD 6.43) and 50.8% were males. Depending on the applied criterion, prevalence of sarcopenia ranged between 12.0-75.9% in males and 3.1-75.3% in females. Males had a higher prevalence of sarcopenia compared with females in all but one of the applied diagnostic criteria. In males, highest prevalence of sarcopenia was found using muscle mass as diagnostic criterion while in females this was observed when using muscle strength. Five male and one female hospitalized older patients were sarcopenic according to all applied diagnostic criteria.

Lower Skeletal Muscle Mass at Admission Independently Predicts Falls and Mortality 3 Months Post-discharge in Hospitalized Older Patients.

BACKGROUND: Approximately 10% of older adults are annually admitted to a hospital. Hospitalization is associated with a higher risk of falls and mortality after discharge. This study aimed to identify predictors at admission for falls and mortality 3 months post-discharge in hospitalized older patients. METHODS: The Evaluation of Muscle parameters in a Prospective cohort of Older patients at clinical Wards Exploring Relations with bed rest and malnutrition (EMPOWER) study is an observational, prospective longitudinal inception cohort of 378 patients aged 70 years and older who were subsequently admitted to a tertiary hospital (the Netherlands). Potential predictors for falls and mortality 3 months post-discharge were tested using univariate and multivariate logistic regression analyses and included the following domains: demographic (age, sex, living independently), lifestyle (alcohol, smoking), nutrition (SNAQ score), muscle mass (absolute, relative), physical function (handgrip strength, Katz ADL score), cognition (six-item cognitive impairment test score), and disease (medications, diseases). RESULTS: The mean age was 79.6 years (standard deviation 6.23) and 50% were male. Within 3 months post-discharge, 19% reported a fall and 13% deceased. Univariate predictors for falls were higher age, lower absolute muscle mass and higher six-item cognitive impairment test score. Lower absolute muscle mass independently predicted falls post-discharge (multivariate). Univariate predictors for mortality were higher age, male sex, no current alcohol use, higher SNAQ score, lower absolute and higher relative muscle mass, higher Katz ADL score and higher number of diseases. Male sex, higher SNAQ score, and lower absolute muscle mass independently predicted mortality post-discharge (multivariate). CONCLUSIONS: In hospitalized older adults, muscle mass should be measured to predict future outcome. Future intervention studies should investigate if increasing muscle mass prevent short-term falls and mortality.

Lower Cognitive Function in Older Patients with Lower Muscle Strength and Muscle Mass.

BACKGROUND: Low muscle strength and muscle mass are associated with adverse outcomes in older hospitalized patients. The aim of this study was to assess the association between cognitive functioning and muscle strength and muscle mass in hospitalized older patients. METHODS: This prospective inception cohort included 378 patients aged 70 years or older. At admission patients were assessed for cognitive functioning by use of the Six-Item Cognitive Impairment Test (6-CIT). Muscle strength and muscle mass were assessed using handheld dynamometry and segmental multifrequency bioelectrical impedance analysis, within 48 h after admission and on day 7, or earlier on the day of discharge. RESULTS: The data of 371 patients (mean age ± standard deviation 80.1 ± 6.4 years, 49.3% female) were available for analyses. The median (interquartile range) 6-CIT score was 4 (0-8) points. At admission, lower cognitive functioning was associated with lower muscle strength, lower skeletal muscle mass (SMM), lower appendicular lean mass, and lower SMM index. Cognitive functioning was not associated with change in muscle strength and muscle mass during hospitalization. CONCLUSION: This study further strengthens evidence for an association between lower cognitive functioning and lower muscle strength and muscle mass, but without a further decline during hospitalization.

Muscle mass and muscle strength are associated with pre- and post-hospitalization falls in older male inpatients: a longitudinal cohort study.

BACKGROUND: Low muscle mass and strength are highly prevalent in inpatients. It is acknowledged that low muscle mass and strength are associated with falls in community-dwelling older adults, but it is unknown if these muscle measures are also associated with falls in a population of older inpatients. This study aimed to investigate the association between muscle measures and pre- and post-hospitalization falls in older inpatients. METHODS: An inception cohort of patients aged 70 years and older, admitted to an academic teaching hospital, was included in this study. Muscle mass and hand grip strength were measured at admission using bioelectrical impedance analysis and handheld dynamometry. Pre-hospitalization falls were dichotomized as having had at least one fall in the six months prior to admission. Post-hospitalization falls were dichotomized as having had at least one fall during the three months after discharge. Associations were analysed with logistic regression analysis. RESULTS: The study cohort comprised 378 inpatients (mean age, SD: 79.7, 6.4 years). Fifty per cent of female and 41% of male patients reported at least one fall prior to hospitalization. Post-hospitalization, 18% of female and 23% of male patients reported at least one fall. Lower muscle mass was associated with post-hospitalization falls, and lower hand grip strength was associated with both pre- and post-hospitalization falls in male, but not in female, patients. CONCLUSIONS: These findings confirm the likely involvement of muscle mass and strength in the occurrence of pre- and post-hospitalization falls in a population of older inpatients, but only in males.

Reduced dietary intake of micronutrients with antioxidant properties negatively impacts muscle health in aged mice.

BACKGROUND: Inadequate intake of micronutrients with antioxidant properties is common among older adults and has been associated with higher risk of frailty, adverse functional outcome, and impaired muscle health. However, a causal relationship is less well known. The aim was to determine in old mice the impact of reduced dietary intake of vitamins A/E/B6/B12/folate, selenium, and zinc on muscle mass, oxidative capacity, strength, and physical activity (PA) over time. METHODS: Twenty-one-month-old male mice were fed either AIN-93-M (control) or a diet low in micronutrients with antioxidant properties (=LOWOX-B: 50% of mouse recommended daily intake of vitamins A, E, B6, and B12, folate, selenium, and zinc) for 4 months. Muscle mass, grip strength, physical activity (PA), and general oxidative status were assessed. Moreover, muscle fatigue was measured of m. extensor digitorum longus (EDL) during an ex vivo moderate exercise protocol. Effects on oxidative capacity [succinate dehydrogenase (SDH) activity], muscle fibre type, number, and fibre cross-sectional area (fCSA) were assessed on m. plantaris (PL) using histochemistry. RESULTS: After 2 months on the diet, bodyweight of LOWOX-B mice was lower compared with control (P < 0.0001), mainly due to lower fat mass (P < 0.0001), without significant differences in food intake. After 4 months, oxidative status of LOWOX-B mice was lower, demonstrated by decreased vitamin E plasma levels (P < 0.05) and increased liver malondialdehyde levels (P = 0.018). PA was lower in LOWOX-B mice (P < 0.001 vs. control). Muscle mass was not affected, although PL-fCSA was decreased (~16%; P = 0.028 vs. control). SDH activity and muscle fibre type distribution remained unaffected. In LOWOX-B mice, EDL force production was decreased by 49.7% at lower stimulation frequencies (P = 0.038), and fatigue resistance was diminished (P = 0.023) compared with control. CONCLUSIONS: Reduced dietary intake of vitamins A, E, B6, and B12, folate, selenium, and zinc resulted in a lower oxidative capacity and has major impact on muscle health as shown by decreased force production and PA, without effects on muscle mass. The reduced fCSA in combination with similar SDH activity per fibre might explain the reduced oxidative capacity resulting in the increased fatigue after exercise in LOWOX-B mice.

Sufficient levels of 25-hydroxyvitamin D and protein intake required to increase muscle mass in sarcopenic older adults - The PROVIDE study.

BACKGROUND: Inadequate nutritional intake and altered response of aging muscles to anabolic stimuli from nutrients contribute to the development of sarcopenia. Nutritional interventions show inconsistent results in sarcopenic older adults, which might be influenced by their basal nutritional status. OBJECTIVE: To test if baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations and dietary protein intake influenced changes in muscle mass and function in older adults who received nutritional intervention. METHODS AND DESIGN: Post-hoc analysis was performed in the PROVIDE study that was a randomized controlled, double blind trial among 380 sarcopenic older adults. This study showed that those who received a vitamin D and leucine-enriched whey protein medical nutrition drink for 13 weeks gained more appendicular muscle mass (aMM), and improved lower-extremity function as assessed by the chair stand test compared with controls. To define low and high groups, a baseline serum concentration of 50 nmol/L 25(OH)D and baseline dietary protein intake of 1.0 g/kg/d were used as cut offs. RESULTS: At baseline, participants with lower 25(OH)D concentrations showed lower muscle mass, strength and function compared with participants with a high 25(OH)D, while the group with lower protein intake (g/kg/day) had more muscle mass at baseline compared with the participants with higher protein intake. Participants with higher baseline 25(OH)D concentrations and dietary protein intake had, independent of other determinants, greater gain in appendicular muscle mass, skeletal muscle index (aMM/h2), and relative appendicular muscle mass (aMM/body weight × 100%) in response to the nutritional intervention. There was no effect modification of baseline 25(OH)D status or protein intake on change in chair-stand test. CONCLUSIONS: Sufficient baseline levels of 25(OH)D and protein intake may be required to increase muscle mass as a result of intervention with a vitamin D and protein supplement in sarcopenic older adults. This suggests that current cut-offs in the recommendations for vitamin D and protein intake could be considered the "minimum" for adults with sarcopenia to respond adequately to nutrition strategies aimed at attenuating muscle loss.

Supplementing Breakfast with a Vitamin D and Leucine-Enriched Whey Protein Medical Nutrition Drink Enhances Postprandial Muscle Protein Synthesis and Muscle Mass in Healthy Older Men.

Background: A promising strategy to help older adults preserve or build muscle mass is to optimize muscle anabolism through providing an adequate amount of high-quality protein at each meal.Objective: This "proof of principle" study investigated the acute effect of supplementing breakfast with a vitamin D and leucine-enriched whey protein medical nutrition drink on postprandial muscle protein synthesis and longer-term effect on muscle mass in healthy older adults.Methods: A randomized, placebo-controlled, double-blind study was conducted in 24 healthy older men [mean ± SD: age 71 ± 4 y; body mass index (in kg/m2) 24.7 ± 2.8] between September 2012 and October 2013 at the Unit of Human Nutrition, University of Auvergne, Clermont-Ferrand, France. Participants received a medical nutrition drink [test group; 21 g leucine-enriched whey protein, 9 g carbohydrates, 3 g fat, 800 IU cholecalciferol (vitamin D3), and 628 kJ] or a noncaloric placebo (control group) before breakfast for 6 wk. Mixed muscle protein fractional synthesis rate (FSR) was measured at week 0 in the basal and postprandial state, after study product intake with a standardized breakfast with the use of l-[2H5]-phenylalanine tracer methodology. The longer-term effect of the medical nutrition drink was evaluated by measurement of appendicular lean mass, representing skeletal muscle mass at weeks 0 and 6, by dual-energy X-ray absorptiometry.Results: Postprandial FSR (0-240 min) was higher in the test group than in the control group [estimate of difference (ED): 0.022%/h; 95% CI: 0.010%/h, 0.035%/h; ANCOVA, P = 0.001]. The test group gained more appendicular lean mass than the control group after 6 wk (ED: 0.37 kg; 95% CI: 0.03, 0.72 kg; ANCOVA, P = 0.035), predominantly as leg lean mass (ED: 0.30 kg; 95% CI: 0.03, 0.57 kg; ANCOVA, P = 0.034).Conclusions: Supplementing breakfast with a vitamin D and leucine-enriched whey protein medical nutrition drink stimulated postprandial muscle protein synthesis and increased muscle mass after 6 wk of intervention in healthy older adults and may therefore be a way to support muscle preservation in older people. This trial was registered at www.trialregister.nl as NTR3471.

Muscle Strength and Muscle Mass in Older Patients during Hospitalization: The EMPOWER Study.

BACKGROUND: Low muscle strength and muscle mass are associated with an increased length of hospital stay and higher mortality rate in inpatients. To what extent hospitalization affects muscle strength and muscle mass is unclear. OBJECTIVE: We aimed to assess muscle strength and muscle mass at admission and during hospitalization in older patients and its relation with being at risk of geriatric conditions. METHODS: The EMPOWER study included patients aged 70 years and older, admitted to 4 wards of the VU University Medical Center in the Netherlands between April and December 2015. At admission, patients were screened for being at risk of 4 geriatric conditions: delirium, falls, malnutrition, and functional disability. At admission and at discharge, muscle strength and muscle mass were assessed. RESULTS: A total of 373 patients (mean age, standard deviation [SD]: 79.6, 6.38 years) were included at admission, and 224 patients (mean age, SD: 80.1, 6.32 years) at discharge. At admission, lower muscle strength in both female and male patients and low muscle mass in male patients were associated with being at risk of a higher cumulative number of geriatric conditions. Muscle strength increased during hospitalization, but no change in muscle mass was observed. Changes in muscle measures were not associated with being at risk of geriatric conditions. DISCUSSION: Older patients with lower muscle strength and muscle mass at admission were at risk of a higher cumulative number of geriatric conditions. However, being at risk of geriatric conditions did not forecast further decrease in muscle strength and muscle mass during hospitalization.