Rachel R. Deer

Protein intake and muscle function in older adults

Purpose of reviewWe provide an update on the recent advances in nutrition research regarding the role of protein intake in the development and treatment of sarcopenia of aging. Recent findingsSpecific muscle mass, strength and function cut-points for the diagnosis of sarcopenia have been identified. There is mounting evidence, as highlighted by multiple consensus statements, that the Recommended Dietary Allowance (0.8 g/kg body weight) may be inadequate to promote optimal health in older adults. Recent research indicates that in addition to total daily protein intake the timing of protein intake is also important to best stimulate muscle protein synthesis, and maintain muscle mass and function in older adults. SummaryRecent evidence suggests that the Recommended Dietary Allowance for protein is inadequate, and that the timing and distribution of protein consumption throughout daily meals may be as important as the total quantity. Research has continued to advance our understanding of proteins effects on muscle metabolism; however, there remains a need for large, long-term, randomized clinical trials examining whether the positive effects of dietary protein on muscle metabolism seen in acute studies will translate over the long term into gains of muscle mass, function, and the overall health of older adults.

Protein Supplementation Has Minimal Effects on Muscle Adaptations during Resistance Exercise Training in Young Men: A Double-Blind Randomized Clinical Trial

Background: To our knowledge the efficacy of soy-dairy protein blend (PB) supplementation with resistance exercise training (RET) has not been evaluated in a longitudinal study. Objective: Our aim was to determine the effect of PB supplementation during RET on muscle adaptation. Methods: In this double-blind randomized clinical trial, healthy young men [18–30 y; BMI (in kg/m2): 25 ± 0.5] participated in supervised whole-body RET at 60–80% 1-repetition maximum (1-RM) for 3 d/wk for 12 wk with random assignment to daily receive 22 g PB (n = 23), whey protein (WP) isolate (n = 22), or an isocaloric maltodextrin (carbohydrate) placebo [(MDP) n = 23]. Serum testosterone, muscle strength, thigh muscle thickness (MT), myofiber cross-sectional area (mCSA), and lean body mass (LBM) were assessed before and after 6 and 12 wk of RET. Results: All treatments increased LBM (P < 0.001). ANCOVA did not identify an overall treatment effect at 12 wk (P = 0.11). There tended to be a greater change in LBM from baseline to 12 wk in the PB group than in the MDP group (0.92 kg; 95% CI: −0.12, 1.95 kg; P = 0.09); however, changes in the WP and MDP groups did not differ. Pooling data from combined PB and WP treatments showed a trend for greater change in LBM from baseline to 12 wk compared with MDP treatment (0.69 kg; 95% CI: −0.08, 1.46 kg; P = 0.08). Muscle strength, mCSA, and MT increased (P < 0.05) similarly for all treatments and were not different (P > 0.10) between treatments. Testosterone was not altered. Conclusions: PB supplementation during 3 mo of RET tended to slightly enhance gains in whole-body and arm LBM, but not leg muscle mass, compared with RET without protein supplementation. Although protein supplementation minimally enhanced gains in LBM of healthy young men, there was no enhancement of gains in strength. This trial was registered at clinicaltrials.gov as NCT01749189.

Exercise training enhances multiple mechanisms of relaxation in coronary arteries from ischemic hearts

Exercise training of coronary artery disease patients is of considerable interest, since it has been shown to improve vascular function and, thereby, enhance blood flow into compromised myocardial regions. However, the mechanisms underlying exercise-induced improvements in vascular function have not been fully elucidated. We tested the hypothesis that exercise training increases the contribution of multiple mediators to endothelium-dependent relaxation of coronary arteries in the underlying setting of chronic coronary artery occlusion. To induce gradual occlusion, an ameroid constrictor was placed around the proximal left circumflex coronary artery in Yucatan miniature swine. At 8 wk postoperatively, pigs were randomly assigned to sedentary or exercise (treadmill, 5 days/wk) regimens for 14 wk. Exercise training significantly enhanced the contribution of nitric oxide, prostanoids, and large-conductance Ca(2+)-dependent K(+) (BKCa) channels to endothelium-dependent, bradykinin-mediated relaxation in nonoccluded and collateral-dependent arteries. Combined nitric oxide synthase, prostanoid, and BKCa channel inhibition ablated the enhanced relaxation associated with exercise training. Exercise training significantly increased nitric oxide levels in response to bradykinin in endothelial cells isolated from nonoccluded and collateral-dependent arteries. Bradykinin treatment significantly increased PGI2 levels in all artery treatment groups and tended to be further enhanced after nitric oxide synthase inhibition in exercise-trained pigs. No differences were found in whole cell BKCa channel currents, BKCa channel protein levels, or arterial cyclic nucleotide levels. Although redundant, upregulation of parallel vasodilator pathways appears to contribute to enhanced endothelium-dependent relaxation, potentially providing a more refined control of blood flow after exercise training.

Inpatient Walking Activity to Predict Readmission in Older Adults

OBJECTIVE To compare the 30-day readmission predictive power of in-hospital walking activity and in-hospital activities of daily living (ADLs) in older acutely ill patients. In addition, we sought to identify preliminary walking thresholds that could support the targeting of interventions aimed at minimizing rehospitalizations. DESIGN Prospective, observational clinical cohort study. Step counts during hospitalization were assessed via accelerometry. ADL function was assessed within 48 hours of admission. SETTING Acute care hospital. PARTICIPANTS One hundred sixty-four ambulatory persons aged 65 years and older admitted to the hospital from the community with an acute medical illness. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Readmission back to the index hospital (yes vs no) within 30 days of discharge. RESULTS Twenty-six patients (15.8%) were readmitted within 30 days of discharge. Walking activity during hospitalization was more strongly and significantly associated with 30-day readmission (odds ratio=0.90; 95% confidence interval, 0.82-0.98) than ADL function (odds ratio=0.45; 95% confidence interval, 0.14-1.45) after adjusting for relevant readmission risk factors. The predictive accuracy (area under the curve) was highest for models that included walking activity and changed little with the addition of ADLs. A walking threshold of 275 steps or more per day identified patients at reduced 30-day readmission risk. CONCLUSIONS Walking activity was a stronger predictor of readmission than ADLs. Monitoring patient activity during hospitalization may provide clinicians with valuable information on early readmission risk not captured by measures of ADLs. Further study is needed to replicate these findings and monitor walking activity posthospitalization to further advance our understanding of readmission risk.

Protein supplementation does not affect myogenic adaptations to resistance training

It has been proposed that protein supplementation during resistance exercise training enhances muscle hypertrophy. The degree of hypertrophy during training is controlled in part through the activation of satellite cells and myonuclear accretion. Purpose This study aimed to determine the efficacy of protein supplementation (and the type of protein) during traditional resistance training on myofiber cross-sectional area, satellite cell content, and myonuclear addition. Methods Healthy young men participated in supervised whole-body progressive resistance training 3 d·wk−1 for 12 wk. Participants were randomized to one of three groups ingesting a daily 22-g macronutrient dose of soy–dairy protein blend (PB, n = 22), whey protein isolate (WP, n = 15), or an isocaloric maltodextrin placebo (MDP, n = 17). Lean mass, vastus lateralis myofiber-type–specific cross-sectional area, satellite cell content, and myonuclear addition were assessed before and after resistance training. Results PB and the pooled protein treatments (PB + WP = PRO) exhibited a greater whole-body lean mass %change compared with MDP (P = 0.057 for PB) and (P = 0.050 for PRO), respectively. All treatments demonstrated similar leg muscle hypertrophy and vastus lateralis myofiber-type–specific cross-sectional area (P < 0.05). Increases in myosin heavy chain I and II myofiber satellite cell content and myonuclei content were also detected after exercise training (P < 0.05). Conclusion Protein supplementation during resistance training has a modest effect on whole-body lean mass as compared with exercise training without protein supplementation, and there was no effect on any outcome between protein supplement types (blend vs whey). However, protein supplementation did not enhance resistance exercise–induced increases in myofiber hypertrophy, satellite cell content, or myonuclear addition in young healthy men. We propose that as long as protein intake is adequate during muscle overload, the adaptations in muscle growth and function will not be influenced by protein supplementation.

Soy-Dairy Protein Blend or Whey Protein Isolate Ingestion Induces Similar Postexercise Muscle Mechanistic Target of Rapamycin Complex 1 Signaling and Protein Synthesis Responses in Older Men

Background: Previous work demonstrated that a soy-dairy protein blend (PB) prolongs hyperaminoacidemia and muscle protein synthesis in young adults after resistance exercise. Objective: We investigated the effect of PB in older adults. We hypothesized that PB would prolong hyperaminoacidemia, enhancing mechanistic target of rapamycin complex 1 (mTORC1) signaling and muscle protein anabolism compared with a whey protein isolate (WPI). Methods: This double-blind, randomized controlled trial studied men 55–75 y of age. Subjects consumed 30 g protein from WPI or PB (25% soy, 25% whey, and 50% casein) 1 h after leg extension exercise (8 sets of 10 repetitions at 70% one-repetition maximum). Blood and muscle amino acid concentrations and basal and postexercise muscle protein turnover were measured by using stable isotopic methods. Muscle mTORC1 signaling was assessed by immunoblotting. Results: Both groups increased amino acid concentrations (P < 0.05) and mTORC1 signaling after protein ingestion (P < 0.05). Postexercise fractional synthesis rate (FSR; P ≥ 0.05), fractional breakdown rate (FBR; P ≥ 0.05), and net balance (P = 0.08) did not differ between groups. WPI increased FSR by 67% (mean ± SEM: rest: 0.05% ± 0.01%; postexercise: 0.09% ± 0.01%; P < 0.05), decreased FBR by 46% (rest: 0.17% ± 0.01%; postexercise: 0.09% ± 0.03%; P < 0.05), and made net balance less negative (P < 0.05). PB ingestion did not increase FSR (rest: 0.07% ± 0.03%; postexercise: 0.09% ± 0.01%; P ≥ 0.05), tended to decrease FBR by 42% (rest: 0.25% ± 0.08%; postexercise: 0.15% ± 0.08%; P = 0.08), and made net balance less negative (P < 0.05). Within-group percentage of change differences were not different between groups for FSR, FBR, or net balance (P ≥ 0.05). Conclusions: WPI and PB ingestion after exercise in older men induced similar responses in hyperaminoacidemia, mTORC1 signaling, muscle protein synthesis, and breakdown. These data add new evidence for the use of whey or soy-dairy PBs as targeted nutritional interventions to counteract sarcopenia. This trial was registered at clinicaltrials.gov as NCT01847261.

Identifying effective and feasible interventions to accelerate functional recovery from hospitalization in older adults: A randomized controlled pilot trial

Hospitalization induces functional decline in older adults. Many geriatric patients fail to fully recover physical function after hospitalization, which increases the risk of frailty, disability, dependence, re-hospitalization, and mortality. There is a lack of evidence-based therapies that can be implemented following hospitalization to accelerate functional improvements. The aims of this Phase I clinical trial are to determine 1) the effect size and variability of targeted interventions in accelerating functional recovery from hospitalization and 2) the feasibility of implementing such interventions in community-dwelling older adults. Older patients (≥65years, n=100) will be recruited from a single site during hospitalization for an acute medical condition. Subjects will be randomized to one of five interventions initiated immediately upon discharge: 1. protein supplementation, 2. in-home rehabilitation plus placebo supplementation, 3. in-home rehabilitation plus protein supplementation, 4. single testosterone injection, or 5. isocaloric placebo supplementation. Testing will occur during hospitalization (baseline) and at 1 and 4weeks post-discharge. Each testing session will include measures of muscle strength, physical function/performance, body composition, and psychological function. Physical activity levels will be continuously monitored throughout study participation. Feasibility will be determined through collection of the number of eligible, contacted, and enrolled patients; intervention adherence and compliance; and reasons for declining enrollment and study withdrawal. This research will determine the feasibility of post-hospitalization strategies to improve physical function in older adults. These results will also provide a foundation for performing larger, multi-site clinical trials to improve physical function and reduce readmissions in geriatric patents.

Effect of Home- and Community-Based Physical Activity Interventions on Physical Function Among Cancer Survivors: A Systematic Review and Meta-Analysis

OBJECTIVE To examine the effect of home- and community-based physical activity interventions on physical functioning among cancer survivors based on the most prevalent physical function measures, randomized trials were reviewed. DATA SOURCES Five electronic databases-Medline Ovid, PubMed, CINAHL, Web of Science, and PsycINFO-were searched from inception to March 2016 for relevant articles. STUDY SELECTION Search terms included community-based interventions, physical functioning, and cancer survivors. A reference librarian trained in systematic reviews conducted the final search. DATA EXTRACTION Four reviewers evaluated eligibility and 2 reviewers evaluated methodological quality. Data were abstracted from studies that used the most prevalent physical function measurement tools-Medical Outcomes Study 36-Item Short-Form Health Survey, Late-Life Function and Disability Instrument, European Organisation for the Research and Treatment of Cancer Quality-of-Life Questionnaire, and 6-minute walk test. Random- or fixed-effects models were conducted to obtain overall effect size per physical function measure. DATA SYNTHESIS Fourteen studies met inclusion criteria and were used to compute standardized mean differences using the inverse variance statistical method. The median sample size was 83 participants. Most of the studies (n=7) were conducted among breast cancer survivors. The interventions produced short-term positive effects on physical functioning, with overall effect sizes ranging from small (.17; 95% confidence interval [CI], .07-.27) to medium (.45; 95% CI, .23-.67). Community-based interventions that met in groups and used behavioral change strategies produced the largest effect sizes. CONCLUSIONS Home and community-based physical activity interventions may be a potential tool to combat functional deterioration among aging cancer survivors. More studies are needed among other cancer types using clinically relevant objective functional measures (eg, gait speed) to accelerate translation into the community and clinical practice.

A randomized controlled pilot trial of interventions to improve functional recovery after hospitalization in older adults: Feasibility and adherence

Background Hospitalization is a major risk factor for functional decline, disability, loss of independence, and mortality in older adults. Evidence-based interventions to improve functional recovery from hospitalization are difficult to evaluate and implement in geriatric patients. The goal of this pilot study was to test the feasibility of recruiting geriatric inpatients and implementing pragmatic interventions to improve physical function following hospitalization. Methods Enrolled subjects were randomized to one of five 30-day posthospitalization interventions: isocaloric placebo (P), whey protein supplement (W), in-home rehabilitation+placebo (R+P), rehabilitation+whey protein (R+W), or testosterone (T). Data were collected from a single-site university hospital to determine: (i) institution-based feasibility (nonmodifiable factors including number of patients screened, eligible, contacted) and (ii) patient-based feasibility (modifiable factors including number of patients refusing, enrolled, randomized, intervention adherence, and withdrawal). Results From January 2014 to July 2016, 4,533 patients were chart screened; 594 (13.1%) were eligible to participate; 384 eligible subjects were contacted; 113 were enrolled; and 100 were randomized. Supplement adherence was 75% and was not different by age, education, level of independence, depression, supplement type, or dual intervention, but was significantly higher in subjects who completed the intervention (p < .01). Rehabilitation session adherence was 77% and did not vary significantly by age, education, level of independence, depression, or supplement type, but was significantly higher for sessions directly supervised (p < .01). Adherence was 100% in the testosterone arm with 94.7% of injections given within 24 hours of discharge. Conclusions Findings from this clinical trial indicate that posthospitalization interventions in geriatric patients are feasible at both the institution and patient level.

Androgen Therapy and Rehospitalization in Older Men With Testosterone Deficiency

OBJECTIVE To assess whether the receipt of androgen therapy is associated with a reduced 30-day rehospitalization rate among older men with testosterone deficiency. PATIENTS AND METHODS We conducted a retrospective cohort study using a 5% national sample of Medicare beneficiaries. We identified 6372 nonsurgical hospitalizations between January 1, 2007, and December 31, 2012, for male patients aged 66 years and older with a previous diagnosis of testosterone deficiency. Patients who died or lost Medicare coverage in the 30 days after hospital discharge or who were discharged to another inpatient setting were excluded from the analysis. Logistic regression was used to calculate odds ratios (ORs) and 95% CIs for the risk of 30-day hospital readmissions associated with receipt of androgen therapy. RESULTS In older men with testosterone deficiency, receipt of androgen therapy was associated with a reduced risk of rehospitalization (91 of 929 androgen users [9.8%] vs 708 of 5443 non-androgen users [13.0%]; OR, 0.73; 95% CI, 0.58-0.92) in the 30 days after hospital discharge. In a logistic regression analysis adjusting for multiple demographic, clinical, and health service variables, the OR was similar (OR, 0.75; 95% CI, 0.59-0.95). The adjusted OR for unplanned 30-day hospital readmissions was 0.62 (95% CI, 0.47-0.83). Each of these findings persisted across a range of propensity score analyses-including adjustment, stratification, and inverse probability treatment weighting-and several sensitivity analyses. CONCLUSION Androgen therapy may reduce the risk of rehospitalization in older men with testosterone deficiency. Given the high rates of early hospital readmission among older adults, further exploration of this intervention holds broad clinical and public health relevance.