The Influence of Branched-Chain Amino Acid Supplementation on Fatigue and Tryptophan Metabolism After Acute and Chronic Exercise in Older Adults: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: Fatigue is a strong predictor of negative health outcomes in older adults. Kynurenine, a metabolite of tryptophan, is strongly associated with fatigue. Reductions in fatigue are observed with exercise; however, exercise training does not completely alleviate symptoms. Branched-chain amino acids (BCAAs) have been shown to have advantageous effects on exercise performance and compete with kynurenine for transport into the central nervous system. Thus, the combination of BCAA and exercise may exert synergized effects of mental and physical fatigue. Therefore, we hypothesize that BCAA added to exercise will shift kynurenine metabolism toward enhanced synthesis of kynurenic acid, thereby reducing fatigue. OBJECTIVE: This randomized, double-blind, placebo-controlled trial aims to compare the effects of acute (approximately 45 min) and chronic (8 wk) exercise with and without BCAA supplementation on mental and physical fatigue and assess whether the hypothesized outcomes are modulated by changes in kynurenine metabolism in 30 older adults (n=15, 50% per group). METHODS: Older adults (aged 60-80 y) who do not exercise >2 days per week and self-report fatigue (≥3 on a scale of 1-10) will be recruited. Participants will be randomized to either the exercise+BCAA group or exercise+placebo group. Participants will engage in high-volume, moderate-intensity, whole-body exercise training (aerobic and resistance exercise; either in-person or web-based sessions) 3 times per week for 8 weeks. In addition, participants will consume daily either 100 mg/kg body weight of BCAA (2:1:1 leucine:isoleucine:valine) or placebo (maltodextrin) throughout the 8-week intervention. BCAA and placebo powders will be identical in color and dissolved in 400 mL of water and 2.5 g of a calorie-free water flavor enhancer. Muscle biopsies will be collected before and after the intervention after a 12-hour fast to examine changes in the biomarkers of tryptophan metabolism and inflammation. Our primary outcomes include changes in mental and physical fatigue and metabolism after the 8-week exercise training between the 2 groups. Mental and physical fatigue will be measured before and after the intervention. Mental fatigue will be subjectively assessed through the completion of validated questionnaires. Physical fatigue will be measured by isometric handgrip, 1-repetition maximum, chair rise, 400-meter walk, and cardiopulmonary exercise tests. RESULTS: The study was funded in March 2022, with an anticipated projected data collection period lasting from January 2023 through December 2023. CONCLUSIONS: The discovery that kynurenine concentrations are associated with fatigue and are responsive to BCAA supplementation during exercise training could have important implications for the development of future interventions, both lifestyle and pharmacologic, to treat fatigue in older adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT05484661; https://www.clinicaltrials.gov/study/NCT05484661. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52199.

Prevalence and socio-economic determinates of food insecurity in Veterans: findings from National Health and Nutrition Examination Survey.

OBJECTIVE: To determine predictors of the association between being a Veteran and adult food security, as well as to examine the relation of potential covariates to this relationship. DESIGN: Data collected during 2011-2012, 2013-2014 and 2015-2016 National Health and Nutrition Examination Survey (NHANES) were pooled for analyses. Veterans (self-reported) were matched to non-Veterans on age, race/ethnicity, sex and education. Adjusted logistic regression was used to determine the odds of Veterans having high food security v. the combination of marginal, low and very low food security compared with non-Veterans. SETTING: 2011-2012, 2013-2014 and 2015-2016 NHANES. PARTICIPANTS: 1227 Veterans; 2432 non-Veterans. RESULTS: Veteran status had no effect on the proportion of food insecurities between Veterans and non-Veterans reporting high (Veterans v. non-Veteran: 79 % v. 80 %), marginal (9 % v. 8 %), low (5 % v. 6 %) and very low (8 % v. 6 %) food security (P = 0·11). However, after controlling for covariates, Veterans tended to be less likely to have high food security (OR: 0·82 (95 % CI 0·66, 1·02), P = 0·07). Further, non-Hispanic White Veterans (OR: 0·72 (95 % CI 0·55, 0·95), P = 0·02) and Veterans completing some college (OR: 0·71 (95 % CI 0·50, 0·99), P < 0·05) were significantly less likely to experience high food security compared with non-Veterans. CONCLUSION: This study supports previous research findings that after controlling for covariates, Veterans tend to be less likely to have high food security. It also highlights ethnicity and level of education as important socio-economic determinates of food security status in Veterans.

Randomization to Treadmill Training Improves Physical and Metabolic Health in Association With Declines in Oxidative Stress in Stroke.

OBJECTIVE: To investigate the effect of aerobic exercise vs control (stretching/balance) on inflammatory and oxidative stress biomarkers in stroke survivors and whether these changes are associated with improvements in physical and metabolic health. DESIGN: Randomized controlled trial. SETTING: The general communities of Baltimore, Maryland, and Atlanta, Georgia. PARTICIPANTS: Two hundred forty-six older (>50 years), chronic (>6 months) survivors of stroke (N=246) with hemiparetic gait were recruited, with 51 completing pre-intervention testing and 39 completing postintervention testing. Participants were required to have completed all conventional physical therapy and be capable of walking 3 minutes on a treadmill (N=246). INTERVENTION: Participants completed 6 months of 2 times/wk stretching or balance (ST; n=19) or 3 times/wk aerobic treadmill rehabilitation (TM; n=20;). MAIN OUTCOME MEASURE(S): Peak oxygen uptake rate (V̇o2peak), 6-minute walking distance (6MWD), fasting plasma glucose, insulin, oxidative stress, and inflammatory biomarkers were assessed pre- and postintervention. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was calculated. RESULTS: Physical function and metabolic health parameters tended to improve after TM but not ST (ST vs TM: V̇o2peak: -9% vs 24%, P<.01; 6MWD: 1% vs 15%, P=.05; insulin: -1% vs -31%, P=.05; HOMA-IR: -3% vs -29%, P=.06). Plasma concentrations of nitrotyrosine, protein carbonyls, and oxidized low-density lipoprotein (oxLDL) tended to decrease from pre-intervention concentrations in response to TM compared to ST (ST vs TM: nitrotyrosine: 2% vs -28%, P=.01; protein carbonyls: -4% vs -34%, P=.08; oxLDL: -3% vs -32%, P<.01). Changes in circulating concentrations of C-reactive protein, protein carbonyls, and oxLDL were negatively associated with changes in V̇o2peak and 6MWD (r's=-0.40 to -0.76) and positively associated with fasting plasma insulin and HOMA-IR (r's=0.52-0.81, Ps<.01). CONCLUSIONS: Six months of TM tends to be associated with increased functional capacity and reduced oxidative stress in chronic stroke survivors. Our findings identify potentially modifiable systemic markers of inflammation and oxidative stress important to stroke rehabilitation and provide potential targets for novel therapeutics in future studies.

Intervention in Older Urban-Dwelling Veterans With Dysmobility: Protocol for a Pilot Feasibility Clinical Trial.

BACKGROUND: The majority of older veterans do not meet the minimum healthy diet or physical activity recommendations despite known benefits. Identifying ways to increase adherence to programs that improve dietary quality and physical activity may reduce the risk of disability in older veterans. Peer-based interventions may be one method for facilitating lasting behavior change because peers often share a common culture and knowledge regarding problems their community experiences. OBJECTIVE: This study aims to develop, pilot, and evaluate a theory-driven, 12-week, peer-led nutrition and exercise intervention that targets older veterans with dysmobility and assess its feasibility in 2 diverse urban areas with underrepresented populations. METHODS: Community-dwelling veterans aged >65 years with self-reported dysmobility (defined as difficulty in at least 1 of the following: walking quickly across a street, walking a mile, ascending a flight of stairs, rising from a chair without the use of arms, or a fear of falling) from 2 Department of Veterans Affairs Geriatric Research, Education, and Clinic Centers (Baltimore, Maryland, and San Antonio, Texas) will be eligible to participate. First, this study will use validated mixed methods via web-based surveys (n=50 per site) to assess potential physical, social or environmental, and behavioral or lifestyle barriers that affect physical activity and dietary quality (phase 1). Next, we will use knowledge gained from these assessments and feedback from a focus group (n=10 per site) to adapt established Department of Veterans Affairs diet and exercise program materials to develop peer-led intervention materials and train peer leaders (n=3 per site). Finally, we will determine the feasibility and acceptability of the intervention to assess reach (recruitment and retention), adoption (satisfaction, perceived utility, attendance, and engagement), and implementation (fidelity of intervention), as well as the estimated magnitude and potential impact on selected outcomes (ie, diet quality and mobility) in 20 older veterans with dysmobility (n=10 per site). RESULTS: The study was funded on January 1, 2022, with a projected data collection period of June 1, 2022, to December 31, 2023. CONCLUSIONS: This study offers an innovative approach to identifying strategies that increase long-term adherence to lifestyle modification programs that improve dietary quality and physical activity in older veterans with dysmobility. TRIAL REGISTRATION: ClinicalTrials.gov NCT04994938; https://clinicaltrials.gov/ct2/show/NCT04994938. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/39192.

Kynurenine Metabolism as a Mechanism to Improve Fatigue and Physical Function in Postmenopausal Breast Cancer Survivors Following Resistance Training.

This pilot examines whether resistance training (RT) can induce changes in kynurenine (KYN) metabolism, which may contribute to improved physical function in breast cancer survivors (BCSs). Thirty-six BCSs (63.2 ± 1.1 years) underwent assessments of physical function and visual analog scale (100 cm) fatigue and quality of life before and after 12 weeks of RT (N = 22) or non-exercise control (CBCT©: Cognitively Based Compassion Training, N = 10). Blood was collected before and after interventions for assessment of KYN, kynurenic acid (KYNA), and peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α). At baseline, the women were moderately fatigued (mean score: 46 cm) and at risk of poor functional mobility. A group*time interaction was observed for all measures of strength with improvements (~25−35%) following RT (p's < 0.01), but not CBCT. Time effects were observed for fatigue (−36%) and quality of life (5%) (p's < 0.01), where both groups improved in a similar manner. A group*time interaction was observed for KYN (p = 0.02) and PGC-1α (p < 0.05), with KYN decreasing and PGC-1α increasing following RT and the opposite following CBCT. These changes resulted in KYN/KYNA decreasing 34% post-RT, but increasing 21% following CBCT. These data support RT as a therapeutic intervention to counteract the long-term side effect of fatigue and physical dysfunction in BCSs. Additionally, the results suggest that this effect may be mediated through the activation of PGC-1α leading to alterations in KYN metabolism.

Effect of Dietary Intake Through Whole Foods on Cognitive Function: Review of Randomized Controlled Trials.

PURPOSE OF REVIEW: This review evaluated recent randomized controlled trials (RCTs) examining the chronic intake of whole foods associated with the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), Mediterranean-DASH Intervention for Neurogenerative Delay (MIND), and ketogenic (KETO) diets on cognitive function. RECENT FINDINGS: We identified RCTs related to olive oil (N = 3), nuts (N = 7), fatty fish (N = 1), lean meats (N = 4), fruits and vegetables (N = 9), legumes (N = 1), and low-fat dairy (N = 4), with 26/29 reporting positive results on at least one measure of cognition. We also identified 6 RCTs related to whole food-induced KETO diets, with half reporting positive effects on cognition. Variations in study design (i.e., generally the studies are < 6 months and include middle-aged and older, cognitively intact participants) and small sample sizes make it difficult to draw conclusions across studies; however, the current evidence from RCTs generally supports individual component intakes of these dietary patterns as an effective, nonpharmacological approach to improve cognitive health in adults.

Efficacy of various prescribed vitamin D supplementation regimens on 25-hydroxyvitamin D serum levels in long-term care.

OBJECTIVE: The aims of this study were to examine the efficacy among various vitamin D supplementation regimens on serum 25-hydroxyvitamin D (25(OH)D) concentrations and determine the minimal dose rate required to achieve sufficient serum concentrations (≥75 nmol/l) among older adults in long-term care (LTC). DESIGN: A 1-year medical history was abstracted from medical records, and a one-time blood draw to measure serum 25(OH)D concentrations was obtained. Individuals were stratified into vitamin D-supplemented and non-supplemented groups. The supplemented group was further categorised into four treatment forms: single-ingredient vitamin D2or3, multivitamin, Ca with vitamin D or combination of the three, and by daily prescribed doses: 0-9·9, 10-19·9, 20-49·9, 50-99·9 and >100 µg/d. SETTING: Five LTC communities in Austin, Texas. PARTICIPANTS: One hundred seventy-three older (≥65 years) adults. RESULTS: Of the participants, 62% received a vitamin D supplement and 55% had insufficient (≤75 nmol/l) 25(OH)D serum concentrations. Individuals receiving single-ingredient vitamin D2or3 supplementation received the highest daily vitamin D mean dose (72·5 µg/d), while combination of forms was the most frequent treatment (44%) with the highest mean serum concentration (108 nmol/l). All supplementation doses were successful at reaching sufficient serum concentrations, except those<20 µg/d. Using a prediction model, it was observed that 0·025 µg/d of vitamin D supplementation resulted in a 0·008 nmol/l increase in serum 25(OH)D concentrations. CONCLUSIONS: Based on the predictive equation, results suggest that supplementation of 37·5 µg/d of vitamin D2or3 or combination of vitamin D is most likely to achieve sufficient serum 25(OH)D concentrations in older adults in LTC.