Dietary isoleucine content defines the metabolic and molecular response to a Western diet.

The amino acid composition of the diet has recently emerged as a critical regulator of metabolic health. Consumption of the branched-chain amino acid isoleucine is positively correlated with body mass index in humans, and reducing dietary levels of isoleucine rapidly improves the metabolic health of diet-induced obese male C57BL/6J mice. However, it is unknown how sex, strain, and dietary isoleucine intake may interact to impact the response to a Western Diet (WD). Here, we find that although the magnitude of the effect varies by sex and strain, reducing dietary levels of isoleucine protects C57BL/6J and DBA/2J mice of both sexes from the deleterious metabolic effects of a WD, while increasing dietary levels of isoleucine impairs aspects of metabolic health. Despite broadly positive responses across all sexes and strains to reduced isoleucine, the molecular response of each sex and strain is highly distinctive. Using a multi-omics approach, we identify a core sex- and strain- independent molecular response to dietary isoleucine, and identify mega-clusters of differentially expressed hepatic genes, metabolites, and lipids associated with each phenotype. Intriguingly, the metabolic effects of reduced isoleucine in mice are not associated with FGF21 - and we find that in humans plasma FGF21 levels are likewise not associated with dietary levels of isoleucine. Finally, we find that foods contain a range of isoleucine levels, and that consumption of dietary isoleucine is lower in humans with healthy eating habits. Our results demonstrate that the dietary level of isoleucine is critical in the metabolic and molecular response to a WD, and suggest that lowering dietary levels of isoleucine may be an innovative and translatable strategy to protect from the negative metabolic consequences of a WD.

Updated Systematic Review and Quantitative Synthesis of Physical Activity Levels in Multiple Sclerosis.

OBJECTIVE: This article provided an updated quantitative synthesis of physical activity levels in persons with multiple sclerosis compared with controls and other clinical populations. DESIGN: A systematic search through PubMed, Scopus, and PsycINFO was conducted for articles published between August 2016 and July 2022. Articles that included a group comparison of at least one measurement of physical activity between adults with multiple sclerosis and controls or other clinical populations were included in the meta-analysis. RESULTS: Twenty-four studies met the inclusion criteria and yielded a total of 119 comparisons. There was a moderate difference in physical activity levels between persons with multiple sclerosis and controls (effect size = -0.56, P < 0.01), but no significant difference between persons with multiple sclerosis and other clinical populations (effect size = 0.01, P = 0.90). The pooled effect sizes comparing multiple sclerosis with controls ( Q104 = 457.9, P < 0.01) as well as with clinical populations ( Q13 = 108.4, P < 0.01) were heterogeneous. Moderating variables included sex, disability status, measurement method, outcome, intensity, and application of a multiple sclerosis-specific cut-point. CONCLUSIONS: Physical activity levels remain significantly lower in persons with multiple sclerosis compared with controls, but the magnitude of difference has become smaller over the past decade. There is a need for continued development of effective physical activity programs that can reach the greater community with multiple sclerosis.

Support moment distribution during the back squat at different depths and loads in recreationally trained females.

OBJECTIVES: The squat is used in athletic and clinical settings. However, the coordination of the lower extremity during the lift is not well understood. The purpose was to compare the peak moments of the lower extremity joints at three squat depths (above parallel, parallel and full) and three squat loads (unloaded, 50 % 1 repetition maximum, and 85 % of depth specific 1 repetition maximum) and find their contribution to support (Ms). DESIGN: Nineteen females performed squats in a randomized order. METHODS: Inverse dynamics and Winter's Ms equation were used to calculate peak moments of the hip, knee and ankle and calculate their contribution to Ms (α < 0.05). RESULTS: Peak hip and ankle extensor moments varied with load but not depth and were greatest when using 85 % 1 repetition maximum. Peak knee extensor moments demonstrated a depth by load interaction. Within each depth as load increased so too did peak knee extensor moments and were highest squatting below parallel when loaded. The hip and knee contribution to Ms demonstrated a depth by load interaction while the ankle was only influenced by load. Within each depth as load increased hip contribution increased whereas the knee decreased contribution. When squatting with load the contribution of the hip decreased at below parallel while the knee increased. CONCLUSIONS: To maximize peak hip moments squat with high load and to maximize peak knee moments squat deep with high load; however, depth and load dosages should be taken into consideration based on the status and goals of the individual.

Systematic review and meta-analysis of sedentary behavior in persons with multiple sclerosis.

BACKGROUND: Persons with multiple sclerosis (MS) engage in less physical activity than the general population, and the disease manifestations and comorbidity conditions might further predispose them toward sedentary behavior (SB) among this population. We performed a systematic review with meta-analysis of studies that compared SB in persons with MS and non-MS controls, and examined factors that may moderate the difference in SB between the two groups. METHODS: We conducted a systematic search using PubMed, PsycINFO, Scopus, and CINAHL from inception up to August 2022, and identified studies that involved group comparison of SB outcomes between MS and non-MS controls. Effect sizes were calculated as standardized mean differences (SMDs) using Hedge's g. We generated a multilevel random-effects model for estimating an overall effect, and performed moderator analyses. Methodological quality was assessed using the Appraisal Tool for Cross-Sectional Studies (AXIS tool). RESULTS: Eleven studies were included (1403 MS vs. 449 controls) and yielded 17 effects for meta-analysis. Results indicated an overall small, but significant effect (SMD [95% CI] = 0.27 [0.02, 0.53], p = 0.03) with significant heterogeneity (Q16 = 72.2, p < 0.01; I2total = 75.8%). There were larger effects when the MS sample had a higher proportion of females, or when SB was reported as percent sedentary time per day compared with other SB outcomes (p = 0.03 and 0.05, respectively). The included studies achieved fairly good quality (91.4%) using the AXIS tool. CONCLUSIONS: The cumulative evidence supports that persons with MS engage in more SB than non-MS controls. Our findings may support the design of targeted behavioral change interventions for reducing SB and improving health and function in the MS population.

Eight Weeks of Daily Cannabidiol Supplementation Improves Sleep Quality and Immune Cell Cytotoxicity.

BACKGROUND: The endocannabinoid system is active in nervous and immune cells and involves the expression of two cannabinoid receptor genes (CB1 and CB2), along with endogenous endocannabinoid ligands, 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (anandamide), and their synthetic enzymes. Cannabidiol (CBD) is a non-intoxicating exogenous cannabinoid agonist derived from plants that, at high doses, has received FDA approval as an anticonvulsant for epileptic seizures, and at low doses is marketed as a food-grade supplement for improved mental health, sleep quality, and immunological function. At present, the predominance of published CBD clinical research has focused on ameliorative or disease-specific intervention, with few trials investigating CBD effects in healthy populations. METHODS: This clinical study aimed to investigate the effects of 8 weeks of 50 mg oral CBD on mental health, sleep quantity and quality, and immune cell function in healthy, college-aged individuals. Twenty-eight participants (average age 25.9 ± 6.1 y) were randomized to receive either daily oral capsules of 50 mg of CBD (CB, n = 14) or a calorie-matched placebo (CN, n = 14). Participants completed pre- and post-intervention assessments, including anthropometric measurements, mental health surveys, sleep analysis, and immunological function assessments. RESULTS: After completing the 8-week intervention, there were no significant changes in body weight and BMI (CN: 1.09 ± 0.89%: CB: 1.41 ± 1.07%), or body fat percentage (CN: 9.01 ± 7.51%: CB: 8.57 ± 7.81%), respectively (values are % change pre to post, p > 0.05). There were also no significant differences between CB and CN groups with respect to mental health measures, sleep quantity, or circulating immunophenotype as a result of the intervention. However, the CB group experienced significant improvements in sleep quality measured objectively using a sleep questionnaire (p = 0.0023) and enhanced Natural Killer (NK) immune cell function assessed in situ (p = 0.0125). CONCLUSIONS: Eight weeks of daily 50 mg CBD may improve sleep quality, and NK immunosurveillance in healthy, younger adults.

Genome-wide tracing to decipher nuclear organization.

Nuclear organization impacts gene expression activity and cell phenotype. Our current understanding is mainly derived from ensemble-level sequencing studies that reflect the 3D genome structure of millions of cells. These approaches have provided invaluable details on the 3D organizations of the genome and their relation to other nuclear landmarks. However, they mostly lack the ability to provide multimodal information simultaneously at the single-cell level. In recent years, cutting-edge imaging technologies have risen to the challenge of simultaneously describing multiple components of the nuclear space at the single-cell level, paving the way for a deeper understanding of the genome structure-function relationship. This review will focus on the development and utilization of such technologies to gain a multi-component view of the nucleus at single-cell resolution, dissecting the complexity and heterogeneity of nuclear organization.

Effects of Oral Cannabidiol on Health and Fitness in Healthy Adults: An 8-Week Randomized Trial.

BACKGROUND: There is a lack of research on the effects of cannabidiol (CBD) on health-related fitness, physical activity, cognitive health, psychological wellbeing, and concentrations of C-reactive protein (CRP) in healthy individuals. CBD has potential anti-inflammatory and neuroprotective effects. METHODS: This study aimed to investigate the effects of 8 weeks of CBD on the above-mentioned measures in healthy individuals. Forty-eight participants were randomized into two groups receiving either oral capsules of 50 mg of CBD or a calorie-matched placebo daily. Participants completed pre- and post-intervention assessments, including blood draws, body composition, fitness, physical activity, and self-reported surveys. RESULTS: There were no significant differences between groups regarding body composition, aerobic fitness, muscular strength, physical activity, cognitive health, psychological wellbeing, and resting CRP concentrations. However, the placebo group experienced a decline in mean peak power and relative peak power compared to the CBD group. CONCLUSIONS: The results suggest that 8 weeks of CBD supplementation may prevent declines in anaerobic fitness over time. However, long-term CBD supplementation may not be beneficial for altering measures of health-related fitness, mental health, and inflammation in healthy individuals.

Effects of aerobic, resistance, and combined exercise training on health-related quality of life in multiple sclerosis: Systematic review and meta-analysis.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated, neurodegenerative disease of the central nervous system that manifests in symptoms that compromise health-related quality of life (HRQOL). HRQOL focuses on a person's overall, subjective evaluation of health status primarily in the physical and mental domains. Exercise training is a form of rehabilitation for managing MS-related outcomes that might influence HRQOL. Reviews on exercise training are available, but we are unaware of a recent comprehensive review and meta-analysis of exercise effects for improving physical and mental domains of HRQOL. This analysis provides an updated review and meta-analysis of randomized controlled trials (RCTs) examining interventions consisting of aerobic, resistance and combined exercise training for improving HRQOL in persons with MS. This systematic review 1) assessed the overall strength of evidence for exercise interventions on HRQOL, 2) evaluated the relative effect of exercise interventions on physical and mental domains of HRQOL, and 3) determined moderators of exercise intervention effects on HRQOL. METHODS: Seven databases were searched for RCTs evaluating physical and/or mental domains of HRQOL with adults diagnosed with MS and undergoing an intervention of aerobic, resistance or combined exercise training compared with a non-exercise comparator. Data extraction included participant and intervention characteristics, and pre- and post-intervention HRQOL outcome data. Effect sizes (ESs) were calculated as standardized mean differences (SMDs) and a multilevel random-effects model was used to generate an aggregated SMD that compared exercise with non-exercise control conditions. RESULTS: Twelve RCTs met the inclusion criteria and yielded 23 ESs to be analyzed. Participants (N = 593; 308 intervention vs. 285 control conditions) had a mean (±standard deviation) age of 42.4 (6.5) years and 80% (18.3%) were female. Results generated a medium effect of exercise for improving overall HRQOL (ES=0.64, p = 0.0001) with high heterogeneity (Q11=58.8, I2=86.7%). Exercise training yielded a large effect on the physical domain (k = 12, ES=0.82, p<0.0009) and a medium effect on the mental domain (k = 11, ES=0.41, p<0.0001). Moderator analyses identified exercise modality, supervision level, intervention delivery and length, HRQOL tool, and number of participants with relapsing-remitting MS as significant influences of ES for HRQOL. CONCLUSIONS: Exercise training is clinically effective for improving overall HRQOL in MS and produces greater improvements in the physical domain of HRQOL than the mental domain. The moderator analysis suggests that supervised, aerobic, and group-delivered exercise training of ≥3 months yields the most influence on HRQOL. Such results may have major implications for MS treatment and care.

Chronic cannabis use is associated with altered monocyte phenotype, immune response, and depression in physically active individuals.

Introduction: This study evaluated depression, monocyte phenotype, and immune function in physically active cannabis users. Methods: Participants (N = 23) were classified as either cannabis users (CU, n = 11) or non-users (NU, n = 12). White blood cells isolated from blood were analyzed for co-expression of cluster of differentiation 14 and 16 using flow cytometry. Lipopolysaccharide (LPS) was cultured with whole blood and assessed for interleukin-6 and tumor necrosis factor-α (TNF-α) release. Results: The percentage of white blood cells classified as monocytes was not different between groups; however, CU had a significantly greater percentage of monocytes classified as intermediate (p = 0.02). When standardized per milliliter of blood, CU had significantly greater numbers of total monocytes (p = 0.01), classical monocytes (p = 0.02), and intermediate monocytes (p = 0.01). Intermediate monocytes per milliliter of blood were positively correlated to the number of times CU used cannabis per day (r = 0.864, p < 0.01) and Beck Depression Inventory-II (BDI-II) score (r = 0.475, p = 0.03), which was significantly greater in CU (5.1 ± 4.8) compared with NU (0.8 ± 1.0; p < 0.01). CU released significantly less TNF-α per monocyte in response to LPS. Conclusions: CU had altered monocyte phenotypes and functions compared with NU. Elevations in intermediate monocytes were positively correlated with measures of cannabis use and BDI-II score.

Regular Use of Cannabis in Female Athletes Is Associated With a Reduction in Early Anaerobic Power Production.

ABSTRACT: Lisano, JK, Flores, VA, Kisiolek, JN, and Stewart, LK. Regular use of cannabis in female athletes is associated with a reduction in early anaerobic power production. J Strength Cond Res 37(3): 616-622, 2023-Despite a growing number of claims related to the ability of cannabis use to affect health and performance, there is limited research available, especially in female athletes. This cross-sectional study aimed to determine whether chronic cannabis use in physically active female athletes is related to altered health and performance. Healthy, physically active, female cannabis users (CU: n = 12) and noncannabis users (NU: n = 12) with an average age of 23.8 ± 3.7 years and 19.3 ± 4.2% body fat completed athletic performance and health assessments. Significance was set at alpha = 0.05. The age of onset of regular cannabis use was 20.1 ± 2.8 years in CU with an average duration of cannabis use of 5.8 ± 3.1 years. There were no differences between groups with respect to body size, body composition, pulmonary function, cardiorespiratory function, or muscular strength. Cannabis users produced significantly less power in the first 2 stages of the Wingate assessment, but CU experienced significantly less anaerobic fatigue. Although body composition and cardiovascular fitness were comparable, average C-reactive protein concentration classified CU with higher risk for cardiovascular disease (CVD). Athletes and coaches who rely heavily on anaerobic performance should consider these findings because they indicate that regular cannabis use may affect early power production and CVD risk.

Targeted exercise for African-Americans with multiple sclerosis: Project TEAAMS.

BACKGROUND: We propose a randomized controlled trial (RCT) that examines the effects of a remotely-delivered, cultrally-tailored exercise training program for immediate and sustained improvements in patient-reported outcomes (PROs) of walking dysfunction, symptoms, and health-related quality of life (HRQOL) among African-Americans with multiple sclerosis (MS). METHODS/DESIGN: The study will be conducted using a parallel group RCT design. The RCT examines the effects of a remotely-delivered, culturally-tailored exercise training program compared with an active control condition among 100 African-Americans with MS. The primary PROs focus on walking dysfunction. The secondary PROs include symptoms of fatigue, depression, anxiety, and HRQOL. The tertiary PROs include exercise behavior and mediator variables based on social cognitive theory. Participants will be randomly assigned into one of two conditions, intervention (Aerobic and Resistance Exercise Training) or active control (Stretching and Flexibility), using a random numbers sequence with concealed allocation. The conditions will be administered over four months by a trained behavioral coach who will be uninvolved in recruitment, screening, random assignment, and outcome assessment. We will monitor the outcomes of interest before and after the 4-month intervention period, and then again 4 months after intervention cessation for capturing stability of intervention effects. The data analysis will follow intent-to-treat principles with a linear mixed model. DISCUSSION: If successful, this RCT will provide initial evidence for the uptake and implementation of the program in clinics/environments providing healthcare for African-Americans with MS.

Regulation of metabolic health by dietary histidine in mice.

Low-protein (LP) diets are associated with a decreased risk of diabetes in humans, and promote leanness and glycaemic control in both rodents and humans. While the effects of an LP diet on glycaemic control are mediated by reduced levels of the branched-chain amino acids, we have observed that reducing dietary levels of the other six essential amino acids leads to changes in body composition. Here, we find that dietary histidine plays a key role in the response to an LP diet in male C57BL/6J mice. Specifically reducing dietary levels of histidine by 67% reduces the weight gain of young, lean male mice, reducing both adipose and lean mass without altering glucose metabolism, and rapidly reverses diet-induced obesity and hepatic steatosis in diet-induced obese male mice, increasing insulin sensitivity. This normalization of metabolic health was associated not with caloric restriction or increased activity, but with increased energy expenditure. Surprisingly, the effects of histidine restriction do not require the energy balance hormone Fgf21. Histidine restriction that was started in midlife promoted leanness and glucose tolerance in aged males but not females, but did not affect frailty or lifespan in either sex. Finally, we demonstrate that variation in dietary histidine levels helps to explain body mass index differences in humans. Overall, our findings demonstrate that dietary histidine is a key regulator of weight and body composition in male mice and in humans, and suggest that reducing dietary histidine may be a translatable option for the treatment of obesity. KEY POINTS: Protein restriction (PR) promotes metabolic health in rodents and humans and extends rodent lifespan. Restriction of specific individual essential amino acids can recapitulate the benefits of PR. Reduced histidine promotes leanness and increased energy expenditure in male mice. Reduced histidine does not extend the lifespan of mice when begun in midlife. Dietary levels of histidine are positively associated with body mass index in humans.

Sex and genetic background define the metabolic, physiologic, and molecular response to protein restriction.

Low-protein diets promote metabolic health in humans and rodents. Despite evidence that sex and genetic background are key factors in the response to diet, most protein intake studies examine only a single strain and sex of mice. Using multiple strains and both sexes of mice, we find that improvements in metabolic health in response to reduced dietary protein strongly depend on sex and strain. While some phenotypes were conserved across strains and sexes, including increased glucose tolerance and energy expenditure, we observed high variability in adiposity, insulin sensitivity, and circulating hormones. Using a multi-omics approach, we identified mega-clusters of differentially expressed hepatic genes, metabolites, and lipids associated with each phenotype, providing molecular insight into the differential response to protein restriction. Our results highlight the importance of sex and genetic background in the response to dietary protein level, and the potential importance of a personalized medicine approach to dietary interventions.

Short Term, Oral Supplementation with Optimized Curcumin Does Not Impair Performance Improvements Associated with High Intensity Interval Training.

Curcumin may improve athletic performance through a reduction in inflammation following exercise and improve mental states of well-being. The purpose of this investigation was to explore the effects of a 14 day HIIT intervention and oral supplementation with Longvida® optimized curcumin on athletic performance, lactate response, and well-being. Sixteen males and twenty females participated in a double-blinded, randomized, placebo-controlled trial to explore the effects of Longvida(R) optimized curcumin (1.0 g/day) and or a placebo (PLA) taken daily during a 14 day HIIT protocol. Participants were randomized into two groups, then evaluated in three groups, curcumin-fast (CURF), curcumin-slow (CURS) and placebo. Curcumin-fast and curcumin-slow were separated by their 16.1 km cycling time trial performance (TT) with CURF and CURS determined by a TT <30 min and >30 min at the pre intervention time point, respectively. Cycling time-trial performance, blood lactate response, and well-being assessments were determined at pre and post 14 day HIIT intervention time points. Blood lactate was recorded at baseline, 8.01 km, 15.1 km, and 1 min post, and 4 min post of the pre and post intervention TT. Following the internvetion, CONP and CURS experienced with 8.15% and 5.04% improvements in TT performance times, while CURF experienced a 0.57% improvement in TT performance time. No changes were observed with respect to other measures. When curcumin is taken daily in conjunction with 14 days of HIIT on a cycle ergometer, cycling performance in either well trained or more recreationally trained athletes is not impaired. Although the improvements in TT performance were not stasticially significant, they are noteworthy.

Nitric oxide enhancement supplement containing beet nitrite and nitrate benefits high intensity cycle interval training.

This study investigated the effects of a beet nitric oxide enhancing (NOE) supplement comprised of nitrite and nitrate on cycling performance indices in trained cyclists. METHODS: Subjects completed a lactate threshold test and a high-intensity interval (HIIT) protocol at 50% above functional threshold power with or without oral NOE supplement. RESULTS: NOE supplementation enhanced lactate threshold by 7.2% (Placebo = 191.6 ± 37.3 W, NOE = 205.3 ± 39.9; p = 0.01; Effect Size (ES) = 0.40). During the HIIT protocol, NOE supplementation improved time to exhaustion 18% (Placebo = 1251 ± 562s, NOE = 1474 ± 504s; p = 0.02; ES = 0.42) and total energy expended 22.3% (Placebo = 251 ± 48.6 kJ, NOE = 306.6 ± 55.2 kJ; p = 0.01; ES = 1.079). NOE supplementation increased the intervals completed (Placebo = 7.00 ± 2.5, NOE = 8.14 ± 2.4; p = 0.03; ES = 0.42) and distance cycled (Placebo = 10.9 ± 4.0 km, NOE = 13.5 ± 3.9 km; p = 0.01; ES = 0.65). Also, target power was achieved at a higher cadence during the HIIT work and rest periods (p = 0.02), which enhanced muscle oxygen saturation (SmO2) recovery. Time-to-fatigue was negatively correlated with the degree of SmO2, desaturation during the HIIT work interval segment (r = -0.67; p 0.008), while both SmO2 desaturation and the SmO2 starting work segment saturation level correlated with a cyclist's kJ expended (SmO2 desaturation: r = -0.51, p = 0.06; SmO2 starting saturation: r = 0.59, p = 0.03). CONCLUSION: NOE supplementation containing beet nitrite and nitrate enhanced submaximal (lactate threshold) and HIIT maximal effort work. The NOE supplementation resulted in a cyclist riding at higher cadence rates with lower absolute torque values at the same power during both the work and rest periods, which in-turn delayed over-all fatigue and improved total work output.

Kefir Is a Viable Exercise Recovery Beverage for Cancer Survivors Enrolled in a Structured Exercise Program.

PURPOSE: This study investigated the effects of 12 wk of postexercise kefir consumption in cancer survivors who have undergone chemotherapy and/or radiation therapy. METHODS: All participants were enrolled in a structured exercise training program and separated into kefir (KEF) or control (CON) treatment groups. KEF consumed 8 oz. of kefir after exercise sessions (3 d·wk-1) for 12 wk. Outcome measures included assessments for body size and composition, aerobic fitness and muscular strength, medical history, and psychological state at pre- and postintervention time points. Blood was collected and analyzed for C-reactive protein (CRP), interleukin 6 (IL-6), and lipopolysaccharide (LPS) concentrations, and LPS-stimulated whole blood IL-6 and tumor necrosis factor α production were obtained using enzyme-linked immunosorbent assays at both time points. Monocyte numbers and phenotype were obtained using flow cytometry. RESULTS: Participants (N = 24; 9 males and 15 females) were an average of 61 ± 9.9 yr old. Kefir consumption was associated with 6.3% (P = 0.034) improvements in lean body mass, as well as 51.4% (P = 0.046), 39.3% (P = 0.017), and 64.7% (P = 0.021) improvements in measures of depression, fatigue, and gastric distress, respectively. KEF also experienced a significant 35.4% (P = 0.01) reduction in circulating LPS along with an 18.0% increase (P < 0.001) in classical monocytes % and a 22.3% decrease (P = 0.04) in nonclassical monocytes %. There were no significant changes in any other variables. CONCLUSION: Twelve weeks of kefir consumption improved lean body mass, depression, fatigue, gastric distress, and a biomarker of gut dysbiosis. Kefir improved overall and classical monocyte numbers. Kefir should be considered as a component of a postexercise dietary regimen for cancer survivors.

Structured Exercise in Cancer Survivors: Is it Enough for Neural, Mental Health and Well-being?

The purpose of this cross-sectional study was to explore physical activity, depression, fatigue, and quality of life (QOL), and their relationship to brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in cancer survivors enrolled in a structured exercise program. Participants were recruited into two groups: in-treatment (IT), currently receiving chemotherapy and/or radiotherapy, and out of treatment (OT), not undergoing therapy. Participants wore accelerometers for 7 days and completed cardiorespiratory fitness, muscular strength, and depression, fatigue, and QOL assessments. Circulating BDNF and NGF concentrations were obtained using enzyme-linked immunosorbent assays. Thirty-two participants (IT: n = 13, OT: n = 19) with an average age of 63 years and BMI of 27.5, spent 78% of their waking hours engaged in sedentary behavior outside of exercise training. Significant correlations were observed between light physical activity (LPA) outside of exercise training and QOL in IT (r = 0.626, p = 0.030), and fatigue in OT (r = 0.553, p = 0.021). Moderate to vigorous physical activity (MVPA) outside of exercise training significantly correlated with leg press strength (r = 0.700, p = 0.008) in IT, and cardiorespiratory fitness (r = 0.440, p = 0.013) when groups were combined. Concentrations of NGF did not differ between groups, and in IT, BDNF was positively related to LPA outside of training and was significantly lower (87 ± 28.5 pg/mL) than in OT (137 ± 54 pg/mL; p=0.010). While structured exercise programs should focus on improving cardiorespiratory fitness and muscular strength during exercise training, these programs should consider physical activity outside of training, if well-tolerated, to potentially further lower fatigue and improve QOL in cancer survivors.

Lifelong restriction of dietary branched-chain amino acids has sex-specific benefits for frailty and lifespan in mice.

Protein restricted (PR) diets promote health and longevity in many species. While the precise components of a PR diet that mediate the beneficial effects to longevity have not been defined, we recently showed that many metabolic effects of PR can be attributed to reduced dietary levels of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine. Here, we demonstrate that restricting dietary BCAAs increases the survival of two different progeroid mouse models, delays frailty and promotes the metabolic health of wild-type C57BL/6J mice when started in midlife, and leads to a 30% increase in lifespan and a reduction in frailty in male, but not female, wild-type mice when fed lifelong. Our results demonstrate that restricting dietary BCAAs can increase healthspan and longevity in mice, and suggest that reducing dietary BCAAs may hold potential as a translatable intervention to promote healthy aging.

The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine.

Low-protein diets promote metabolic health in rodents and humans, and the benefits of low-protein diets are recapitulated by specifically reducing dietary levels of the three branched-chain amino acids (BCAAs), leucine, isoleucine, and valine. Here, we demonstrate that each BCAA has distinct metabolic effects. A low isoleucine diet reprograms liver and adipose metabolism, increasing hepatic insulin sensitivity and ketogenesis and increasing energy expenditure, activating the FGF21-UCP1 axis. Reducing valine induces similar but more modest metabolic effects, whereas these effects are absent with low leucine. Reducing isoleucine or valine rapidly restores metabolic health to diet-induced obese mice. Finally, we demonstrate that variation in dietary isoleucine levels helps explain body mass index differences in humans. Our results reveal isoleucine as a key regulator of metabolic health and the adverse metabolic response to dietary BCAAs and suggest reducing dietary isoleucine as a new approach to treating and preventing obesity and diabetes.

Patellofemoral joint kinetics in females when using different depths and loads during the barbell back squat.

Back squats are a common strengthening exercise for knee and hip musculature. However, repetitive loaded movements like backs squats result in high patellofemoral joint loading and therefore may contribute to the development of common overuse injuries. Thus, it is important to understand how changing parameters such as squat depth or load influences patellofemoral loading. This study investigated differences in patellofemoral loading when experienced female lifters squatted to three depths (above parallel, parallel, and below parallel) and with three loads (unloaded, 50%, and 85% of depth-specific one repetition maximums). Patellofemoral joint reaction forces (pfJRF) and stresses (pfJS) were calculated from biomechanical models incorporating knee extensor moments (KEM) and joint angles. Peak KEMs displayed a depth-by-load interaction such that within each depth, as load increased so did peak KEM. However, within each load, the effects of depth were different. Peak pfJRF also increased with load and was higher at below parallel than above or parallel depths. Peak pfJS also displayed a depth-by-load interaction, increasing with load within a given depth, and being greatest at the below parallel depths within a given load. If patellofemoral joint loading is a concern, clinicians or coaches should carefully monitor the depth and load combinations being used.