Sex differences in the effects of inorganic nitrate supplementation on exercise economy and endurance capacity in healthy young adults.

Dietary nitrate (NO3-) is a widely used supplement purported to provide beneficial effects during exercise. Most studies to date include predominantly males. Therefore, the present study aimed to investigate if there is a sex-dependent effect of NO3- supplementation on exercise outcomes. We hypothesized that both sexes would exhibit improvements in exercise economy and exercise capacity following NO3- supplementation, but males would benefit to a greater extent. In a double-blind, randomized, crossover study, twelve females (24 ± 4 yr) and fourteen males (23 ± 4 yr) completed two 4-min moderate-intensity (MOD) exercise bouts followed by a time-to-exhaustion (TTE) task after following 3 days of NO3- supplementation (beetroot juice or BRJ) or NO3--depleted placebo (PL). Females were tested during the early follicular phase of the menstrual cycle. During MOD exercise, BRJ reduced the steady-state V̇o2 by ∼5% in males (M: Δ -87 ± 115 mL·min-1; P < 0.05) but not in females (F: Δ 6 ± 195 mL·min-1). Similarly, BRJ extended TTE by ∼15% in males (P < 0.05) but not in females. Dietary NO3- supplementation improved exercise economy during moderate-intensity exercise and exercise capacity during severe-intensity TTE in males but not in females. These differences could be related to estrogen levels, antioxidant capacity, nitrate-reducing bacteria, or a variety of known physiologic differences such as skeletal muscle calcium handling, and/or fiber type. Overall, our data suggests the ergogenic benefits of oral NO3- supplementation found in studies predominantly on male subjects may not be applicable to females.NEW & NOTEWORTHY While inorganic nitrate (NO3-) supplementation has increased in popularity as an ergogenic aid to improve exercise performance, the role of sex in NO3- supplementation on exercise outcomes is lacking despite known physiological differences during exercise between sex. This study revealed that males, but not females, improved exercise economy during submaximal exercise and exercise capacity during exercise within the severe-intensity domain following NO3- supplementation.

The acute effects of exercise intensity and inorganic nitrate supplementation on vascular health in females after menopause.

Menopause is associated with reduced nitric oxide bioavailability and vascular function. Although exercise is known to improve vascular function, this is blunted in estrogen-deficient females post-menopause (PM). Here, we examined the effects of acute exercise at differing intensities with and without inorganic nitrate (NO3-) supplementation on vascular function in females PM. Participants were tested in a double-blinded, block-randomized design, consuming ∼13 mmol NO3- in the form of beetroot juice (BRJ; n = 12) or placebo (PL; n = 12) for 2 days before experimental visits and 2 h before testing. Visits consisted of vascular health measures before (time point 0) and every 30 min after (time points 60, 90, 120, 150, and 180) calorically matched high-intensity exercise (HIE), moderate-intensity exercise (MIE), and a nonexercise control (CON). Blood was sampled at rest and 5-min postexercise for NO3-, NO2-, and ET-1. BRJ increased N-oxides and decreased ET-1 compared with PL, findings which were unchanged after experimental conditions (P < 0.05). BRJ improved peak Δflow-mediated dilation (FMD) compared with PL (P < 0.05), defined as the largest ΔFMD for each individual participant across all time points. FMD across time revealed an improvement (P = 0.05) in FMD between BRJ + HIE versus BRJ + CON, while BRJ + MIE had medium effects compared with BRJ + CON. In conclusion, NO3- supplementation combined with HIE improved FMD in postmenopausal females. NO3- supplementation combined with MIE may offer an alternative to those unwilling to perform HIE. Future studies should test whether long-term exercise training at high intensities with NO3- supplementation can enhance vascular health in females PM.NEW & NOTEWORTHY This study compared exercise-induced changes in flow-mediated dilation after acute moderate- and high-intensity exercise in females postmenopause supplementing either inorganic nitrate (beetroot juice) or placebo. BRJ improved peak ΔFMD postexercise, and BRJ + HIE increased FMD measured as FMD over time. Neither PL + MIE nor PL + HIE improved FMD. These findings suggest that inorganic nitrate supplementation combined with high-intensity exercise may benefit vascular health in females PM.

Limited Effects of Inorganic Nitrate Supplementation on Exercise Training Responses: A Systematic Review and Meta-analysis.

BACKGROUND: Inorganic nitrate (NO3-) supplementation is purported to benefit short-term exercise performance, but it is unclear whether NO3- improves longer-term exercise training responses (such as improvements in VO2peak or time to exhaustion (TTE)) versus exercise training alone. The purpose of this systematic review and meta-analysis was to determine the effects of NO3- supplementation combined with exercise training on VO2peak and TTE, and to identify potential factors that may impact outcomes. METHODS: Electronic databases (PubMed, Medscape, and Web of Science) were searched for articles published through June 2022 with article inclusion determined a priori as: (1) randomized placebo-controlled trials, (2) exercise training lasted at least three weeks, (3) treatment groups received identical exercise training, (4) treatment groups had matched VO2peak at baseline. Study quality was assessed using the Cochrane Risk-of-Bias 2 tool. Standardized mean difference (SMD) with 95% confidence intervals (CI) were calculated using restricted maximum likelihood estimation between pre- and post-training differences in outcomes. Moderator subgroup and meta-regression analyses were completed to determine whether the overall effect was influenced by age, sex, NO3- dosage, baseline VO2peak, health status, NO3- administration route, and training conditions. RESULTS: Nine studies consisting of eleven trials were included: n = 228 (72 females); age = 37.7 ± 21 years; VO2peak: 40 ± 18 ml/kg/min. NO3- supplementation did not enhance exercise training with respect to VO2peak (SMD: 0.18; 95% CI: -0.09, 0.44; p = 0.19) or TTE (SMD: 0.08; 95% CI: - 0.21, 0.37; p = 0.58). No significant moderators were revealed on either outcome. Subset analysis on healthy participants who consumed beetroot juice (BRJ) revealed stronger trends for NO3- improving VO2peak (p = 0.08) compared with TTE (p = 0.19), with no significant moderators. Sunset funnel plot revealed low statistical power in all trials. CONCLUSIONS: NO3- supplementation combined with exercise training may not enhance exercise outcomes such as VO2peak or TTE. A trend for greater improvement in VO2peak in healthy participants supplemented with BRJ may exist (p = 0.08). Overall, future studies in this area need increased sample sizes, more unified methodologies, longer training interventions, and examination of sex as a biological variable to strengthen conclusions.

The effects of inorganic nitrate supplementation on exercise economy and endurance capacity across the menstrual cycle.

Oral inorganic nitrate (NO3-) supplementation has been shown to increase bioavailable NO and provide potential ergogenic benefits in males; however, data in females is scarce. Estrogen is known to increase endogenous NO bioavailability and to fluctuate throughout the menstrual cycle (MC), being lowest in the early follicular (EF) phase and highest during the late follicular (LF) phase. This study examined the effects of oral NO3- supplementation on exercise economy, endurance capacity, and vascular health in young females across the MC. Ten normally menstruating females' MCs were tested in a double-blinded, randomized design during both the EF and LF phases of the MC. Participants consumed ∼13 mmol NO3-, in the form of 140 mL beetroot juice (BRJ) or an identical NO3--depleted placebo (PL) for ∼3 days before lab visits and 2 h before testing on lab visits. Plasma nitrate, nitrite, and estradiol were assessed, as was blood pressure and pulse wave velocity. Moderate-intensity exercise economy and severe intensity time to exhaustion (TTE) were tested on a cycle ergometer. As expected, plasma estradiol was elevated in the LF phase, and plasma nitrite and nitrate were elevated in the BRJ condition. Exercise economy was unaltered by BRJ or the MC, however TTE was significantly worsened by 48 s (∼10%) after BRJ supplementation (P = 0.04), but was not different across the MC with no interaction effects. In conclusion, NO3- supplementation did not affect exercise economy or vascular health and worsened aerobic endurance capacity (TTE), suggesting healthy females should proceed with caution when considering supplementation with BRJ.NEW & NOTEWORTHY Although inorganic nitrate (NO3-) supplementation has increased in popularity as a means of improving exercise performance, data in females at different phases of the menstrual cycle are lacking despite known interactions of estrogen with NO. This study revealed neither NO3- supplementation nor the menstrual cycle influenced exercise economy or vascular health in healthy young naturally menstruating females, while NO3- supplementation significantly worsened endurance capacity (10%) independent of the menstrual cycle phase.

Neural network methods for diagnosing patient conditions from cardiopulmonary exercise testing data.

BACKGROUND: Cardiopulmonary exercise testing (CPET) provides a reliable and reproducible approach to measuring fitness in patients and diagnosing their health problems. However, the data from CPET consist of multiple time series that require training to interpret. Part of this training teaches the use of flow charts or nested decision trees to interpret the CPET results. This paper investigates the use of two machine learning techniques using neural networks to predict patient health conditions with CPET data in contrast to flow charts. The data for this investigation comes from a small sample of patients with known health problems and who had CPET results. The small size of the sample data also allows us to investigate the use and performance of deep learning neural networks on health care problems with limited amounts of labeled training and testing data. METHODS: This paper compares the current standard for interpreting and classifying CPET data, flowcharts, to neural network techniques, autoencoders and convolutional neural networks (CNN). The study also investigated the performance of principal component analysis (PCA) with logistic regression to provide an additional baseline of comparison to the neural network techniques. RESULTS: The patients in the sample had two primary diagnoses: heart failure and metabolic syndrome. All model-based testing was done with 5-fold cross-validation and metrics of precision, recall, F1 score, and accuracy. As a baseline for comparison to our models, the highest performing flow chart method achieved an accuracy of 77%. Both PCA regression and CNN achieved an average accuracy of 90% and outperformed the flow chart methods on all metrics. The autoencoder with logistic regression performed the best on each of the metrics and had an average accuracy of 94%. CONCLUSIONS: This study suggests that machine learning and neural network techniques, in particular, can provide higher levels of accuracy with CPET data than traditional flowchart methods. Further, the CNN performed well with a small data set showing that these techniques can be designed to perform well on small data problems that are often found in health care and the life sciences. Further testing with larger data sets is needed to continue evaluating the use of machine learning to interpret CPET data.

Nitric oxide-dependent micro- and macrovascular dysfunction occurs early in adolescents with type 1 diabetes.

Arterial stiffness and endothelial dysfunction are both reported in children with type 1 diabetes (DM1) and may predict future cardiovascular events. In health, nitric oxide (NO) relaxes arteries and increases microvascular perfusion. The relationships between NO-dependent macro- and microvascular functional responses and arterial stiffness have not been studied in adolescents with DM1. Here, we assessed macro- and microvascular function in DM1 adolescents and age-matched controls at baseline and during an oral glucose challenge (OGTT). DM1 adolescents (n = 16) and controls (n = 14) were studied before and during an OGTT. At baseline, we measured: 1) large artery stiffness using both aortic augmentation index (AI) and carotid-femoral pulse wave velocity (cfPWV); 2) brachial flow-mediated dilation (FMD) and forearm endothelial function using postischemic flow velocity (PIFV); and 3) forearm muscle microvascular blood volume (MBV) using contrast-enhanced ultrasound. Following OGTT, AI, cfPWV, and MBV were reassessed at 60 min and MBV again at 120 min. Within individual and between-group, comparisons were made by paired and unpaired t tests or repeated measures ANOVA. Baseline FMD was lower (P = 0.02) in DM1. PWV at 0 and 60 min did not differ between groups. Baseline AI did not differ between groups but declined with OGTT only in controls (P = 0.02) and was lower than DM1 at 60 min (P < 0.03). Baseline MBV was comparable in DM1 and control groups, but declined in DM1 at 120 min (P = 0.01) and was lower than the control group (P < 0.03). There was an inverse correlation between plasma glucose and MBV at 120 min (r = -0.523, P < 0.01). No differences were noted between groups for V̇O2max (mL/min/kg), body fat (%), or body mass index (BMI). NO-dependent macro- and microvascular function, including FMD and AI, and microvascular perfusion, respectively, are impaired early in the course of DM1, precede increases of arterial stiffness, and may provide an early indicator of vascular risk.NEW & NOTEWORTHY This is the first study to show that type 1 diabetes impairs multiple nitric oxide-dependent vascular functions.

The effect of acute exercise on pre-prandial ghrelin levels in healthy adults: A systematic review and meta-analysis.

BACKGROUND: Ghrelin is a gut hormone with numerous physiological effects, including the regulation of energy balance, insulin sensitivity, vascular health, and body composition. Acylated (AG) and des-acylated (DAG) ghrelin constitute approximately 22 % and 78 % of total plasma ghrelin (TG), respectively. Alterations in the TG concentration and the AG/DAG ratio may be implicated in conditions involving energy imbalances and insulin resistant states (e.g., metabolic syndrome or Type 2 diabetes mellitus). Exercise is a therapeutic option that can potentially optimize ghrelin levels. Understanding the precise intensity and dose of exercise to optimize ghrelin levels may lead to targeted interventions to restore metabolic regulation in obesity and other clinical conditions. OBJECTIVE: To perform a systematic review and meta-analysis on the effects of acute exercise on pre-prandial levels of TG, AG, and DAG in healthy adults and to determine if sample demographics or exercise doses moderate such effects. METHODS: Electronic databases (PubMed, Medline, SPORTDiscus, Web of Science, and Google Scholar) were searched with articles published through August 2020. The following criteria was determined a priori for article inclusion: (i) the study was a randomized controlled trial (RCT),(ii) exercise was an acute bout, (iii) the exercise bout for the intervention group(s)/condition was structured, (iv) the control group/condition received no exercise, (v) participants were adults age 18 or older, (vi) ghrelin was sampled through blood, (vii) there was at least one baseline measure and one post-exercise measure of ghrelin, (viii) there were at least 3 timepoints where ghrelin was measured while participants were fasted to allow for pre-prandial total area-under-the-curve (AUCtotal) calculation, (ix) participants were healthy with no overt disease, (x) interventions were carried out without any environmental manipulations. Standardized mean difference (SMD) with 95 % confidence intervals were calculated using the restricted maximum likelihood estimation Moderator analyses to determine whether the overall pooled effect was influenced by: sex, ghrelin form, method of ghrelin analysis, age, body mass index, body fat percentage, fitness, intensity of exercise bout, duration of exercise bout, energy expenditure, and length of AUCtotal data. RESULTS: The analysis included 24 studies that consisted of 52 trials, n = 504 (age 27.0 (8.8) years, BMI 24.7 (2.7) kg/m2) and measured AG (n = 38 trials), DAG (n = 7), and TG (n = 7). The overall model indicated that exercise lowered ghrelin levels compared to control (no exercise); (SMD=-0.44, p < 0.001), and exercise intensity exhibited an inverse relationship with ghrelin levels (regression coefficient (ß)=-0.016, p = 0.04). There was no significant difference by ghrelin form (p = 0.18). DISCUSSION: Acute exercise significantly lowers plasma ghrelin levels, with higher intensity exercise associated with greater ghrelin suppression. The majority of studies applied a moderate intensity exercise bout and measured AG, with limited data on DAG. This exercise dose may be clinically significant in individuals with metabolic dysregulation and energy imbalance as a therapy to optimize AG levels. More work is needed to compare moderate and high intensity exercise and the ghrelin response in clinical populations.

"Moving Away From Cancer" Prospective Exercise Trial for Female Rural Cancer Survivors: How Can We Step It Up?

PURPOSE: This prospective trial's objective was to determine feasibility and outcomes of an exercise-based intervention for rural overweight/obese female cancer survivors. MATERIALS AND METHODS: Survivors of endometrial, breast, or ovarian cancer enrolled in a 6-month program of increased aerobic activity (30 minutes daily walking) and strength-training exercises using exercise bands (THERABAND; Akron, OH) with personalized telephone motivational coaching. Baseline demographics, anthropomorphic measurements, quality of life (QOL), fitness, and readiness to adopt exercise changes were assessed; daily steps, band use, and follow-up measurements were assessed at 3 and 6 months. Study completion was modeled using logistic regression. RESULTS: The mean age of the 99 women was 59.9 years, the mean body mass index (BMI) was 35.9 kg/m2, 88.9% were white, and 41.4% reported current exercise. Fifty-five women (55.6%) completed the 6-month program, and 36 (36.4%) completed exercise interventions. Using logistic regression to model study completion, only baseline QOL scores (physical component summary) and mental component summary) remained significant predictors. The mean weight change was a gain (0.88 kg). Higher MCS baseline scores and prior regular exercise predicted continued exercise and increased step counts, whereas higher BMI and baseline sleep predicted decreased QOL. Top walking barriers were feeling unwell and weather; barriers to strength exercises were band dislike and pain. CONCLUSION: The most significant predictor of trial completion and improved exercise outcomes was a higher baseline mental QOL. Motivation, belief in the importance of exercise, and prescribed/monitored exercise regimens were not sufficient; supportive and cognitive behavioral therapy interventions for survivors are needed to sustain uptake.

ISB clinical biomechanics award winner 2019: Knee extensor fatigue resistance in individuals following anterior cruciate ligament reconstruction.

BACKGROUND: Individuals following anterior cruciate ligament reconstruction demonstrate quadriceps weakness throughout the post-operative recovery and at the time of returning to sport. This is often accompanied with patterns of quadriceps fatigue resistance. As such, fatigue may be an identifier of individuals with delayed recovery. The purpose was to assess quadriceps fatigue in anterior cruciate ligament reconstructed patients at the time of return to sport in comparison to healthy controls. METHODS: A total of 215 individuals, 120 following anterior cruciate ligament reconstruction (21.0 (2.9) years, 63 Female, 5.96 (0.48) months post-surgery) and 95 healthy controls (21.5 (8.4) years, 49 Female), participated in this study. All participants completed a 30-s knee extensor maximum voluntary isometric contraction. Knee extensor strength, limb symmetry index, and fatigue (%) were compared between groups. Between-limb fatigue comparisons were made through the Fatigue Index Limb Difference = [(Involved Limb Fatigue Index) - (Uninvolved Limb Fatigue Index)]. FINDINGS: Individuals following anterior cruciate ligament reconstruction (18.7 (10.9)%, -5.6 (11.2)) demonstrated lower values of unilateral fatigue and Fatigue Index Limb Difference compared to healthy participants (22.5 (8.2)%, P = .002; 2.2 (7.9), P < .001). For anterior cruciate ligament reconstructed patients, there was a weak, negative, significant relationship between the involved limb strength and fatigue (r = -0.184, P = .048). There was no relationship between limb symmetry and Fatigue Index Limb Difference (r = 0.137, P = .142). For Healthy individuals, there was a positive, moderate relationship between limb symmetry and Fatigue Index Limb Difference (r = 0.400, P < .001). INTERPRETATION: Individuals following anterior cruciate ligament reconstruction demonstrate fatigue resistance compared to healthy active controls and greater resistance to fatigue in their involved limb compared to their contralateral limb.

Pre-operative aerobic exercise on metabolic health and surgical outcomes in patients receiving bariatric surgery: A pilot trial.

OBJECTIVE: Examine if adding aerobic exercise to standard medical care (EX+SC) prior to bariatric surgery improves metabolic health in relation to surgical outcomes. METHODS: Fourteen bariatric patients (age: 42.3±2.5y, BMI: 45.1±2.5 kg/m2) met inclusion criteria and were match-paired to pre-operative SC (n = 7) or EX+SC (n = 7; walking 30min/d, 5d/wk, 65-85% HRpeak) for 30d. A 120min mixed meal tolerance test was performed pre- and post-intervention (~2d prior to surgery) to assess insulin sensitivity (Matsuda Index) and metabolic flexibility (indirect calorimetry). Aerobic fitness (VO2peak), body composition (BodPod), and adipokines (adiponectin, leptin) were also measured. Omental adipose tissue was collected during surgery to quantify gene expression of adiponectin and leptin, and operating time and length of hospital stay were recorded. ANOVA and Cohen's d effect size (ES) was used to test group differences. RESULTS: SC tended to increase percent body fat (P = 0.06) after the intervention compared to EX+SC. Although SC and EX+SC tended to raise insulin sensitivity (P = 0.11), EX+SC enhanced metabolic flexibility (P = 0.01, ES = 1.55), reduced total adiponectin (P = 0.01, ES = 1.54) with no change in HMW adiponectin and decreased the length of hospital stay (P = 0.05) compared to SC. Albeit not statistically significant, EX+SC increased VO2peak 2.9% compared to a 5.9% decrease with SC (P = 0.24, ES = 0.91). This increased fitness correlated to shorter operating time (r = -0.57, P = 0.03) and length of stay (r = -0.58, P = 0.03). Less omental total adiponectin (r = 0.52, P = 0.09) and leptin (r = 0.58, P = 0.05) expression correlated with shorter operating time, and low leptin expression was linked to shorter length of stay (r = 0.70, P = 0.01), and low leptin expression was linked to shorter length of stay (r = 0.70, P = 0.01). CONCLUSION: Adding pre-operative aerobic exercise to standard care may improve surgical outcomes through a fitness and adipose tissue derived mechanism.

Impact of Pre-operative Aerobic Exercise on Cardiometabolic Health and Quality of Life in Patients Undergoing Bariatric Surgery.

OBJECTIVE: Examine the effect of aerobic exercise (EX) combined with standard medical care (SC) (EX + SC) compared to SC alone on cardiometabolic health and quality of life in relation to surgical outcomes. METHODS: Patients receiving bariatric surgery were match-paired to 30 days of pre-operative SC (n = 7, 1 male, 39.0 ± 5.3 years, body mass index 46.4 ± 3.0 kg/m2; low calorie diet) or EX + SC (n = 7, 0 males, 45.6 ± 4.8 years, body mass index 43.9 ± 4.2 kg/m2; walking 30 min/day, 5 days/week, 65-85% HR peak ). Body mass, waist circumference, cardiorespiratory fitness (VO2peak), high sensitivity C-reactive protein (hs-CRP), cytokeratin 18 (CK18), weight related quality of life (QoL), and a 120 min mixed meal tolerance test (MMTT) was performed to assess arterial stiffness via augmentation index normalized to a heart rate of 75 beats per minute (AIx@75), whole-body insulin sensitivity, and glucose total area under the curve (tAUC) pre- and post-intervention (∼2 days prior to surgery). Length of hospital stay (admission to discharge) was recorded. RESULTS: EX + SC had a greater effect for decreased intake of total calories (P = 0.14; ES = 0.86) compared to SC, but no change in body weight or waist circumference was observed in either group. EX + SC had a greater effect for increased VO2peak (P = 0.24; ES = 0.91) and decreased hs-CRP (P = 0.31; ES = 0.69) compared to SC. EX + SC reduced circulating CK18 (P = 0.05; ES = 3.05) and improved QoL (P = 0.02) compared to SC. Although EX + SC had no statistical effect on arterial stiffness compared to SC, we observed a modest effect size for AIx@75 tAUC (P = 0.36; ES = 0.52). EX + SC had a significantly shorter length of hospital stay (P = 0.05; ES = 1.38) than SC, and a shorter length of hospital stay was associated with decreased sugar intake (r = 0.55, P = 0.04). Decreased AIx@75 tAUC significantly correlated with improved whole-body insulin sensitivity (r = -0.59, P = 0.03) and glucose tAUC (r = 0.57, P = 0.04). CONCLUSION: EX with SC for 30 days prior to bariatric surgery may be important for cardiometabolic health, quality of life, and surgical outcomes in the bariatric patient.

Randomized, Controlled Trial of Exercise on Objective and Subjective Sleep in Parkinson's Disease.

BACKGROUND: Sleep dysfunction is common and disabling in persons with Parkinson's Disease (PD). Exercise improves motor symptoms and subjective sleep quality in PD, but there are no published studies evaluating the impact of exercise on objective sleep outcomes. The goal of this study was to to determine if high-intensity exercise rehabilitation combining resistance training and body-weight interval training, compared with a sleep hygiene control improved objective sleep outcomes in PD. METHODS: Persons with PD (Hoehn & Yahr stages 2-3; aged ≥45 years, not in a regular exercise program) were randomized to exercise (supervised 3 times a week for 16 weeks; n = 27) or a sleep hygiene, no-exercise control (in-person discussion and monthly phone calls; n = 28). Participants underwent polysomnography at baseline and post-intervention. Change in sleep efficiency was the primary outcome, measured from baseline to post-intervention. Intervention effects were evaluated with general linear models with measurement of group × time interaction. As secondary outcomes, we evaluated changes in other aspects of sleep architecture and compared the effects of acute and chronic training on objective sleep outcomes. RESULTS: The exercise group showed significant improvement in sleep efficiency compared with the sleep hygiene group (group × time interaction: F = 16.0, P < 0.001, d = 1.08). Other parameters of sleep architecture also improved in exercise compared with sleep hygiene, including total sleep time, wake after sleep onset, and slow-wave sleep. Chronic but not acute exercise improved sleep efficiency compared with baseline. CONCLUSIONS: High-intensity exercise rehabilitation improves objective sleep outcomes in PD. Exercise is an effective nonpharmacological intervention to improve this disabling nonmotor symptom in PD. © 2020 International Parkinson and Movement Disorder Society.

Interval Exercise Lowers Circulating CD105 Extracellular Vesicles in Prediabetes.

BACKGROUND: Extracellular vesicles (EV) are purported to mediate type 2 diabetes and CVD risk and development. Physical activity and a balanced diet reduce disease risk, but no study has tested the hypothesis that short-term interval (INT) training would reduce EV compared with continuous (CONT) exercise in adults with prediabetes. METHODS: Eighteen obese adults (age, 63.8 ± 1.5 yr; body mass index, 31.0 ± 1.3 kg·m) were screened for prediabetes using American Diabetes Association criteria (75 g oral glucose tolerance test). Subjects were randomized to INT (n = 10, alternating 3-min intervals at 90% and 50% HRpeak, respectively) or CONT (n = 8, 70% HRpeak) training for 12 supervised sessions over 13 d for 60 min·d. Cardiorespiratory fitness (V˙ O2peak), weight (kg), as well as ad libitum dietary intake were assessed and arterial stiffness (augmentation index via applanation tonometry) was calculated using total AUC during a 75-g oral glucose tolerance test performed 24 h after the last exercise bout. Total EV, platelet EV (CD31/CD41), endothelial EV (CD105; CD31/ CD41), platelet endothelial cell adhesion molecule (PECAM) (CD31), and leukocyte EV (CD45; CD45/CD41) were analyzed via imaging flow cytometry preintervention/postintervention. RESULTS: The INT exercise increased V˙O2peak (P = 0.04) compared with CONT training. Although training had no effect on platelet or leukocyte EV, INT decreased Annexin V- endothelial EV CD105 compared with CONT (P = 0.04). However, after accounting for dietary sugar intake, the intensity effect was lost (P = 0.18). Increased ad libitum dietary sugar intake after training was linked to elevated AV+ CD105 (r = 0.49, P = 0.06) and AV- CD45 (r = 0.59, P = 0.01). Nonetheless, increased V˙O2peak correlated with decreased AV+ CD105 (r = -0.60, P = 0.01). CONCLUSIONS: Interval exercise training decreases endothelial-derived EV in adults with prediabetes. Although increased sugar consumption may alter EV after a short-term exercise intervention, fitness modifies EV count.

Sex affects gait adaptations after exercise in individuals with anterior cruciate ligament reconstruction.

BACKGROUND: Osteoarthritis after anterior cruciate ligament reconstruction has been linked with changes in gait. Individuals with reconstruction demonstrate gait changes after exercise, however there is no information on altered gait after exercise based on sex. The purpose of this study was to examine the association of sex on changes in running gait after exercise in individuals with reconstruction compared to healthy. METHODS: Forty females (22 reconstructed) and 22 men (11 reconstructed) ran before and after exercise. Triplanar lower extremity kinematics and kinetics were measured on the involved limb. Data were reduced to 0-100% of gait. Change scores were calculated for each 1% with 90% confidence intervals. Mean differences were calculated for all significant differences. FINDINGS: After exercise, females with reconstruction increased knee valgus (1.81°), knee external rotation (2.02°), lateral trunk flexion (1.24°) and trunk rotation (2.15°) compared to healthy females. Females with reconstruction increased knee extension moment (0.07 Nm/kg), knee abduction moment (0.08 Nm/kg), hip extension moment (0.14 Nm/kg) and hip internal rotation moment (0.04 Nm/kg) compared to healthy females. After exercise, males with reconstruction decreased knee varus (-4.83°), hip adduction (-1.99°), and hip internal rotation (-4.44°), however increased lateral trunk flexion (1.94°) compared to healthy males. Males with reconstruction increased knee extension moment (0.07 Nm/kg), knee adduction moment (0.31 Nm/kg), knee internal rotation moment (0.13 Nm/kg), hip flexion moment (0.17 Nm/kg), and hip external rotation moment (0.05 Nm/kg) compared to healthy males. INTERPRETATION: Males with reconstruction increased hip loading while women with reconstruction increased trunk motion post-exercise. Sex should be considered when evaluating response to exercise after reconstruction.

Two Weeks of Interval Training Enhances Fat Oxidation during Exercise in Obese Adults with Prediabetes.

Prediabetes is associated with impaired oxidative capacity and altered substrate utilization during exercise. The effects of continuous (CONT) versus interval (INT) exercise training on fat oxidation during an acute exercise bout at the same absolute and relative intensities are unknown in this population. Obese females/males (n = 17, n = 5) with prediabetes (BMI 32.2 ± 1.2 kg·m-2; age 62.8 ± 1.6 y; fasting glucose 103.4 ± 1.6 mg·dL-1; 2-hour glucose 153.7 ± 7.1 mg·dL-1; VO2peak 19.9 ± 1.0 mL·kg-1·min-1) were screened with a 75g OGTT. Subjects completed a peak oxygen consumption test and a submaximal exercise substrate utilization test consisting of 5min stages at absolute (30W) and relative (70%HRpeak) intensities before and after randomization to 12 sessions (60min each) of CONT (70% HRpeak) or INT (alternating 3min 90% HRpeak, 3min 50% HRpeak) over a two-week period. Body mass decreased and VO2peak increased more after INT than CONT (INT: -0.6 ± 0.2 kg, CONT: -0.1 ± 0.2 kg; p = 0.04; INT: 1.9 ± 0.6 mL/kg/min, CONT: 0.1 ± 0.6 mL·kg-1·min-1; p = 0.04). Training increased fat oxidation by 0.7 ± 0.2 mL·kg-1·min-1 during the absolute intensity test (p < 0.001), independent of intensity. During the relative intensity test, fat oxidation increased more after INT than CONT (INT: 1.3 ± 0.4 mL·kg-1·min-1, CONT: 0.3 ± 0.3 mL·kg-1·min-1; p = 0.03), with no difference in exercise energy expenditure between groups. Enhanced fat oxidation during the relative test was correlated with increased VO2peak (r = 0.53 p = 0.01). High intensity INT training enhances fat oxidation during the same relative intensity exercise in people with prediabetes.

Effects of Low-Fat and High-Fat Meals, with and without Dietary Fiber, on Postprandial Endothelial Function, Triglyceridemia, and Glycemia in Adolescents.

The consumption of fiber-rich foods may negate the deleterious effects of high-fat meals on postprandial triglyceridemia and endothelial function. Despite supportive data in adults, little is known about the effects of high-fat and high-fiber foods on cardiovascular health parameters in pediatric populations. In this crossover trial, male and female adolescents (n = 10; 14.1 + 2.6 years; range 10-17 years) consumed (1) low-fat, low-fiber, (2) low-fat, high-fiber, (3) high-fat, low-fiber, and (4) high-fat, high-fiber breakfast meals in randomized order, each following an overnight fast. Baseline and 4 h post-meal blood was obtained for determination of glucose, insulin and triglyceride concentrations. Endothelial function was assessed via brachial artery flow-mediated dilation (FMD). Postprandial FMD was not significantly changed after any meal. However, regression analyses revealed a significant inverse relationship between the change in 4 h triglyceride concentration and change in 4 h FMD for the high-fat, low-fiber meal (ß = -0.087; 95% CI = -0.138 to -0.037; p = 0.001) that was no longer significant in the high-fat, high-fiber meal (ß = -0.044; 95% CI = -0.117 to 0.029; p = 0.227). Interpretation of these analyses must be qualified by acknowledging that between-meal comparison revealed that the two regression lines were not statistically different (p = 0.226). Addition of high-fiber cereal to the high-fat meal also reduced 4 h postprandial triglyceride increases by ~50% (p = 0.056). A high-fiber breakfast cereal did not attenuate postprandial glucose and insulin responses after consumption of a low-fat meal. While further work is needed to confirm these results in larger cohorts, our findings indicate the potential importance of cereal fiber in blunting the inverse relationship between postprandial hypertriglyceridemia and FMD after consumption of a high-fat meal in adolescents.

How Lifestyle Factors Affect Cognitive and Executive Function and the Ability to Learn in Children.

In today's research environment, children's diet, physical activity, and other lifestyle factors are commonly studied in the context of health, independent of their effect on cognition and learning. Moreover, there is little overlap between the two literatures, although it is reasonable to expect that the lifestyle factors explored in the health-focused research are intertwined with cognition and learning processes. This thematic review provides an overview of knowledge connecting the selected lifestyle factors of diet, physical activity, and sleep hygiene to children's cognition and learning. Research from studies of diet and nutrition, physical activity and fitness, sleep, and broader influences of cultural and socioeconomic factors related to health and learning, were summarized to offer examples of research that integrate lifestyle factors and cognition with learning. The literature review demonstrates that the associations and causal relationships between these factors are vastly understudied. As a result, current knowledge on predictors of optimal cognition and learning is incomplete, and likely lacks understanding of many critical facts and relationships, their interactions, and the nature of their relationships, such as there being mediating or confounding factors that could provide important knowledge to increase the efficacy of learning-focused interventions. This review provides information focused on studies in children. Although basic research in cells or animal studies are available and indicate a number of possible physiological pathways, inclusion of those data would distract from the fact that there is a significant gap in knowledge on lifestyle factors and optimal learning in children. In a climate where childcare and school feeding policies are continuously discussed, this thematic review aims to provide an impulse for discussion and a call for more holistic approaches to support child development.

An Oral Glucose Load Decreases Postprandial Extracellular Vesicles in Obese Adults with and without Prediabetes.

Although extracellular vesicles (EVs) are a novel biomediator of type 2 diabetes (T2D) and cardiovascular disease (CVD), the effects of hyperglycemia on EVs in humans is unknown. We tested the hypothesis that a 75-g oral glucose tolerance test (OGTT) would promote changes in EVs in relation to CVD risk. Twenty-five obese adults (Age: 52.4 ± 3.2 year, BMI: 32.5 ± 1.2 kg/m²) were screened for normal glucose tolerance (NGT, n = 8) and prediabetes (PD, n = 17) using American Diabetes Association criteria (75 g OGTT and/or HbA1c). Body composition (bioelectrical impedance) and fitness (VO2peak) were measured. Arterial stiffness (augmentation index; AIx) was measured at 0, 60- and 120-min while insulin, glucose, and free fatty acids were evaluated every 30 min during the OGTT to assess CVD risk. Annexin V positive (AV+) and Annexin V negative (AV-) total EVs, platelet EVs (CD31⁺/CD41⁺; CD41⁺), leukocyte EVs (CD45⁺; CD45⁺/CD41-), platelet endothelial cell adhesion molecule (PECAM) (CD31⁺) and endothelial EVs (CD 31⁺/CD41-; CD105⁺) were collected at 0 and 120 min. There were no differences in age, BMI, or body fat between NGT and PD (all P > 0.63). Total EVs, AV+ CD31+ (PECAM), and AV+ CD31⁺/CD41- (endothelial) EVs decreased after the OGTT (P ≤ 0.04). Circulating insulin at 2-h correlated with elevated post-prandial AV- CD45⁺ (r = 0.48, P = 0.04) while arterial stiffness related to reduced total EVs (r = -0.49, P = 0.03) and AV+CD41⁺ (platelet) (r = -0.52, P = 0.02). An oral glucose load lowers post-prandial total, platelet, and endothelial EVs in obese adults with NGT and prediabetes in relation to CVD risk.

A low-calorie diet with or without interval exercise training improves adiposopathy in obese women.

The objective of this study was to test if a low-calorie diet plus interval exercise (LCD+INT) improves adiposopathy, an endocrine dysfunction, when compared with an energy-deficit-matched LCD in obese women. Subjects (age: 48.2 ± 2.4 years, body mass index: 37.8 ± 1.3 kg/m2) were randomized to a 13-day LCD (n = 12; mixed meals of ∼1200 kcal/day) or LCD+INT (n = 12; 12 sessions of 60 min/day alternating 3 min at 50% and 90% peak heart rate). Exercise was estimated to expend 350 kcal per oxygen uptake-heart rate regression analysis and individuals were refed calories expended to match energy availability between groups. Absolute (post - pre caloric intake) and relative (total daily and exercise energy expenditure relative to calorie intake) energy deficits were calculated. Fitness (peak oxygen uptake) and body composition (BodPod; Cosmed USA Inc.) were measured and a 120-min, 75g oral glucose tolerance test was performed at pre- and post-intervention to assess adiposopathy (i.e., ratio of high molecular weight-adiponectin to leptin) and estimate insulin sensitivity. LCD and LCD+INT had similar absolute (P = 0.55) and relative (P = 0.76) energy deficits. LCD and LCD+INT had similar reductions in fat mass (both P < 0.001), despite LCD inducing greater weight loss (P = 0.02) than LCD+INT. Both treatments improved adiposopathy (P = 0.003) and peripheral insulin sensitivity (P = 0.02). Absolute energy deficit correlated to improved adiposopathy (r = -0.41, P = 0.05), and absolute and relative energy deficits were associated with increased insulin sensitivity (r = -0.47, P = 0.02; and r = -0.40, P = 0.05, respectively), independent of body composition changes and increased peak oxygen uptake. Taken together, LCD, with or without INT, improves adiposopathy in relation to insulin sensitivity in obese women, suggesting that a short-term energy deficit is key for reducing risk of type 2 diabetes.