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.

Endogenous Ghrelin Levels and Perception of Hunger: A Systematic Review and Meta-Analysis.

BACKGROUND: Ghrelin is an orexigenic hormone primarily released by the stomach and has 2 isoforms: acylated ghrelin (AG) and de-acylated ghrelin (DAG), that appear to have different functions in humans. OBJECTIVES: To perform a systematic review and meta-analysis of the association between plasma concentrations of total ghrelin (TG), AG, and DAG and perceptions of hunger in healthy adults. METHODS: The following criteria were used for inclusion: 1) sample contained adults ≥18 y of age, 2) body mass index [BMI kg/m2] was ≥18.5, 3) ghrelin was sampled through blood, 4) subjective hunger was measured on a validated scale, 5) study reported a Pearson product correlation of ghrelin or had relevant figure(s) for data extraction, 6) participants were healthy with no overt disease, 7) protocols contained no physical activity or weight loss medication that suppressed appetite, 8) interventions were conducted without environmental manipulations. Moderators assessed were age, BMI, percentage of body fat (%BF), macronutrient content of test meals, energy intake (kcals), sex, and ghrelin isoform (AG, DAG, or TG). RESULTS: The analysis included 47 studies (110 trials, n = 1799, age: 31.4 ± 12.0 y, BMI: 26.0 ± 4.75 kg/m2) and measured AG (n = 47 trials), DAG (n = 12 trials), and TG (n = 51 trials). The overall model indicated that ghrelin concentrations and perceptions of hunger were moderately correlated (r = 0.43, P < 0.001), and ghrelin isoform significantly moderated this relationship (AG: r = 0.60, P < 0.001; TG: r = 0.215, P = 0.01; DAG: r = 0.53, P = 0.695). Other significant moderators included age (b = -0.02, P = 0.01), BMI (b = -0.03, P = 0.05), %BF (b = -0.03, P = 0.05), energy intake (b = 0.0003, P = 0.04), and percentage of carbohydrates of test meals (b = 0.008, P = 0.05). CONCLUSIONS: Ghrelin is associated with perceptions of hunger in humans, and this relationship is strengthened when AG is isolated; thus, AG may have a large impact on hunger signals in various populations. Future research should attempt to understand the role of DAG in hunger sensations.

Characterization and prevalence of obesity among normal weight college students.

Normal weight obesity (NWO) describes individuals who have a normal weight body mass index (BMI), but have an unhealthy amount of body fat. Based on the life-long habits that develop during college, exploring NWO among a college-aged population may be essential in identifying and preventing obesity that develops in early adulthood. This study aimed to characterize NWO among young adults with normal weight BMI. 94 college students (Mean ± SD: Age: 19.6 ± 1.5 yrs; BMI: 21.9 ± 1.8 kg/m2) enrolled during the Fall semester (Aug-Oct) were assessed for body composition by dual energy X-ray absorptiometry to determine body fat percentage, fat mass, lean mass and trunk fat; lifestyle habits were characterized from validated questionnaires. Mean arterial pressure and metabolic biomarkers [total cholesterol, high density lipoproteins, non-high density lipoproteins, and glucose] were evaluated for cardiometabolic health. NWO was defined using data from the National Health and Nutrition Examination Survey (NHANES) for body fat percentage. Data was analyzed by group (NWO vs NWL) and sex. with independent t-tests to investigate continuous data, and chi-square test of independence for categorical data. Rates of NWO for the total sample were 13.8%. Males (n=30) had a higher rate of NWO (26.7%) compared to females (n=64; 7.8%). NWO individuals had higher fat mass (p=0.024), trunk fat (p<0.001), and larger waist to hip ratio (p<0.001) than normal weight lean. NWO also engaged in less vigorous physical activity (p=0.043). The occurrence of NWO among otherwise healthy college students is evident. Identification of these individuals may be an effective component for obesity prevention and treatment. Determining feasible methods to measure body fat in this population is essential, as BMI may mask obesity in a young adult population.

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.

Metabolic and physiological effects of high intensity interval training in patients with knee osteoarthritis: A pilot and feasibility study.

Objective: To examine the feasibility of a 6-week high intensity interval training (HIIT) program in patients with symptomatic knee osteoarthritis (OA). A secondary aim was to evaluate the change in whole-body metabolism. Design: In a single-arm intervention, 16 adults (mean age 59.9 yrs; BMI: 29.0 ± 4.3 kg/m2; 77% female) with radiographically diagnosed knee OA (Kellgren-Lawrence [KLG]: 2-4) and moderate to severe pain score (≥6) from the Western Ontario and McMasters Universities Index (WOMAC) enrolled in a 6-week, twice weekly, supervised HIIT cycle ergometry intervention. The primary outcome was feasibility; secondary outcomes included change in peak oxygen consumption (VO2peak), WOMAC, and circulating biomarkers of metabolism. Results: Feasibility was moderate; of the 21 participants screened by phone, 16 were enrolled; 13 completed pre- and post-testing. The average adherence rate (sessions completed/available) was >96%. VO2peak was significantly improved (mean ± SD: 2.6 ± 3.0 mL/min/kg; 95% CI [0.70-4.56]). Significant improvements in WOMAC (mean ± SD: -8.7 ± 12.5; CI: [18.9 to -2.80]), pain [-5.15 to -1.01], and function [-12.9 to -0.98] resulted. There was a significant reduction in concentrations of amino acids: methionine, phenylalanine, and tyrosine (p < 0.02 for all), with trends towards lower concentrations of serine (p = 0.08; [-20.66-1.18]) and greater aspartate/asparagine (p = 0.06; [-1.99-65.73].). Post-training acylcarnitine concentrations were reduced with training. Conclusions: In this cohort of overweight adults with symptomatic knee OA, 6-weeks of HIIT cycling showed excellent rates of retention and adherence with no adverse events, improved cardiorespiratory fitness and OA symptoms, in concert with metabolic alterations indicative of improved skeletal muscle energetics. Trial registration number: clinicaltrials.gov: NCT03039452.

Body Composition Is Associated With Physical Performance in Individuals With Knee Osteoarthritis.

BACKGROUND/OBJECTIVE: The purpose of this cross-sectional study was to determine associations between body composition, self-reported function, and physical performance after accounting for body mass index (BMI) in individuals with knee osteoarthritis. METHODS: Percent fat and lean mass were evaluated using dual energy x-ray absorptiometry. Self-reported function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] function subscale) and physical performance (20-m walk, chair stand, and stair climb) were collected on 46 adults (30% male; BMI, 29.6 ± 3.8 kg/m) with radiographically defined knee osteoarthritis (Kellgren-Lawrence grades 2-4). Linear regressions determined the unique association between WOMAC and physical performance explained individually by percent fat and lean mass ([INCREMENT]R) after accounting for BMI. RESULTS: Lower percent fat mass significantly associated with better physical performance after accounting for BMI (20-m walk: [INCREMENT]R = 0.10, p = 0.03; chair stand: [INCREMENT]R = 0.16, p = 0.01; stair climb: [INCREMENT]R = 0.11, p = 0.03). Higher percent lean mass significantly associated with better chair stand ([INCREMENT]R = 0.09, p = 0.04) but not 20-m walk or stair climb ([INCREMENT]R range, 0.04-0.07, p > 0.05). After accounting for BMI, neither percent fat nor lean mass associated with WOMAC. Body mass index did not significantly associate with WOMAC or physical performance. CONCLUSIONS: Lower percent fat and higher percent lean mass associated with better physical performance after accounting for BMI. Body composition and BMI may be used together in the future to more comprehensively understand the association between obesity and disability.

The effects of nutrient timing on training adaptations in resistance-trained females.

OBJECTIVES: The purpose of this study was to determine the effects of pre- vs. post-workout nutrition on strength, body composition, and metabolism in trained females over 6 weeks of high intensity resistance training (HIRT). DESIGN: Forty-three trained females (mean±SD; age: 20.5±2.2 yrs; height: 165.2±5.7cm; body mass: 66.5±11.4kg) were measured for strength, body composition, and metabolic variables before and after a HIRT intervention. Participants were randomized using a 2:2:1 matched block randomization scheme by baseline leg press strength into a group that consumed a 1:1.5 carbohydrate-protein supplement (16g CHO/25g PRO) pre-training (PRE), post-training (POST), or no supplement (CON). METHODS: Dual-energy X-ray absorptiometry was used to evaluate fat mass (FM), lean mass (LM), and percent fat (%fat). Strength was analyzed using a one repetition max on the leg and bench press (LP1RM and BP1RM, respectively). Participants completed HIRT twice per week for 6 weeks. At the first and last trainings, metabolic variables [resting energy expenditure (REE) and respiratory exchange ratio, RER] were measured. RESULTS: There were no significant differences between groups for any changes in body composition variables or LP1RM (p=0.170-0.959). There were significant differences for BP1RM (p=0.007), with PRE and POST experiencing greater increases than CON (p=0.010 and 0.015, respectively). REE changes were not significant between groups (p=0.058-0.643). PRE demonstrated greater fat oxidation (RER) at 30min post-exercise (p=0.008-0.035). CONCLUSION: Peri-workout nutrition is potentially important for upper body strength and metabolism. PRE may be more effective for promoting fat utilization immediately post-workout.