Beet supplementation mitigates post-exercise inflammation.

Objectives: This study investigated the efficacy of a mixed beet-based supplement (BEET) versus placebo (PL) in countering inflammation during recovery from 2.25 h of intensive cycling in 20 male and female cyclists. A multi-omics approach was used that included untargeted proteomics and a targeted oxylipin panel. Methods: A randomized, placebo-controlled, double-blind, crossover design was used with two 2-week supplementation periods and a 2-week washout period. Supplementation periods were followed by a 2.25 h cycling bout at close to 70%VO2max. The BEET supplement provided 212 mg of nitrates per day, 200 mg caffeine from green tea extract, 44 mg vitamin C from Camu Camu berry, B-vitamins from quinoa sprouts (40% Daily Value for thiamin, riboflavin, niacin, and vitamin B6), and 2.5 g of a mushroom blend containing Cordyceps sinensis and Inonotus obliquus. Six blood samples were collected before and after supplementation (overnight fasted state), immediately post-exercise, and at 1.5 h-, 3 h-, and 24 h-post-exercise. Results: The 2.25 h cycling bout increased plasma levels of 41 of 67 oxylipins detected. BEET supplementation significantly increased plasma nitrate (NO3 -) and nitrite (NO2 -) (sum, NO3 - + NO2 -) concentrations (interaction effect, p < 0.001) and two anti-inflammatory oxylipins [18-hydroxyeicosapentaenoic acid (18-HEPE) and 4-hydroxy-docosahexanoic acid (4-HDoHE)]. The untargeted proteomics analysis identified 616 proteins (458 across all times points), and 2-way ANOVA revealed a cluster of 45 proteins that were decreased and a cluster of 21 that were increased in the BEET versus PL trials. Functional enrichment supported significant BEET-related reductions in inflammation-related proteins including several proteins related to complement activation, the acute phase response, and immune cell adhesion, migration, and differentiation. Discussion: Intake of a BEET-based supplement during a 2-week period was linked to higher plasma levels of NO3 - + NO2 -, elevated post-exercise levels of two anti-inflammatory oxylipins, and a significant decrease in a cluster of proteins involved in complement activation and inflammation. These data support that 2-weeks intake of nitrate from a mixed beet-based supplement moderated protein biomarkers of exercise-induced inflammation in athletes.

Untargeted metabolomics reveal signatures of a healthy lifestyle.

This cross-sectional study investigated differences in the plasma metabolome in two groups of adults that were of similar age but varied markedly in body composition and dietary and physical activity patterns. Study participants included 52 adults in the lifestyle group (LIFE) (28 males, 24 females) and 52 in the control group (CON) (27 males, 25 females). The results using an extensive untargeted ultra high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) metabolomics analysis with 10,535 metabolite peaks identified 486 important metabolites (variable influence on projections scores of VIP ≥ 1) and 16 significantly enriched metabolic pathways that differentiated LIFE and CON groups. A novel metabolite signature of positive lifestyle habits emerged from this analysis highlighted by lower plasma levels of numerous bile acids, an amino acid profile characterized by higher histidine and lower glutamic acid, glutamine, ß-alanine, phenylalanine, tyrosine, and proline, an elevated vitamin D status, higher levels of beneficial fatty acids and gut microbiome catabolism metabolites from plant substrates, and reduced levels of N-glycan degradation metabolites and environmental contaminants. This study established that the plasma metabolome is strongly associated with body composition and lifestyle habits. The robust lifestyle metabolite signature identified in this study is consistent with an improved life expectancy and a reduced risk for chronic disease.

Cardiorespiratory coupling is associated with exercise capacity in athletes: A cross-sectional study.

PURPOSE: To determine the association between exercise capacity based on peak oxygen uptake (VO2peak) and resting cardiorespiratory coupling (CRC) levels in athletes and non-athletes' subjects. METHODS: A cross-sectional study was carried out in 42 apparently healthy male subjects, aged between 20 and 40 years old. The participants were allocated into athletes (n = 21) and non-athletes (n = 21) groups. Resting electrocardiogram and respiratory movement (RESP) were simultaneously acquired during 15 min in supine position and quiet breathing. The beat-to-beat heart period (HP) and RESP series were determined from the recorded signals. Traditional analysis of HP based on frequency domain indexes was performed considering the high-frequency (0.15 - 0.45 Hz) components. To compute the CRC, the linear association between HP and RESP series was determined via squared coherence function and directionality of interaction was investigated through the causal extension of this approach. The exercise capacity was assessed through incremental cardiopulmonary exercise testing in order to determine the VO2peak. RESULTS: Traditional analysis of HP based on high-frequency index was not correlated with exercise capacity in the athletes (r = -0.1, p = 0.5) and non-athletes (r = -0.1, p = 0.3) cohorts. However, resting CRC values was associated with exercise capacity in athletes (r = 0.4, p = 0.03), but not in the non-athletes group (r = -0.2, p = 0.3). CONCLUSION: These results suggest that improved resting values of CRC is associated with higher exercise capacity (VO2peak) in endurance athletes. Moreover, frequency domain of HP was not sensitive to identifying this relationship, probably because effects of training on parasympathetic modulation might be affected by respiratory dynamics, and this influence has a directionality (i.e., from RESP to HP).

Healthy lifestyle linked to innate immunity and lipoprotein metabolism: a cross-sectional comparison using untargeted proteomics.

This study used untargeted proteomics to compare blood proteomic profiles in two groups of adults that differed widely in lifestyle habits. A total of 52 subjects in the lifestyle group (LIFE) (28 males, 24 females) and 52 in the control group (CON) (27 males, 25 females) participated in this cross-sectional study. Age, education level, marital status, and height did not differ significantly between LIFE and CON groups. The LIFE and CON groups differed markedly in body composition, physical activity patterns, dietary intake patterns, disease risk factor prevalence, blood measures of inflammation, triglycerides, HDL-cholesterol, glucose, and insulin, weight-adjusted leg/back and handgrip strength, and mood states. The proteomics analysis showed strong group differences for 39 of 725 proteins identified in dried blood spot samples. Of these, 18 were downregulated in the LIFE group and collectively indicated a lower innate immune activation signature. A total of 21 proteins were upregulated in the LIFE group and supported greater lipoprotein metabolism and HDL remodeling. Lifestyle-related habits and biomarkers were probed and the variance (> 50%) in proteomic profiles was best explained by group contrasts in indicators of adiposity. This cross-sectional study established that a relatively small number of proteins are associated with good lifestyle habits.

Blueberry intake elevates post-exercise anti-inflammatory oxylipins: a randomized trial.

This study determined if 18 days of supplementation with blueberries (BL) compared to placebo (PL) could mitigate muscle soreness and damage and improve inflammation resolution in untrained adults (n = 49, ages 18-50 years) after engaging in a 90-min bout of "weekend warrior" eccentric exercise. The BL freeze dried supplement provided 1 cup of fresh blueberries per day equivalent with 805 mg/day total phenolics and 280 mg/day anthocyanins. Urine levels of eight BL gut-derived phenolics increased after 14- and 18-days supplementation with 83% higher concentrations in BL vs. PL (p < 0.001). The 90-min exercise bout caused significant muscle soreness and damage during 4d of recovery and a decrease in exercise performance with no significant differences between PL and BL. Plasma oxylipins were identified (n = 76) and grouped by fatty acid substrates and enzyme systems. Linoleic acid (LA) oxylipins generated from cytochrome P450 (CYP) (9,10-, 12,13-dihydroxy-9Z-octadecenoic acids) (diHOMEs) were lower in BL vs. PL (treatment effect, p = 0.051). A compositive variable of 9 plasma hydroxydocosahexaenoic acids (HDoHEs) generated from docosahexaenoic acid (DHA, 22:6) and lipoxygenase (LOX) was significantly higher in BL vs. PL (treatment effect, p = 0.008). The composite variable of plasma 14-HDoHE, 17-HDoHE, and the eicosapentaenoic acid (EPA)-derived oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE) (specialized pro-resolving lipid mediators, SPM, intermediates) was significantly higher in BL vs PL (treatment effect, p = 0.014). Pearson correlations showed positive relationships between post-exercise DHA-LOX HDoHEs and SPM intermediates with urine blueberry gut-derived phenolics (r = 0.324, p = 0.023, and r = 0.349, p = 0.015, respectively). These data indicate that 18d intake of 1 cup/day blueberries compared to PL was linked to a reduction in pro-inflammatory diHOMES and sustained elevations in DHA- and EPA-derived anti-inflammatory oxylipins in response to a 90-min bout of unaccustomed exercise by untrained adults.

Astaxanthin supplementation counters exercise-induced decreases in immune-related plasma proteins.

Objectives: Astaxanthin is a dark red keto-carotenoid found in aquatic animals such as salmon and shrimp, and algae (Haematococcus pluvialis). Astaxanthin has a unique molecular structure that may facilitate anti-oxidative, immunomodulatory, and anti-inflammatory effects during physiological stress. The primary objective of this study was to examine the efficacy of 4-week ingestion of astaxanthin in moderating exercise-induced inflammation and immune dysfunction using a multi-omics approach. Methods: This study employed a randomized, double blind, placebo controlled, crossover design with two 4-week supplementation periods and a 2-week washout period. Study participants were randomized to astaxanthin and placebo trials, with supplements ingested daily for 4 weeks prior to running 2.25 h at close to 70%VO2max (including 30 min of 10% downhill running). After the washout period, participants repeated all procedures using the counterbalanced supplement. The astaxanthin capsule contained 8 mg of algae astaxanthin. Six blood samples were collected before and after supplementation (overnight fasted state), immediately post-exercise, and at 1.5, 3, and 24 h-post-exercise. Plasma aliquots were assayed using untargeted proteomics, and targeted oxylipin and cytokine panels. Results: The 2.25 h running bout induced significant muscle soreness, muscle damage, and inflammation. Astaxanthin supplementation had no effect on exercise-induced muscle soreness, muscle damage, and increases in six plasma cytokines and 42 oxylipins. Notably, astaxanthin supplementation countered exercise-induced decreases in 82 plasma proteins (during 24 h recovery). Biological process analysis revealed that most of these proteins were involved in immune-related functions such as defense responses, complement activation, and humoral immune system responses. Twenty plasma immunoglobulins were identified that differed significantly between the astaxanthin and placebo trials. Plasma levels of IgM decreased significantly post-exercise but recovered after the 24 h post-exercise recovery period in the astaxanthin but not the placebo trial. Discussion: These data support that 4-week astaxanthin versus placebo supplementation did not counter exercise-induced increases in plasma cytokines and oxylipins but was linked to normalization of post-exercise plasma levels of numerous immune-related proteins including immunoglobulins within 24 h. Short-term astaxanthin supplementation (8 mg/day during a 4-week period) provided immune support for runners engaging in a vigorous 2.25 h running bout and uniquely countered decreases in plasma immunoglobulin levels.

Influence of 2 Weeks of Mango Ingestion on Inflammation Resolution after Vigorous Exercise.

Mangoes have a unique nutrient profile (carotenoids, polyphenols, sugars, and vitamins) that we hypothesized would mitigate post-exercise inflammation. This study examined the effects of mango ingestion on moderating exercise-induced inflammation in a randomized crossover trial with 22 cyclists. In random order with trials separated by a 2-week washout period, the cyclists ingested 330 g mango/day with 0.5 L water or 0.5 L of water alone for 2 weeks, followed by a 2.25 h cycling bout challenge. Blood and urine samples were collected pre- and post-2 weeks of supplementation, with additional blood samples collected immediately post-exercise and 1.5-h, 3-h, and 24 h post-exercise. Urine samples were analyzed for targeted mango-related metabolites. The blood samples were analyzed for 67 oxylipins, which are upstream regulators of inflammation and other physiological processes. After 2 weeks of mango ingestion, three targeted urine mango-related phenolic metabolites were significantly elevated compared to water alone (interaction effects, p ≤ 0.003). Significant post-exercise increases were measured for 49 oxylipins, but various subgroup analyses showed no differences in the pattern of change between trials (all interaction effects, p > 0.150). The 2.25 h cycling bouts induced significant inflammation, but no countermeasure effect was found after 2 weeks of mango ingestion despite the elevation of mango gut-derived phenolic metabolites.

Effects of Physical Exercise on Left Ventricular Function in Type 2 Diabetes Mellitus: A Systematic Review

Abstract Background The incidence of diabetes mellitus in younger adults is rising over the years. The diabetic population has an increased risk of developing heart failure, and diabetic individuals with heart failure have four times greater mortality rate. Studies results about exercise effect on left ventricular function in type 2 diabetes mellitus are heterogenous. Objective This review aimed to analyze the effects of physical exercise on left ventricular dysfunction in type 2 diabetes mellitus (T2DM). Methods Only randomized clinical trials with humans published in English were included. Inclusion criteria were studies with type 2 diabetes patients, physical exercise, control group and left ventricular function. Exclusion criteria were studies with animals, children, teenagers, elderly individuals and athletes, presence of diet intervention, and patients with type 1 diabetes, cancer, cardiac, pulmonary, or neurological diseases. Electronic databases PubMed, Web of Science, Cochrane, and Scopus were last searched in September 2021. Risk of bias was assessed by the Physiotherapy Evidence Database (PEDro) scale. Results Five studies were included, representing 314 diabetic individuals submitted to resistance and aerobic exercise training. Of the variables analyzed, physical exercise improved peak torsion (PTo), global longitudinal strain, global strain rate (GSR), time to peak untwist rate (PUTR), early diastolic filling rate (EDFR) and peak early diastolic strain rate (PEDSR). Conclusion To our knowledge, this is the first systematic review on the effects of exercise on left ventricular function in T2DM including only randomized clinical trials with humans. Physical exercise seems to improve systolic and diastolic strain, twist, and torsion. High intensity exercise was reported to be superior to moderate intensity exercise in one study. This review was limited by the small number of studies and their heterogeneity regarding exercise protocols, follow-up period, exercise supervision and left ventricular function variables analyzed. This review was registered in PROSPERO (CRD42021234964).

Physical activity lowers the risk for acute respiratory infections: Time for recognition.

Physical inactivity is a well-established risk factor for chronic diseases, such as cardiovascular disease, cancer, and diabetes mellitus. There is a growing awareness that physical inactivity should also be regarded as a risk factor for acute respiratory infections (ARIs). ARIs, such as the common cold, influenza, pneumonia, and coronavirus disease 2019 (COVID-19), are among the most pervasive diseases on earth and cause widespread morbidity and mortality. Evidence in support of the linkage between ARIs and physical inactivity has been strengthened during the COVID-19 pandemic because of increased scientific scrutiny. Large-scale studies have consistently reported that the risk for severe COVID-19 outcomes is elevated in cohorts with low physical activity and/or physical fitness, even after adjusting for other risk factors. The lowered risk for severe COVID-19 and other ARIs in physically active groups is attributed to exercise-induced immunoprotective effects, including enhanced surveillance of key immune cells and reduced chronic inflammation. Scientific consensus groups, including those who submitted the Physical Activity Guidelines for Americans, have not yet given this area of research the respect that is due. It is time to add "reduced risk for ARIs" to the "Exercise is Medicine" list of physical activity-related health benefits.

Cardiorespiratory coupling strength in athletes and non-athletes.

PURPOSE: Despite the relevant presence of nonlinear components on heart period (HP) likely due to cardiorespiratory coupling (CRC), the HP is frequently analyzed in absence of concomitant recordings of respiratory movements (RESP). This study aims to assess the cardiovascular dynamics and CRC during postural challenge in athletes and non-athletes via joint symbolic analysis (JSA). METHODS: A cross-sectional study was conducted in 50 men, aged between 20 and 40 yrs, divided into athletes (n = 25) and non-athletes (n = 25) groups. The electrocardiogram, blood pressure and RESP signals were recorded during 15 min in both supine position (REST) and after active postural maneuver (STAND). From the beat-to-beat series of HP, systolic arterial pressure (SAP) and RESP, we computed the time and frequency domain indexes and baroreflex sensitivity. The JSA was based on the definition of symbolic HP and RESP patterns and on the evaluation of the rate of their simultaneous occurrence in both HP and RESP series. RESULTS: The JSA analysis was able to identify higher CRC strength at REST in athletes. Moreover, the response of CRC to STAND depended on the time scales of the analysis and was much more evident in athletes than in non-athletes, thus indicating a more reactive autonomic control in athletes. CONCLUSION: Assessing CRC in athletes via JSA provides additional information compared to standard linear time and frequency domain tools likely due to the more relevant presence of nonlinearities in HP-RESP variability relationship.

Almond intake alters the acute plasma dihydroxy-octadecenoic acid (DiHOME) response to eccentric exercise.

Introduction: This investigation determined if 4-weeks ingestion of nutrient-dense almonds mitigated post-exercise inflammation and muscle soreness and damage. Methods: An acute 90-min of eccentric exercise (90-EE) was used to induce muscle damage in 64 non-obese adults not engaging in regular resistance training (ages 30-65 years, BMI < 30 kg/m2). Using a parallel group design, participants were randomized to almond (AL) (57 g/d) or cereal bar (CB) (calorie matched) treatment groups for a 4-week period prior to the 90-EE (17 exercises). Blood and 24-h urine samples were collected before and after supplementation, with additional blood samples collected immediately post-90-EE, and then daily during 4 additional days of recovery. Changes in plasma oxylipins, urinary gut-derived phenolics, plasma cytokines, muscle damage biomarkers, mood states, and exercise performance were assessed. Results: The 90-EE protocol induced significant muscle damage, delayed onset of muscle soreness (DOMS), inflammation, reduced strength and power performance, and mood disturbance. Interaction effects (2 group × 7 time points) supported that AL vs. CB was associated with reduced post-exercise fatigue and tension (p = 0.051, 0.033, respectively) and higher levels of leg-back strength (p = 0.029). No group differences were found for post-90-EE increases in DOMS and six cytokines. AL was associated with lower levels of serum creatine kinase immediately- and 1-day post-exercise (p = 0.034 and 0.013, respectively). The 90-EE bout increased plasma levels immediately post-exercise for 13 oxylipins. Interaction effects revealed significantly higher levels for AL vs. CB for 12,13-DiHOME (p < 0.001) and lower levels for 9,10-DiHOME (p < 0.001). Urine levels increased in AL vs. CB for seven gut-derived phenolics including 5-(3',4'-dihydroxyphenyl)-γ-valerolactone that was inversely related to changes in plasma 9,10-DiHOME (r = -0.029, p = 0.021). Discussion: These data support some positive effects of almond intake in improving mood state, retaining strength, decreasing muscle damage, increasing the generation of gut-derived phenolic metabolites, and altering the plasma oxylipin DiHOME response to unaccustomed eccentric exercise in untrained adults. The elevated post-exercise plasma levels of 12,13-DiHOME with almond intake support positive metabolic outcomes for adults engaging in unaccustomed eccentric exercise bouts.

Optimizing phase variability threshold for automated synchrogram analysis of cardiorespiratory interactions in amateur cyclists.

We propose a procedure suitable for automated synchrogram analysis for setting the threshold below which phase variability between two marker event series is of such a negligible amount that the null hypothesis of phase desynchronization can be rejected. The procedure exploits the principle of maximizing the likelihood of detecting phase synchronization epochs and it is grounded on a surrogate data approach testing the null hypothesis of phase uncoupling. The approach was applied to assess cardiorespiratory phase interactions between heartbeat and inspiratory onset in amateur cyclists before and after 11-week inspiratory muscle training (IMT) at different intensities and compared to a more traditional approach to set phase variability threshold. The proposed procedure was able to detect the decrease in cardiorespiratory phase locking strength during vagal withdrawal induced by the modification of posture from supine to standing. IMT had very limited effects on cardiorespiratory phase synchronization strength and this result held regardless of the training intensity. In amateur athletes training, the inspiratory muscles did not limit the decrease in cardiorespiratory phase synchronization observed in the upright position as a likely consequence of the modest impact of this respiratory exercise, regardless of its intensity, on cardiac vagal control. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'.

Moderate- and High-Intensity Inspiratory Muscle Training Equally Improves Inspiratory Muscle Strength and Endurance-A Double-Blind Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Inspiratory muscle training (IMT) produced outstanding results in the physical performance of active subjects; however, little is known about the best training intensity for this population. The objective was to investigate the impact of an IMT of high intensity, using the critical inspiratory pressure (CIP), on inspiratory muscle strength (IMS), inspiratory muscle endurance (IME), peak power, and oxygen uptake of recreational cyclists; and to compare these results with moderate-intensity IMT (60% of maximal inspiratory pressure [MIP]). METHODS: Thirty apparently healthy male recreational cyclists, 20-40 years old, underwent 11 weeks of IMT (3 times per week; 55 min per session). Participants were randomized into 3 groups: sham group (6 cmH2O; n = 8); 60% MIP (MIP60; n = 10) and CIP (n = 12). All participants performed the IMS test and incremental IME test at the first, fifth, ninth, and 13th weeks of the experimental protocol. Cardiopulmonary exercise testing was performed on an electromagnetic braking cycle ergometer pre-IMT and post-IMT. Data were analyzed using a 2-way repeated measures ANOVA (group and period factors). RESULTS: IMS increased in CIP and MIP60 groups at the ninth and 13th weeks compared with the sham group (P < .001; ß = 0.99). Regarding IME, there was an interaction between the CIP and MIP60 groups in all periods, except in the initial evaluation (P < .001; ß = 1.00). Peak power (in watts) increased after IMT in CIP and MIP60 groups (P = .01; ß = 0.67). Absolute oxygen uptake did not increase after IMT (P = .49; ß = 0.05). Relative oxygen uptake to lean mass values did not change significantly (P = .48; ß = 0.05). CONCLUSION: High-intensity IMT is beneficial on IMS, IME, and peak power, but does not provide additional gain to moderate intensity in recreational cyclists.

Oxylipin Response to Acute and Chronic Exercise: A Systematic Review.

Oxylipins are oxidized compounds of polyunsaturated fatty acids that play important roles in the body. Recently, metabololipidomic-based studies using advanced mass spectrometry have measured the oxylipins generated during acute and chronic physical exercise and described the related physiological effects. The objective of this systematic review was to provide a panel of the primary exercise-related oxylipins and their respective functions in healthy individuals. Searches were performed in five databases (Cochrane, PubMed, Science Direct, Scopus and Web of Science) using combinations of the Medical Subject Headings (MeSH) terms: "Humans", "Exercise", "Physical Activity", "Sports", "Oxylipins", and "Lipid Mediators". An adapted scoring system created in a previous study from our group was used to rate the quality of the studies. Nine studies were included after examining 1749 documents. Seven studies focused on the acute effect of physical exercise while two studies determined the effects of exercise training on the oxylipin profile. Numerous oxylipins are mobilized during intensive and prolonged exercise, with most related to the inflammatory process, immune function, tissue repair, cardiovascular and renal functions, and oxidative stress.

A Transfer Entropy Approach for the Assessment of the Impact of Inspiratory Muscle Training on the Cardiorespiratory Coupling of Amateur Cyclists.

The strength of cardiorespiratory interactions diminishes with age. Physical exercise can reduce the rate of this trend. Inspiratory muscle training (IMT) is a technique capable of improving cardiorespiratory interactions. This study evaluates the effect of IMT on cardiorespiratory coupling in amateur cyclists. Thirty male young healthy cyclists underwent a sham IMT of very low intensity (SHAM, n = 9), an IMT of moderate intensity at 60% of the maximal inspiratory pressure (MIP60, n = 10) and an IMT of high intensity at the critical inspiratory pressure (CIP, n = 11). Electrocardiogram, non-invasive arterial pressure, and thoracic respiratory movement (RM) were recorded before (PRE) and after (POST) training at rest in supine position (REST) and during active standing (STAND). The beat-to-beat series of heart period (HP) and systolic arterial pressure (SAP) were analyzed with the RM signal via a traditional non-causal approach, such as squared coherence function, and via a causal model-based transfer entropy (TE) approach. Cardiorespiratory coupling was quantified via the HP-RM squared coherence at the respiratory rate (K 2 HP-R M), the unconditioned TE from RM to HP (TER M → HP) and the TE from RM to HP conditioned on SAP (TER M → HP| SAP). In PRE condition we found that STAND led to a decrease of TER M → HP| SAP. After SHAM and CIP training this tendency was confirmed, while MIP60 inverted it by empowering cardiorespiratory coupling. This behavior was observed in presence of unvaried SAP mean and with usual responses of the baroreflex control and HP mean to STAND. TER M → HP and K 2 HP- RM were not able to detect the post-training increase of cardiorespiratory coupling strength during STAND, thus suggesting that conditioning out SAP is important for the assessment of cardiorespiratory interactions. Since the usual response of HP mean, SAP mean and baroreflex sensitivity to postural stressor were observed after MIP60 training, we conclude that the post-training increase of cardiorespiratory coupling during STAND in MIP60 group might be the genuine effect of some rearrangements at the level of central respiratory network and its interactions with sympathetic drive and vagal activity.

Chronic Influence of Inspiratory Muscle Training at Different Intensities on the Serum Metabolome.

This study investigated the chronic effect of inspiratory muscle training (IMT) on the human serum metabolome in healthy male recreational cyclists. Using a randomized, parallel group design, twenty-eight participants were randomized to three IMT groups: low intensity (LI, n = 7); moderate intensity (MI, n = 10); and high intensity (HI, n = 11). The IMT was performed for 11 weeks. Another group of participants under the same conditions, who did not perform the IMT but participated in all procedures, was included as controls (CG, n = 6). Blood samples were collected one week before and after 11 weeks of IMT and analyzed for metabolite shifts using 1H NMR. Statistical analysis included a 4 (group) × 2 (time) repeated measures ANOVA using the general linear model (GLM), and multivariate principal component analysis (PCA). Untargeted metabolomics analysis of serum samples identified 22 metabolites, including amino acids, lipids, and tricarboxylic acid cycle intermediates. Metabolites shifts did not differ between groups, indicating that IMT at three intensity levels did not alter the serum metabolome relative to the control group. These results reveal novel insights into the metabolic effects of the IMT and are consistent with the results from other studies showing negligible chronic alterations in the serum metabolome in response to physical training.

Mixed Flavonoid Supplementation Attenuates Postexercise Plasma Levels of 4-Hydroxynonenal and Protein Carbonyls in Endurance Athletes.

This double-blinded, placebo controlled, randomized crossover trial investigated the influence of 2-week mixed flavonoid versus placebo supplementation on oxinflammation markers after a 75-km cycling time trial in 22 cyclists (42.3 ± 1.7 years). Blood samples were collected before and after the 2-week supplementation, and then 0 hr, 1.5 hr, and 21 hr post 75-km cycling (176 ± 5.4 min, 73.4 ±2.0% maximal oxygen consumption). The supplement provided 678-mg flavonoids with quercetin (200 mg), green tea catechins (368 mg, 180-mg epigallocatechin gallate), and anthocyanins (128 mg) from bilberry extract, with caffeine, vitamin C, and omega-3 fatty acids added as adjuvants. Blood samples were analyzed for blood leukocyte counts, oxinflammation biomarkers, including 4-hydroxynonenal, protein carbonyls, and peripheral blood mononuclear mRNA expression for cyclooxygenease-2 and glutathione peroxidase. Each of the blood biomarkers was elevated postexercise (time effects, all ps < .01), with lower plasma levels for 4-hydroxynonenal (at 21-hr postexercise) in flavonoid versus placebo (interaction effect, p = .008). Although elevated postexercise, no trial differences for the neutrophil/lymphocyte ratio (p = .539) or peripheral blood mononuclear mRNA expression for cyclooxygenease-2 (p = .322) or glutathione peroxidase (p = .839) were shown. Flavonoid supplementation prior to intensive exercise decreased plasma peroxidation and oxidative damage, as determined by 4-hydroxynonenal. Postexercise increases were similar between the flavonoid and placebo trials for peripheral blood mononuclear mRNA expression for cyclooxygenease-2 and the nuclear factor erythroid 2-related factor 2 related gene glutathione peroxidase (NFE2L2). The data support the strategy of flavonoid supplementation to mitigate postexercise oxidative stress in endurance athletes.

Acute Ingestion of a Mixed Flavonoid and Caffeine Supplement Increases Energy Expenditure and Fat Oxidation in Adult Women: A Randomized, Crossover Clinical Trial.

This randomized, double-blinded, crossover study measured the acute effect of ingesting a mixed flavonoid-caffeine (MFC) supplement compared to placebo (PL) on energy expenditure (EE) and fat oxidation (FATox) in a metabolic chamber with premenopausal women (n = 19, mean ± SD, age 30.7 ± 8.0 year, BMI 25.7 ± 3.4 kg/m2). The MFC supplement (658 mg flavonoids, split dose 8:30, 13:00) contained quercetin, green tea catechins, and anthocyanins from bilberry extract, and 214 mg caffeine. Participants were measured twice in a metabolic chamber for a day, four weeks apart, with outcomes including 22 h EE (8:30-6:30), substrate utilization from the respiratory quotient (RQ), plasma caffeine levels (16:00), and genotyping for the single-nucleotide polymorphism (SNP) rs762551. Areas under the curve (AUC) for metabolic data from the MFC and PL trials were calculated using the trapezoid rule, with a mixed linear model (GLM) used to evaluate the overall treatment effect. The 22 h oxygen consumption and EE were significantly higher with MFC than PL (1582 ± 143, 1535 ± 154 kcal/day, respectively, p = 0.003, trial difference of 46.4 ± 57.8 kcal/day). FATox trended higher for MFC when evaluated using GLM (99.2 ± 14.0, 92.4 ± 14.4 g/22 h, p = 0.054). Plasma caffeine levels were significantly higher in the MFC versus PL trial (5031 ± 289, 276 ± 323 ng/mL, respectively, p < 0.001). Trial differences for 22 h EE and plasma caffeine were unrelated after controlling for age and body mass (r = -0.249, p = 0.139), and not different for participants with the homozygous allele 1, A/A, compared to C/A and C/C (p = 0.50 and 0.56, respectively). In conclusion, EE was higher for MFC compared to PL, and similar to effects estimated from previous trials using caffeine alone. A small effect of the MFC on FATox was measured, in contrast to inconsistent findings previously reported for this caffeine dose. The trial variance for 22 h EE was not significantly related to the variance in plasma caffeine levels or CYP1A2*1F allele carriers and non-carriers.

Effects of inspiratory muscle-training intensity on cardiovascular control in amateur cyclists.

Chronic effects of inspiratory muscle training (IMT) on autonomic function and baroreflex regulation are poorly studied. This study aims at evaluating chronic effects of different IMT intensities on cardiovascular control in amateur cyclists. A longitudinal, randomized, controlled blind study was performed on 30 recreational male cyclists undergoing IMT for 11 wk. Participants were randomly allocated into sham-trained group (SHAM, n = 9), trained group at 60% of the maximal inspiratory pressure (MIP60, n = 10), and trained group at critical inspiratory pressure (CIP, n = 11). Electrocardiogram, finger arterial pressure, and respiratory movements were recorded before (PRE) and after (POST) training at rest in supine position (REST) and during active standing (STAND). From the beat-to-beat series of heart period (HP) and systolic arterial pressure (SAP), we computed time domain markers, frequency domain indexes in the low frequency (0.04-0.15 Hz) and high frequency (HF, 0.15-0.4 Hz) bands, an entropy-based complexity index (CI), and baroreflex markers estimated from spontaneous HP-SAP sequences. Compared with SHAM, the positive effect of MIP60 over the HP series led to the HF power increase during REST (PRE: 521.2 ± 447.5 ms2; POST: 1,161 ± 878.9 ms2) and the CI rise during STAND (PRE: 0.82 ± 0.18; POST: 0.97 ± 0.13). Conversely, the negative effect of CIP took the form of the decreased HP mean during STAND (PRE: 791 ± 71 ms; POST: 737 ± 95 ms). No effect of IMT was visible over SAP and baroreflex markers. These findings suggest that moderate-intensity IMT might be beneficial when the goal is to limit cardiac sympathetic hyperactivity at REST and/or in response to STAND.

Metabolomics-Based Studies Assessing Exercise-Induced Alterations of the Human Metabolome: A Systematic Review.

This systematic review provides a qualitative appraisal of 24 high-quality metabolomics-based studies published over the past decade exploring exercise-induced alterations of the human metabolome. Of these papers, 63% focused on acute metabolite changes following intense and prolonged exercise. The best studies utilized liquid chromatography mass spectrometry (LC-MS/MS) analytical platforms with large chemical standard libraries and strong, multivariate bioinformatics support. These studies reported large-fold changes in diverse lipid-related metabolites, with more than 100 increasing two-fold or greater within a few hours post-exercise. Metabolite shifts, even after strenuous exercise, typically return to near pre-exercise levels after one day of recovery. Few studies investigated metabolite changes following acute exercise bouts of shorter durations (< 60 min) and workload volumes. Plasma metabolite shifts in these types of studies are modest in comparison. More cross-sectional and exercise training studies are needed to improve scientific understanding of the human system's response to varying, chronic exercise workloads. The findings derived from this review provide direction for future investigations focused on the body's metabolome response to exercise.