Angiotensin-converting enzyme and exercise adaptations: Genetic variability, pharmacological modulation and future directions.

Individual responses to exercise training vary widely, shaping athletic performance, rehabilitation outcomes and long‑term health trajectories. This review synthesizes evidence on how angiotensin-converting enzyme (ACE) activity, influenced by genetic variation, epigenetic regulation and pharmacological modulation, shapes adaptations in skeletal muscle hypertrophy, cardiac remodelling, erythropoiesis, endurance capacity and injury susceptibility. We highlight ACE's nuanced role, showing that pharmacological inhibition selectively attenuates cardiac and haematological adaptations, such as haemoglobin mass and lean body mass, without affecting peripheral muscle adaptations and aerobic performance.

Exercise- and diet-induced glycogen depletion impairs performance during one-legged constant-load, high-intensity exercise in humans.

Introduction: The effect of muscle glycogen stores on performance during intense short-duration exercises in humans is unclear. We hypothesized that low initial muscle glycogen levels would impair constant-load intense one-legged knee extensor exercise lasting approximately 5 min and human muscle contractile function, as determined by maximal voluntary contraction (MVC), electrically induced single-twitch maximal force, rate of force development (RFD), and rate of relaxation. Furthermore, alter phosphorylation of the Na/K-ATPase (NKA) regulatory proteins AMPK and FXYD1 indicating attenuated NKA activity.

mRNA Biomarkers in Dried Blood Spots May Improve Detection of Autologous Blood Micro-Transfusions Using an Individualized Approach.

Autologous blood transfusions (ABTs) are prohibited by the World Anti-Doping Agency (WADA), yet detecting autologous blood micro-transfusions (ABMTs) remains a challenge. Due to smaller transfused volumes, ABMTs cause attenuated biomarker changes, limiting detection sensitivity within the Athlete Biological Passport (ABP). This study assessed whether mRNA expression of 5-aminolevulinic acid synthase (ALAS2) and carbonic anhydrase 1 (CA1), measured from dried blood spots (DBS), could serve as sensitive biomarkers of ABMT.

Investigating the combined effects of statins and exercise on skeletal muscle mitochondrial content and function, cardiorespiratory fitness and quality of life in individuals with dyslipidaemia: protocol for a randomised placebo-controlled trial.

Introduction: Dyslipidaemia, affecting approximately 39% of adults worldwide, is a major risk factor for cardiovascular disease. Individuals with dyslipidaemia are often prescribed statins, which effectively lower plasma low-density lipoprotein cholesterol (LDL-C), thereby reducing the risk of cardiovascular events and mortality. Although statins lower LDL-C, emerging evidence suggests that they may counteract the beneficial adaptations to exercise in skeletal muscle mitochondria and whole-body aerobic capacity.

Genetic and training adaptations in the Haenyeo divers of Jeju, Korea.

Natural selection and relative isolation have shaped the genetics and physiology of unique human populations from Greenland to Tibet. Another such population is the Haenyeo, the all-female Korean divers renowned for their remarkable diving abilities in frigid waters. Apnea diving induces considerable physiological strain, particularly in females diving throughout pregnancy.

Time-course of muscle fatigue development during intense exercise in hypoxia and normoxia.

This study is the first to determine how hypoxia affects human muscle fatigue kinetics and metabolic perturbations during intense dynamic exercise. Using randomized, single-blinded crossover designs, three trials of two-legged knee extensions were performed under hypoxic (HYP, FiO₂ 0.135) and normoxic (NOR) conditions.

Additive Effect of EPO and Altitude on Hemoglobin Mass But Not Peak Oxygen Uptake.

Purpose: This study evaluated whether recombinant human erythropoietin (rhEpo) treatment combined with hypoxia provided an additive effect on hemoglobin mass (Hb mass ) and peak oxygen uptake (V̇O 2peak ) compared with altitude or rhEpo alone.

Methods: Thirty-nine participants underwent two interventions, each containing 4-wk baseline (PRE 1-4), 4-wk exposure at sea level or 2320 m of altitude (INT 1-4), and 4-wk follow-up (POST 1-4). Participants were randomly assigned to 20 IU·kg -1 rhEpo or placebo injections every second day for 3 wk during the exposure period at sea level (SL-EPO, n = 25; SL-PLA, n = 9) or at altitude (ALT-EPO, n = 12; ALT-PLA, n = 27).

Exercise echocardiography for improved assessment of diastolic filling dynamics.

During exercise stress, heart rate (HR) increases to support cardiac output, which also reduces ventricular filling time. Although echocardiography is widely used to assess cardiac function, studies display conflicting data on the dynamic changes in the healthy trained and untrained heart during rest and acute exercise stress. To address these discrepancies, we tested a new echocardiography exercise protocol on two groups with significant differences in cardiorespiratory fitness.

Generation Healthy Kids: Protocol for a cluster-randomized controlled trial of a multi-component and multi-setting intervention to promote healthy weight and wellbeing in 6-11-year-old children in Denmark.

Background: Childhood obesity can have significant negative consequences for children's wellbeing and long-term health. Prior school-based interventions to prevent child overweight and obesity have shown limited effects, highlighting the necessity for comprehensive approaches addressing complex drivers of childhood obesity. "Generation Healthy Kids" (GHK) is a multi-setting, multi-component intervention to promote healthy weight development, health and wellbeing in Danish children aged 6-11 years.

Exercise Training Counteracts Compromised Mitochondrial Capacity Induced by Energy Restriction in Prediabetics in a Sex-Dependent Manner.

The objective of this randomized controlled trial was to examine if exercise training can counteract energy restriction-induced impairment of mitochondrial capacity in skeletal muscle of 55-70-years people with prediabetes and metabolic syndrome. The potential impact of sex was explored. Fifty sedentary men and women with prediabetes and metabolic syndrome (age: 61 ± 6 (±SD) years, BMI: 29.

The impact of exercise intensity and duration for swim training-induced adaptations in cardiac structure and function in women with mild hypertension.

This study aimed to investigate the impact of swim training intensity and duration on cardiac structure and function in mildly hypertensive women. Sixty-two mildly hypertensive women were randomized to 15 weeks of either (1) high-intensity swimming (HIS, n = 21), (2) moderate-intensity swimming (MOD, n = 21) or (3) control (CON, n = 20). Training sessions occurred three times per week.

Duplicate measures of hemoglobin mass within an hour: feasibility, reliability, and comparison of three devices in supine position.

Duplicate measure of hemoglobin mass by carbon monoxide (CO)-rebreathing is a logistical challenge as recommendations prompt several hours between measures to minimize CO-accumulation. This study investigated the feasibility and reliability of performing duplicate CO-rebreathing procedures immediately following one another. Additionally, it was evaluated whether the obtained hemoglobin mass from three different CO-rebreathing devices is comparable.

15 weeks of soccer training increases left ventricular mass and improves indices of left ventricular diastolic function in previously sedentary, mildly hypertensive, middle-aged women.

Purpose: To investigate the impact of soccer training on cardiac adaptations in mildly hypertensive middle-aged women.

Methods: Hypertensive premenopausal women (n = 41; age (mean ± SD): 44 ± 7 years; height: 166 ± 6 cm; weight: 78.6 ± 11.

Long-term continuous exercise training counteracts the negative impact of the menopause transition on cardiometabolic health in hypertensive women - a 9-year RCT follow-up.

Purpose: The study examined effects of 9-yrs of multicomponent exercise training during the menopause interval on cardiometabolic health in hypertensive women.

Methods: Sedentary, middle-aged women (n = 25) with mild-to-moderate arterial hypertension were randomized into a soccer training (multicomponent exercise; EX; n = 12) or control group (CON; n = 13). EX took part in 1-h football training sessions, 1-3 times weekly, for a consecutive 9-years, totaling ∼800 training sessions, while CON did not take part in regular exercise training.

The angiotensin-converting enzyme I/D polymorphism does not impact training-induced adaptations in exercise capacity in patients with stable coronary artery disease.

Systematic exercise training effectively improves exercise capacity in patients with coronary artery disease (CAD), but the magnitude of improvements is highly heterogeneous. We investigated whether this heterogeneity in exercise capacity gains is influenced by the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene. Patients with CAD (n = 169) were randomly assigned to 12 weeks of exercise training or standard care, and 142 patients completed the study.

Serum Insulin-like Factor 3, Testosterone, and LH in Experimental and Therapeutic Testicular Suppression.

Background: Serum insulin-like factor 3 (INSL3) is a Leydig cell biomarker, but little is known about the circulating concentration of INSL3 during hypothalamus-pituitary-testicular suppression.

Aim: To study the concomitant changes in serum concentrations of INSL3, testosterone, and LH during experimental and therapeutic testicular suppression.

Methods: We included serum samples from 3 different cohorts comprising subjects before and after testicular suppression: (1) 6 healthy young men who were treated with androgens (Sustanon, Aspen Pharma, Dublin, Ireland); 2) 10 transgender girls (male sex assigned at birth) who were treated with 3-monthly GnRH agonist injections (Leuprorelinacetat, Abacus Medicine, Copenhagen, Denmark); and (3) 55 patients with prostate cancer who were randomized to surgical castration (bilateral subcapsular orchiectomy) or treatment with GnRH agonist (Triptorelin, Ipsen Pharma, Kista, Sweden).

Changes in Immature Reticulocytes Aid the Indirect Detection of Microdose Recombinant Erythropoietin Use in Men and Women.

Purpose: We investigated whether immature reticulocyte fraction (IRF) and the immature reticulocytes to red blood cells ratio (IR/RBC) are sensitive and specific biomarkers for microdose recombinant human erythropoietin (rHuEPO) and whether the inclusion of reticulocyte percentage (RET%) and the algorithm "abnormal blood profile score (ABPS)" increased the athlete biological passport (ABP) sensitivity compared with hemoglobin concentration ([Hb]) and the OFF-hr score ([Hb]-60 × √RET%).

Methods: Forty-eight (♀ = 24, ♂ = 24) participants completed a 2-wk baseline period followed by a 4-wk intervention period with three weekly intravenous injections of 9 IU·kg -1 ·bw -1 epoetin β (♀ = 12, ♂ = 12) or saline (0.9% NaCl, ♀ = 12, ♂ = 12) and a 10-d follow-up.

Glucocorticoids Accelerate Erythropoiesis in Healthy Humans-Should the Use in Sports Be Reevaluated?

Purpose: The World Anti-Doping Agency prohibits glucocorticoid administration in competition but not in periods out of competition. Glucocorticoid usage is controversial as it may improve performance, albeit debated. A hitherto undescribed but performance-relevant effect of glucocorticoids in healthy humans is accelerated erythropoiesis.

Does Hypoxia and Stress Erythropoiesis Compromise Cardiac Function in Healthy Adults? A Randomized Trial.

Objectives: To investigate whether recombinant human erythropoietin (rHuEPO) injections during an altitude training camp impact heart function.

Methods: Thirty (12 women) moderately trained subjects stayed at 2320 m altitude for 4 weeks while training. Subjects were randomized to placebo (isotonic saline) or rHuEPO (20 IU/kg body weight) i.

Microdoses of Recombinant Human Erythropoietin Enhance Time Trial Performance in Trained Males and Females.

Purpose: We investigated the effects of recombinant human erythropoietin (rHuEPO) administration on exercise endurance, maximal aerobic performance, and total hemoglobin mass (tHb). We hypothesized that frequent, small intravenous injections of epoetin β would increase time trial performance, peak oxygen uptake (V̇O 2peak ), and tHb in both males and females.

Methods: We included 48 healthy, recreational to trained males ( n = 24, mean ± SD V̇O 2peak = 55 ± 5 mL O 2 ·kg -1 ⋅min -1 ) and females ( n = 24; V̇O 2peak of 46 ± 4 mL O 2 ·kg -1 ⋅min -1 ) in a counterbalanced, double-blind, randomized, placebo-controlled study design stratified by sex.

Robust arm and leg muscle adaptation to training despite ACE inhibition: a randomized placebo-controlled trial.

Purpose: Angiotensin-converting enzyme (ACE) inhibitor treatment is widely applied, but the fact that plasma ACE activity is a potential determinant of training-induced local muscular adaptability is often neglected. Thus, we investigated the hypothesis that ACE inhibition modulates the response to systematic aerobic exercise training on leg and arm muscular adaptations.

Methods: Healthy, untrained, middle-aged participants (40 ± 7 yrs) completed a randomized, double-blinded, placebo-controlled trial.

Moderate hypoxic exposure for 4 weeks reduces body fat percentage and increases fat-free mass in trained individuals: a randomized crossover study.

Purpose: We evaluated whether or not changes in body composition following moderate hypoxic exposure for 4 weeks were different compared to sea level exposure.

Methods: In a randomized crossover design, nine trained participants were exposed to 2320 m of altitude or sea level for 4 weeks, separated by > 3 months. Body fat percentage (BF%), fat mass (FM), and fat-free mass (FFM) were determined before and after each condition by dual X-ray absorptiometry (DXA) and weekly by a bioelectrical impedance scanner to determine changes with a high resolution.

Effect of angiotensin-converting enzyme inhibition on cardiovascular adaptation to exercise training.

Angiotensin-converting enzyme (ACE) activity may be one determinant of adaptability to exercise training, but well-controlled studies in humans without confounding conditions are lacking. Thus, the purpose of the present study was to investigate whether ACE inhibition affects cardiovascular adaptations to exercise training in healthy humans. Healthy participants of both genders (40 ± 7 years) completed a randomized, double-blind, placebo-controlled trial.