Whole-body repeated hyperthermia increases irisin and brain-derived neurotrophic factor: A randomized controlled trial.

CONTEXT: Hyperthermia is known to be beneficial to patients affected by various diseases. Irisin is a key regulators of fat metabolism known to be released as response to cold. Brain Derived Neurotrophic Factor (BDNF) is a marker of neuroplasticity usually increased as response to acute exposure to human body stressors. OBJECTIVE: Effect of a repeated hyperthermia exposure programme on changes in circulating irisin and serum BDNF in healthy humans. DESIGN: Setting, Participants: Randomized, single-blind, cross-over trial in healthy humans conducted at Sechenov University Physiology Laboratory from April 2019. The treatment period was 2 weeks (wash-out 3 weeks). Researchers analysing serum biomarkers and questionnaires data were blinded to participants allocation. Participants were 20 healthy male (age 21.5 ± 2.1 years). INTERVENTION: Hyperthermia exposure programme (WBPH) versus sham exposure (SHAM) to hyperthermia (10 sessions in two weeks). MAIN OUTCOME MEASURE: Changes in irisin and BDNF before and after short hyperthermia exposure. RESULTS: Twenty participants were analyzed. Irisin increased significantly in group WBPH only: 6.3 µg/ml (mean with SD = 1.6) compared to 5.4 µg/ml (SD = 1.7) in SHAM group; This value was also higher than baseline (5.0 mean with SD = 1.1) in WBPH. After 10 sessions mean change in BDNF was higher in WBPH group vs SHAM: BDNF was 28,263 (SD = 4213) pg/ml in WBPH group and 24,064 (SD = 5600) pg/ml in SHAM group. BDNF concentrations were significantly higher than baseline values in WBPH group only, 28,263 (SD 4213) vs 25,888 (SD 4316) pg/ml. CONCLUSION: In healthy young humans a 2-week, ten sessions programme consisting of repeated exposure to hyperthermia resulted in a significantly higher increase of circulating Irisin and BDNF.

Repeated hyperthermia exposure increases circulating Brain Derived Neurotrophic Factor levels which is associated with improved quality of life, and reduced anxiety: A randomized controlled trial.

CONTEXT: Hyperthermia is known to be beneficial to patients affected by various diseases. Brain Derived Neurotrophic Factor (BDNF) is a marker of neuroplasticity usually increased as response to acute exposure to human body stressors. Little is known about BDNF changes after repeated exposure to hyperthermia. OBJECTIVE: To investigate the effect of a repeated hyperthermia exposure programme (HTC) on serum BDNF in healthy humans. DESIGN, SETTING, PARTICIPANTS: Randomized, single-blind, controlled trial in healthy humans conducted at Sechenov University Physiology Laboratory between December 2016 and November 2018. The treatment period was 10 weeks. Researchers analysing serum BDNF and questionnaires data were blinded to participants allocation. PARTICIPANTS: Were 34 healthy male (age 20.2 ± 1.6 years). INTERVENTION: Repeated Hyperthermia exposure programme, HTC, versus Light Intermittent Exercise, LIE, programme as control (10 weeks). MAIN OUTCOME MEASURE: Change in BDNF from baseline to final visit three days after treatment completion. RESULTS: 25 participants were analyzed. One participant withdrew before signing the informed consent and 8 participants (n = 3 in HTC and n = 5 in LIE) could not undertake the first assessment and were excluded. Mean change in BDNF was higher in HTC group vs LIE after both time points (after 12 and after 24 sessions). After 24 sessions BDNF was 30170 (SD 5268) pg/ml in HTC group a value that was significantly higher than 24104 (SD 2876) pg/ml measured in LIE group. BDNF concentrations were significantly higher than baseline values in HTC group only, 30170 (SD 5268) vs 26710 (SD 5437) pg/ml. CONCLUSION: A 10-week programme consisting of repeated exposure to hyperthermia resulted in a significantly higher increase of circulating BDNF compared to a programme consisting of intermittent light intensity exercise.

Assessing the importance and safety of hypoxia conditioning for patients with occupational pulmonary diseases: A recent clinical perspective.

Occupational pulmonary diseases (OPDs) pose a significant global health challenge, contributing to high mortality rates. This review delves into the pathophysiology of hypoxia and the safety of intermittent hypoxic conditioning (IHC) in OPD patients. By examining sources such as PubMed, Relemed, NLM, Scopus, and Google Scholar, the review evaluates the efficacy of IHC in clinical outcomes for OPD patients. It highlights the complexities of cardiovascular and respiratory regulation dysfunctions in OPDs, focusing on respiratory control abnormalities and the impact of intermittent hypoxic exposures. Key areas include the physiological effects of hypoxia, the role of hypoxia-inducible factor-1 alpha (HIF-1α) in occupational lung diseases, and the links between brain ischemia, stroke, and OPDs. The review also explores the interaction between intermittent hypoxic exposures, mitochondrial energetics, and lung physiology. The potential of IHE to improve clinical manifestations and underlying pathophysiology in OPD patients is thoroughly examined. This comprehensive analysis aims to benefit molecular pathologists, pulmonologists, clinicians, and physicians by enhancing understanding of IHE's clinical benefits, from research to patient care, and improving clinical outcomes for OPD patients.

Safety and Efficacy of Intermittent Hypoxia Conditioning as a New Rehabilitation/ Secondary Prevention Strategy for Patients with Cardiovascular Diseases: A Systematic Review and Meta-analysis.

BACKGROUND: Once used by mountaineers to facilitate rapid adaptations to altitude and by athletes to improve their aerobic capacity, exposure to hypoxia has been proven to affect various physiological, clinically relevant parameters. A form of conditioning known as Intermittent Hypoxia Conditioning (IHC) consists of repeated exposures to intermittent hypoxia, combined with normoxia and hyperoxia, which has been shown to have potential as a treatment to improve cardio- metabolic risks profile in cardiac patients but results across studies are inconsistent. This systematic review and meta-analysis aimed to evaluate the clinical effectiveness of IHC. METHODS: Four electronic databases (PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials) were searched (from inception to December 2019) to retrieve all studies focused on IHC in elderly patients with cardiovascular disease. A meta-analysis of functional, efficacy and safety outcomes in cardiac patients was completed to compare IHC to sham treatments. RESULTS: Fourteen studies with 320 patients in the Interval Hypoxia-normoxia Group (IHNG) or Interval Hypoxia-hyperoxia training Group (IHHG) and 111 patients in the control group were included in our meta-analysis. IHNT and IHHT were associated with significant reduction in heart rate, SBP, and DBP at rest after treatment [MD= -5.35 beat/min, 95% CI (-9.19 to -1.50), p=0.006], [MD= -13.72 mmHg, 95% CI (-18.31 to -9.132), p<0.001], and [MD= -7.882 mmHg, 95% CI (-13.163 to -2.601), p=0.003], respectively. There were no significant complications or serious adverse events related to IHNT/IHHT. CONCLUSION: The current evidence suggested that the use of the IHNT/IHHT program in elderly patients with CVDs can be safe and effective in terms of heart rate and elevated blood pressure. However, currently, there is no supporting evidence that IHNT/IHHT can significantly improve hematological parameters or lipid profile. Exercise tolerance increased at the end of the course of hypoxic conditioning within IHC group, but did not differ from controls. Further research is needed.

Redox Homeostasis in Humans Exposed to Intermittent Hypoxia-Normoxia and to Intermittent Hypoxia-Hyperoxia.

Aim: Exposure to hypoxia is known to increase oxidative stress and to impair antioxidant defenses in humans. The aim of the study was to measure oxidative stress and antioxidant capacity in healthy humans after being acutely exposed to both intermittent hypoxia-normoxia (IHN) and intermittent hypoxia-hyperoxia (IHH). Methods: Twenty-one healthy, young male participants were exposed to both IHN and IHH (fraction of inspired oxygen [FIO2] 0.11 for up to 7 minutes followed by 3-5 minutes of exposure to normoxia (room air) or hyperoxia, FIO2 0.3-0.35) in a crossover design study. In each participant, oxidative stress and antioxidant capacity were measured before and after each exposure in both experimental conditions. Results: After IHN, compared with baseline, neither oxidative stress (289.1 ± 63.2 vs. 262.2 ± 85.2 UCarr) nor antioxidant capacity (2376.1 ± 452.9 vs. 2525.0 ± 400.7 UCor) was significantly different. After IHH, neither oxidative stress (285.1 ± 94.2 vs. 277.5 ± 86.7 UCarr) nor antioxidant capacity (2653.6 ± 492.7 vs. 2568.4 ± 427.4 UCor) was significantly different compared with baseline. When the two studied exposure modalities were compared, there was no significant difference between groups with respect to both oxidative stress and antioxidant capacity. Conclusions: These data suggest that exposing healthy individuals to short-term IHN and IHH does not increase oxidative stress and it does not impair antioxidant defenses.

Intermittent Hypoxia-Hyperoxia Conditioning Improves Cardiorespiratory Fitness in Older Comorbid Cardiac Outpatients Without Hematological Changes: A Randomized Controlled Trial.

AIM: To compare a program based on intermittent hypoxia-hyperoxia training (IHHT) consisting of breathing hypoxic-hyperoxic gas mixtures while resting to a standard exercise-based rehabilitation program with respect to cardiorespiratory fitness (CRF) in older, comorbid cardiac outpatients. MATERIALS AND METHODS: Thirty-two cardiac patients with comorbidities were randomly allocated to IHHT and control (CTRL) groups. IHHT completed a 5-week program of exposure to hypoxia-hyperoxia while resting, CTRL completed an 8-week tailored exercise program, and participants in the CTRL were also exposed to sham hypoxia exposure. CRF and relevant hematological biomarkers were measured at baseline and after treatment in both groups. RESULTS: After intervention, CRF in the IHHT group was not significantly different (n = 15, 19.9 ± 6.1 mlO2 minutes-1 kg-1) compared with the CTRL group (n = 14, 20.6 ± 4.9 mlO2 minutes-1 kg-1). CRF in IHHT increased significantly from baseline (6.05 ± 1.6 mlO2 minutes-1 kg-1), while no difference was found in CTRL. Systolic and diastolic blood pressures were not significantly different between groups after treatment. Hemoglobin content was not significantly different between groups. Erythrocytes and reticulocytes did not change pre/post interventions in both experimental groups. CONCLUSIONS: IHHT is safe in patients with cardiac conditions and common comorbidities and it might be a suitable option for older patients who cannot exercise. A 5-week IHHT is as effective as an 8-week exercise program in improving CRF, without hematological changes. Further studies are needed to clarify the nonhematological adaptations to short, repeated exposure to normobaric hypoxia-hyperoxia.

A programme based on repeated hypoxia-hyperoxia exposure and light exercise enhances performance in athletes with overtraining syndrome: a pilot study.

Overtraining syndrome (OTS) is a major concern among endurance athletes and is a leading cause in preventing them to perform for long periods. Intermittent exposure to hypoxia has been shown to be an effective way of improving performance without exercising. Aim of this pilot study was to evaluate intermittent hypoxia-hyperoxia training combined with light exercise as an intervention to facilitate athletes with OTS to restore their usual performance level. Thirty-four track and field athletes were recruited: 15 athletes with OTS volunteered to participate and undertook a conditioning programme consisting of repeated exposures to hypoxia (O2 at 10%) and hyperoxia (O2 at 30%) (6-8 cycles, total time 45 min-1 h), three times a week, delivered 1·5-2 h after a low-intensity exercise session (2 bouts of 30 min, running at 50% of VO2max with 10 min rest between bouts) over 4 weeks. Nineteen healthy track and field athletes volunteered to participate as a control group and followed their usual training schedule. Measurements before and after the intervention included exercise capacity, analysis of heart rate variability and hematological parameters. In athletes with OTS, a 4-week light exercise combined with intermittent hypoxia-hyperoxia training improved exercise performance (191·9 ± 26·9 W versus 170·8 ± 44·8 W in exercise capacity test, P = 0·01). Heart rate variability analysis revealed an improved sympatho-parasympathetic index (low frequency/high frequency ratio, 8·01 ± 7·51 before and 1·45 ± 1·71 after, P = 0·007). Hematological parameters were unchanged. Our pilot study showed that intermittent hypoxia-hyperoxia training and low-intensity exercise can facilitate functional recovery among athletes with OTS in a relatively short time.

Adaptations following an intermittent hypoxia-hyperoxia training in coronary artery disease patients: a controlled study.

BACKGROUND: Repeated exposure to intermittent normobaric hypoxia improves exercise tolerance in cardiac patients. Little is known on the effects of intermittent normobaric hypoxia-hyperoxia exposure in coronary artery disease (CAD) patients (New York Heart Association II-III). HYPOTHESIS: IHHT improves exercise tolerance, cardiometabolic profile, and quality of life in CAD patients. METHODS: The study design was a nonrandomized, controlled, before-and-after trial. Forty-six CAD patients volunteered to take part in the study: a group of 27 patients undertook the intermittent hypoxia (O2 at 10%)-hyperoxia (O2 at 30%) training (IHHT), whereas a control group (CTRL) of 19 patients, who already completed an 8-week standard cardiac rehabilitation program, was allocated to sham-IHHT treatment (breathing room air, O2 at 21%). Exercise performance, blood and metabolic profiles, and quality of life (Seattle Angina Questionnaire [SAQ]) were measured before and after in the IHHT group (IHHG) and sham-IHHT in the CTRL group. RESULTS: The IHHG showed improved exercise capacity, reduced systolic and diastolic blood pressures, enhanced left ventricle ejection fraction, and reduced glycemia, but only at 1-month follow-up. Angina as a reason to stop exercising was significantly reduced after treatment and at 1-month follow-up. The IHHT SAQ profile was improved in the IHHG and not significantly different to the CTRL group after standard rehabilitation. The IHHG was also compared to the CTRL group at 1-month follow-up, and no differences were found. CONCLUSIONS: In CAD patients, an IHHT program is associated with improved exercise tolerance, healthier risks factors profile, and a better quality of life. Our study also suggests that IHHT is as effective as an 8-week standard rehabilitation program.