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BACKGROUND: Medical gases, inhaled nitric oxide (iNO) and molecular hydrogen (iH2), have been used in the therapy for various medical conditions. When combined, these gases have shown to be more effective and safer for patients, and may become a promising treatment option for various diseases рost-COVID-19 syndrome (PS). AIM: To compare the efficacy and safety of combined therapy iNO/iH2 with monotherapy iNO and a control group in patients with respiratory disorders during with PS. MATERIALS AND METHODS: A prospective, open-label, controlled trial involving 60 patients with PS was conducted in parallel groups (the mean age of the participants was 58.1 ± 12.9 years, and the sample consisted of 18 men and 42 women). The participants were randomly assigned to 3 groups: 1 (n = 20) - iNO/iH2 treatment; 2 (n = 20) - only iNO treatment; and 3 (n = 20) - control group. The duration of treatment was 10 days, and the treatment involved inhalation through a nasal cannula for 90 minutes (flow rate of 4 liters per minute, iH2 concentrations < 4%, iNO - 60 pmm). Clinical outcomes were assessed using self-observation diaries, Modified Medical Research Council Dyspnea Scale questionnaires, the "Language of Dyspnea" Scale, Fatigue Assessment Scale, Hospital Anxiety and Depression Scale, and Short Form-36 Health Status Survey questionnaires. Additionally, a 6-Minute Walk Test was performed, and indicators of oxidative status in blood serum and microcirculation in the bulbar conjunctiva were measured. RESULTS: The course of iNO/iН2 and iNO led to regression of the clinical manifestations of PS (dyspnea, cough, fatigue), improved the physical and psychological component of quality of life, and contributed to improvement in microcirculation (increased venule diameter and velocity) compared to the control group (p < 0.05). In combination therapy, there was an increase in distance traveled by 6-minute walk test and decrease in reactive oxygen species compared to iNO and control groups (p < 0.05). No serious adverse events were noted. CONCLUSION: The study demonstrates the advantage of the iNO/iH2 course in comparison with iNO and control in the rehabilitation program of patients with

Molecular hydrogen has gained attention for its potential antioxidant, anti-inflammatory, and ergogenic effects. However, its impact on blood oxygen saturation and autonomic cardiac regulation under resting conditions remains unclear. This randomized, double-blind, placebo-controlled crossover study investigated the effects of a 60 min molecular hydrogen inhalation on oxygen saturation and heart rate variability in healthy females. Twenty physically active participants (22.1 ± 1.6 years) completed two inhalation sessions with either molecular hydrogen or placebo (ambient air), separated by a 7-day washout period. Oxygen saturation and heart rate variability were continuously monitored during the 60 min of inhalation. The results using 60 min averages showed a statistically significant (p ≤ 0.007) decrease in oxygen saturation during molecular hydrogen inhalation (95.9 ± 1.0%) compared to placebo (96.7 ± 0.7%), but this decrease should not be considered clinically significant. No significant changes (all p ≥ 0.32) were observed in time-domain or frequency-domain heart rate variability indices. These findings suggest that, under resting conditions, molecular hydrogen inhalation does not induce functional changes in autonomic cardiac regulation, and the observed reduction in blood oxygen saturation does not compromise homeostatic stability.

AIM: To study the efficacy and safety of the combined use of thermal heliox (t-He/O2), nitric oxide (NO) and molecular hydrogen (H2) in patients with exacerbation of chronic obstructive pulmonary disease (COPD) complicated by hypoxemic, hypercapnic respiratory failure (RF) and secondary pulmonary arterial hypertension (PAH) in the post-COVID period. MATERIALS AND METHODS: The randomized, comparative, controlled, parallel study included patients (n=100, 52 men and 48 women) with exacerbation of COPD levels of evidence C and D (GOLD 2021-2023) with hypoxemic, hypercapnic respiratory failure and secondary PAH, who had pneumonia caused by SARS-CoV-2 before hospitalization. Patients with similar demographic, clinical, and functional parameters, who received non-invasive ventilation (NIV) and oxygen (O2) along with standard drug therapy, were divided into 5 groups: Group 1 (main): (n=22: 12 men, 10 women, who received t-He/O2, NO, and H2 sequentially); Group 2 (n=20: 10 men, 10 women, who received t-He/O2 and NO); Group 3 (n=20: 11 men, 9 women, who received t-He/O2 and H2); Group 4 (n=18: 10 men, 8 women, who received NO and H2); Group 5 (control) (n=20: 9 men, 11 women). The dynamics of the clinical condition of patients, gas exchange in the lungs, acid-base balance, left-to-right discharge fraction, hemodynamic parameters, and exercise tolerance were assessed. RESULTS: A positive effect of the complex use of medical gases on the clinical condition of patients, gas exchange parameters in the lungs, metabolism, hemodynamic parameters and exercise tolerance was found in comparison with these parameters in patients who received medical gases separately and with the control group. CONCLUSION: The combination of t-He/O2, NO and H2 with simultaneous pathogenetic therapy and NIV in patients with exacerbation of COPD complicated by hypoxemic, hypercapnic RF and secondary PAH in the post-COVID period is safe and more effective compared to groups receiving each medical gas separately. Complex therapy improves the clinical condition of patients, reduces signs of hypoxemia and hypercapnia, vascular endothelial dysfunction, metabolic disorders and increases tolerance to physical

Initially, molecular hydrogen was considered a physiologically inert and non-functional gas. However, experimental and clinical studies have shown that molecular hydrogen has anti-inflammatory, anti-apoptotic, and strong selective antioxidant effects. This study aimed to evaluate the effects of 60 minutes of molecular hydrogen inhalation on respiratory gas analysis parameters using a randomized, double-blind, placebo-controlled, crossover design. The study was conducted at Faculty of Physical Culture, Palacký University Olomouc from September 2022 to March 2023. Twenty, physically active female participants aged 22.1 ± 1.6 years who inhaled either molecular hydrogen or ambient air through a nasal cannula (300 mL/min) for 60 minutes while resting were included in this study. Metabolic response was measured using indirect calorimetry. Breath-by-breath data were averaged over four 15-minute intervals. Compared with placebo (ambient air), molecular hydrogen inhalation significantly decreased respiratory exchange ratio and ventilation across all intervals. Furthermore, the change in respiratory exchange ratio was negatively correlated with body fat percentage from 30 minutes onwards. In conclusion, 60 minutes of resting molecular hydrogen inhalation significantly increased resting fat oxidation, as evidenced by decreased respiratory exchange ratio, particularly in individuals with higher body fat percentages.

OBJECTIVE: The Efficacy of Inhaled Hydrogen on Neurologic Outcome Following Brain Ischemia During Post-Cardiac Arrest Care (HYBRID) II trial (jRCTs031180352) suggested that hydrogen inhalation may reduce post-cardiac arrest brain injury (PCABI). However, the combination of hypothermic target temperature management (TTM) and hydrogen inhalation on outcomes is unclear. The aim of this study was to investigate the combined effect of hydrogen inhalation and hypothermic TTM on outcomes after out-of-hospital cardiac arrest (OHCA). DESIGN: Post hoc analysis of a multicenter, randomized, controlled trial. SETTING: Fifteen Japanese ICUs. PATIENTS: Cardiogenic OHCA enrolled in the HYBRID II trial. INTERVENTIONS: Hydrogen mixed oxygen (hydrogen group) versus oxygen alone (control group). MEASUREMENTS AND MAIN RESULTS: TTM was performed at a target temperature of 32-34°C (TTM32-TTM34) or 35-36°C (TTM35-TTM36) per the institutional protocol. The association between hydrogen + TTM32-TTM34 and 90-day good neurologic outcomes was analyzed using generalized estimating equations. The 90-day survival was compared between the hydrogen and control groups under TTM32-TTM34 and TTM35-TTM36, respectively. The analysis included 72 patients (hydrogen [ n = 39] and control [ n = 33] groups) with outcome data. TTM32-TTM34 was implemented in 25 (64%) and 24 (73%) patients in the hydrogen and control groups, respectively ( p = 0.46). Under TTM32-TTM34, 17 (68%) and 9 (38%) patients achieved good neurologic outcomes in the hydrogen and control groups, respectively (relative risk: 1.81 [95% CI, 1.05-3.66], p < 0.05). Hydrogen + TTM32-TTM34 was independently associated with good neurologic outcomes (adjusted odds ratio 16.10 [95% CI, 1.88-138.17], p = 0.01). However, hydrogen + TTM32-TTM34 did not improve survival compared with TTM32-TTM34 alone (adjusted hazard ratio: 0.22 [95% CI, 0.05-1.06], p = 0.06). CONCLUSIONS: Hydrogen + TTM32-TTM34 was associated with improved neurologic outcomes after cardiogenic OHCA compared with TTM32-TTM34 monotherapy. Hydrogen inhalation is a promising treatment option for reducing PCABI when combined with TTM32-TTM34.

Reactive Oxygen Species (ROS) play a key role in physiological processes. However, the imbalance between ROS and antioxidants in favor of the former causes oxidative stress linked to numerous pathologies. Due to its unique attributes, including distinguished permeability and selective antioxidant capability, molecular hydrogen (H2) has become an essential therapeutic agent. Hydrogen Inhalation Therapy (HIT) has come to light as a promising strategy to counteract oxidative stress. In this randomized controlled study, we aimed to evaluate the effectiveness of HIT in reducing blood ROS levels. 37 participants with elevated ROS levels (d-ROMs value > 350 U.CARR) were enrolled in the study. Participants were divided into test and control groups. The test group participants received HIT, and then their blood ROS levels were measured immediately post-treatment and after 24 h. Their results were compared to those of the control group participants who did not undergo HIT. The test group demonstrated a significant reduction in blood ROS levels after the treatment. These findings suggested the efficacy of HIT in reducing oxidative stress.

OBJECTIVES: To assess the impact of medium-term supplementation with dihydrogen and pyrroloquinoline quinone (PQQ) on mitochondrial biomarkers, brain metabolism, and cognition in elderly individuals diagnosed with mild cognitive impairment. DESIGN: A parallel-group, randomized, placebo-controlled, double-blind experimental design, maintaining a 1:1 allocation ratio between the experimental group (receiving the dihydrogen-producing minerals and PQQ) and the control group (receiving the placebo) throughout the trial. SETTING AND PARTICIPANTS: Thirty-four elderly individuals with mild cognitive impairment (mean age 71.9 ± 3.8 years; 28 females) voluntarily provided written consent to participate in this trial. Participants were assigned in a double-blind parallel-group design to receive either a dihydrogen-PQQ mixture (Alpha Hope®, CalerieLife, Irvine, CA) or placebo twice daily for a 6-week intervention period. METHODS: The primary endpoint was the change in serum brain-derived neurotrophic factor (BDNF) from baseline to the 6-week follow-up; secondary outcomes included cognitive function indices, specific metabolites in brain tissue, brain oxygenation, and the prevalence and severity of side effects. Interaction effects (time vs. intervention) were evaluated using two-way ANOVA with repeated measures and Friedman's 2-way ANOVA by ranks, for normally distributed data with homogeneous variances and non-homogeneous variances, respectively. RESULTS: Dihydrogen-PQQ resulted in a significant elevation in serum BDNF levels at the six-week follow-up (P = 0.01); conversely, no changes in BDNF levels were observed in the placebo group throughout the study duration (P = 0.27). A non-significant trend in the impact of interventions on BDNF levels was observed (treatment vs. time interaction, P = 0.14), suggesting a tendency for dihydrogen-PQQ to upregulate BDNF levels compared to the placebo. A significant interaction effect was observed for the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores in the orientation domain (P = 0.03), indicating the superiority of dihydrogen-PQQ over placebo in enhancing this cognitive aspect. Cerebral oxygenation satura

BACKGROUND: Premenstrual syndrome (PMS) consists of psychiatric or somatic symptoms negatively affecting the daily life. PMS treatment can involve the use of complementary-alternative approaches. Hydrogen-rich water (HRW) has antioxidant and anti-inflammatory properties that may treat PMS. This study aimed to investigate the effect of drinking HRW on the severity of premenstrual symptoms and the quality of life of women who suffer from PMS. METHODS: This study is a randomized controlled trial. Participants were randomized into two groups (intervention group=33, control group=32) using the block randomization method. Participants were requested to consume 1500-2000 mL of HRW daily in the intervention group and drink water in the placebo group. Participants began drinking either HRW or placebo water from day 16 of their menstrual cycle until day 2 of the following cycle for three menstrual cycles. The research data were collected using a Demographic Information Form, Premenstrual Syndrome Scale (PMSS), and Short form of the World Health Organization Quality of Life Questionnaire (WHOQOL- BREF). RESULTS: The intervention group had significantly lower mean scores than the control group in both the first and second follow-ups on the PMSS (P<0.05). In the first follow-up, the intervention group had significantly higher mean scores in the Physical Health and Psychological domains of the WHOQOL-BREF compared to the control group (P<0.05). Group × time interaction was significant for PMSS (F = 10.54, P<0.001). Group × time interaction was insignificant for WHOQOL- BREF (P>0.05). CONCLUSIONS: The consumption of HRW reduces the severity of premenstrual symptoms and improves individuals' quality of life in physical and psychological domains. © 2024. The Author(s).

54. Cesk Slov Oftalmol. 2023 Spring;79(4):180-184. doi: 10.31348/2023/23. EFFECT OF ACUTE HYDROGEN-RICH WATER INTAKE ON INTRAOCULAR PRESSURE IN HEALTHY SUBJECTS. [Article in English] Najmanová E, Manethová H, Botek M, Pluháček F. PURPOSES: The primary aim of the study was to assess the response of intraocular pressure (IOP) to the acute ingestion of hydrogen-rich water (HRW) compared to hydrogen-free water (placebo) in healthy subjects. The effect of HRW intake on central corneal thickness (CCT) was also monitored. SUBJECTS AND METHODS: Twenty-four healthy volunteers (5 men, 19 women) aged between 20 and 33 were included in the study, in which one eye of each subject was measured. The study was prospective, randomized and double-blind, with crossover design. Each subject underwent two parts of the experiment, each part on a different day and in random order. In each part of experiment, a total volume of 1260 ml of HRW or placebo was administered over 15 minutes in three doses. IOP and CCT were measured before and during the course of 75 minutes from the start of the HRW or placebo intake. RESULTS: Administration of both HRW and the placebo caused a significant increase in IOP. The maximum IOP increase was 2.7 mmHg ±2.0 mmHg in minute 25 after the commencement of the experiment (HRW intake), and 1.4 mmHg ±2.0 mmHg in minute 35 (placebo intake). The values of IOP did not differ significantly between both parts, but there were significantly more clinically significant individual IOP increases after HRW intake (58%) compared to the placebo (25%). CCT did not change significantly during the experiment. CONCLUSION: The rapid intake of 1260 ml of both HRW and hydrogen-free water causes a statistically significant increase in IOP compared to the baseline in healthy individuals. In the case of HRW, the increase was also clinically significant in most of the subjects. Thus, the results indicate that acute intake of HRW may pose a higher risk than placebo intake in terms of IOP. However, in the case of risk groups such as subjects with glaucoma, ocular hypertension or suspected glaucoma, it is necessary to verify this conclusion by further studies.

This research examined the effects of single-dose molecular hydrogen (H2) supplements on acid-base status and local muscle deoxygenation during rest, high-intensity intermittent training (HIIT) performance, and recovery. Ten healthy, trained subjects in a randomized, double-blind, crossover design received H2-rich calcium powder (HCP) (1500 mg, containing 2.544 μg of H2) or H2-depleted placebo (1500 mg) supplements 1 h pre-exercise. They performed six bouts of 7 s all-out pedaling (HIIT) at 7.5% of body weight separated by 40 s pedaling intervals, followed by a recovery period. Blood gases' pH, PCO2, and HCO3- concentrations were measured at rest. Muscle deoxygenation (deoxy[Hb + Mb]) and tissue O2 saturation (StO2) were determined via time-resolved near-infrared spectroscopy in the vastus lateralis (VL) and rectus femoris (RF) muscles from rest to recovery. At rest, the HCP group had significantly higher PCO2 and HCO3- concentrations and a slight tendency toward acidosis. During exercise, the first HIIT bout's peak power was significantly higher in HCP (839 ± 112 W) vs. Placebo (816 ± 108 W, p = 0.001), and HCP had a notable effect on significantly increased deoxy[Hb + Mb] concentration during HIIT exercise, despite no differences in heart rate response. The HCP group showed significantly greater O2 extraction in VL and microvascular (Hb) volume in RF during HIIT exercise. The HIIT exercise provided significantly improved blood flow and muscle reoxygenation rates in both the RF and VL during passive recovery compared to rest in all groups. The HCP supplement might exert ergogenic effects on high-intensity exercise and prove advantageous for improving anaerobic HIIT exercise performance.

BACKGROUND: Cancer remains a challenging target to cure, with present therapeutic methods unable to exhibit restorative outcomes without causing severe negative effects. Molecular hydrogen (H2) has been reported to be a promising adjunctive therapy for cancer treatment, having the capability to induce anti-proliferative, anti-oxidative, pro-apoptotic and anti-tumoural effects. This review summarises the findings from various articles on the mechanism, treatment outcomes, and overall effectiveness of H2 therapy on cancer management. METHODS: Using Cochrane, PubMed, and Google Scholar as the search engines, full-text articles in the scope of the study, written in English and within 10 years of publication were selected. RESULTS: Out of the 677 articles, 27 articles fulfilled the eligibility criteria, where data was compiled into a table, outlining the general characteristics and findings. Throughout the different forms of H2 administration, study design and types of cancers reported, outcomes were found to be consistent. CONCLUSION: From our analysis, H2 plays a promising therapeutic role as an independent therapy as well as an adjuvant in combination therapy, resulting in an overall improvement in survivability, quality of life, blood parameters, and tumour reduction. Although more comprehensive research is needed, given the promising outcomes, H2 is worth considering for use as a complement to current cancer therapy.

PURPOSE OF REVIEW: The current systematic review summarizes recent, basic clinical achievements regarding the neuroprotective effects of molecular hydrogen in distinct central nervous system conditions. RECENT FINDINGS: Perioperative neuroprotection remains a major topic of clinical anesthesia. Various gaseous molecules have previously been explored as a feasible therapeutic option in neurological disorders. Among them, molecular hydrogen, which has emerged as a novel and potential therapy for perioperative neuroprotection, has received much attention. SUMMARY: Fundamental and clinical evidence supports the antioxidant, antiinflammation, antiapoptosis and mitochondrial protective effects of hydrogen in the pathophysiology of nervous system diseases. The clinically preventive and therapeutic effects of hydrogen on different neural diseases, however, remain uncertain, and the lack of support by large randomized controlled trials has delayed its clinical application.