Authors: Michal Botek, Jakub Krejčí, Michal Valenta, Andrew McKune, Petr Konečný, Iva Klimešová, and Dalibor Pastucha
Source: International Journal of Environmental Research and Public Health, Volume 19, Issue 4 (2022)

Background

Molecular hydrogen (H₂) is emerging as a potential therapeutic gas for patients with acute post-coronavirus disease 2019 (COVID-19), owing to its antioxidant, anti-inflammatory, anti-apoptotic and anti-fatigue properties.

Objective

To determine the effects of a 14-day course of H₂ inhalation on respiratory status and physical fitness in acute post-COVID-19 patients.

Methods

This randomised, single-blinded, placebo-controlled study included 26 men (aged 44 ± 17 years) and 24 women (aged 38 ± 12 years). Participants underwent a six-minute walk test (6MWT) and pulmonary function testing, specifically forced vital capacity (FVC) and forced expiratory volume in one second (FEV₁). Symptomatic participants were recruited between the 21st and 33rd day following a positive polymerase chain reaction (PCR) test for COVID-19. The intervention consisted of H₂ or placebo inhalation, administered twice daily for 60 minutes over a 14-day period.

Results

Compared to the placebo, H₂ therapy led to a statistically significant improvement in the 6MWT distance by 64 ± 39 metres, FVC by 0.19 ± 0.24 litres, and FEV₁ by 0.11 ± 0.28 litres (all p ≤ 0.025).

Conclusion

It can be concluded that H₂ inhalation had beneficial health effects in terms of improving physical and respiratory functions in acute post-COVID-19 patients. Thus, H₂ inhalation may represent a safe and effective approach to accelerating early functional recovery in patients recovering from COVID-19.

Citation

Botek M, Krejčí J, Valenta M, McKune A, Sládečková B, Konečný P, Klimešová I, Pastucha D. Molecular Hydrogen Positively Affects Physical and Respiratory Function in Acute Post-COVID-19 Patients: A New Perspective in Rehabilitation. Int J Environ Res Public Health. 2022 Feb 10;19(4):1992. doi: 10.3390/ijerph19041992. PMID: 35206179; PMCID: PMC8872486.

Authors: Tan YE, Xie YX, Dong GX, Yin MY, Shang ZYT, Zhou KX, Bao DP, Zhou JH
Source: Nutrients, Volume 16, Issue 10 (2024)

Background

Hydrogen (H₂) may serve as a potential therapeutic agent in managing symptoms of Long COVID due to its antioxidant and anti-inflammatory properties. However, further scientific evidence is needed to clarify the effects of H₂ administration on symptom relief.

Objective

This study aimed to examine the impact of hydrogen-rich water (HRW) consumption over 14 consecutive days on fatigue and dyspnoea in patients with Long COVID.

Methods

In this randomised, single-blind, placebo-controlled trial, 55 participants were screened and 23 excluded, resulting in 32 eligible participants who were randomised into the hydrogen-rich water group (HRW; n = 16) and the placebo water group (PW; n = 16). Participants were instructed to consume either HRW or PW daily for 14 days.

Assessments included the Fatigue Severity Scale (FSS), six-minute walk test (6MWT), 30-second chair stand test (30s-CST), the modified Medical Research Council (mMRC) dyspnoea scale, the Pittsburgh Sleep Quality Index (PSQI), and the Depression Anxiety Stress Scales (DASS-21), both pre- and post-intervention.

A linear mixed-effects model was employed to evaluate the effects of HRW. Cohen’s d values were used to assess effect size where statistical significance was observed. Mean change and 95% confidence intervals (CI) were also reported.

Results

Compared to placebo, HRW significantly reduced FSS scores (p = 0.046, 95% CI = –20.607 to –0.198, d = 0.696), increased total 6MWT distance (p < 0.001, 95% CI = 41.972 to 61.891, d = 1.010), improved total repetitions in the 30s-CST (p = 0.002, 95% CI = 1.570 to 6.314, d = 1.190), and enhanced PSQI scores (p = 0.012, 95% CI = –5.169 to –0.742, d = 1.274). However, there were no significant differences in mMRC scores (p = 0.556) or DASS-21 scores (p > 0.143).

Conclusion

This study suggests that HRW may be an effective strategy for alleviating fatigue and improving cardiorespiratory endurance, musculoskeletal function, and sleep quality in Long-COVID patients. However, it does not appear to ameliorate dyspnoea.

Citation

Tan Y, Xie Y, Dong G, Yin M, Shang Z, Zhou K, Bao D, Zhou J. The Effect of 14-Day Consumption of Hydrogen-Rich Water Alleviates Fatigue but Does Not Ameliorate Dyspnoea in Long-COVID Patients: A Pilot, Single-Blind, and Randomised, Controlled Trial. Nutrients. 2024; 16(10):1529. https://doi.org/10.3390/nu16101529

Authors: Singh RB, Halabi G, Fatima G, Rai RH, Tarnava AT, LeBaron TW
Source: Clinical Case Reports, Volume 9, Issue 11 (2021)

Background

COVID-19 is associated with respiratory failure and subsequent hypoxaemia. There is an urgent need for new therapeutic strategies to mitigate hypoxia. Molecular hydrogen therapy may help by reducing inflammation, oxidative stress, and hypoxia.

Case Description

The patient, a 77-year-old physician, presented with symptoms consistent with COVID-19, potentially as a side effect following Covishield vaccination (developed by Oxford-AstraZeneca). After recovery from the acute phase of pneumonia resembling COVID-19, the patient developed chronic hypoxaemia with resting oxygen saturation between 91% and 93%. Ongoing respiratory failure due to pulmonary fibrosis led to persistent resting saturation at 92–93%.

The primary approach included breathing exercises focused on abdominal breathing. Pharmacological treatment involved twice-daily inhalation via nebuliser of withasthalin, budicort, and evolin. After six weeks, substantial recovery was noted; however, high-resolution computed tomography (HRCT) revealed ground-glass opacities in the lower lung zones, indicative of post-COVID fibrotic damage.

Due to persistent pulmonary fibrosis, the patient was prescribed soft gel capsules of Nintedanib (100 mg twice daily) for 45 days, beginning 15 days after symptom onset. He also continued taking coenzyme Q10 (CoQ10) at 200 mg twice daily, along with apixaban and rosuvastatin (5 mg daily).

Results

Hydrogen-rich water (HRW) therapy was associated with significant improvements in oxygen saturation, as measured by pulse oximetry and a multiparameter monitor. Following five minutes of H₂ inhalation in the mornings, the average oxygen saturation over five consecutive days increased from 92.6% to 97.2%, then gradually declined to 96.4%, 95%, and 93.4% after 30, 45, and 60 minutes, respectively. Evening treatments raised saturation from 92.6% to 96% at five minutes post-administration. At 30, 45, and 60 minutes, the minimum average saturation was 95.4%, 94.4%, and 92.6%, respectively.

Exercise tolerance also improved: baseline oxygen saturation (prior to HRW) increased from 83% on day 1 to 90% on day 10. Notably, further increases in saturation were observed at 5, 30, 45, and 60 minutes of treatment each day, with the most pronounced improvement at 30 minutes (from 94% on day 1 to 96% on day 10).

Conclusion

Administration of molecular hydrogen dissolved in water may enhance oxygen saturation levels and physical performance in patients with COVID-19-like symptoms, potentially offering support in managing post-COVID respiratory sequelae.

Citation

Singh RB, Halabi G, Fatima G, Rai RH, Tarnava AT, LeBaron TW. Molecular hydrogen as an adjuvant therapy may be associated with increased oxygen saturation and improved exercise tolerance in a COVID-19 patient. Clin Case Rep. 2021;9:e05039. https://doi.org/10.1002/ccr3.5039

Authors: Aokage T., Iketani M., Seya M., Meng Y., Ageta K., Naito H., Nakao A., Ohsawa I.
Source: Experimental Gerontology, Volume 180 (2023)

Background

With the ageing of the global population, the incidence of sepsis is increasing among older adults — a demographic particularly vulnerable to systemic inflammation.

Objective

This study aimed to assess the therapeutic potential of hydrogen gas, known for its anti-inflammatory and antioxidant properties, in alleviating inflammation — particularly in the lungs and liver — and in modulating age-associated molecular markers in aged mice.

Methods

Male mice aged 21 to 23 months, representative of the elderly human population, were exposed to inflammation via intraperitoneal injection of lipopolysaccharide (LPS). Mice were assigned to eight experimental groups to evaluate the effects of different hydrogen gas concentrations and durations of inhalation:

• Control group

• Saline without hydrogen

• Saline + 24-hour inhalation of 2% hydrogen

• LPS without hydrogen

• LPS + 24-hour 2% hydrogen

• LPS + 6-hour 2% hydrogen

• LPS + 1-hour 2% hydrogen

• LPS + 24-hour 1% hydrogen

Parameters assessed included survival rate, activity levels, inflammatory biomarkers, and organ damage.

Results

Prolonged administration of 2% hydrogen gas for 24 hours resulted in improved prognosis in aged mice by reducing mRNA expression of inflammatory biomarkers in pulmonary and hepatic tissues, attenuating pulmonary damage, and decreasing expression of the ageing-related protein p21.

Hydrogen gas inhalation also selectively improved age-associated markers in lung tissue — such as C-X-C motif chemokine 2, matrix metalloproteinase-3, and arginase-1. Notably, hydrogen gas did not mitigate liver damage induced by LPS under the experimental conditions.

Conclusion

This study highlights that continuous 24-hour inhalation of 2% hydrogen gas may serve as an effective intervention in the elderly by improving survival and physical activity through attenuation of pulmonary inflammation and modulation of senescence-associated markers in aged mice with LPS-induced inflammation. These findings pave the way for further exploration of hydrogen gas as a therapeutic strategy to combat severe inflammatory responses that can lead to organ damage in older individuals.

Citation

Aokage T, Iketani M, Seya M, Meng Y, Ageta K, Naito H, Nakao A, Ohsawa I. Attenuation of pulmonary damage in aged lipopolysaccharide-induced inflammation mice through continuous 2% hydrogen gas inhalation: A potential therapeutic strategy for geriatric inflammation and survival. Experimental Gerontology. 2023;180:112270. https://doi.org/10.1016/j.exger.2023.112270