Right off the bat the Health Rising blog [1] referenced a sports medicine review on HRW benefits. [2] The review authors seemed to be obsessed at first with reaction with the hydroxyl radical and the peroxynitrite anion. [2] The review mentioned reduction of the inflammatory cytokine IL1β, but did not really discuss the reactive thiol in the NLRP3 sub unit of the inflammasome what cleaves the pro-peptide to the active form. [2] The sports medicine review also mentioned the cyclic AMP response element binding protein phosphorylation (activation) and an increase in serum superoxide dismutase activity. [2] Just a gut level impression at this point is that H2 gas might be targeting thiols in more hydrophobic environments.
The Health Rising authors did not say why they were presenting hydrogen bonding of water molecules, but this brings up an important point. H2 does not have a dipole moment making it unable to form hydrogen bonds with water. It is essentially hydrophobic even if it is one of the elements in water. We might predict some targeting of this small molecule.
The Health Rising post then takes the reader to a Japanese hypothesis paper proposing that H2 can be used to treat ME/CFS.
This particular review mentioned the NLRP3 redox sensitive subunit. This review was also very concerned about the hydroxyl radical. Then, in the process of explaining how the ME/CFS study came to the States, Health Rising cites a Chinese review on possible mechanisms of H2 in various neurological diseases . [6]
HRW Clinical trial examples
Then in the whirl wind Health Rising post we move to the Japanese HRW trial. [6] This was a smallish cross over study. Change ratios (post-treatment/pre-treatment) for K6 score and sympathetic nerve activity during the resting state were significantly lower after HRW administration than after PLW administration. The changes didn’t seem that great. A Chinese HRW study of juvenile female football found small improvements in anti oxidant status that included cytokines, lipid peroxidation, and SOD activity. There were some changes in gut flora [7] These protocols were short on details. Here is something from an adult female panic discorder study[8]
Hydrogen water (HW). The model HW generator was used Jarra Hydrogen® from the range Osmostar (Osmostar Soriano, Elche, ALC, Spain), it uses the electrolysis method to break down water (H2O) into hydrogen (H2). The HRW was administered orally with a concentration of H2 diluted in water of 1.2 ppm and an ORP of -550 mV. For its transformation, weak mineralized water was used, with a dry residue of less than 100 mg/liter. The company’s technical staff was in charge of installing and starting the generator, providing information on its operation and maintenance. Aluminum bottles were supplied for transport and maintenance of the properties up to 8 hours.22 The participants had to drink a total of one and a half liters per day, distributed throughout the day (fasting, at noon, before lunch, in the middle of the afternoon, before dinner and before going to bed) in 250 ml. Machines designed with characteristics and anagrams similar to the originals, which provided normal water, were used as placebo.[8]
a further reduction in measured pro-inflammatory cytokine scores, improving body pain and physical health. When between-group treatment effects were removed, psychological treatment significantly decreased measured variables, including cytokines and cortisol.[8]
The Freidberg trial
| rm | Intervention/treatment |
|---|---|
| Active Comparator: Heart Rhythm Biofeedback Heart rhythm biofeedback is a non-invasive physiological treatment that is administered via an app downloaded to personal smart phones. It involves participants attaching a wireless sensor to the ear that monitors heart rate that is displayed on the phone screen app. The participant is actively involved in modifying the heart biofeedback to achieve optimal levels of heart rate variability, an established indicator of health and well-being and a potential factor in chronic fatigue syndrome. The treatment lasts 8 weeks. | Dietary Supplement: Hydrogen Water Hydrogen water, if ingested daily over several weeks, may have antioxidant and anti-inflammatory effects in chronic fatigue syndrome Combination Product: Combined treatment: Heart rhythm biofeedback plus hydrogen water This treatment is intended to explore the possible additive or synergistic effects of combining heart rhythm biofeedback and hydrogen water. |
| Active Comparator: Hydrogen Water Hydrogen pills are mixed in a water glass that is ingested up to 3 times a day for 8 weeks. The hydrogen supplement is intended to reduce oxidative stress and inflammation both of which are implicated in the pathophysiology of chronic fatigue syndrome. This is an 8 week treatment. | Behavioral: Heart Rhythm Biofeedback Heart rhythm biofeedback is a non-invasive intervention intended to improve heart rate variability and physical resilience that is often limited in chronic fatigue syndrome Combination Product: Combined treatment: Heart rhythm biofeedback plus hydrogen water This treatment is intended to explore the possible additive or synergistic effects of combining heart rhythm biofeedback and hydrogen water. |
| Active Comparator: Combined treatment: Heart rhythm biofeedback plus hydrogen water This condition combines heart rhythm biofeedback and hydrogen water, as described above, which is intended to assess any additive or synergistic effects of the two treatments. This is an 8 week treatment. | Behavioral: Heart Rhythm Biofeedback Heart rhythm biofeedback is a non-invasive intervention intended to improve heart rate variability and physical resilience that is often limited in chronic fatigue syndrome Dietary Supplement: Hydrogen Water Hydrogen water, if ingested daily over several weeks, may have antioxidant and anti-inflammatory effects in chronic fatigue syndrome |
Short Form-36 Physical Function Subscale [ Time Frame: 8 weeks ]
- Self-report measure of physical functioning. The short-form 36 physical function subscale is composed of ten items encompassing a hierarchical range of difficulties. Each item is scores on the basis of the limitations perceived by surveyed individuals. Item scores (1, 2, or 3) are summed to obtain a total score, which can then be scaled relative to its range. Higher scores indicate higher physical function. Depression, Anxiety and Stress Scale [ Time Frame: 8 weeks ]
- Self-report measure if depression, anxiety and stress symptoms. This 21 item stress measure contains three 7-item subscales: anxiety, depression and stress. Domain scores are calculated by summing all items in a domain and multiplying by two. Brief Resilience Scale [ Time Frame: 8 weeks ]
- This 6 item self-report scale focuses on how quickly an individuals bounces back and physically and emotionally exhausting events. 5 answer choices range from strongly disagree to strongly agree. Higher scores indicate higher resilience
My general impression is that Friedberg heard a really cool seminar on HRW at Stonybrook and a clinical trial was born. Friedberg has published a lot on CFS but none of his trial really gets to markers in common with autism
References
- https://www.healthrising.org/blog/2022/07/21/hydrogen-rich-water-chronic-fatigue-syndrome-trial/
- Kawamura T, Higashida K, Muraoka I. Application of Molecular Hydrogen as a Novel Antioxidant in Sports Science. Oxid Med Cell Longev. 2020 Jan 14;2020:2328768. PMC free article
- Terawaki H, Zhu WJ, Matsuyama Y, Terada T, Takahashi Y, Sakurai K, Kabayama S, Miyazaki M, Itami N, Nakazawa R, Ito S, Era S, Nakayama M. Effect of a hydrogen (H2)-enriched solution on the albumin redox of hemodialysis patients. Hemodial Int. 2014 Apr;18(2):459-66. PubMed
- Hirano SI, Ichikawa Y, Sato B, Takefuji Y, Satoh F. Molecular Hydrogen as a Medical Gas for the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Possible Efficacy Based on a Literature Review. Front Neurol. 2022 Apr 11;13:841310 PMC free article
- Chen W, Zhang HT, Qin SC. Neuroprotective Effects of Molecular Hydrogen: A Critical Review. Neurosci Bull. 2021 Mar;37(3):389-404. PMC free article
- Mizuno K, Sasaki AT, Ebisu K, Tajima K, Kajimoto O, Nojima J, Kuratsune H, Hori H, Watanabe Y. Hydrogen-rich water for improvements of mood, anxiety, and autonomic nerve function in daily life. Med Gas Res. 2018 Jan 22;7(4):247-255. PMC free article
- Sha JB, Zhang SS, Lu YM, Gong WJ, Jiang XP, Wang JJ, Qiao TL, Zhang HH, Zhao MQ, Wang DP, Xia H, Li ZW, Chen JL, Zhang L, Zhang CG. Effects of the long-term consumption of hydrogen-rich water on the antioxidant activity and the gut flora in female juvenile soccer players from Suzhou, China. Med Gas Res. 2019 Jan 9;8(4):135-143. free article
- Fernández-Serrano AB, Moya-Faz FJ, Giner Alegría CA, Fernández Rodríguez JC, Soriano Guilabert JF, Del Toro Mellado M. Effects of hydrogen water and psychological treatment in a sample of women with panic disorder: a randomized and controlled clinical trial. Health Psychol Res. 2022 May 30;10(3):35468. PMC free article
- Ma L, Tian S, Zhang HL, Wang JY, Wang JW, Yan HL, Hu XG, Shao Q, Guo JM. Transcriptomic and metabolomic studies on the protective effect of molecular hydrogen against nuclear electromagnetic pulse-induced brain damage. Front Public Health. 2023 Feb 1;11:1103022. PMC free article
