A Response to Science Based Medicine

October 11, 2019 20 min read

Sitting down to write a rebuttal and statement regarding a recent negative article, while glancing at my list of “to do’s” containing clarifications and rebuttals for many others with unfortunately large followings putting out frighteningly inaccurate information regarding H2, I realized I had written exactly about this issue and it was time to quote the first 2/3’s of my introduction to why I started my blog.

It’s hard to figure out what is true, what is hype, and what has been disregarded as pseudoscience without a proper assessment. Every year the gap between magical thinkers, and the charlatans who prey on them, and the supposed “skeptics” grows wider. Every year each side feels the need to outdo past feats, diving deeper into their own projected and self-defined philosophy.

I’ve personally heard numerous of my counterparts in industry chuckle about how consumers are more likely to buy something the more ridiculous and implausible it is, even pitching a product as magical when it has real and concrete science with a coherent and logical mode of action. I’ve heard many of the biggest names in the industry admit they do not believe many of the narratives they write about or that their company pushes, acknowledging they jumped the gun and now they cannot break their story.

I have watched this transpire while simultaneously watching the skeptic communities devolve into echo chambers where they recklessly share blog posts written by their ‘friends and allies without properly vetting the evidence. That is exactly the opposite of what a skeptic is supposed to be. Many of these skeptic groups attack subjects they haven’t bothered to verse themselves in, which is ironically the same travesty they rightfully mock the anti-science crowd for.

There is absolutely nothing wrong with being a skeptic, in fact it should be commended, so long as the individual does their due diligence in fully researching the topic at hand. Part of the issue is content, and the need for furthering one’s own ego and fame. My life has been devoted to learning; both conquering my intellect and my body, reading and understanding. That said there is no way I could dream of churning out the content many of these sites do, skeptic and health mavericks alike, for the duration many of them have, while maintaining a modicum of intellectual integrity and honesty.

The prevailing opinion on both sides seems to be this is war. Skeptics cannot concede a single inch to those they perceive as the greatest threats to the population’s health and well being, which further fuels the belief that there is an active conspiracy against the natural community. As someone who has spent considerable time on both sides of the aforementioned fence, and immersed in the third, utterly infuriating and almost incoherent and maddening task of navigating various Governmental departments, I am confident in stating that Occam’s Razor applies, or simply put, the easiest answer is the correct one.

My observation is that most individuals take the path of least resistance. There is no conspiracy. Natural bloggers replicate messages from the top down, and the top fears losing their base so cannot change the message even when they know it is not correct. Those in the middle do not dare go against messaging in fear of financial loss. The skeptics fear giving any credibility to the natural community, so criticize every action. This spiral has continued and grown out of control. Both sides are doing a complete disservice to the general population. As I wrote in our Elite Biohacking line, natural or synthetic, this is irrelevant. Safe and effective. I’ll repeat, safe and effective.

By criticizing virtually every achievement of medical science, natural leaders are discrediting themselves while harming their followers. By criticizing the entire supplement industry, skeptics are discrediting themselves while harming their followers. Many natural substances have been shown to work, and there is ample reason to launch a product as a supplement and not a drug. To paraphrase Ben Goldacre “the medical system is broken, but if the airline industry was broken, we wouldn’t start calling for it to be replaced with flying carpets. We’d fix the airline industry.”

As I write this, Dr. Harriet Hall has just published an incredibly poorly written piece regarding hydrogen water earlier today. Dr. Hall posted this on a website I have referenced before in my own writing, one which I follow, one that I would have bet would have been one of the last two to descend to this unacceptably poor level of investigative analysis. Dr. Hall appears to have largely regurgitated a several year old FOX News article that was written with a lack of any journalistic integrity; those interviewed were misquoted, false information was included, and no actual research was done into the empirical evidence.

I imagine Dr. Hall saw one of our ads, as she cites it, did a quick Amazon and Google search, and wrote away. She certainly didn’t review the literature or any of my writing. She didn’t even go to read the article on Wikipedia, if she had, she would have been able to review several literature reviews cited on the relatively neutral article. For those who tend to criticize Wikipedia, the contributor who volunteered to put in the time to write the current submission has a PhD in Nutritional Biochemistry from MIT and decades of experience in the field (he is retired and a valued Wikipedia contributor and editor).

I fully understand being skeptical of hydrogen water. In fact, I wrote an entire article on the reasons to be skeptical about it here. As we discuss in our recorded talk, Dr. Holland called hydrogen water the worst pseudoscience he’d ever heard and told me to save my money. He went on to quote this:

I have been designing and synthesizing drugs for over 15 years and have a lot of experience in the requirements needed for a compound to prove its effects in a double blind randomized clinical trial, and this formulation would never pass those requirements. The formulation that you are talking about is pseudoscience at best and has absolutely no health benefits other than those experienced by placebo.” 
- Dr. Holland, 2015

What he did after was more important. Rather than ignoring me and maintaining his predetermined position, he read the papers I sent him, got back to me and said he’d work on the contract-based project I had sought him out for. He then continued to read the literature which led him to quickly change his mind. So much so, he became a founding partner. Part of the issue here may be that Dr. Holland is a medicinal chemist, not an MD like Dr. Hall. His specialty would have been more equipped to understand the relevance of the in vitro and animal work, and his extensive experience in drug development would have given him the perspective to know that the science was green, but trending in the right direction. Dr. Hall simply looked for replicated human evidence, a position which is fair when rebutting those pushing a cure or making drugs or definitive claims.

The problem is she didn’t competently look through the literature. She also didn’t reach out to any researchers or attempt to understand the relevance of what has been studied to date. She just went on an attack. Then, her friends at Science Based Medicine (SBM) published the story and reshared on their Skeptics Guide to the Universe Facebook page, trusting her article and not bothering to research and fact check it at all themselves.

Is this the death of skepticism? No. It is another example of the harsh reality I write about, the constantly growing chasm separating sides in a manufactured war of philosophy that is only getting worse. Or maybe it is just an example of a group I once put on a pedestal declining in competence, years of frustration with the pseudoscience and con artists beating them in public opinion amassing more and more. Perhaps it is a sign their cognitive biases are so formed that when a perfect opportunity hits, they drop their defenses. What more fitting than hydrogen water?

There’s a saying in science that it advances one funeral at a time. Leonard Hayflick’s declared limit on the number of times a cell can divide only became consensus over Alexis Carrel’s position that the cell was immortal (and Carrel was a Nobel prize winner). As the opposition for Hayflick’s work slowly died and retired, the new generation of scientists were able to assess the evidence without predetermined biases and beliefs. This is despite Carrel’s work never passing replication.

As it happens, this may be true for skepticism as well. I expect there will be no easy discussions with those whose heuristics are formed so deeply to reject every notion of hydrogen water. I gave the team at SBM (I emailed several of them) three days to respond to my polite email, heavily cited with both peer reviewed literature, databases to peer reviewed literature and articles I have written with hundreds of citations. Not to mention, I referenced articles I have written on the topic of skepticism, while expressing my gratitude for the work they’ve done over the years. They didn’t respond, and I don’t accept being busy as an excuse. I’m busy, I work 100+ hours a week, and I know that when someone directly addresses me over errors in what I have put out to the public it generally takes top priority (if I am aware), at the very least I respond and let them know I am looking into it. The difference is my duty is to truth, not to fighting an imagined war.

This is just the beginning. To address Dr. Hall on her request of “Where is the evidence? I couldn’t find it” (Did you look?), I’ll leave the following:

Publications in humans:

Metabolic and Mitochondrial:

1. Diabetes Type 2, hydrogen water

Kajiyama et al., 2008. Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutrition Research. https://www.ncbi.nlm.nih.gov/pubmed/19083400

2. Metabolic syndrome, hydrogen water

Nakao et al., 2010. Effectiveness of Hydrogen Rich Water on Antioxidant Status of Subjects with Potential Metabolic Syndrome—An Open Label Pilot Study. Journal of Clinical Biochemistry and Nutrition. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831093/

3. Metabolic syndrome, hydrogen water

Song et al., 2013. Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome. Journal of Lipid Research. https://www.ncbi.nlm.nih.gov/pubmed/23610159

4. High cholesterol, hydrogen water

Song et al., 2015. Hydrogen Activates ATP-Binding Cassette Transporter A1-Dependent Efflux Ex Vivo and Improves High-Density Lipoprotein Function in Patients with Hypercholesterolemia: A Double-Blinded, Randomized, and Placebo-Controlled Trial. The Journal of Clinical Endocrinology & Metabolism. https://www.ncbi.nlm.nih.gov/pubmed/25978109

5. Mitochondrial and inflammatory myopathies, hydrogen water

Ito et al., 2011. Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies. Medical Gas Research. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3231939/

6. Body comp/metabolism, oral H2tablets

Korovljev et al., 2018. Molecular hydrogen affects body composition, metabolic profiles, and mitochondrial function in middle-aged overweight women. Irish Journal of Medical Science. https://www.ncbi.nlm.nih.gov/pubmed/28560519

7. Non-Alcoholic Fatty Liver Disease (NAFLD),OUR TABLETS

Korovljev et al., 2019. Hydrogen-rich water reduces liver fat accumulation and improves liver enzyme profiles in patients with non-alcoholic fatty liver disease: a randomized controlled pilot trial. Clinics and Research in Hepatology and Gastroenterology. https://www.sciencedirect.com/science/article/pii/S2210740119300853

8. Secondary analysis on NAFLD via HOMA2- insulin sensitivity,OUR TABLETS

Korovljev et al., 2019. Hydrogen-rich water positively affects HOMA2 variables in

physically inactive population. Abstract from the 5th International Scientific Conference on Exercise and Quality of Life. https://bmcsportsscimedrehabil.biomedcentral.com/track/pdf/10.1186/s13102-019-0119-7

9. Vascular endothelial function, hydrogen water high acute dose

Sakai et al., 2014. Consumption of water containing over 3.5 mg of dissolved hydrogen could improve vascular endothelial function. Vascular Health and Risk Management. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207582/

10. Cardiometabolic risk factors in elderly, hydrogen inhalation

Korovljev et al., 2018. Hydrogen inhalation positively affects cardiometabolic risk factors in men and women aged 65 years or older: a preliminary report. European Geriatric Medicine. https://link.springer.com/article/10.1007/s41999-018-0087-6

11. Reduction in IL-1b mRNA in peripheral blood in type 2 diabetics post meal, acarbose for internal H2 production*

Tamasawa et al, 2015. Hydrogen gas production is associated with reduced interleukin-1β mRNA in peripheral blood after a single dose of acarbose in Japanese type 2 diabetic patients. European Journal of Pharmacology. https://www.sciencedirect.com/science/article/pii/S0014299915004136?via%3Dihub

*acarbose has other animal model studies on H2 production to mitigate issues such as ulcerative colitis.

As can be seen here (the video titled Tyler’s presentation) we have another 60 participant, 6-month trial on metabolic syndrome complete. The team hopes it will be published sometime early 2020. We have 2 replication studies in planning for both NAFLD and metabolic syndrome. As I write here, these issues are 90% bidirectionally causative and could very well be different expressions of the same issue. This is a common belief amongst researchers, not my own wild assertion)

Athletic Performance, Recovery, and Athlete Health

1. Enhances endurances and reduces fatigue, hydrogen water

Mikami et al, 2019. Drinking hydrogen water enhances endurance and relieves psychometric fatigue: a randomized, double-blind, placebo-controlled study. Candian Journal of Physiology and Pharmacology. https://www.ncbi.nlm.nih.gov/pubmed/31251888

2. Gut flora in female athletes, hydrogen water

Sha et al, 2018. 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. Medical Gas Research.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352569/

3. Lowered submaximal heart rate in VO2 max stress test, acute use of OUR TABLETS

LeBaron et al., 2019. Acute Supplementation with Molecular Hydrogen Benefits Submaximal Exercise Indices. Randomized, Double-Blinded, Placebo-Controlled Crossover Pilot Study. Journal of Lifestyle Medicine. https://www.ncbi.nlm.nih.gov/pubmed/30918832   

4. VO2 max and work completed, OUR TABLETS

Ostojic et al., 2018. 28-Days Hydrogen-Rich Water Supplementation Affects Exercise Capacity in Mid-Age Overweight Women. Medicine & Science in Sports & Exercise. https://www.researchgate.net/publication/325634218_28-Days_Hydrogen-Rich_Water_Supplementation_Affects_Exercise_Capacity_in_Mid-Age_Overweight_Women_2942_Board_225_June_1_3

5. Protection against free radical injury in athletes after high intensity exercise, hydrogen water

Sun & Sun, 2017. Selective protective effect of hydrogen water on free radical injury of athletes after high-intensity exercise. Biomedical Research. http://www.biomedres.info/biomedical-research/selective-protective-effect-of-hydrogen-water-on-free-radical-injury-of-athletes-after-highintensity-exercise.pdf

6. Positive effects on redox status after 3 days of strenuous exercise, hydrogen water

Shibayama et al., 2017. Hydrogen-rich Water Modulates Redox Status Repeated Three Consecutive Days Of Strenuous Exercise. Medicine & Science in Sports & Exercise.https://journals.lww.com/acsm-msse/fulltext/2017/05001/Hydrogen_rich_Water_Modulates_Redox_Status.2757.aspx

7. Muscle fatigue, hydrogen water

Aokia et al., 2012. Pilot study: Effects of drinking hydrogen-rich water on muscle fatigue caused by acute exercise in elite athletes. Medical Gas Research. https://www.ncbi.nlm.nih.gov/pubmed/22520831

8. Prolonged intermittent exercise, hydrogen water

Da Ponte et al., 2017. Effects of hydrogen rich water on prolonged intermittent exercise. The Journal of Sports Medicine and Physical Fitness. https://www.ncbi.nlm.nih.gov/pubmed/28474871

9. Exercise induced acidosis, hydrogen water

Drid et al., 2016. Is molecular hydrogen beneficial to enhance post-exercise recovery in female athletes? Science & Sports. https://www.em-consulte.com/en/article/1077114

10. Soft tissue injury in athletes, oral H2 consumption + topical**

Ostojic et al., 2015. Effectiveness of Oral and Topical Hydrogen for Sports-Related Soft Tissue Injuries. Postgraduate Medicine. https://www.tandfonline.com/doi/abs/10.3810/pgm.2014.09.2813

11. Responses to Exercise, hydrogen water.

Botek et al., 2019. Hydrogen Rich Water Improved Ventilatory, Perceptual and Lactate Responses to Exercise. International Journal of Sports Medicine. https://www.researchgate.net/publication/335340278_Hydrogen_Rich_Water_Improved_Ventilatory_Perceptual_and_Lactate_Responses_to_Exercise

12. Hydrogen bathing on muscle fatigue, hydrogen water bath

Kawamura et al., 2016. Effects of hydrogen bathing on exercise-induced oxidative stress and delayed-onset muscle soreness. Western Pacific Region Index Medicus. http://wprim.whocc.org.cn/admin/article/articleDetail?WPRIMID=378181&articleId=378181&locale=zh_CN

13. Koyama et al., 2008. Effect of hydrogen saturated alkaline electrolyzed water on urinary oxidative stress markers after an acute exercise: A randomized controlled trial. Anti-aging Med.***

**We have a case study under review for topical H2 on grade 2 ankle tears. We also have a full RCT underway comparing topical hydrogen water to RICE protocol.
***I have seen this study cited but have never been able to obtain a copy to review.

Brain Recovery from Acute Injury, Neurological Conditions, and Brain Health

1. Mild cognitive impairment, hydrogen water

Ohta et al., 2017. Effects of Molecular Hydrogen Assessed by an Animal Model and a Randomized Clinical Study on Mild Cognitive Impairment. Current Alzheimer Research. https://www.ncbi.nlm.nih.gov/pubmed/29110615

2. Improving outcomes of Alzheimer’s, hydrogen inhalation

Ono et al., 2018. Pilot Study on Therapeutic Inhalation of Hydrogen Gas for Improving Patients with Alzheimer’s Disease Assessed by Cognitive Subscale Scores and Magnetic Resonance Diffusion Tensor Imaging. Bioaccent. https://bioaccent.org/alzheimers-neurological/alzheimers-neurological04.php

3. Acute cerebral infarction, hydrogen inhalation

Ono et al., 2017. Hydrogen Gas Inhalation Treatment in Acute Cerebral Infarction: A Randomized Controlled Clinical Study on Safety and Neuroprotection. Journal of Stroke & Cerebrovascular Diseases. https://www.ncbi.nlm.nih.gov/pubmed/28669654

4. Acute cerebral ischemia, hydrogen inhalation

Ono et al., 2012. A basic study on molecular hydrogen (H2) inhalation in acute cerebral ischemia patients for safety check with physiological parameters and measurement of blood H2 level. Medical Gas Research. https://medicalgasresearch.biomedcentral.com/articles/10.1186/2045-9912-2-21

5. Acute brain stem infarct, hydrogen saline + Edaravone

Ono et al., 2011. Improved brain MRI indices in the acute brain stem infarct sites treated with hydroxyl radical scavengers, Edaravone and hydrogen, as compared to Edaravone alone. A non-controlled study. Medical Gas Research. https://medicalgasresearch.biomedcentral.com/articles/10.1186/2045-9912-1-12

6. Acute cerebral infarction, hydrogen saline + Edaravone

Nagatani et al., 2013. Safety of intravenous administration of hydrogen-enriched fluid in patients with acute cerebral ischemia: initial clinical studies. Medical Gas Research. https://www.ncbi.nlm.nih.gov/pubmed/23799921

7. Newborn Abnormal Neurological Function, Hydrogen Water

Hydrogen water reduces NSE, IL-6, and TNF-α levels in hypoxic-ischemic encephalopathy 2016, Open Med Yang, Li and Chen

8. Parkinson’s, hydrogen water

Yoritaka et al., 2013. Pilot study of H₂ therapy in Parkinson's disease: a randomized double-blind placebo-controlled trial. Movement Disorders. https://www.ncbi.nlm.nih.gov/pubmed/23400965

9. Parkinson’s, no result, hydrogen water****

Yoritaka et al., 2018. Randomized, double‐blind, multicenter trial of hydrogen water for Parkinson's disease. Movement Disorders. https://onlinelibrary.wiley.com/doi/abs/10.1002/mds.27472

10. Concussion recovery case study, hydrogen water (OUR TABLETS)*****

Javorac et al., 2019. Case Report: Buccal administration of hydrogen-producing blend after a mild traumatic brain injury in a professional athlete [version 1; peer review: awaiting peer review]. F1000 Research. https://f1000research.com/articles/8-1024/v1

****This one needs some context. There were massive failures in this trial, namely there were mix ups in the placebo control group where they were intermittently given high doses of hydrogen in the water. Both placebo and control saw significant improvements over expectations and analysis against similar trials, but no benefit against each other. Both were receiving high dose hydrogen. One daily, the other perhaps every other day. The exact routine is unknown. There is currently underway a 52-week, 70 participant trial on PD using our tablets in the USA. The registration can be found here: https://clinicaltrials.gov/ct2/show/NCT03971617

Regardless, we cannot state that H2 is beneficial for PD. We simply do not know. I cannot overstate this enough. We do not know, and it is unethical for marketers to push H2 for patients with PD.

*****We are currently speaking with teams regarding a larger trial.

Skin

1. Psoriasis, hydrogen water baths

Zhu et al., 2018. Positive effects of hydrogen-water bathing in patients of psoriasis and parapsoriasis en plaques. Scientific Reports. https://www.nature.com/articles/s41598-018-26388-3

2. Wrinkles, Kato et al, hydrogen water topical

Kato et al., 2012. Hydrogen-rich electrolyzed warm water represses wrinkle formation against UVA ray together with type-I collagen production and oxidative-stress diminishment in fibroblasts and cell-injury prevention in keratinocytes. Journal of Photochemistry and Photobiology. http://www.sciencedirect.com/science/article/pii/S1011134411002193

3. Red skin/inflamed diseases, hydrogen saline

Ono et al., 2012. Hydrogen(H2) treatment for acute erythymatous skin diseases. A report of 4 patients with safety data and a non-controlled feasibility study with H2 concentration measurement on two volunteers. Medical Gas Research. https://www.ncbi.nlm.nih.gov/pubmed/22607973

4. Psoriasis, skin lesions- case studies, water+saline+gas

Ishibashi et al., 2015. Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: A report of three cases. Molecular Medicine Reports. https://www.ncbi.nlm.nih.gov/pubmed/25936373

5. Pressure ulcers, hydrogen water

Li et al., 2013. Hydrogen water intake via tube-feeding for patients with pressure ulcer and its reconstructive effects on normal human skin cells in vitro. Medical Gas Research. https://www.ncbi.nlm.nih.gov/pubmed/24020833

6. Graft vs host disease case study, hydrogen water (drinking)

Qian & Shen, 2016. Successful treatment with hydrogen rich water in a case of chronic graft-versus-host-disease. Medical Gas Research. http://www.medgasres.com/article.asp?issn=2045-9912;year=2016;volume=6;issue=3;spage=177;epage=179;aulast=Qian

7. UV damage in skin in vivo, topical hydrogen water******

Shin et al., 2013. Atomic Hydrogen Surrounded by Water Molecules, H(H2O)m, Modulates Basal and UV-Induced Gene Expressions in Human Skin In Vivo. PLOS One. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634861/

******This article is quite confusing to read and could be an issue with English translation. It is certainly molecular hydrogen dissolved in water administered topically.

Rheumatoid Arthritis

1. Rheumatoid arthritis, hydrogen saline

Ishibashi et al., 2014. Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: a randomized, double-blind, placebo-controlled pilot study. International Immunopharmacology. https://www.ncbi.nlm.nih.gov/pubmed/24929023

2. Rheumatoid arthritis, hydrogen water

Ishibashi et al., 2012. Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis: an open-label pilot study. Medical Gas Research. https://www.ncbi.nlm.nih.gov/pubmed/23031079

Dialysis

1. Peritoneal dialysis, hydrogen rich dialysate

Terawaki et al., 2013. Transperitoneal administration of dissolved hydrogen for peritoneal dialysis patients: a novel approach to suppress oxidative stress in the peritoneal cavity. Medical Gas Research. https://medicalgasresearch.biomedcentral.com/articles/10.1186/2045-9912-3-14

2. Kidney dialysis for inflammation, saline

Nakayama et al., 2010. A novel bioactive haemodialysis system using dissolved dihydrogen (H2) produced by water electrolysis: a clinical trial. Nephrology Dialysis Transplantation. https://academic.oup.com/ndt/article/25/9/3026/194144

3. Low H2 dialysis

Nakayama et al., 2009. Biological effects of electrolyzed water in hemodialysis. Nephron Clinical Practice. https://www.ncbi.nlm.nih.gov/pubmed/19342864

4. Improvement in chronic dialysis patients, hydrogen rich dialysis

Nakayama et al., 2018. Novel haemodialysis (HD) treatment employing molecular hydrogen (H2)-enriched dialysis solution improves prognosis of chronic dialysis patients: A prospective observational study. Scientific Reports. https://www.nature.com/articles/s41598-017-18537-x

5. Improvement of the fraction of human mercaptalbumin on hemodialysis treatment, hydrogen rich dialysis

Maeda et al, 2016. Improvement of the fraction of human mercaptalbumin on hemodialysis treatment using hydrogen-dissolved hemodialysis fluid: a prospective observational study. Renal Replacement Therapy. https://rrtjournal.biomedcentral.com/articles/10.1186/s41100-016-0054-y

6. Interim analysis, observational improvements over 12 months in 262 patients on dialysis, hydrogen rich dialysis

Nakayama et al., 2017. Possible clinical effects of molecular hydrogen (H2) delivery during hemodialysis in chronic dialysis patients: Interim analysis in a 12 month observation. PLOS One. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0184535

Chemo & Radiation Side Effect Reduction

1. Reduction in side effects in radiation therapy cancer patients, hydrogen water

Kang et al., 2011. Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors. Medical Gas Research. https://www.ncbi.nlm.nih.gov/pubmed/22146004

2. Improved liver function on patients on chemotherapy, hydrogen water

Yang et al., 2017. Protective effect of hydrogen-rich water on liver function of colorectal cancer patients treated with mFOLFOX6 chemotherapy. Molecular and Clinical Onocology. https://www.ncbi.nlm.nih.gov/pubmed/?term=Protective+effect+of+hydrogen-rich+water+on+liver+function+of+colorectal+cancer+patients+treated+with+mFOLFOX6+chemotherapy

Other

1. Hepatitis B, hydrogen water

Xia et al., 2013. Effect of hydrogen-rich water on oxidative stress, liver function, and viral load in patients with chronic hepatitis B. Clinical and Translational Science. https://www.ncbi.nlm.nih.gov/pubmed/24127924

2. Post-cardiac arrest, hydrogen inhalation

Tamura et al, 2016. Feasibility and Safety of Hydrogen Gas Inhalation for Post-Cardiac Arrest Syndrome – First-in-Human Pilot Study. Circulation Journal. https://www.jstage.jst.go.jp/article/circj/80/8/80_CJ-16-0127/_article

3. Heart surgery, hydrogen inhalation

Katsumata et al, hydrogen inhalation The Effects of Hydrogen Gas Inhalation on Adverse Left Ventricular Remodeling After Percutaneous Coronary Intervention for ST-Elevated Myocardial Infarction - First Pilot Study in Humans

https://www.ncbi.nlm.nih.gov/pubmed/?term=The+Effects+of+Hydrogen+Gas+Inhalation+on+Adverse+Left+Ventricular+Remodeling+After+Percutaneous+Coronary+Intervention+for+ST-Elevated+Myocardial+Infarction-+First+Pilot+Study+in+Humans

4. Hydrogen-rich water for improvements of mood, anxiety and autonomic nerve function in daily life, hydrogen water

Mizuno et al., 2017. Hydrogen-rich water for improvements of mood, anxiety, and autonomic nerve function in daily life. Medical Gas Research. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806445/

5. Serum antioxidant status in healthy men, hydrogen water

Trivic et al., 2017. Drinking hydrogen-rich water for 4 weeks positively affects serum antioxidant enzymes in healthy men: a pilot study. Current Topics in Nutraceutical Research. https://www.researchgate.net/publication/318701337_Drinking_hydrogen-rich_water_for_4_weeks_positively_affects_serum_antioxidant_enzymes_in_healthy_men_a_pilot_study

6. Periodontitis and antioxidant status, hydrogen water

Azuma et al., 2015. Drinking Hydrogen-Rich Water Has Additive Effects on Non-Surgical Periodontal Treatment of Improving Periodontitis: A Pilot Study. Antioxidants. https://www.mdpi.com/2076-3921/4/3/513

7. Blood alkalization, hydrogen water

Ostojic et al, 2012. Serum Alkalinization and Hydrogen-Rich Water in Healthy Men. Mayo Clinic Proceedings. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498110/

8. Blood alkalization, hydrogen water

Ostojic & Stojanovic, 2012. Hydrogen-Rich Water Affected Blood Alkalinity in Physically Active Men. Research in Sports Medicine. https://www.tandfonline.com/doi/abs/10.1080/15438627.2013.852092?journalCode=gspm20

9. Blookd alkalization, hydrogen water

Trivic et al., 2017. Drinking hydrogen-rich water for 4 weeks positively affects serum antioxidant enzymes in healthy men: a pilot study. Current Topics in Nutraceutical Research. https://www.researchgate.net/publication/318701337_Drinking_hydrogen-rich_water_for_4_weeks_positively_affects_serum_antioxidant_enzymes_in_healthy_men_a_pilot_study

10. Painful bladder syndrome, hydrogen water (did not work, potential small responder group)

Matsumoto et al., 2013. Effect of Supplementation With Hydrogen-rich Water in Patients With Interstitial Cystitis/Painful Bladder Syndrome. Urology. http://www.goldjournal.net/article/S0090-4295%2812%2901289-7/abstract

11. Hydrogen water

Shimminju (doctoral dissertation). Effects of H2-Rich Water Consumption on Oxidative Stress, PBMC Profiles and Their Transcriptome: A Randomized, Double-blind, Controlled Study2018 http://s-space.snu.ac.kr/handle/10371/142175

Accepted and In Press

1. Javorac D, Stajer V, Ratgeber L, Betlehem J, Ostojic SM. (2019). Short-term H2 inhalation improves exercise performance in healthy adults. Biology of Sport.

2. Korovljev D, Trivic T, Stajer V, Drid P, Sato B, Ostojic SM. (2019). Short-term H2 inhalation improves cognitive function in older women: a pilot study. International Journal of Gerontology.

This is 64 publications concerning humans, from pilot studies to replicative randomized controlled trials in significant population sizes. I am omitting the more than a dozen human studies using “electrolyzed ionized water”, or elemental magnesium-based formulas designed for a “negative ORP” from this list. These are studies done before, or around, the seminal 2007 study in Nature Medicine. Post-hoc analysis determines that all the machines or formulas used dissolve H2 gas in the water, and the benefits declared can now be explained by our understanding of what H2 does. That said, the H2 was not measured. Some authors have cited them in papers, or kept them in tally sheets of total studies, but I am not including them in my tally for a chapter I have been invited to write for Elsevier USA.

H2 studies with no mention of H2

“Ionized water” or “electrolyzed water” uses electrolysis and dissolves H2 gas in varying amounts into the water. This is what gives it the negative “ORP” they cite. Likewise, elemental magnesium based products designed for a “negative ORP” were creating said “negative ORP” by creating molecular hydrogen. That said, exact dosages and concentrations are not known from these studies
  1. “ionized water” diarrhea
Clinical evaluation of alkali-ionized water for chronic diarrhea placebo controlled double blind study
2000, Digestion & Absorpotion
Tashiro, H. et al
  1. “Electrolyzed reduced water” in dialysis
Reduced hemodialysis-induced oxidative stress in end-stage renal disease patients by electrolyzed reduced water.
Kidney Int. 2003 Huang et al
  1. “Anti-oxidant water”
Effects of Drinking a Water Product with Anti-Oxidant Activities In Vitro on the Blood Levels of Biomarker Substances for the Oxidative Stress
Journal of Health Science 2006, Hiraoka et al
*cites hydrogen gas as the antioxidant, no indication of concentration. Cites higher in vitro abilities than observed in vivo without understanding in vitro data using the same concentrations as in vivo will not be close to relatable/transferable.
  1. “Electrolyzed reduced water” in dialysis end stage renal patients
Electrolyzed-reduced water reduced hemodialysis-induced erythrocyte impairment in end-stage renal disease patients.
Kidney Int. 2006 Huang et al
  1. Negative Ion Water -performance
Intra-Individual Ergonomics (I2E): Performance Effects of Ultra-Negative-Ion Water
2007 Bittner et al
  1. Alkaline reduced water, diabetes
A Clinical Trial of Orally Administered Alkaline Reduced Water
2007, Yang et al
  1. Electrolyzed water, dialysis
Biological effects of electrolyzed water in hemodialysis.
2009 Nakayama et al
  1. Electrolyzed water, end stage renal patients dialysis

Electrolysed-reduced water dialysate improves T-cell damage in end-stage renal disease patients with chronic haemodialysis.

2010, Huang et al (3rd trial by this group on subject)

https://www.ncbi.nlm.nih.gov/pubmed/?term=Electrolysed-reduced+water+dialysate+improves+T-cell+damage+in+end-stage+renal+disease+patients+with+chronic+haemodialysis

  1. Negative ORP blend, magnesium based- sports performance
Drinks with alkaline negative oxidative reduction potential improve exercise performance in physically active men and women: Double-blind, randomized, placebo-controlled, cross-over trial of efficacy and safety
2011, Ostojic et al
  1. “Hydrogen containing” ionized water
Daily ingestion of alkaline electrolyzed water containing hydrogen influences human health, including gastrointestinal symptoms
Med Gas Res 2018, Tanaka et al
*mentions it contains hydrogen, does not state how much
There are a further 4 trials listed at http://www.molecularhydrogeninstitute.com/human-studies near the bottom with no links to journals that I have never been able to find. There is a strong possibility they were never written or published in English.


Fujiyama, Y. and T. Kitahora, Alkaline electrolytic water (alkali ions water) for drinking water in medicine. Mizu no Tokusei to Atarashii Riyo Gijutsu, Enu-Ti-Esu, Tokyo, 2004: p. 348-457.

Lee, K.J., et al., Effect of electrolyzed-reduced water: in vivo and in vitro examination and clinical trials, in The 3rd Asia Pacific Conference on Evidence-Based Medicine. 2004: Hong Kong.

Lu, K.C., et al., Electrolyzed reduced water attenuates hemodialysis-induced mononuclear cells apoptosis in end-stage renal disease patients. Nephrology Dialysis Transplantation, 2006. 21: p. 200-201.

Yeung, L.K., et al., Effect of electrolyzed reduced water hemodialysis on peripheral lymphocyte intracellular cytokine expression. Nephrology Dialysis Transplantation, 2006. 21: p. 204-204.


I often lose count of the studies as I am aware of so many that are completed and the manuscripts being written or submitted and under review. Luckily I have been working on this recently, so it was ready to “put down on paper” quickly.

A Sampling of the Many Review Articles:

Metabolic and Cardiac:

LeBaron et al., 2019. A New Approach for the Prevention and Treatment of Cardiovascular Disorders. Molecular Hydrogen Significantly Reduces the Effects of Oxidative Stress. Molecules. https://www.mdpi.com/1420-3049/24/11/2076?fbclid=IwAR1yWXgPmKpojdnOMhNY188tbc4051EV5H_8GH6uG-jovOkEk4pwCRSQmy4

Zhang et al., 2018. Hydrogen Therapy in Cardiovascular and Metabolic Diseases: from Bench to Bedside. Cellular Physiology and Biochemistry. https://www.karger.com/Article/FullText/489737

Alzheimer’s and Neurological Conditions:


Tan et al., 2018. The role of hydrogen in Alzheimer’s disease. Medical Gas Research. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352568/

Ohta & Asada, 2018. Molecular Hydrogen as an Emerging Candidate for Preventing Alzheimer’s Disease. Bioaccent. https://bioaccent.org/alzheimers-neurological/alzheimers-neurological03.pdf

Dohi et al., 2017. Molecular hydrogen in the treatment of acute and chronic neurological conditions: mechanisms of protection and routes of administration. Journal of Clinical Biochemistry and Nutrition. https://www.jstage.jst.go.jp/article/jcbn/61/1/61_16-87/_article


Iketani & Ohsawa et al., 2017. Molecular hydrogen as a neuroprotective agent. Current Neuropharmacology. http://www.eurekaselect.com/143094/article

Exercise Performance:

LeBaron et al., 2019. Hydrogen gas: from clinical medicine to an emerging ergogenic molecule for sports athletes. Canadian Journal of Physiology and Pharmacology. https://www.nrcresearchpress.com/doi/pdf/10.1139/cjpp-2019-0067


Radiation Injury:
Kura et al., 2018. Molecular hydrogen: potential in mitigating oxidative-stress-induced radiation injury. Canadian Journal of Physiology and Pharmacology. https://www.nrcresearchpress.com/doi/abs/10.1139/cjpp-2018-0604#.XZ4_IUZKh3g

Sepsis:

Qiu et al., 2019. Recent Advances in Studies of Molecular Hydrogen against Sepsis. International Journal of Biological Sciences. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567800/


Emergency and Critical Care:

Sano et al., 2017. Promising novel therapy with hydrogen gas for emergency and critical care medicine. Acute Medicine & Surgery. https://onlinelibrary.wiley.com/doi/full/10.1002/ams2.320



General reviews:

Ichihara et al., 2015. Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles -. Medical Gas Research. https://medicalgasresearch.biomedcentral.com/articles/10.1186/s13618-015-0035-

Dixon et al., 2013. The evolution of molecular hydrogen: a noteworthy potential therapy with clinical significance. Medical Gas Research. https://www.ncbi.nlm.nih.gov/pubmed/23680032

Nicolson et al., 2016. Clinical Effects of Hydrogen Administration: From Animal and Human Diseases to Exercise Medicine. International Journal of Clinical Medicine. http://www.scirp.org/journal/PaperInformation.aspx?paperID=62945

Li et al., 2017. The transfer of hydrogen from inert gas to therapeutic gas. Medical Gas Research. https://www.ncbi.nlm.nih.gov/pubmed/?term=The+transfer+of+hydrogen+from+inert+gas+to+therapeutic+gas

As for the claim on over 1,200 publications? While I am not going to manually copy and paste 1,200 papers to this post, the Molecular Hydrogen Institute has a fairly comprehensive database conveniently broken down into appropriate sub sections. You can find it here:

molecularhydrogeninstitute.com/studies/

It’s illogical to not give weight to these studies when similar benefits have been shown in the human literature which is growing every year. To respond to Dr. Hall who quoted

“There were several positive studies in test tubes and lab rats, but we have no way of knowing whether this data translates to human benefits.”

If you’d looked for the human evidence you would have found it is available and growing, with early replication work having been done on several outcomes. There is also supportive work amongst human studies pointing to similar benefits for similar end points, despite not being completely replicative. Combined with the hundreds of studies in vitro and in animals exploring mechanisms of action, the pharmacodynamics and outcomes for many models, we can begin extrapolating when hydrogen therapy may be appropriate. Considering it is incredibly safe, has had significant success in humans, and is more affordable than a morning coffee, it seems absurd to stand against consumer access to it or make statements that it has no benefits above tap water.

None of this is evidence that hydrogen, whether it be drinking hydrogen water or inhalation of gas, should currently be advised for the treatment of any disease. That said, there is evidence and it is growing every year. We firmly believe the evidence justifies supplemental use, particularly for exercise performance and improving metabolic health. For metabolic health, particularly in overweight populations that do not yet have diabetes, such as metabolic syndrome and NAFLD. These are outcomes that have no medication. The evidence is not yet strong enough to state that it will absolutely benefit these models, but it is getting stronger each year, with each publication. Since the only treatments are currently increased exercise and diet modification, the addition of hydrogen water could prove to be another key ally.

As I stated in replies to those at Science Based Medicine; the evidence they claimed doesn’t exist, does. They simply didn’t look and didn’t ask.

PS as for Dr. Hall’s claim that “Hydrogen gas is highly combustible: remember the Hindenburg disaster?  It is not medicine.”

Actually, Dr. Hall, hydrogen gas is only combustible when above 4.6% of atmospheric pressure so that there is sufficient oxygen also present- and it is not combustible when dissolved in water (and neither is gunpowder, FYI) That's ok, there is no reason a Medical Doctor would be required to know that... Which is EXACTLY why you should have fact checked your statement.

 


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