The Science behind Hydrogen Therapy: Research Update (Updated August 2020)

There are over 1500 published papers on the benefits of molecular hydrogen in health and wellness. As of August 2020, there are more than 700 on-going studies related to molecular hydrogen on clinicaltrials.gov.

Surprisingly, scientific studies revealed that a simple molecule like hydrogen has antioxidant benefit and is able to protect cells against free radicals. Let's check out the science and evidence behind this.

Since we published this article few months ago, there has been many new studies and evidence related to hydrogen water in healthcare. This is an updated article to review hydrogen water and the scientific evidence behind it to help you make an informed decision.

hydrogen water malaysia

What Is Hydrogen Water?

Hydrogen (H2) is the most abundant molecule in the Universe. It’s an odorless, colorless, and tasteless gas.

Published in 1988, the association between high dietary fibre intakes and reduced disease incidence was studied. It was proposed that molecular hydrogen (acting as a powerful antioxidant), produced in quite large amounts as a by-product of colonic fermentation of dietary fibre and unabsorbed carbohydrate may play an important role (Med Hypotheses. 1988).

In 2007 and reported in a reputable journal (Nature Medicine. 2007) by a team in Japan, discovered that inhaled hydrogen gas could act as an antioxidant and protect the brain from free radicals. This sparked the interest in its potential health benefits worldwide and led to many published and on-going clinical research.

Following the landmark publication in Nature Medicine in 2007, many other studies regarding the potential application of hydrogen therapy on various conditions were subsequently published. Since the Japanese discovery, the effects of hydrogen have been researched in 63 diseases [Ref]!

It’s less known that hydrogen was therapeutically used for the first time in humans in the early 90s. It was given to 3 divers to successfully help them overcome the effects of high pressure on the brain in deep-sea diving [RR].

Hydrogen is the smallest existent gas molecule. Because of this unique property, molecular hydrogen could penetrate into virtually every organ and cell in the body (including the brain) where it may have antioxidant, anti-inflammatory, weight-loss, and anti-allergy activity. Molecular hydrogen seems like the perfect therapeutic the world has been eagerly searching for – with very few known side effects and such wide-ranging action [R, R].

Hydrogen water is loaded with hydrogen molecules. It was formulated as the most practical and easy way to get hydrogen into the whole body. But it’s not the only way – hydrogen can also be inhaled, injected, or absorbed through a bath [R].


Hydrogen Water and Molecular Hydrogen Research

Here, we have listed and compiled all significant scientific publications related to hydrogen water and hydrogen molecule. The list was complied by running various searches on PubMed. Each study and is hyperlinked to the abstract in the U.S. National Library of Medicine or the full text article.

Here is the list by category.

1) Antioxidant, Ischaemia-Reperfusion Injury and Brain-Protective Effects 

It was first shown in 2007 that molecular hydrogen (H2) could protect cells from damage by reducing reactive oxygen species (ROS). Inhaled hydrogen also easily reached the brain to reduce injury in rats with stroke [Nat Med. 2007].

In 2009, it was shown that hydrogen water prevented cognitive, learning, and memory problems in mice under stress by acting as an antioxidant. It also protected cells in the brain’s memory hub from
the detrimental effects of stress [Neuropsychopharmacology. 2009].

In the first pilot study of 38 stroke patients (2013), a hydrogen solution (IV) was safe and had a mild antioxidant effect [ref].

In 2017, one randomised controlled study assessing the effectiveness and safety of Hydrogen Gas inhalation treatment in stroke patients was published. Hydrogen gas inhalation treatment was safe and effective in patients with acute stroke (cerebral infarction) [Ref].

In 2019, a study on performed in a large animal model, suggests that adding hydrogen to the usual mix of respiratory gases could further protect babies' brains. The study was published in the Journal of the American College of Cardiology (JACC): Basic to Translational Science. The research team includes medical scientists from Harvard Medical School and Boston Children's Hospital United States.

Inhalation of hydrogen gas in patients with PCAS (post cardiac arrest syndrome) was approved as advanced medical care by the Ministry of Health, Labour and Welfare of Japan in November 2016 (Acute Med Surg. 2018). The study protocol for a randomized controlled trial was published as “Efficacy of inhaled HYdrogen on neurological outcome following BRain Ischemia During post-cardiac arrest care (HYBRID II trial)” (Trials. 2017).


2) Parkinson Disease

In 2013, another small study of 17 patients with Parkinson’s disease was published. Those who drank hydrogen water had improved symptoms. Those who drank regular “placebo” water, however, experienced a worsening. There were also no adverse effects to drinking 1 L of hydrogen water daily for almost one year [ref].

Led by the same lead author, the results of the pilot study will be confirmed in this longer and larger-scale study that includes patients who are not medicated with levodopa. This study will confirm the safety and tolerability of H2-water and if H2-water can improve Parkinson Disease symptoms.


3) Side Effects of Chemotherapy and Radiation

Published in August 2020 (Biomed Pharmacother. 2020), this review aims to provide an overview of recent findings in this field that studied the radio-protective effect of hydrogen treatment.

Presently ionizing radiation (IR) has extensive applications in medical diagnostics (e.g. CT scan) and tumor therapy (e.g.Radiotherapy).

There has always been a strong demand for safe and potent radioprotectants. The only U.S. FDA approved radioprotectant available today is the synthetic thiol amifostine. However, it has many shortcomings such as short protection time, unfavorable routes of administration, and comparatively high toxicity. Natural antioxidants such as melatonin, vitamin E, and others, while having fewer adverse effects, they also offer much weaker protection compared against thiol agents. H2 can be easily applied with little adverse effects and great efficacy as a potential radioprotective agent. This article reviewed up to date medical progress related to H2 as a radioprotectant, covering its unique properties, potential mechanisms of action, delivery techniques, findings in vitro/vivo studies even clinical practice.

In 2011, a study of 49 patients (published in 2011) on radiation therapy for liver cancer, drinking hydrogen water (1.5 – 2 L/day) improved the patients’ quality of life and appetite. Hydrogen water could reduce oxidative stress and damage from radiation without compromising its cancer-killing effects [R].

In 2017,  a study (published in the Molecular and Clinical Oncology), evaluated the protective effect of hydrogen-rich water on liver function of colorectal cancer patients treated with chemotherapy in 152 patients. The hydrogen-rich water group exhibited protective effect against the chemotherapy related liver injury [R].


4) Anti-Cancer Potential



Although hydrogen gas was studied as a therapy in a skin squamous carcinoma mouse model back in 1975 (Science. 1975), its potential in medical application has not been vastly explored until 2007, when Oshawa et al. reported that hydrogen could ameliorate cerebral ischemia-reperfusion injury by selectively reducing cytotoxic reactive oxygen species (ROS), including hydroxyl radical (•OH) and peroxynitrite (ONOO-) [Nat Med. 2007], which then provoked a worldwide attention.

In human cancer cells, hydrogen water suppressed tumor growth by reducing oxidative stress (Oncol Res. 2008). Hydrogen water combined with increased temperature (hyperthermia) had a strong cancer-killing effect in cells [Oncol Rep. 2010].

Hydrogen water also blocked the creation of new blood vessels in human lung cancer cells, preventing cancer from spreading and growing [Biol Pharm Bull. 2008].

In a lab study published in 2015 (PeerJ. 2015), hydrogen water administration improved the survival of mice with colon 26-induced cancer. Furthermore, hydrogen water enhanced cell death in cancer cells. Hydrogen water also increased the inhibitory effect of 5-FU on colon 26 cells. Additionally, high-content hydrogen water exhibited stronger anti-oxidative and anticancer activity than did the natural hydrogen water.

The first case report of hydrogen inhalation therapy in a patient with metastatic Gall Bladder Cancer was published by a team in China. The patient has gradually improved and has survived for more than 10 months (Onco Targets Ther. 2019).

In a review on hydrogen gas and cancer treatment, it was suggested that hydrogen gas may work alone or synergistically with other therapy to suppress tumor growth (Front Oncol. 2019).

In Japan, patients with stage IV colorectal cancer inhaled H2 gas for 3 h/day in their own homes and received chemotherapy. H2 gas improved progression-free survival and overall survival times (Oncol Rep. 2019).

In China, 82 patients with stage III and IV cancer were prospectively followed-up, after treatment with Hydrogen (H2) inhalation. No severe blood toxicity was observed. H2 Inhalation of H2 gas induced complete and partial remission in tumors of the 80 patients (Med Gas Res. 2019). Cancer types are mainly solid tumors with 19 non-small cell lung cancer, 16 gynecological cancer, 11 hepato-cellular cancer, 10 breast cancer, 6 gastrointestinal cancer, 6 urological cancer and 8 other type of advanced cancer.

One clinical trial (NCT03818347) is now on-going to study hydrogen gas in cancer rehabilitation for multiple cancer types in China. 2 publications that are associated with this research data have been
published.

The first publication (Ann Palliat Med. 2019) was case reports of 3 nasopharyngeal cancer (NPC) patients with radiotherapy-induced hearing loss. This is the first study to show that, after treatment for nasopharyngeal carcinoma, hearing loss can be reduced using hydrogen-oxygen therapy.

The second publication (Med Gas Res. 2020), 58 patients with advanced non-small lung cancer were enrolled into 5 groups:
1) refused drug treatment (control group)
2) refused drug treatment (hydrogen therapy only)
3) H2 + chemotherapy, 
4) H2 + targeted therapy, and 
5) H2 + immunotherapy group.

After 16 months of follow-up, progression-free survival of the control group was lower than that of the H2-only group, and significantly lower than that of H2 + chemotherapy, H2 + targeted therapy, and H2 + immunotherapy groups.

Related: Hydrogen and Cancer


5) Diabetes and Metabolic Syndrome (Hydrogen Water for Endocrine Disorders)

Published in 2008, a study showed that drinking hydrogen water decreased cholesterol, improved glucose tolerance and insulin resistance in 36 patients with type 2 diabetes or pre-diabetes (impaired glucose tolerance). The patients drank 900 mL of hydrogen water daily for 8 weeks [R].

In another pilot study published in 2010, patients prone to metabolic syndrome drank hydrogen water (1.5 – 2 L/day) for 8 weeks. Subjects demonstrated an 8% increase in HDL-cholesterol (good cholesterol) and a 13% decrease in total cholesterol from baseline to week 4 [R].

Further, subjects demonstrated an 8% increase in high density lipoprotein (HDL)-cholesterol and a 13% decrease in total cholesterol/HDL-cholesterol from baseline to week 4.


6) Eye Injuries

In acute glaucoma of the eyes, transient elevation of intra-ocular pressure causes significant reductions in the thickness of the retina by injury mediated through the generation of free radicals. Hydrogen-loaded eye drops aided the recovery of eye injuries in rats. It protected the nerves in the eye by its antioxidant action [ref].

A hydrogen solution reduced detrimental blood vessel growth in mice with eye injuries from chemicals. Hydrogen solutions could be used as a first-aid rinse to prevent blindness from chemical burns [ref].


7) Lungs

In a study published in 2016, 96 workers exposed to haze were randomised to 2 groups; the treatment group inhaled hydrogen and oxygen mixture (66.67%∶33.33%) 1 hour per day for 30 days, while the control group inhaled nitrogen and oxygen mixture (66.67%∶33.33%) 1 hour per day for 30 days.

The study concluded that inhalation of hydrogen gas could protect lungs of sanitation workers exposed to air pollution. Importantly, inhalation of hydrogen could improve respiratory symptoms such as cough as well.


8) Suppressing Inflammation and joint disorders

In one pilot study, 20 patients with rheumatoid arthritis drank 0.5 L/day of hydrogen water for 4 weeks. By the end of the study, all patients with early rheumatoid arthritis achieved remission and
20% became symptom-free [R, R].


9) Muscle Fatigue and Weakness

In an experiment with 10 young athletes (DB-CT), drinking hydrogen water reduced lactic acid build-up during heavy exercise and decreased muscle fatigue [R].

Drinking 2 L of hydrogen water daily helped 8 cyclists power through sprints with more energy and less exhaustion in one small 2-week study [R].


10) Hydrogen Water Enhances Energy Metabolism

Drinking hydrogen water protected the body’s energy powerhouse, the mitochondria, in several studies of 41 people with muscle diseases. They drank 0.5 – 1 L of hydrogen water per day [R].


11) Boosts Skin Health

Hydrogen water given through an IV solution safely improved skin health in 4 patients with skin redness and inflammation, and pain. The skin redness went away after a couple of days of treatment and did not come back [R].

Bathing in hydrogen water for 3 months noticeably reduced skin wrinkles in 6 people. Hydrogen water could also boost collagen production, reduce UV damage and act as an antioxidant in skin cells. Warm hydrogen-infused baths could be a pleasant, safe way to reverse skin aging [R].

In a study published in Nature in 2018, hydrogen-water bathing therapy could fulfill the unmet need for chronic inflammatory skin diseases such as psoriasis after 8 weeks of treatment.


12) Enhances Wound Healing

Hydrogen water intake via tube feeding in elderly patients reduced the wound size of pressure ulcers and enhanced recovery [R].


13) May Improve Bladder Health

In rats with a blockage in the bladder, drinking hydrogen water reduced bladder volume by neutralising oxidative stress. It also improved the responsiveness of bladder muscles. As a strong antioxidant, hydrogen water could potentially help those with a bladder obstruction [R].


14) May Protect the Kidneys

Hydrogen added to the dialysis solution reduced inflammation and high blood pressure in 21 kidney failure patients on dialysis [R].


15) May Protect the Liver

In 60 patients with Hepatitis B (a viral infection that attacks the liver and can cause both acute and chronic disease), drinking hydrogen water as an add-on to regular treatment was safe and reduced oxidative stress [R].

Hydrogen water also significantly improved liver function and reduced oxidative stress in patients with chronic hepatitis B [R].

In 2011, a study of 49 patients on radiation therapy for liver cancer, drinking hydrogen water (1.5 – 2 L/day) improved the patients’ quality of life and appetite. Hydrogen water could reduce oxidative stress and damage from radiation without compromising its cancer-killing effects [R].


16) Anti-aging and Longevity

The ability of molecular hydrogen to protect the DNA and the mitochondria from oxidative damage may have beneficial effects on chronic diseases and cancer. But perhaps it could help slow down or reverse the aging process itself. A couple of cellular studies give us some interesting clues [R, R].

It was already discovered that hydrogen can prolong the life of stem cells by reducing oxidative stress [R].

A hydrogen-rich environment reduced both oxidative stress and aging in cells. Some scientists think
that drinking hydrogen water could increase longevity in humans (Circ J. 2016).


17) May Kill Bacteria and Improve Oral Health

Drinking hydrogen water 4 – 5X daily improved gum health in 13 patients with inflamed gums after 8 weeks. It also boosted blood antioxidants and enhanced the effects of other gum disease treatments [R].

Hydrogen water could kill the bacteria that most commonly cause gum disease and cavities. It could be used to improve overall oral health [R].


18) Preserves Transplant Organs

Hydrogen water could help preserve and reduce damage to transplant organs without any toxic effects. It reduced the inflammation and injury that usually happens when donated organs are stored, which could help save more lives [R].


19) Molecular Hydrogen and COVID-19

Published in June 2020 (Reactive Oxygen Species), the aim is to review the current research into COVID-19 and to better understand how treatment with molecular hydrogen is likely to affect cellular responses during COVID-19 infection.

Application of H2, may provide an effective adjunctive medicament to O2 inhalation in the treatment of COVID-19 for the critically ill. Although this method is recommended and practiced in the People’s Republic of China with oxygen/hydrogen mixed gas noted to significantly reduce dyspnea, it is not widely used elsewhere. To date, only one clinical trial using oxyhydrogen for the treatment of COVID-19 infection has been registered with the US National Library of Medicine, with a further four clinical trials registered with The Centre for Evidence-Based Medicine (CEBM).

It is the authors’ opinion that inhalation of H2 would be a more effective delivery mechanism for patients with moderate/severe symptoms of COVID19. Also worthy of notation is that currently, most, but not all clinical trials have been based on inhalation of H2, with this also being the preferred delivery method as recommended by The National Health Commission of the People's Republic of China.

In another publication, published in June 2020 (Journal of Thoracic Disease. 2020), this China study is the first multicenter randomized clinical trial that verifies the efficacy and safety of H2-O2 (mixed hydrogen gas and oxygen gas) inhalation in patients (n=90) with COVID-19.

Patients with COVID-19 frequently presented with dyspnea, coughing, chest pain and distress, and oxygen desaturation which cannot be rapidly relieved with other existing therapies (including oxygen therapy). The therapeutic effects of H2-O2 became significant as early as days 2 and 3 and the reduction of most respiratory symptoms persisted till the end-of-treatment.

The authors also concluded that the safety profiles of H2-O2 have rendered H2-O2 inhalation particularly suitable for relieving difficulty in breathing and other breathing symptoms in patients with COVID-19, regardless of the disease severity.


20) May protect babies from brain injury

Published in June 2020 (Pediatric Research 2020), researchers review therapeutic gases, particularly hydrogen, and their potentials and limitations in the treatment of HIE (Hypoxic Ischemic Encephalopathy) in newborns.

In translational research into adult diseases, hydrogen has been shown to be neuroprotective in disorders such as cerebral ischemia and traumatic brain injury, and in neurodegenerative diseases such as Alzheimer's disease.

However, despite extensive research on its effectiveness in adults, only a few studies have investigated its application in pediatric and neonatal medicine. Neonatal hypoxic–ischemic encephalopathy (HIE) is characterized by damage to neurons and other cells of the nervous system. One of the major contributing factors is excessive exposure to oxidative stress. Current research interest in HIE is shifting toward new neuroprotective agents, as single agents or as adjuncts to therapeutic hypothermia.

Hydrogen ventilation as a single agent or in combination with therapeutic hypothermia shows short- and long-term neuroprotection in neonatal translational HIE models.


Hydrogen Water Safety, Dosage, Side effects

Molecular hydrogen (H2) has no known side effects. It’s not toxic even at high concentrations. However, the long-term risks remain unknown until additional studies are carried out [R].

In most clinical studies, people drank 0.5 – 2 L of hydrogen water daily.

After drinking hydrogen water, about 40% of the H2 is absorbed by the body [R].


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