Following an important article published in Nature Medicine in 2007 detailing the ability of hydrogen to selectively scavenge peroxynitrite and hydroxyl radicals in vitro, the research on the health benefits of hydrogen continues to make progress.

At present, more and more evidence shows that hydrogen molecules are indeed effective for diseases and injuries. However, medical research pays more attention to evidence, while human trials are relatively high-level evidence, especially large-scale multicenter double-blind placebo-controlled clinical trials, which are the most important clinical evidence to determine the effect of hydrogen intervention.

1. Research on the intervention of hydrogen in cancer

In some cases, antioxidant therapy may increase the spread of cancer throughout the body, as demonstrated by metastatic melanoma in mice. These findings, as well as the problem trends that began to appear in human research, have led to the abortion of several large-scale clinical trials using high-dose antioxidant therapy. Even in some cases, Nrf2 activation has been proved to be carcinogenic and may lead to chemotherapy resistance.

In 1975, a research team from Baylor University and Texas A&M University studied high-pressure hydrogen therapy as a potential cancer therapy. They found the powerful anti-tumor ability of hydrogen in mice. It wasn’t until 2019, 44 years later, those human studies specifically targeting cancer appeared. Three papers showed that hydrogen inhalation may effectively slow down the progress of some cancers. These articles have great limitations, because there is no double-blind or single-blind.

The first article by a Japanese scholar is a case study of a single participant. The author hypothesized that hydrogen might inhibit the expression of programmed cell death protein 1 (PD-1). This is similar to the expected result of typical anti-PD-1 treatment. The second research article of the same group is an open-label study of 55 patients with stage IV colorectal cancer. The authors point out that hydrogen can reverse the imbalance of PD-11 CD81 T cells and provide a way to improve the prognosis. The third study is from an observational study in China in 2019, which followed 82 patients for 3-46 months. According to the report, from 4 weeks, hydrogen inhalation improved many outcomes, such as fatigue, insomnia, anorexia and pain. In 36.2% of cases with abnormally elevated tumor markers, inhaled hydrogen reduced the markers within 1345 days (median: 23 days). Researchers pointed out that hydrogen therapy is a low-cost intervention method, which can improve patients’ quality of life and control the progress of cancer.

It is worth noting that in several rodent studies and one human study, hydrogen has been shown to reduce the side effects of chemotherapy and other radiotherapy, such as inhibiting the cytotoxic effects of drugs such as fluorouracil (5FU) and cisplatin, without causing resistance to chemotherapy.

2. Hydrogen resists radiation damage.

High dose radiation has many known negative side effects, including death. Radiation damage is a less discussed topic of aging, but it may be an important reason. Low dose ionizing radiation is considered to have potential benefits, including prolonging life by acting as an exciting effect.

Just like exposure to other forms of stimulation, such as exercise and alcohol, hydrogen has been proved to protect human body from radiation. This protective effect has been observed in rodent models with systemic injury, and the burn healing after irradiation in rats. Several mechanisms of hydrogen assisting these models have been described in detail in two review articles. A paper provided the original results of a rodent model, in which radiation changed the levels of SOD and phosphorylated akt, a signal molecule for cell growth and survival. The radiation protection effect of hydrogen has prompted NASA scientists to put forward the hypothesis that hydrogen dissolved in water and/or inhaled can protect astronauts from excessive radiation exposure.

A human study in 2011 showed that hydrogen water was used to reduce the side effects of radiotherapy for cancer patients. Researchers observed significant improvements in various quality of life scores and markers of oxidative stress. Despite these positive benefits, no more human studies have been conducted. At present, there is an ongoing clinical trial conducted by Stony Brook Medicine in the United States, which will follow up 15 patients with high-grade glioma who received radiotherapy and chemotherapy for one year, and measure the changes of their quality of life.

3. Metabolic disorder

Metabolic disorders are a group of problems and classifications, including metabolic syndrome and nonalcoholic fatty liver disease (NAFLD), which can increase the risk of heart disease, stroke and type 2 diabetes.

A recently published article pointed out that hydrogen donor material can prevent aging aorta of low-density lipoprotein receptor mice from feeding high-fat diet atherosclerosis. This may be an important factor for hydrogen to reduce the symptoms of metabolic syndrome. At present, nine human studies have shown that hydrogen has certain effects on metabolic disorders related diseases. Metabolic disorder may be the best evidence of dose and time dependence in clinical research of hydrogen. However, in the research of measuring different metabolism, the crossover of markers is very limited. This makes it difficult to conduct a reasonable meta-analysis of these studies and draw a clear conclusion. Only relative comparison is allowed, such as the ratio of important results to invalid results.
Two open label studies and a double-blind, placebo-controlled study showed that the effect was limited at relatively low doses. For example, the first open label study showed that 0.5 mg hydrogen per day for 8 consecutive weeks significantly improved 5 biomarkers out of 13 by 38%. Another open-label study reported that 0.5 mg hydrogen per day lasted for 10 weeks, which improved 13 biomarkers in 22 by 59%. Another group of studies found that 13% of biomarkers of metabolic syndrome changed when hydrogen was 1 mg per day for 8 weeks.

Subsequent studies suggest that the effect of long-term hydrogen supply is more obvious. For example, within 10 weeks, 1 mg of hydrogen per day showed that 75% of biomarkers (9 out of 12 markers) were improved, and two of them showed a strong trend, although not statistically significant. Finally, within 24 weeks, 12 mg hydrogen per day showed significant improvement of 90% biomarkers (18 out of 20 markers), and another marker showed a strong trend. These repeated trials adopted randomized, double-blind and placebo-controlled designs, with larger study groups, and the results of the trials were significantly better than those of the earlier work.

It should be noted that human and animal experiments cannot be simply converted, because there is a huge difference between human and rodent in the relationship between water consumption and body weight. Compared with the beneficial response observed in animals, the dose-dependent response in humans is more obvious. Most human studies usually provide 300 ml to 1 liter of hydrogen water every day, while mice generally provide hydrogen water at will. In the clinical study of drinking the same concentration of hydrogen water, mice get 13 to 26 times more hydrogen than humans. For typical drugs, the molecular dose required to act in mice is usually 12 times larger than that in humans. But this conversion is not suitable for hydrogen and hydrogen water. Because the metabolism of hydrogen in human and mice is completely different from that of chemical drugs. The metabolic rate of gas in the body is closely related to the body edge. The larger the volume, the slower the metabolic rate, and this change is not linear. From this point of view, the human body needs an effective dose instead of the same dose as chemical drugs, or a relatively low dose can produce sufficient effect.

Through HOMA2 analysis, a study found that liver fat was significantly improved, aspartate aminotransferase decreased by 10% and insulin sensitivity improved by 11% in a short observation period of 28 days. The observation time of these effects is shorter than that of previous studies. In this study, the dose of hydrogen was 0.5 mg/day. It is worth noting that the dose of metabolic syndrome was not significantly improved at the 4th week, but by the 8th week, 5 of the 13 biomarkers were significantly improved. In a study, middle-aged overweight women ate 6mg of hydrogen every day, and their body composition and metabolic status were improved. Among the 20 results, 5 had significant results, 2 had significant trends, and 7 had weak trends. In another study, a single acute dose of high-concentration hydrogen water, 500 ml of 7 mg/L (3.5 mg hydrogen) was used, and hydrogen immediately improved vascular endothelial function. With the research progress of hydrogen intervention on metabolic dysfunction, we should pay attention to the phenomenon that high dose and long duration produce better effects.

4. Neurodegenerative diseases

Age related neurological disorders, such as Alzheimer’s disease and Parkinson’s disease, have a great influence on people. Although a lot of research has been done worldwide, there are few potential candidates to improve the results.

For many molecules, after strong early research in animal experiments, the results in humans are disappointing. In contrast, hydrogen water has not only made strong research achievements in rodents, but also made great positive achievements in humans.

Portable Hydrogen Inhalation Machine manufacturer. In the hydrogen rodent model, it shows evidence to solve various effects, such as reducing the toxic effect of cellular amyloid, tau protein entanglement, neuroinflammation and excessive oxidative stress. The research results of hydrogen treatment of Parkinson’s disease are mixed, with two negative studies and one single study showing remarkable curative effect.

Age-related neurological disorders, such as Alzheimer’s disease and Parkinson’s disease, have a great influence on people. Although a lot of research has been done worldwide, there are few potential candidates to improve the results. For many molecules, after strong early research in animal experiments, the results in humans are disappointing. In contrast, hydrogen water has not only made strong research achievements in rodents, but also made great positive achievements in humans. In the hydrogen rodent model, it shows evidence to solve various effects, such as reducing the toxic effect of cellular amyloid, tau protein entanglement, neuroinflammation and excessive oxidative stress. The research results of hydrogen treatment of Parkinson’s disease are mixed, with two negative studies and one single study showing remarkable curative effect.

5. The role of hydrogen in emergency medicine

Hydrogen has attracted wide attention because of its potential in alleviating acute stress injury.

Based on the published evidence of myocardial infarction in rats and dogs, a small preliminary study was used to explore the possibility of inhaling hydrogen during out-of-hospital cardiac arrest. The positive results of this trial led to the approval of hydrogen inhalation as an advanced medical technology for cardiac arrest syndrome in Japan, and a large multi-center clinical study was launched to explore this application.

Studies on rodents and early clinical studies have proved that molecular hydrogen is a safe and effective intervention for acute nervous attacks, such as cerebral ischemia and cerebral infarction. Some results show that hydrogen molecule is more effective than edaravone, a clinical free radical scavenger. Other human results show that edaravone combined with hydrogen is more effective than edaravone alone in the intervention of cerebral ischemia.
These promising results, coupled with the high safety of hydrogen, led to another clinical trial registered by Stony Brook Medical, hydrogen water and minocycline. This study observed 100 patients who recovered from acute ischemic stroke.

In an acute traumatic brain injury model, a promising study on the recovery of concussion was published, which confirmed the research of early rodents in the recovery of traumatic brain injury. A human study shows that hydrogen water has obvious protective effect on neonatal hypoxic-ischemic encephalopathy.

6. Application of hydrogen in sports medicine

Exercise is widely regarded as one of the best preventive strategies to keep healthy and delay aging.

It has been proved that hydrogen can be rescued from exercise-induced injuries by various methods, such as reducing redox damage and preventing the decline of exercise performance. Local application of hydrogen can accelerate the healing of soft tissue injury and reduce delayed muscle soreness. In a double-blind, placebo-controlled, crossover trial design, drinking hydrogen water has also been shown to significantly improve the health status of middle-aged overweight women. A registered clinical trial to explore the effect of local hydrogen water and RICE regimen (rest, ice, compression and elevation) in the intervention of grade 2 ankle tear (recently completed, the manuscript is currently being prepared. It is found that the application of hydrogen-rich water therapy within 24 hours after injury can reduce joint swelling and pain, and at the same time restore range of motion and balance, and its effect is not inferior to that of standard RICE regimen. Future studies using hydrogen-rich hydrotherapy may evaluate the difference in healing time compared with standard therapies (such as RICE).

Aging can lead to some complications, including that the elderly are prone to sarcopenia, lose weight during inactivity, are more likely to be injured, and take longer to recover from exercise. With the increase of age, sports performance will decline, and hydrogen seems likely to alleviate this trend.

7. Hydrogen alleviates drug toxicity.

Early evidence shows that hydrogen can alleviate the toxicity of human chemotherapy drugs, and more drug toxicity alleviation effects have been observed in animal studies. It can protect stomach injury induced by hydrogen aspirin, hepatotoxicity induced by acetaminophen, hangover induced by ethanol and neurotoxicity induced by methamphetamine.

In a rodent study published in 2020, hydrogen molecules restored the redox state induced by long-term administration of cyclosporine A, inhibited oxidative damage and improved kidney function. In the future, human trials, whether selective or accidental, should be explored to use hydrogen to combat man-made injuries caused by toxic substances.

Early evidence shows that hydrogen can alleviate the toxicity of human chemotherapy drugs, and more drug toxicity alleviation effects have been observed in animal studies. It can protect stomach injury induced by hydrogen aspirin, hepatotoxicity induced by acetaminophen, hangover induced by ethanol and neurotoxicity induced by methamphetamine. In a rodent study published in 2020, hydrogen molecules restored the redox state induced by long-term administration of cyclosporine A, inhibited oxidative damage and improved kidney function. In the future, human trials, whether selective or accidental, should be explored to use hydrogen to combat man-made injuries caused by toxic substances.