Two Decades of Hydrogen Research: Current Status (Part 3) – From Gut Bacteria to Mechanisms of Action: Unresolved Challenges in Hydrogen Research
September 2, 2026 | Compiled by Annie Nguyen, VAHC Secretariat
Hideaki Karaki, Professor Emeritus, The University of Tokyo
When considering the health effects of hydrogen, there is one factor that cannot be overlooked: the gut bacteria inhabiting the human intestine.
Hydrogen is produced within the human body on a daily basis, even without inhaling hydrogen gas or consuming products like hydrogen water or hydrogen jelly. This occurs because gut bacteria generate hydrogen during the process of fermenting substances such as dietary fiber.
Moreover, comparing this internally produced amount with the hydrogen intake from sources like hydrogen water reveals interesting differences. If there is significance to ingesting hydrogen from external sources, it may not be explainable solely by the sheer "quantity" involved.
In this final installment reviewing approximately two decades of hydrogen research, we examine the differences between hydrogen produced by gut bacteria and hydrogen ingested from external sources, and consider what can currently be stated regarding hydrogen's safety and efficacy.
Gut Bacteria Also Produce Hydrogen
The large intestine is home to a vast number of bacteria—estimated at tens of trillions—comprising hundreds to thousands of different species.
Some of these gut bacteria ferment components that human digestive enzymes cannot break down, such as dietary fiber and indigestible carbohydrates. This fermentation process generates hydrogen alongside substances like short-chain fatty acids and carbon dioxide.
Some of the hydrogen produced in the gut is utilized by other gut bacteria. A portion is absorbed through the intestinal wall into the bloodstream, circulates throughout the body, and is eventually exhaled through the lungs. Hydrogen that is not absorbed is expelled from the intestinal tract as gas.
Consequently, measuring hydrogen concentration in exhaled breath allows for an estimation of the level of hydrogen production by gut bacteria.
There are significant individual differences in the amount of hydrogen produced within the gut. This is because levels vary depending on factors such as the composition of the gut microbiota, dietary habits, and—in particular—the intake of dietary fiber and indigestible carbohydrates that serve as substrates for fermentation.
Studies involving healthy individuals estimate the median daily amount of hydrogen produced by gut bacteria—and subsequently expelled via breath or intestinal gas—to be approximately 30 mg.
Of course, this does not mean that every person utilizes 30 mg of hydrogen within their body every day. Some of the hydrogen produced by gut bacteria is consumed by other bacteria, while the rest is expelled from the body. Furthermore, there are significant individual differences in production levels. Nevertheless, this figure is intriguing when compared to the amount of hydrogen obtained from external sources.
Even with 2 Liters of Hydrogen Water, the Theoretical Maximum is Only About 3.2 mg
Let us consider the amount of hydrogen one can obtain from hydrogen water.
At 20°C and 1 atmosphere of pressure, the saturation concentration of hydrogen in water is approximately 1.62 mg/L. If one were to drink 2 liters of hydrogen water at this saturation level in a single day, the theoretical upper limit of hydrogen intake would be approximately 3.2 mg.
In reality, however, hydrogen dissipates very easily. Factors such as container material, storage duration, and the time elapsed between opening and consumption cause the hydrogen concentration to drop, meaning the actual amount ingested may be lower than this theoretical maximum.
In the case of hydrogen water products labeled as "Foods with Function Claims" (discussed in the first part of this series), the recommended daily intake of 300 mL contains 0.36 mg of hydrogen molecules. For hydrogen jelly products registered under the same category, the recommended daily intake contains 0.9 mg of hydrogen molecules.
When simply comparing these figures to the median daily production of approximately 30 mg of hydrogen by gut bacteria, it becomes clear that the amount of hydrogen routinely produced within the gut is significantly higher.
Does this mean that, since humans naturally produce large quantities of hydrogen in their intestines, there is no point in consuming small amounts through products like hydrogen water or hydrogen jelly? The matter is not quite that simple. The Limitation of Comparing Based Solely on "Quantity"
There is a significant difference between the hydrogen produced by gut bacteria and the hydrogen introduced into the body from external sources, such as hydrogen water or hydrogen gas. One key difference lies in the "timing" of the body's exposure.
Although hydrogen production by gut bacteria fluctuates depending on factors like diet, it generally occurs over an extended period. This results in a chronic supply of hydrogen at relatively low concentrations.
In contrast, consuming hydrogen water or inhaling hydrogen gas causes a rapid rise in hydrogen concentration, followed by a decline.
In other words, hydrogen from gut bacteria can be viewed as a "chronic supply," whereas externally ingested hydrogen represents an "acute spike." Regarding pharmacological effects, the total amount ingested is not the only critical factor; the peak concentration reached and the duration for which that level is maintained can also be crucial.
Regarding hydrogen, one cannot rule out the possibility that a rapid rise in blood concentration itself triggers specific biological responses. However, this aspect is not yet fully understood.
Do hydrogen continuously produced by gut bacteria and hydrogen introduced externally over a short period truly have different effects on the body? If they do differ, what concentration levels or intake amounts are required? Further research is needed to address these questions.
The Significance of Hydrogen-Producing Gut Bacteria
Research is also investigating whether hydrogen derived from gut bacteria has beneficial effects on the body in its own right. High intake of dietary fiber, for instance, can stimulate fermentation by gut bacteria and increase hydrogen production. However, it is difficult to isolate the hydrogen produced by gut bacteria and evaluate its specific health effects.
Consuming dietary fiber leads to the production of various metabolites in the gut—such as short-chain fatty acids—in addition to hydrogen. It also alters the gut microbiota itself. Therefore, even if health benefits associated with dietary fiber intake are observed, one cannot attribute them entirely to the effects of hydrogen. Conversely, one cannot conclude that externally ingested hydrogen is meaningless simply because large amounts of hydrogen are produced by gut bacteria. It is necessary to clarify where in the body hydrogen exists, at what concentrations, and for how long—as well as what biological reactions it triggers.
**Mechanism of Action Remains Unresolved**
Let us return to the starting point of hydrogen research.
A 2007 paper drew attention to the hypothesis that hydrogen selectively scavenges highly toxic hydroxyl radicals, thereby suppressing cellular damage caused by oxidative stress.
However, subsequent research has revealed that hydrogen's effects are difficult to explain solely through the simple scavenging of reactive oxygen species (ROS).
Hydrogen is a molecule with low reactivity; questions remain regarding which molecules it reacts with in the body and how those interactions lead to intracellular signaling.
Consequently, other mechanisms of action have been proposed in recent years. One such mechanism is the activation of the Nrf2 pathway, which is involved in the cell's antioxidant defense system.
It is hypothesized that rather than directly scavenging all reactive oxygen species, hydrogen indirectly suppresses oxidative stress by activating the cell's innate antioxidant defense mechanisms.
Furthermore, theories have been reported suggesting that Fe-porphyrin (hematin) or proteins involved in the mitochondrial electron transport chain serve as targets for hydrogen. If these hypotheses prove correct, the "total amount" of hydrogen present in the body might not be sufficient to explain its effects.
This is because a brief spike in hydrogen concentration could trigger specific signals, with biological reactions continuing even after the hydrogen itself has been eliminated from the body. However, it must be emphasized that all these mechanisms of action remain hypotheses currently under investigation. There is currently no consensus regarding which specific molecules in the body serve as the initial targets for hydrogen, or the precise pathways through which it leads to clinical changes.
**"Safe" vs. "Effective": Separate Issues**
Discussions surrounding hydrogen require a distinction between safety and efficacy.
Regarding safety, research to date has yielded relatively favorable data. Large amounts of hydrogen are naturally produced in the human gut on a daily basis. Clinical studies on hydrogen gas inhalation have reported almost no serious adverse events. Similarly, no major safety issues attributable to hydrogen itself have been identified with the consumption of hydrogen water at typical intake levels.
While hydrogen gas is flammable—necessitating careful concentration management and safe equipment design—this is a separate issue from the toxicity of hydrogen itself to the human body.
For hydrogen-containing supplements, safety must be considered not only for the hydrogen itself but also for the ingredients used to generate it. Despite these nuances, there appear to be few significant safety concerns regarding the hydrogen molecule itself at this time. However, "safety" does not equate to "efficacy." This distinction must not be overlooked.
**Research Has Increased, But...**
Hydrogen research has expanded rapidly since 2007.
Beyond basic research, numerous clinical studies have been conducted using methods such as hydrogen gas inhalation, hydrogen water, hydrogen jelly, and hydrogen-containing supplements.
The scope of this research is broad, covering areas such as post-cardiac arrest syndrome, cerebral infarction, Parkinson's disease, cognitive function, respiratory diseases, diabetes, obesity, lipid metabolism, exercise-induced fatigue, sleep, and stress.
Systematic reviews and meta-analyses aggregating multiple studies have also been published.
There is no doubt that the volume of research has increased compared to about a decade ago, when hydrogen water sparked significant public debate. However, the mere fact that research has increased does not mean that the health benefits of hydrogen have been conclusively established. Regarding the Parkinson's disease study mentioned earlier, while significant improvement was reported in a small-scale trial involving 17 participants, a subsequent multi-center trial involving approximately 178 participants failed to replicate those results.
Similarly, in the HYBRID II trial investigating hydrogen gas inhalation for post-cardiac arrest syndrome, while secondary endpoints suggested improvements, no statistically significant difference was confirmed for the primary endpoint.
In trials involving hydrogen jelly, even though improvements were observed in certain areas within the hydrogen-consuming group, no clear difference could be confirmed when compared to the placebo group.
These studies do not prove that hydrogen is ineffective. At the same time, they do not prove that the efficacy of hydrogen has been established. In science, after promising initial results emerge, it is necessary to conduct follow-up studies using more rigorous methods and larger participant groups to verify whether the same results can be replicated. Much of the research on hydrogen is currently at precisely that stage.
For whom, what, and how much?
One of the remaining challenges in hydrogen research is that diverse studies cannot simply be lumped together under the single term "hydrogen." The way hydrogen enters the body differs depending on whether one inhales hydrogen gas or drinks hydrogen water.
Hydrogen water and hydrogen jelly differ in terms of the amount consumed and the rate at which the hydrogen enters the body. Conditions change again with supplements designed to generate hydrogen within the gastrointestinal tract. The target population also matters; the implications naturally differ between patients with serious illnesses and healthy individuals. Even if a treatment study involving patients with post-cardiac arrest syndrome yields certain results, that does not automatically prove the efficacy of healthy people drinking hydrogen water on a daily basis.
Conversely, the fact that a trial involving healthy individuals failed to show a clear effect does not rule out the medical potential for treating specific diseases. What was the target population? What method of hydrogen administration was used? What dosage and duration were employed? And what exactly was evaluated? To assess the efficacy of hydrogen, it is necessary to consider each of these factors separately. Current Status: Promising but Still Developing
How, then, should we evaluate the roughly 20 years of hydrogen research?
Triggered by research conducted in 2007, hydrogen shifted from being viewed merely as an "inert gas" to becoming a subject of study as a molecule capable of exerting some form of influence on living organisms.
Since then, a body of basic research, animal experiments, and clinical trials has accumulated, with promising results reported regarding certain diseases and health indicators. The scope of research has expanded, and methods of intake have diversified to include not only hydrogen gas but also hydrogen water, hydrogen jelly, and hydrogen-containing supplements.
Regarding hydrogen water, the hydrogen concentration in products—which had been an issue around 2016—has seen some improvement, and "Foods with Function Claims" featuring hydrogen as a functional ingredient have also appeared on the market.
The scientific research landscape has changed compared to a decade ago. However, the mechanisms of action remain at the hypothesis stage, and many clinical studies are small in scale. There have also been instances where promising results failed to be replicated in large-scale trials.
For which diseases or health conditions, using which administration methods, and at what dosage
Can clinically significant effects be achieved through the use of hydrogen? A definitive answer to this question has not yet been fully established.
While a relatively solid body of data regarding safety has been accumulated, the quality of evidence concerning efficacy must still be evaluated based on specific target conditions and methods of administration. Consequently, from a scientific standpoint, it is inappropriate to either dismiss hydrogen’s health benefits entirely as ineffective or to make sweeping generalizations claiming its efficacy has been proven. If one were to summarize the current status of hydrogen—based on approximately two decades of research—in a single phrase, it would be "promising but still in the developmental stage."
Moving forward, it is essential to conduct more large-scale, high-quality randomized controlled trials, verify the reproducibility of research findings, and elucidate the mechanisms by which hydrogen interacts with the human body. Will the accumulation of research confirm the true potential of hydrogen, or will its effects prove limited to specific conditions or contexts? Future research will provide the answer.
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Hideaki Karaki
Professor Emeritus, The University of Tokyo; Doctor of Agriculture. Graduated from the Department of Veterinary Medicine, Faculty of Agriculture, The University of Tokyo. Has served as a professor at the same university, a member and vice-president of the Science Council of Japan, and an expert committee member and expert witness for the Food Safety Commission of the Cabinet Office. He conducts extensive research and disseminates information regarding food safety and the evaluation of the efficacy and safety of health foods. Currently serves as Representative of the Association for Improving Trust in Food and Representative of the Research Group on Testing Methods for Health Foods.
