Hydrogen in medical research – An overview

In recent years, molecular hydrogen (H₂) has gained increasing international attention in basic and clinical research. Numerous studies suggest that, due to its physicochemical properties, H₂ could play an interesting role in oxidative stress, inflammation regulation, and cellular signaling pathways. Scientific investigation of these properties is taking place in various disciplines—from molecular biology to cell physiology to clinical prevention.


This website provides an overview of the current state of research and highlights the contexts in which molecular hydrogen is being investigated—both in preclinical models and initial clinical trials. The focus is not on promoting a specific product, but rather on objectively presenting scientific findings.


A notice:

The potential effects described here refer to molecular hydrogen as a substance and not to a specific product or device. This is not a medical recommendation or claim, but rather a presentation of the current state of research from the perspective of international research.


Please also read the neutral information page:

 https://www.wasserstoff-therapie.info


In Youtube we recommend the info channel: Hydrogen Therapy

Hydrogen is the primordial substance of life and contains everything on the level of vibration, light and information that we as body, soul and spirit beings need for life, regulation, growth and protection.


🔹Introductory knowledge about H2

Hydrogen (H) is the first and smallest chemical element in the periodic table. In its molecular form (H₂), it consists of two covalently bonded hydrogen atoms. This molecule is colorless, odorless, tasteless, and has a very low molecular mass—properties that give it exceptionally high diffusivity into biological tissues.


Since the publication of the first study by Dole et al. in 1975, reporting the effects of hyperbaric hydrogen on melanoma tumors², molecular hydrogen has been increasingly studied scientifically. A decisive impetus for this research came in 2007 from Ohsawa et al., who demonstrated in the journal Nature Medicine that hydrogen can selectively neutralize cytotoxic hydroxyl radicals³. This study also described that hydrogen can be administered by inhalation or dissolved in water and can exert a biological effect – without toxic effects.


These findings have led to a surge in international research. Over 500 peer-reviewed articles have now been published addressing the potential biological benefits of hydrogen. The studies range from cell biology studies and animal models to initial clinical applications, for example, in oxidative stress, ischemia-reperfusion, or chronic inflammatory processes.


Note: The content presented in this section is based on scientific literature on molecular hydrogen as a substance—not on specific products or application devices. It does not constitute medical advice or a recommendation.


References (excerpt):

² Dole, M. et al. (1975). Science, 190(4210): 152–154.

³ Ohsawa, I. et al. (2007). Nat Med, 13(6): 688–694.

⁴ Ohta, S. (2014). Pharmacol Ther, 144(1): 1–11.

⁵ Ichihara, M. et al. (2015). Med Gas Res, 5: 12.

🔹Forms of hydrogen

  • Atomic hydrogen (H
  • )
    •

  • A single hydrogen atom with an unpaired electron is called atomic hydrogen (H
  • ). Due to its reactivity, it rarely occurs in a stable state in nature. During electrolysis, atomic hydrogen can be formed briefly, but it quickly combines with another hydrogen atom to form a stable H₂ molecule.

    • Previous assumptions that atomic hydrogen was the key component in electroactivated water are now considered outdated. The term "active hydrogen," as it appears in some marketing texts, is not a scientifically recognized concept and was likely mistranslated from Japanese.⁶ Nevertheless, there is evidence that traces of atomic hydrogen can occur in so-called Brown's gas mixtures.⁶


    Molecular hydrogen (H2)

    

    Molecular hydrogen consists of two covalently bonded hydrogen atoms. This diatomic molecule is the primary form in which hydrogen occurs in biological and technical contexts. Due to its small size and high lipid solubility, H₂ can very efficiently cross cell membranes and even the blood-brain barrier⁷.

    H₂ is colorless, odorless, and non-toxic. Studies show that it exists in biologically relevant concentrations and can be absorbed through inhalation or dissolved in water (so-called "hydrogen-rich water")³ 4. In this context, H₂ is also considered a so-called "biologically active gas," similar to nitric oxide (NO), hydrogen sulfide (H₂S), or carbon monoxide (CO)⁷.


    Hydride (H⁻)

    A hydride is a negatively charged hydrogen ion (H⁻) that carries an extra electron. This form is a strong base and reacts rapidly in an aqueous environment to form H₂ and OH⁻. H⁻ is not naturally stable. Hydride compounds such as sodium borohydride or lithium aluminum hydride are used industrially as reducing agents in organic chemistry⁶.


    Hydrogen cation (H⁺ / proton)

    A positively charged hydrogen ion (H⁺) consists of only one proton. This form plays a central role in energy metabolism, particularly in ATP synthesis in the mitochondria⁸. The pH of water is based on the concentration of these hydrogen ions. The self-ionization of water to H₂O ⇌ H⁺ OH⁻ is fundamental to many biological processes.




    🔹 Differentiation from H₂O₂ (hydrogen peroxide)

    A common confusion exists between H₂ (molecular hydrogen) and H₂O₂ (hydrogen peroxide). The latter is a strong oxidizing agent with a completely different effect and is not comparable to molecular hydrogen. Applications of H₂O₂ belong to the field of disinfection or chemistry—not to the discussion of molecular hydrogen⁹.

    Note: The hydrogen forms described here are for scientific explanation purposes only. Statements about possible health effects – if any – refer exclusively to the molecular form H₂ and are presented in the context of international scientific literature.

    References (Excerpt): ³ Ohsawa, I. et al. (2007). Nat Med, 13(6): 688–694. ⁴ Ohta, S. (2014). Pharmacol Ther, 144(1): 1–11. ⁶ Ichihara, M. et al. (2015). Med Gas Res, 5: 12. ⁷ Fandrey, J. (2015). Sci Signal, 8(373): fs10. ⁸ Nakayama, M. et al. (2007). Hemodial Int, 11(3): 322–327. ⁹ Chen, O. et al. (2016). Med Gas Res, 6(1): 57.

    🔹 Pharmacokinetics – uptake, distribution and excretion of H₂



    Molecular hydrogen can be delivered to the body in a variety of ways. Scientific studies have examined the following application methods, among others:


    • Inhalation of gaseous H₂ in concentrations between 2% and 66.7%¹¹
    • Drinking hydrogen-enriched water¹²
    • Intravenous injection of H₂-enriched saline solution¹⁴
    • Hydrogen-rich baths and topical applications¹⁵
    • Hyperbaric chambers with H₂ atmosphere²
    • Taking hydrogen-releasing tablets or metal compounds¹⁵
    • Modulation of the intestinal flora by hydrogen-producing prebiotics¹⁶
    • Rectal application of H₂ gas¹⁷


    Thanks to its physical properties—small molecular size, high lipid solubility, and neutrality—H₂ can rapidly penetrate biological membranes, including the blood-brain barrier and mitochondrial membranes.15 Distribution throughout the body is rapid and depends largely on the route of administration.



    Inhalation


    When inhaling a gas mixture containing H₂, studies show that a maximum plasma level can be reached after approximately 30 minutes. Degradation in the blood occurs within 60–90 minutes.¹⁸ Since distribution occurs via the bloodstream, it is possible that H₂ can also diffuse into difficult-to-access tissues—including extracellular spaces.

    A typical gas mixture used in research contains 66.7% H₂ and 33.3% O₂ – a concentration that has been described as non-toxic under controlled conditions.¹¹ In practice, concentrations below the flammability limit (4.6 vol%) are usually used for safety reasons.



    Drinking hydrogen-enriched water


    Under standard conditions (25 °C, 1 atm), the maximum solubility of H₂ in water is approximately 1.6 ppm (0.8 mM).12 A dose of just 1.6 mg of H₂ contains more molecules than 100 mg of vitamin C – due to its low molecular weight (2.02 g/mol).4

    After drinking, plasma hydrogen concentrations typically peak after 5–15 minutes and return to baseline levels within 45–90 minutes.¹² Interestingly, studies have also measured a correlating increase in exhaled hydrogen concentrations, suggesting rapid systemic absorption.¹²



    Special feature: Tissue distribution and cell compartments


    While blood measurements quickly show equilibrium, it remains unclear how long H₂ is present in non-vascularized tissues (e.g., intervertebral discs, vitreous body, lymph nodes). Research on this is still limited. There is evidence that H₂ penetrates deeper cellular compartments and may exert its effects there as well.¹⁵

    Note: The pharmacokinetic properties described refer to research using molecular hydrogen as a substance—not to specific devices or applications. They are intended to provide information on physiological principles and are not to be understood as a therapeutic recommendation.


    References (Author): 2 Dole, M. et al. (1975). Science, 190(4210): 152–154. 11 Hayashida, K. et al. (2014). Resuscitation, 85(11): 1512–1519. 12 Ohta, S. (2014). Pharmacol Ther, 144(1):1–11. 14 Sun, H. et al. (2011). J Hepatol, 54(3):471–480. 15 Ichihara, M. et al. (2015). Med Gas Res, 5: 12. 16 Nishimura, N. et al. (2012). Br J Nutr, 107(4): 485–492. 17 Senn, N. (1888). JAMA, 10(25): 767–777. 18 Liu, C. et al. (2014). Sci Rep, 4:5485.

    🔹 Pharmacodynamics -

    Mechanisms of action of molecular hydrogen

    Although research on the effects of molecular hydrogen is still relatively young, numerous preclinical and clinical studies provide evidence that H₂ may intervene at various levels of cellular regulation.¹⁹ The focus is not only on antioxidant effects, but above all on the modulation of signaling pathways, gene expression, and cellular stress responses.



    Selective reduction of reactive oxygen species (ROS)


  • Early studies showed that H₂ can selectively reduce cytotoxic hydroxyl radicals (
  • OH) and peroxynitrite (ONOO⁻) without reacting with other physiologically important ROS such as superoxide or hydrogen peroxide. This selective mechanism distinguishes H₂ from classical antioxidants.

    • However, researchers point out that direct radical scavenging alone is not sufficient to explain all observed effects.²³ In a study on rheumatoid arthritis, positive clinical effects persisted for weeks after cessation of H₂ supplementation²⁴ – suggesting longer-term cellular adaptations.



    Activation of the Nrf2 signaling pathway


    A well-studied mechanism is the activation of the Nrf2/Keap1/ARE signaling pathway, which is considered a central system for regulating antioxidants and cytoprotective enzymes.34 H2 can activate Nrf2 under oxidative stress, leading to increased production of glutathione, superoxide dismutase (SOD), catalase, and other protective molecules.35 36

    This effect occurs specifically in response to cellular stress—not permanently. This means that H₂ acts adaptively and not pro-oxidatively.⁴² Studies using Nrf2 knockout models confirm that many of the protective effects of H₂ are mediated via this pathway.³⁷ ³⁸



    Modulation of cellular signal transduction


    Furthermore, H₂ has been shown to influence various cellular signaling pathways, such as NF-κB, TNF-α, MAPK, JNK, ERK, and PI3K/Akt. These signaling pathways control a variety of biological functions, including inflammation, cell growth, apoptosis, and metabolism.

    H₂ appears to have neither a nonspecific inhibitory nor a sustained activating effect, but rather modulates the response depending on the cell's initial state. This homeostatic modulation is a central aspect of current research interest.



    Gene expression and epigenetic effects


    In animal and cell studies, over 1,000 gene expression changes have been observed due to H₂⁶³. These include, in particular, genes encoding stress response, metabolism, immune regulation, and mitochondrial function. Some data suggest possible epigenetic effects, such as altered microRNA patterns and histone modifications⁶².

    Conclusion (scientific): The pharmacodynamic effects of H₂ encompass both direct and indirect mechanisms, including ROS modulation, gene regulation, and signaling pathway interference. Currently, it is believed that the effect strongly depends on the context (cell type, stress level, duration of exposure).


    Note: All mechanisms presented here are based on scientific studies using molecular hydrogen—not on any specific product. The findings presented serve as unbiased information on the current state of research.


    References: 3 Ohsawa, I. et al. (2007). Nat Med, 13(6):688–694. 19 Ohta, S. (2011). Curr Pharm Des, 17(22):2241–2252. 20 Buxton, GV et al. (1988). J Phys Chem Ref Data, 17:513–886. 23 Ohta, S. (2015). Enzymol Methods, 555: 289–317. 24 Ishibashi, T. et al. (2014). Int Immunopharmacol, 21(2):468–473. 34 Yu, J. et al. (2015). Toxicol Lett, 238(3):11–19. 35 Diao, M. et al. (2016). Inflammation, 39(2): 587–593. 36 Xie, K. et al. (2012). Br J Anesth, 108(3): 538–539. 37 Kawamura, T. et al. (2013). Am J Physiol Lung Cell Mol Physiol, 304(10):L646–L656. 38 Xie, Q. et al. (2014). Mol Med Rep, 10(2):1143–1149. 42 Wakabayashi, N. et al. (2003). Nat Genes, 35(3): 238–245. 47 Kishimoto, Y. et al. (2015). J Thorac Cardiovasc Surg, 150(3):645–653.e3. 59 Sun, Y. et al. (2013). Osteoporosis Int, 24(3): 969–978. 62 Lin, C.-L. et al. (2015). Chem Biol Interact, 240: 12–21. 63 Iuchi, K. et al. (2016). Sci Rep , 6 : 18971 .

    🔹 Cell modulation – inflammation, metabolism and gene response

    In addition to antioxidant mechanisms and activation of the Nrf2 system, studies show that molecular hydrogen can also influence cellular signaling and immune regulation in a variety of ways. These so-called cell-modulating effects are considered a central factor in the biological effects of H₂.



    Influence on inflammatory processes


    H₂ can modulate pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-6, IL-8, and tumor necrosis factor-α (TNF-α). Furthermore, inhibition of central inflammatory mediators has been observed in various models, including:

    • NF-κB (Nuclear Factor kappa B)⁴⁷
    • NLRP3-Inflammasom⁴⁹
    • HMGB1 (High Mobility Group Box 1)⁵¹
    • **NFAT, STAT3, ERK1/2, TXNIP u. a.**³⁰ ⁵⁶ ⁵⁹

    This modulation occurs depending on the situation – i.e. depending on the degree of inflammation or other cellular stress signals.



    Metabolic regulation & anti-obesity effect


    Animal studies have shown that H₂ can influence lipid metabolism and hormonal regulation. For example, upregulation of the following markers has been documented:


    • **FGF21 (Fibroblast Growth Factor 21)**⁵²
    • **PGC-1α (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha)**⁵³
    • **PPARα (Peroxisome proliferator-activated receptor alpha)**⁵³

    This metabolic modulation could be a reason for the fat resistance, glucose regulation, and weight stabilization observed in studies—e.g., in rodent models of metabolic syndrome⁵⁴.



    Epigenetic & hormonal effects


    Some studies suggest that H₂ may also exert epigenetic activating effects. This affects, for example, the expression of ghrelin, a hormone associated with appetite regulation, neuroprotective processes, and stress responses.⁵⁵ Other modulating influences include:


    • JNK-1, ASK1, MEK, GSK-3, PKC⁴⁵ ⁵⁷ ⁶⁰
    • SIRT1, an enzyme that influences aging processes and mitochondria⁶²

    These far-reaching cellular effects demonstrate that H₂ is more than a simple reducing agent – rather, it appears to play a systemic regulatory role in cellular metabolism.


    Summary: The cell-modulating effects of H₂ affect inflammatory, metabolic, and epigenetic processes. These may be central mechanisms by which molecular hydrogen demonstrates positive effects on many disease models in preclinical studies. The precise hierarchy of these signaling networks is currently being intensively investigated.


    Note: All statements in this section are based on scientific studies using molecular hydrogen as a substance. No statements are made regarding specific products, therapeutic recommendations, or application devices.


    References: 24 Ishibashi, T. et al. (2014). Int Immunopharmacol, 21(2):468–473. 30 Sobue, S. et al. (2015). Mol Cell Biochem, 403(1–2):231–241. 44 Ohta, S. (2015). Enzymol Methods, 555: 289–317. 45 Wang, C. et al. (2011). Neurosci Lett, 491(2):127–132. 46 Kishimoto, Y. et al. (2015). J Thorac Cardiovasc Surg, 150(3):645–653.e3. 47 Ren, JD et al. (2014). Mediators Inflamm, 2014: 930894. 49 Shao, A. et al. (2015). Mol Neurobiol, 52(1): 1–11. 51 Xie, KL et al. (2010). Zhejiang Da Xue Xue Bao Yi Xue Ban, 39(5): 454–457. 52 Kamimura, N. et al. (2011). Obesity, 19(7):1396–1403. 53 Kamimura, N. et al. (2016). NPJ Aging Mech Dis, 2:16008.54 Zhang, JY et al. (2012). Hepato-Gastroenterology, 59(116): 1026–1032. 55 Matsumoto, A. et al. (2013). Sci Rep, 3: 3273. 56 Sun, Y. et al. (2013). Osteoporosis Int, 24(3): 969–978. 57 Hong, Y. et al. (2014). PLoS One, 9(4): e96212. 59 Sun, Y. et al. (2013). Osteoporosis Int, 24(3): 969–978. 60 Li, Q. et al. (2013). Med Gas Res, 3(1):20.62 Lin, C.-L. et al. (2015). Chem Biol Interact, 240: 12–21.

    🔹 Scientific recognition – state of research

    Despite unanswered questions about the precise mechanism of action of molecular hydrogen, there is growing interest in its potential benefits in biomedical research. More than 1,600 research groups worldwide have investigated H₂, and the number of published papers now exceeds 500 peer-reviewed articles.

    These studies range from fundamental molecular biology to animal models and initial human studies. The quality of the publications is continuously improving—according to one analysis, the average impact factor of the journals is around 3. Some articles have even been published in high-profile journals such as Nature Medicine, Scientific Reports, and Free Radical Research.



    Research areas and organ reference


    The scientific literature on H₂ covers a wide spectrum:

    • Neurology (e.g. ischemic brain damage, neurodegenerative diseases)¹¹ ⁷⁵
    • Cardiology (e.g. reperfusion injury, heart failure)⁶⁵ ⁶⁶
    • Metabolism (e.g., metabolic syndrome, type 2 diabetes, lipid disorders)⁷¹–⁷⁴
    • Inflammatory and autoimmune diseases (e.g. rheumatoid arthritis, chronic hepatitis)²⁴ ⁸³
    • Sports medicine (regeneration, oxidative stress response, lactate reduction)⁷⁸ ⁷⁹
    • Oncology (in combination with radiotherapy to improve quality of life)⁸⁸
    • Urology, ophthalmology, dermatology, dentistry, etc.

    Many of these studies show significant effects, while others show only moderate or individual differences. A consistent pattern of effects has not yet been fully defined.



    Limiting factors & outlook


    Despite the growing number of publications, research still has certain limitations:

    • Many studies are preclinical (animal model, cell culture)
    • Human studies are often small or short-term
    • Comparable dosages and application methods are often missing
    • Genetic or gender-specific differences have so far been little researched

    Nevertheless, research is actively continuing in international networks such as the Molecular Hydrogen Institute (MHI)⁶⁴ or within the framework of university programs. Molecular hydrogen is already an integral part of basic biomedical research projects, particularly in Japan, China, South Korea, and the USA.



    A notice:

    The scientific recognition presented here refers to molecular hydrogen as a research subject—not to specific products, therapies, or devices. A final clinical evaluation is still pending in many areas of application.



    References (excerpt):

    ³ Ohsawa, I. et al. (2007). Nat Med, 13(6): 688–694. ⁵ Ichihara, M. et al. (2015). Med Gas Res, 5: 12. ¹¹ Hayashida, K. et al. (2014). Resuscitation, 85(11): 1512–1519. ¹⁸ Liu, C. et al. (2014). Sci Rep, 4: 5485. ²⁴ Ishibashi, T. et al. (2014). Int Immunopharmacol, 21(2): 468–473. 6³ Iuchi, K. et al. (2016). Sci Rep, 6: 18971. ⁶⁴ Chen, O. et al. (2016). Med Gas Res, 6(1): 57. ⁶⁵ Dixon, BJ et al. (2013). Med Gas Res, 3(1): 10. 66 Dohi, K. et al. (2014). PLoS One, 9(9): e108034. 7¹ Nakao, A. et al. (2010). J Clin Biochem Nutr, 46(2): 140–149. ⁷² Kajiyama, S. et al. (2008). Nutr Res, 28: 137–143. 7³ Song, G. et al. (2013). J Lipid Res, 54(7): 1884–1893. ⁷⁴ Zong, C. et al. (2015). Lipids Health Dis, 14: 159. ⁷⁵ Yoritaka, A. et al. (2013). Purple Disord, 28(6): 836–839. ⁷⁸ Aoki, K. et al. (2012). Med Gas Res, 2(1): 12. ⁷⁹ Ostojic, SM et al. (2014). Postgrad Med, 126(5): 187–195. ⁸³ Xia, C. et al. (2013). Clin Transl Sci, 6(5): 372–375. ⁸⁸ Kang, K.-M. et al. (2011). Med Gas Res, 1: 11.

    🔹Medical applications – perspectives from research and practice

    Molecular hydrogen is increasingly being discussed in research as a potentially supportive factor in acute and chronic disease processes. Numerous studies show evidence of biological effects that could be beneficial in certain health conditions—particularly where oxidative stress, ischemia, or cell damage play a role.

    

    Observed effects in animal models and early-phase studies


    • Acute neurological damage: In a rat model, H₂ has been shown to reduce the size of a cerebral infarct after ischemic stroke and influence neuroprotective markers.¹¹ Positive effects have also been observed in animal studies in traumatic brain injury—including reduction of cerebral edema, modulation of tau expression, and stabilization of ATP levels⁶⁸.
    • Cardioprotective effect: In animal models of reperfusion injury after cardiac arrest, inhalation of hydrogen led to improved cardiac function and reduced cell damage¹¹.
    • Anti-inflammatory & cell protection: In various models, H₂ was able to reduce the activity of pro-inflammatory cytokines and DNA oxidation in damaged tissue²³ ⁴⁴.


    First observations in human application


    Some early clinical studies and reports (e.g. in patients with metabolic syndrome, rheumatoid arthritis or dialysis treatments) indicate possible short-term effects such as:

    • Improvement of subjective well-being
    • reduced inflammatory markers
    • lower oxidative stress parameters
    • faster recovery after physical exertion

    hin⁷¹–⁷⁴ ⁸³–⁸⁴. These effects have not yet been confirmed by large, multicenter studies and are therefore considered exploratory.



    Individual reaction and perception


    In practice, it has been shown that some people respond quickly and significantly to H₂ applications, while others notice hardly any changes. These differences are linked in the literature to genetic factors, metabolic state, and duration of exposure.⁶⁹ Placebo effects or physical sensitivity may also play a role.



    Limitations & clinical classification


    Hydrogen is not an approved drug and is not a substitute for therapy. Studies have shown that its mode of action is potentially supporting physiological balance. Some researchers therefore refer to it as a "cellular homeostasis aid" rather than a traditional drug therapy.



    A notice:

    The observations presented are based on scientific publications and experience reports from basic and clinical research. This does not constitute a product statement or treatment recommendation, but rather an overview of the current scientific discourse.



    References (excerpt):

    11 Hayashida, K. et al. (2014). Resuscitation, 85(11): 1512–1519. 23 Ohta, S. (2015). Enzymol Methods, 555: 289–317. 44 Ohta, S. (2015). Enzymol Methods, 555: 289–317. 65 Dixon, BJ et al. (2013). Med Gas Res, 3(1): 10. 66 Dohi, K. et al. (2014). PLoS One, 9(9):e108034. 68 Dohi, K. et al. (2014). PLoS One, 9(9):e108034. 69 Xie, F. & Ma, X. (2014). Brain Disord Ther, 2. 71–74 see previous references for metabolic syndrome 83 Xia, C. et al. (2013). Clin Transl Sci, 6(5): 372–375. 84 Sakai, T. et al. (2014). Vasc Health Risk Manag, 10: 591–597.

    🔹 Human studies – clinical results & research situation

    While much of the evidence on the effects of molecular hydrogen has come from cell culture and animal models, several human studies have also been conducted. Overall, the number of published human studies is in the mid-double digits—the majority of which involve limited numbers of subjects, are short-term, and exploratory in nature.⁷⁰



    Clinical applications – Initial study results

    The clinical studies published so far suggest that H₂ could have potentially positive effects on:

    🔹 Safety – Tolerability & toxicological assessment

    A key reason for the international interest in molecular hydrogen is its exceptionally favorable safety profile. H₂ is a naturally occurring molecule that is also produced in the human body—for example, in the intestine during the fermentation of fiber by bacteria⁹⁰.



    Human metabolism & bacterial production


    Studies show that people with healthy intestinal flora produce measurable amounts of H₂ endogenously every day. Experimental models have shown that this can be specifically increased by administering certain bacterial strains or dietary fiber.⁹¹ These findings support the assumption that H₂ is not a foreign or toxic substance to the body.



    Toxicological safety studies


    • Deep-sea diving: Since the 1940s, hydrogen has been used as a component of breathing gas mixtures in professional deep-sea diving—at concentrations many times higher than those used for medical purposes. Hundreds of human studies in this field have shown no long-term adverse effects.


    • Intravenous and oral applications: Human studies with hydrogen-enriched saline or oral H₂ water have also not documented any serious adverse effects.⁹⁷ Occasionally, softer stools or mild reductions in blood sugar levels have been reported in diabetics—the latter being easily controlled by adjusting insulin doses.⁷⁷


    • Animals & Cells: Even in long-term studies on mice and cell cultures, no carcinogenic, mutagenic or teratogenic effects of H₂ could be detected.



    Consideration of paradoxical effects


    Some authors argue that molecular hydrogen remains safe even when it exhibits biological effects—which is unusual from the perspective of classical pharmacology. It is thought that H₂ acts through so-called hormetic mechanisms, in which mild stress leads to positive adaptive effects.



    Conclusion:

    Molecular hydrogen is described in the scientific literature as a highly tolerable substance with a very low toxicological risk. Current evidence suggests that H₂, even at high concentrations, has no harmful effects—neither acute nor chronic.



    A notice:

    This information is based on published scientific studies. It refers to H₂ as a molecule—not to specific devices or products. For individual medical advice, please consult a qualified professional.


    References: 77 Ito, M. et al. (2011). Med Gas Res, 1(1): 24. 90 Eastwood, MA (1992). Annu Rev Nutr, 12:19–35. 91 Kajiya, M. et al. (2009). Biochem Biophys Res Commun, 386(2): 316–321. 94 Case, EM & Haldane, JBS (1941). J Hyg (London), 41(3):225–249. 95 Dougherty, JH Jr. . (1976). Aviat Space Environ Med, 47(6): 618–626. 97 Nagatani, K. et al. (2013). Med Gas Res, 3:13.

    🔹 Conclusion & legal notice

    The scientific investigation of molecular hydrogen (H₂) is in a dynamic phase of development. Initial results from cell culture, animal, and human studies indicate that H₂ can modulate biological processes—particularly in the context of oxidative stress, inflammation, and mitochondrial function.

    At the same time, hydrogen has demonstrated a remarkably good safety profile in various studies. It is well tolerated by the body, is naturally present in the metabolism, and has so far shown no toxic effects, even at high concentrations.

    Despite these positive signals, research is still underway. Many clinical trials are still pending or in early phases. A proven therapeutic effect in the medical sense is currently not recognized in Europe.

    ⚖️ Legal Notice

    The content provided on this website is intended solely to provide general scientific information about molecular hydrogen as a substance. It does not constitute a promise of healing or a recommendation for therapy, and it does not replace medical advice. No statement is made regarding the effectiveness of a specific product, device, or manufacturing process. The research results described refer to international studies whose clinical significance is currently being scientifically evaluated. Please consult a medically qualified professional if you have any health-related questions or complaints.

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    3. Ohsawa, I., et al., Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med, 2007. 13(6): pp. 688–694.
    4. Ohta, S., Molecular hydrogen as a preventive and therapeutic medical gas: Initiation, development, and potential of hydrogen medicine. Pharmacol Ther, 2014.
    5. Ichihara, M., et al., Beneficial biological effects and underlying mechanisms of molecular hydrogen – a comprehensive review of 321 original articles. Med Gas Res, 2015, 5: p. 12.
    6. Fandrey, J., A roundup of the usual suspects in O2 sensing: CO, NO, and H2S! Sci Signal, 2015. 8(373): p. fs10.
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    8. Ohta, S., Molecular hydrogen is a novel antioxidant for efficient reduction of oxidative stress with potential for amelioration of mitochondrial diseases. Biochimica et Biophysica Acta, 2012. 1820(5): pp. 586–94.
    9. Martin, W. and M. Muller, The hydrogen hypothesis for the first eukaryote. Nature, 1998. 392(6671): pp. 37–41.
    10. Chen, O., Z.-h. Y., and C. Li., Proceedings: Second Hydrogen Molecule Biomedical Symposium in Beijing, China. Medical Gas Research, 2016. 6(1): p. 57. (See LeBaron)
    11. Hayashida, K., et al., Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest, independent of targeted temperature management. 2014 edition.
    12. Kawai, D., et al., Hydrogen-rich water prevents the progression of nonalcoholic steatohepatitis and associated hepatocarcinogenesis in mice. Hepatologie, 2012. 56(3): pp. 912–21.
    13. Nakayama, M., et al., Less oxidative hemodialysis solution prepared by cathode-side application of electrolyzed water. Hemodial Int, 2007. 11(3): pp. 322–7.
    14. Sun, H., et al., The protective role of hydrogen-rich saline in experimental liver injury in mice. Journal of Hepatology, 2011. 54(3): pp. 471–80.
    15. Qian, L., J. Shen, and X. Sun, Methods of Hydrogen Application. Hydrogen Molecular Biology and Medicine. 2015: Springer Netherlands.
    16. Nishimura, N., et al., Pectin and high-amylose corn starch increase cecal hydrogen production and ameliorate hepatic ischemia-reperfusion injury in rats. Br J Nutr, 2012. 107(4): pp. 485–92.
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