Molecular Hydrogen

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    Last Updated: May 9, 2024

    Molecular hydrogen is a naturally occurring gas that is usually supplemented through hydrogen-rich water or inhaling hydrogen gas. Preliminary research suggests that it may provide antioxidant, anti-inflammatory, and cell-protective effects which could be especially useful in conditions associated with high levels of oxidative stress.

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    What is molecular hydrogen?

    Molecular hydrogen (H2) is the lightest and smallest chemical element that exists naturally. It is a colorless and odorless gas. Hydrogen was long thought to have a negligible effect on the human body, but emerging evidence suggests that it may have therapeutic potential as a medical gas. Regardless, research on molecular hydrogen is still in its infancy. While there seems to be promise, it may be too soon to recommend molecular hydrogen for any particular purpose.

    What are molecular hydrogen’s main benefits?

    Research suggests that molecular hydrogen has antioxidant, anti-inflammatory, and cell-protective properties. These effects may benefit various conditions, particularly those associated with high levels of oxidative stress, but current research is too limited to draw any meaningful conclusions.

    One of the most long-standing, albeit niche, uses of molecular hydrogen is for deep-sea diving. Adding hydrogen gas to the breathing mixture as a substitute for nitrogen is one method for reducing the side effects of nitrogen gas in high-pressure environments. This isn’t through any drug-like effects of hydrogen, though; it’s simply because it’s replacing nitrogen gas so that less nitrogen can dissolve into the blood during a dive.[7][8]

    Preliminary research also points to potential benefits in metabolic syndrome, nonalcoholic fatty liver disease, recovery following a heart attack or cardiac arrest, rheumatoid arthritis, cancer, exercise capacity, and some respiratory conditions.[1][9][10]

    Does molecular hydrogen support exercise capacity?

    Does molecular hydrogen have a role in metabolic disease?

    Does molecular hydrogen have a role in cancer treatment?

    Does molecular hydrogen improve respiratory conditions?

    What are molecular hydrogen’s main drawbacks?

    Molecular hydrogen is generally considered nontoxic, even at high doses, and side effects have rarely been reported.[9] In one study using hydrogen-rich water, a few participants experienced loose stools, heartburn, and headaches; however, there was no placebo group to compare to.[11] In patients inhaling hydrogen gas for several hours daily, drowsiness and agitation have been reported.[9]

    There are some additional risks depending on the administration method. Hydrogen gas at concentrations above 4% can be explosive when mixed with oxygen, and injectable hydrogen-rich saline raises the risk of infection and injury. Furthermore, these dosage forms generally require specialized equipment and medical supervision.[1][12]

    How does molecular hydrogen work?

    Molecular hydrogen has an incredibly small size and low molecular weight, allowing it to rapidly diffuse throughout the body, including through cell membranes and the blood-brain barrier. While it readily penetrates bodily tissues, it’s also eliminated quickly through exhalation. Overall, hydrogen seems to work by activating various biological pathways in ways that promote cellular homeostasis.[10]

    Molecular hydrogen is a unique antioxidant in that it selectively scavenges hydroxyl and peroxynitrite radicals but not other reactive species that play important roles in cellular signaling (e.g., hydrogen peroxide). Its small size allows it to interact directly with mitochondria, possibly benefiting mitochondrial function and energy metabolism. Furthermore, hydrogen seems to increase the body’s own antioxidant mechanisms, resulting in a prolonged antioxidant effect even once it has been cleared from the body.[13]

    The anti-inflammatory effects of molecular hydrogen may be related to the antioxidant effects, but hydrogen also seems to inhibit inflammatory pathways directly. Additionally, hydrogen may influence gene expression, lipid metabolism, apoptosis (programmed cell death), and autophagy (the process of breaking down and recycling cellular materials).[1][10]

    What are other names for Molecular Hydrogen

    Note that Molecular Hydrogen is also known as:
    • H2
    • Hydrogen
    • Hydrogen gas
    • Hydrogen-rich water
    • Hydrogen-rich saline

    Dosage information

    Molecular hydrogen can be administered in several ways, including inhaling hydrogen gas, drinking or bathing in hydrogen-rich water (HRW), or injecting/infusing hydrogen-rich saline. Injecting, infusing, or inhaling molecular hydrogen is generally done under medical supervision and with specialized equipment. Drinking HRW is probably the safest and most accessible option for most people.[1] Regardless, more research is needed to determine the optimal dosage and administration method of molecular hydrogen.

    HRW is simply water with added hydrogen. The extra hydrogen diffuses out of the water fairly quickly; therefore, it’s generally necessary to prepare the HRW immediately before consumption.[1] There are two methods of doing this: effervescent hydrogen-generating tablets, which usually contain magnesium and an acid which will lead to the production of hydrogen when added to a glass of water,[2] and hydrogen-generating water bottles, which use an electric current to produce hydrogen.[3]

    In clinical studies, HRW (0.3 mM to 7.5 mM) has been consumed in amounts ranging from 250 mL to 2 L (2,000 mL) per day, usually divided into several daily doses with higher volumes.[1][4]

    In metabolic syndrome, HRW (~7.3 mM) at a dose of 750 mL daily may be safe and effective for up to 24 weeks.[5]

    When used to reduce fatigue during exercise (an effect possibly relevant in untrained individuals), HRW can be taken as a single dose immediately before exercise.[6]

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    Frequently asked questions

    What is molecular hydrogen?

    Molecular hydrogen (H2) is the lightest and smallest chemical element that exists naturally. It is a colorless and odorless gas. Hydrogen was long thought to have a negligible effect on the human body, but emerging evidence suggests that it may have therapeutic potential as a medical gas. Regardless, research on molecular hydrogen is still in its infancy. While there seems to be promise, it may be too soon to recommend molecular hydrogen for any particular purpose.

    What are molecular hydrogen’s main benefits?

    Research suggests that molecular hydrogen has antioxidant, anti-inflammatory, and cell-protective properties. These effects may benefit various conditions, particularly those associated with high levels of oxidative stress, but current research is too limited to draw any meaningful conclusions.

    One of the most long-standing, albeit niche, uses of molecular hydrogen is for deep-sea diving. Adding hydrogen gas to the breathing mixture as a substitute for nitrogen is one method for reducing the side effects of nitrogen gas in high-pressure environments. This isn’t through any drug-like effects of hydrogen, though; it’s simply because it’s replacing nitrogen gas so that less nitrogen can dissolve into the blood during a dive.[7][8]

    Preliminary research also points to potential benefits in metabolic syndrome, nonalcoholic fatty liver disease, recovery following a heart attack or cardiac arrest, rheumatoid arthritis, cancer, exercise capacity, and some respiratory conditions.[1][9][10]

    Does molecular hydrogen support exercise capacity?

    Molecular hydrogen might influence several aspects of exercise capacity to a small degree, but whether this is actually meaningful to an exercising person requires more research.

    Molecular hydrogen may reduce fatigue, blood lactate levels, and the perception of exertion during high-intensity exercise. However, the reduction in fatigue and perceived exertion may only be significant in untrained individuals, possibly due to the body being less adapted to the stress of exercise. Furthermore, most studies have reported that hydrogen did not affect VO2max (a metric of aerobic exercise performance) or endurance performance in trained or untrained individuals.[6][10]

    When benefits have been observed, they appear to be greater in intermittent, high-intensity exercise as opposed to continuous exercise and with molecular hydrogen provided as a single dose immediately before exercise rather than multiple-day dosing or after exercise.[6][14]

    Does molecular hydrogen have a role in metabolic disease?

    Molecular hydrogen is an intriguing option for metabolic conditions which are often associated with high levels of oxidative stress and inflammation. While some trials have pointed to potential benefits, the research is mixed, and all outcomes require replication in further trials.

    Hydrogen-rich water (HRW) might improve lipid profiles, more specifically by reducing LDL cholesterol, total cholesterol, and triglycerides. However, the effects appear small or marginally beneficial.[4]

    A randomized controlled trial in people with metabolic syndrome reported that HRW reduced oxidative stress biomarkers, improved lipid profiles, and reduced fasting glucose and HbA1c after 24 weeks.[5] The participants consumed 750 mL (0.75 L) of HRW (7.3 millimolar (mM)) daily. Studies providing HRW at lower concentrations and for shorter durations have not found these benefits, aside from reduced oxidative stress biomarkers.[11][15]

    In nonalcoholic fatty liver disease (NAFLD), a small trial reported that 1 L (1,000 mL) of HRW (3 mM) daily for 28 days reduced liver fat accumulation compared to a placebo.[16] In another trial, hydrogen gas (66% hydrogen and 33% oxygen) inhaled for 1 hour daily for 13 weeks was reported to reduce liver enzymes, inflammatory markers, and oxidative stress biomarkers compared to baseline, with no changes observed in the control group.[17]

    Does molecular hydrogen have a role in cancer treatment?

    Molecular hydrogen has demonstrated some potentially promising effects in cancer therapy. However, this is based on several small clinical trials and case reports and requires more research.[9]

    In 20 patients with stage III or IV non-small-cell lung cancer (NSCLC) who refused standard treatment, inhaled hydrogen reportedly led to significantly reduced respiratory symptoms (e.g., shortness of breath, cough, chest pain) and prolonged progression-free survival time compared to a placebo (7.9 months vs 4.4 months). Hydrogen gas (66.7% hydrogen and 33.3% oxygen) was inhaled for 4 to 6 hours daily over 5 months.[18] Similarly, another clinical trial in patients with stage IV lung cancer reported that inhaled hydrogen (~3 hours daily) in addition to standard treatment (nivolumab) led to prolonged overall survival compared to standard treatment alone.[19][20]

    In one clinical trial, patients with liver cancer who were undergoing radiation drank 1.5 L to 2 L (1,500 mL to 2,000 mL) of hydrogen-rich water daily (0.55–0.65 millimolar) for 6 weeks and reported reduced side effects of radiation (appetite loss and altered taste), had improved oxidative stress biomarkers, and showed no difference in tumor response to radiation.[21]

    More research is needed to confirm the validity of these findings, but a few trials have suggested that hydrogen may alter immune function in a way that could improve cancer prognosis.[1]

    Does molecular hydrogen improve respiratory conditions?

    Molecular hydrogen, particularly inhaled hydrogen gas, may be beneficial in various respiratory conditions, including COVID-19, asthma, and chronic obstructive pulmonary disease (COPD). This may be due to its antioxidant and anti-inflammatory properties as well as its low density, which may improve lung airflow.[1]

    In a randomized controlled trial, people experiencing persistent symptoms following a COVID-19 infection reported improved physical function (6-minute walking test) and lung function (forced vital capacity and forced expiratory volume) with inhaled hydrogen gas compared to a placebo. Hydrogen gas (100% hydrogen) was inhaled for 1 hour twice a day for 14 days.[22] In an open-label, multicenter trial in hospitalized patients with COVID-19, inhaled hydrogen gas (66.7% hydrogen and 33.3% oxygen) led to reduced disease severity, reduced chest pain, and a faster improvement in shortness of breath and cough compared to participants receiving oxygen gas alone.[23]

    Similar benefits have been observed in people with asthma and COPD. In a multicenter randomized controlled trial, patients with an acute exacerbation (a sudden worsening of disease/symptoms) of COPD saw a greater reduction in symptoms when inhaling hydrogen and oxygen gas over 7 days compared to oxygen alone, but there were no differences in lung function.[24] In a study including people with either asthma or COPD, a single dose of hydrogen gas (2.4% hydrogen inhaled for 45 minutes) led to decreased markers of inflammation in the blood and exhaled breath.[25]

    This could represent a novel approach to managing respiratory conditions and is certainly worthy of further research.

    What are molecular hydrogen’s main drawbacks?

    Molecular hydrogen is generally considered nontoxic, even at high doses, and side effects have rarely been reported.[9] In one study using hydrogen-rich water, a few participants experienced loose stools, heartburn, and headaches; however, there was no placebo group to compare to.[11] In patients inhaling hydrogen gas for several hours daily, drowsiness and agitation have been reported.[9]

    There are some additional risks depending on the administration method. Hydrogen gas at concentrations above 4% can be explosive when mixed with oxygen, and injectable hydrogen-rich saline raises the risk of infection and injury. Furthermore, these dosage forms generally require specialized equipment and medical supervision.[1][12]

    How does molecular hydrogen work?

    Molecular hydrogen has an incredibly small size and low molecular weight, allowing it to rapidly diffuse throughout the body, including through cell membranes and the blood-brain barrier. While it readily penetrates bodily tissues, it’s also eliminated quickly through exhalation. Overall, hydrogen seems to work by activating various biological pathways in ways that promote cellular homeostasis.[10]

    Molecular hydrogen is a unique antioxidant in that it selectively scavenges hydroxyl and peroxynitrite radicals but not other reactive species that play important roles in cellular signaling (e.g., hydrogen peroxide). Its small size allows it to interact directly with mitochondria, possibly benefiting mitochondrial function and energy metabolism. Furthermore, hydrogen seems to increase the body’s own antioxidant mechanisms, resulting in a prolonged antioxidant effect even once it has been cleared from the body.[13]

    The anti-inflammatory effects of molecular hydrogen may be related to the antioxidant effects, but hydrogen also seems to inhibit inflammatory pathways directly. Additionally, hydrogen may influence gene expression, lipid metabolism, apoptosis (programmed cell death), and autophagy (the process of breaking down and recycling cellular materials).[1][10]

    Update History

    New page created

    major

    Molecular hydrogen benefits: Currently, there's not much solid evidence on the benefits of molecular hydrogen, but it does possess antioxidant effects and has an established use in deep-sea diving.

    Molecular hydrogen drawbacks: Molecular hydrogen seems to be well-tolerated for most people, but further research is needed. Certain administration methods carry unique risks, like the risk of explosion with hydrogen gas and the risk of infection/injury when hydrogen is injected.

    Molecular hydrogen & exercise: Molecular hydrogen might reduce perceived exertion/fatigue in untrained individuals, but there's currently no clear evidence that it improves exercise performance in trained or untrained individuals.

    Molecular hydrogen & metabolic disease: Molecular hydrogen has been linked to some potential benefits in preliminary research, particularly in the context of metabolic syndrome, NAFLD, and high cholesterol.

    Molecular hydrogen & cancer: Molecular hydrogen might have a positive effect as an adjunct in cancer treatment. Research is very preliminary but has suggested reduced side effects of radiotherapy, reduced respiratory symptoms in lung cancer, and prolonged progression-free survival.

    We added 3 new meta-analyses to the Examine database covering hydrogen's effects on exercise and blood lipid profiles.

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    References

    1. ^Johnsen HM, Hiorth M, Klaveness JMolecular Hydrogen Therapy-A Review on Clinical Studies and Outcomes.Molecules.(2023 Nov 26)
    2. ^Rosch M, Lucas K, Al-Gousous J, Pöschl U, Langguth PFormulation and Characterization of an Effervescent Hydrogen-Generating Tablet.Pharmaceuticals (Basel).(2021 Dec 18)
    3. ^Hatae T, Miwa NElectrolytic hydrogen-generating bottle supplies drinking water with free/combined chlorine and ozone repressed within safety standard under hydrogen-rich conditions.Med Gas Res.(2021 Apr-Jun)
    4. ^Todorovic N, Fernández-Landa J, Santibañez A, Kura B, Stajer V, Korovljev D, Ostojic SMThe Effects of Hydrogen-Rich Water on Blood Lipid Profiles in Clinical Populations: A Systematic Review and Meta-Analysis.Pharmaceuticals (Basel).(2023 Jan 18)
    5. ^Tyler W LeBaron, Ram B Singh, Ghizal Fatima, Kumar Kartikey, Jagdish P Sharma, Sergej M Ostojic, Anna Gvozdjakova, Branislav Kura, Mami Noda, Viliam Mojto, Mohammad Arif Niaz, Jan SlezakThe Effects of 24-Week, High-Concentration Hydrogen-Rich Water on Body Composition, Blood Lipid Profiles and Inflammation Biomarkers in Men and Women with Metabolic Syndrome: A Randomized Controlled TrialDiabetes Metab Syndr Obes.(2020 Mar 24)
    6. ^Zhou K, Liu M, Wang Y, Liu H, Manor B, Bao D, Zhang L, Zhou JEffects of molecular hydrogen supplementation on fatigue and aerobic capacity in healthy adults: A systematic review and meta-analysis.Front Nutr.(2023)
    7. ^BJURSTEDT H, SEVERIN GThe prevention of decompression sickness and nitrogen narcosis by the use of hydrogen as a substitute for nitrogen, the Arne Zetterstrôm method for deep-sea diving.Mil Surg.(1948 Aug)
    8. ^Abraini JH, Gardette-Chauffour MC, Martinez E, Rostain JC, Lemaire CPsychophysiological reactions in humans during an open sea dive to 500 m with a hydrogen-helium-oxygen mixture.J Appl Physiol (1985).(1994 Mar)
    9. ^Mohd Noor MNZ, Alauddin AS, Wong YH, Looi CY, Wong EH, Madhavan P, Yeong CHA Systematic Review of Molecular Hydrogen Therapy in Cancer Management.Asian Pac J Cancer Prev.(2023 Jan 1)
    10. ^Dhillon G, Buddhavarapu V, Grewal H, Sharma P, Verma RK, Munjal R, Devadoss R, Kashyap RHydrogen Water: Extra Healthy or a Hoax?-A Systematic Review.Int J Mol Sci.(2024 Jan 12)
    11. ^Nakao A, Toyoda Y, Sharma P, Evans M, Guthrie NEffectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study.J Clin Biochem Nutr.(2010 Mar)
    12. ^Artamonov MY, Martusevich AK, Pyatakovich FA, Minenko IA, Dlin SV, LeBaron TWMolecular Hydrogen: From Molecular Effects to Stem Cells Management and Tissue Regeneration.Antioxidants (Basel).(2023 Mar 3)
    13. ^Tian Y, Zhang Y, Wang Y, Chen Y, Fan W, Zhou J, Qiao J, Wei YHydrogen, a Novel Therapeutic Molecule, Regulates Oxidative Stress, Inflammation, and Apoptosis.Front Physiol.(2021)
    14. ^Li Y, Bing R, Liu M, Shang Z, Huang Y, Zhou K, Bao D, Zhou JCan molecular hydrogen supplementation reduce exercise-induced oxidative stress in healthy adults? A systematic review and meta-analysis.Front Nutr.(2024)
    15. ^Kajiyama S, Hasegawa G, Asano M, Hosoda H, Fukui M, Nakamura N, Kitawaki J, Imai S, Nakano K, Ohta M, Adachi T, Obayashi H, Yoshikawa TSupplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance.Nutr Res.(2008 Mar)
    16. ^Korovljev D, Stajer V, Ostojic J, LeBaron TW, Ostojic SMHydrogen-rich water reduces liver fat accumulation and improves liver enzyme profiles in patients with non-alcoholic fatty liver disease: a randomized controlled pilot trial.Clin Res Hepatol Gastroenterol.(2019 Nov)
    17. ^Tao G, Zhang G, Chen W, Yang C, Xue Y, Song G, Qin SA randomized, placebo-controlled clinical trial of hydrogen/oxygen inhalation for non-alcoholic fatty liver disease.J Cell Mol Med.(2022 Jul)
    18. ^Chen JB, Kong XF, Mu F, Lu TY, Lu YY, Xu KCHydrogen therapy can be used to control tumor progression and alleviate the adverse events of medications in patients with advanced non-small cell lung cancer.Med Gas Res.(2020 Apr-Jun)
    19. ^Akagi J, Baba HHydrogen gas restores exhausted CD8+ T cells in patients with advanced colorectal cancer to improve prognosis.Oncol Rep.(2019 Jan)
    20. ^Akagi J, Baba HHydrogen gas activates coenzyme Q10 to restore exhausted CD8(+) T cells, especially PD-1(+)Tim3(+)terminal CD8(+) T cells, leading to better nivolumab outcomes in patients with lung cancer.Oncol Lett.(2020 Nov)
    21. ^Kang KM, Kang YN, Choi IB, Gu Y, Kawamura T, Toyoda Y, Nakao AEffects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors.Med Gas Res.(2011 Jun 7)
    22. ^Botek M, Krejčí J, Valenta M, McKune A, Sládečková B, Konečný P, Klimešová I, Pastucha DMolecular Hydrogen Positively Affects Physical and Respiratory Function in Acute Post-COVID-19 Patients: A New Perspective in Rehabilitation.Int J Environ Res Public Health.(2022 Feb 10)
    23. ^Guan WJ, Wei CH, Chen AL, Sun XC, Guo GY, Zou X, Shi JD, Lai PZ, Zheng ZG, Zhong NSHydrogen/oxygen mixed gas inhalation improves disease severity and dyspnea in patients with Coronavirus disease 2019 in a recent multicenter, open-label clinical trial.J Thorac Dis.(2020 Jun)
    24. ^Zheng ZG, Sun WZ, Hu JY, Jie ZJ, Xu JF, Cao J, Song YL, Wang CH, Wang J, Zhao H, Guo ZL, Zhong NSHydrogen/oxygen therapy for the treatment of an acute exacerbation of chronic obstructive pulmonary disease: results of a multicenter, randomized, double-blind, parallel-group controlled trial.Respir Res.(2021 May 13)
    25. ^Wang ST, Bao C, He Y, Tian X, Yang Y, Zhang T, Xu KFHydrogen gas (XEN) inhalation ameliorates airway inflammation in asthma and COPD patients.QJM.(2020 Dec 1)

    Examine Database References

    1. Oxidative Stress Biomarkers - Li Y, Bing R, Liu M, Shang Z, Huang Y, Zhou K, Bao D, Zhou JCan molecular hydrogen supplementation reduce exercise-induced oxidative stress in healthy adults? A systematic review and meta-analysis.Front Nutr.(2024)
    2. Blood Lactate (Exercise) - Zhou K, Liu M, Wang Y, Liu H, Manor B, Bao D, Zhang L, Zhou JEffects of molecular hydrogen supplementation on fatigue and aerobic capacity in healthy adults: A systematic review and meta-analysis.Front Nutr.(2023)
    3. Low-density lipoprotein (LDL) - Todorovic N, Fernández-Landa J, Santibañez A, Kura B, Stajer V, Korovljev D, Ostojic SMThe Effects of Hydrogen-Rich Water on Blood Lipid Profiles in Clinical Populations: A Systematic Review and Meta-Analysis.Pharmaceuticals (Basel).(2023 Jan 18)