Molecular Hydrogen and Autoimmune Disease
Share this post
Multiple clinical studies report improvements in autoimmune disease with hydrogen treatment
Although hydrogen (H2) is well known as an alternative fuel, recognized as such in the Energy Policy Act of 1992, only in 2007 did it begin to really make the scene in medicine. Although used for the purpose of preventing decompression sickness in divers since the 1940s,, it wasn’t practically useful as a therapy due to its high flammability, being easily ignited at a concentration of approximately 4% in air. In 2007, the first research using H2 in a format that is practical clinically (dissolved in air at a concentration of less than 4% or in a cellular nutrient medium) was published in Nature Medicine, and the research exploded.
Since then, H2 has been administered in clinical studies as an inhaled gas, dissolved in water for oral delivery or topical application,, and delivered in saline intravenously. From human research we have seen that molecular H2 has potential benefits for metabolic health, fatty liver disease, exercise performance, autonomic nervous system balance, acute cerebral infarction,4 Parkinson’s disease, and in patients receiving radiation treatment for liver cancer, among many other things.,
H2 has been demonstrated to be a selective antioxidant, an anti-inflammatory,, and an activator of the body’s endogenous antioxidant production via the Nrf2 cell-signaling pathway. Given each of these things, should we find it surprising that it also has been investigated as a treatment for autoimmune disease?
Clinical application of hydrogen in autoimmune disease
Multiple clinical studies have shown that treatment with H2-rich water may be of benefit to individuals with autoimmune disease. The first publication of this nature was an open-label pilot study that investigated the impact of consumption of supersaturated H2 water on patients with rheumatoid arthritis (RA). In this study, participants consumed 530 mL of H2-rich water (containing 4 to 5 ppm of H2) daily for four weeks, then had a four-week washout, followed by another four weeks of H2 water consumption. Of the 20 patients in the study, five of them had early RA (duration of less than 12 months), and four of these individuals were not on any medication. The other participants were either on methotrexate or abatacept, a combination of these, or no medications (abandoned due to side effects). No one in the study was being treated with steroid hormones.
During each period of treatment with the H2-rich water, RA disease activity scores improved.
During each period of treatment with the H2-rich water, RA disease activity scores, based on assessment of 28 joints (DAS28), improved. In the first four weeks, scores decreased in 18 of the 20 patients. By the end of the study, the average DAS28 score for all participants had decreased from the baseline of 3.83 to 2.26, and the five patients having early RA all achieved remission (defined for the purpose of this study as a DAS28 < 2.3, although a cutoff value of 2.6 is often used), with four of them becoming symptom-free.
One particularly interesting finding in this study was that the DAS28 score continued to improve during the four-week washout period, suggesting that the H2 treatment continued to have residual effects. Urinary 8-hydroxy-deoxyguanosine (8-OHdG) levels, a marker of DNA oxidative damage, also improved not only during treatment but during the washout phase as well, remaining below the baseline through the end of the study. It has been suggested that some of the longer term effects seen with H2 as a therapy are due to its impact on cellular signal transduction, protein activity, and genetic transcription, as its direct antioxidant effects would be limited roughly to its time in circulation which is 45 to 90 minutes, as evidenced by its level in expired air.
Prolonged benefits with hydrogen treatment were also seen in a follow-on randomized, double-blind, placebo-controlled study of rheumatoid arthritis patients that looked at the impact of treatment for five days with 500 mL of intravenous, H2-enhanced saline.7 In this study, the DAS28 score in the H2-treated group decreased from the baseline of 5.18 to 4.02 immediately after infusions and to 3.74 by four weeks while there was no change in the score of the placebo group. Additionally, the level of interleukin-6 (IL-6) and matrix metalloproteinase-3 (MMP-3), markers of inflammation and joint damage, decreased significantly in the H2-treated group while they increased in the placebo group.
Bathing in H2-rich water also has been studied as a treatment for psoriasis and resulted in an improvement of 75% or more in the Psoriasis Area Severity Index score in 10 of 41 of patients after eight weeks.
A publication of three psoriasis case studies using a variety of different H2 administration techniques (inhalation, intravenous, and taken orally in water) reported improvements in skin lesions and psoriatic arthritis symptoms regardless of the route of intervention. Bathing in H2-rich water also has been studied as a treatment for psoriasis and resulted in an improvement of 75% or more in the Psoriasis Area Severity Index (PASI) score in 10 of 41 of patients after eight weeks, while only 1 of 34 patients in the control group had the same level of improvement.6 Although a whole body bath may not be practical for most, soaking a portion of the body that is affected with psoriasis lesions in H2-rich water is not tremendously difficult and worthy of consideration.
The positive outcomes of these studies, and other findings from numerous animal models of autoimmune disease,,, make it evident that we will continue to see research surrounding the use of H2 in autoimmune disease. The improvements or sustained benefits seen post-intervention for a prolonged period also are particularly exciting, as this would minimize cost and the burden of taking a daily supplement. Clearly, many exciting applications for H2 as a therapy will be seen in years to come.
Click here to see References
 Bjurstedt H, Severin G. The prevention of decompression sickness and nitrogen narcosis by the use of hydrogen as a substitute for nitrogen (the Arne ZetterstrÖm method for deep-sea diving). The Military Surgeon (United States). 1948 Aug 1;103(2):107-16.
 Dougherty JJ. Use of H2 as an inert gas during diving: pulmonary function during H2-O2 breathing at 7.06 ATA.Aviat Space Environ Med. 1976 Jun;47(6):618-26.
 Ohsawa I, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007 Jun;13(6):688-94.
 Ono H, et al. Hydrogen gas inhalation treatment in acute cerebral infarction: a randomized controlled clinical sStudy on safety and neuroprotection. J Stroke Cerebrovasc Dis. 2017 Nov;26(11):2587-94.
 Zhu Q, et al. Positive effects of hydrogen-water bathing in patients of psoriasis and parapsoriasis en plaques. Sci Rep. 2018 May 23;8(1):8051.
 Kajiyama S, et al. Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutr Res. 2008 Mar;28(3):137-43.
 Ishibashi T, et al. Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: a randomized, double-blind, placebo-controlled pilot study. Int Immunopharmacol. 2014 Aug;21(2):468-73.
 Nakao A, et al. Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study. J Clin Biochem Nutr. 2010 Mar;46(2):140-9.
 Korovljev D, et al. Hydrogen-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 Apr 11.
 LeBaron TW, et al. Acute supplementation with molecular hydrogen benefits submaximal exercise indices. Randomized, double-blinded, placebo-controlled crossover pilot study. J Lifestyle Med. 2019 Jan;9(1):36-43.
 Mizuno K, et al. Hydrogen-rich water for improvements of mood, anxiety, and autonomic nerve function in daily life. Med Gas Res. 2018 Jan 22;7(4):247-55.
 Yoritaka A, et al. Pilot study of H₂ therapy in Parkinson’s disease: a randomized double-blind placebo-controlled trial. Mov Disord. 2013 Jun;28(6):836-9.
 Kang KM, et al. Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors. Med Gas Res. 2011 Jun 7;1(1):11.
 Ichihara M, et al. Beneficial biological effects and the underlying mechanisms of molecular hydrogen – comprehensive review of 321 original articles. Med Gas Res. 2015 Oct 19;5:12.
 Ge L, et al. Molecular hydrogen: a preventive and therapeutic medical gas for various diseases. Oncotarget. 2017 Sep 21;8(60):102653-73.
 Ohta S. Molecular hydrogen as a novel antioxidant: overview of the advantages of hydrogen for medical applications. Methods Enzymol. 2015;555:289-317.
 Matei N, et al. Emerging mechanisms and novel applications of hydrogen gas therapy. Med Gas Res. 2018 Sep 25;8(3):98-102.
 Ren JD, et al. Molecular hydrogen inhibits lipopolysaccharide-triggered NLRP3 inflammasome activation in macrophages by targeting the mitochondrial reactive oxygen species. Biochim Biophys Acta. 2016 Jan;1863(1):50-5.
 Xie K, et al. Nrf2 is critical in the protective role of hydrogen gas against murine polymicrobial sepsis. Brit J Anaesthesia. 2012;108(3):538-9.
 Ishibashi T, et al. Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis: an open-label pilot study. Med Gas Res. 2012 Oct 2;2(1):27.
 Mäkinen H, et al. Definitions of remission for rheumatoid arthritis and review of selected clinical cohorts and randomised clinical trials for the rate of remission. Clin Exp Rheumatol. 2006 Nov-Dec;24(6 Suppl 43):S-22-8.
 Wu LL, et al. Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics. Clin Chim Acta. 2004 Jan;339(1-2):1-9.
 Qian L, et al. Methods of hydrogen application. In: Sun X, Ohta S, Nakao S, eds. Hydrogen Molecular Biology and Medicine. Dordrecht, Netherlands: Springer; 2015.
 Yamanaka H, et al. Serum matrix metalloproteinase 3 as a predictor of the degree of joint destruction during the six months after measurement, in patients with early rheumatoid arthritis. Arthritis Rheum. 2000 Apr;43(4):852-8.
 Ishibashi T, et al. Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: A report of three cases. Mol Med Rep. 2015 Aug;12(2):2757-64.
 Zhao M, et al. Hydrogen-rich water improves neurological functional recovery in experimental autoimmune encephalomyelitis mice. J Neuroimmunol. 2016 May 15;294:6-13.
 Liu Y, et al. Hydrogen-rich saline ameliorates experimental autoimmune encephalomyelitis in C57BL/6 mice via the Nrf2-ARE signaling pathway. Inflammation. 2019 Apr;42(2):586-97.
 Ishibashi T. Molecular hydrogen: new antioxidant and anti-inflammatory therapy for rheumatoid arthritis and related diseases. Curr Pharm Des. 2013;19(35):6375-81.
Share this post
Dr. Carrie Decker
The Power of Echinacea
A natural alternative for sneeze and sniffle prevention Perhaps you know it for its distinct flower – a pronounced brown central cone, surrounded by delicate purple petals – and its common botanical name, purple coneflower. Or maybe, you know it as a natural remedy to take for protection against the sniffles and sneezes of…
The Healing Power of Colostrum
From infants to top-notch athletes to the critically ill, this “first milk” provides immune and gastrointestinal benefits What’s the nutritional superfood almost all of us have had at some time in our life, and new mothers, dairy farmers, and Ob/Gyns know best? It’s colostrum, the first milk that comes at birth. It actually comes…
Health Benefits of Alpha-Lipoic Acid
Its use in weight management, metabolic syndrome, and diabetes Alpha-lipoic acid (ALA), also known simply as lipoic acid, is a naturally-occurring substance that is an essential cofactor for several enzymes. ALA, synthesized in the body from a medium-chain fatty acid known as octanoic acid, plays a key role in mitochondrial metabolism and energy production.,…
Lactobacillus rhamnosus GG: A Probiotic for All Ages
The benefits of L. rhamnosus GG for gut health and immunity Today’s probiotic story began in 1983, when Drs. Sherwood Gorbach and Barry Goldin, colleagues at Tufts University, were poring over stool specimens from healthy adults – a task few of us would envy. They managed to isolate “a strain of bacteria of a…
Vitamin D: The Sunshine Vitamin
The role of vitamin D in autoimmunity and mood Vitamin D is known as the “sunshine vitamin” because it is generated within the skin upon exposure to ultraviolet B (UVB) rays, the rays responsible for suntans. Vitamin D is essential for strong bones, immunity, and many other bodily functions.,, In the absence of sun…
How many psychotherapists does it take to change a light bulb? None. The light bulb has to want to change itself. This joke makes light of a prevailing truth about human psychology: the most powerful shifts happen when we are ready to lean in and change ourselves. There are all kinds of incentives out…