Hydrogen therapy as treatment and prevention - a report from Norway, 2023.

The present summarizing medical report reached the H2MEDICAL team thanks to an inquisitive gentleman from Plovdiv, who previously acquired our device, had informed himself quite well on the subject. Thanks for the useful information! The document was published on November 28, 2023. by doctors in Oslo, Norway. It is based on a large number of clinical studies and shows the impressive therapeutic effect of hydrogen therapy in many severe and socially significant diseases. Results of clinical observations in people with oncological, cardiovascular, respiratory, neurological and other pathologies are presented. Due to the large volume of information, our team presents the most important points translated into Bulgarian, namely: Introduction and results of research by disease groups. If you would like to read the contents of the full medical report, click on this link: Molecular Hydrogen Therapy - Review of Clinical Trials and Results /see report/

Due to its antioxidant properties, hydrogen gas (H2) has been evaluated “in vitro”, in animal and human studies for a wide range of therapeutic indications. A basic search for "hydrogen gas" in various medical databases revealed more than 2,000 publications related to hydrogen gas as a potential new drug substance. A parallel search of clinical trial registries also yielded many results reflecting the diversity of ongoing clinical trials involving hydrogen therapy. The purpose of the current report is to evaluate and discuss the current findings on hydrogen therapy in 81 identified clinical trials and 64 human observational scientific publications. Positive indications have been found in major disease areas including cardiovascular, cancer, respiratory, central nervous system diseases, infections and many others.

1. Introduction to Hydrogen Therapy

The most commonly used medical gases include medical air, oxygen, nitrogen, nitrous oxide, and carbon dioxide, and hydrogen gas (H2) is emerging as a promising new element with unique antioxidant properties. It has been shown to selectively counteract harmful reactive oxygen species (ROS), such as the hydroxyl radical. Hydrogen (H2) can maintain tissue homeostasis and may be clinically more useful than strong antioxidants that neutralize both beneficial and harmful species indiscriminately. Originally used as a diving gas around 1970, H2 was believed to be non-toxic and biologically inert [2]. Interest in using H2 to treat diseases has increased since its antioxidant properties were discovered in 2007 [3]. Since then, over 2,000 scientific publications have elucidated its therapeutic promise from in vitro, in vivo animal and human studies.

An expanding literature confirms the therapeutic effects of H2, and clinical trials are being conducted in major disease areas such as cardiovascular, respiratory, and cancer, with an emphasis on diseases associated with ROS accumulation. H2 is the smallest molecule with a molecular weight of only 2 Da, a kinetic diameter of 289 pm [5] and a density of about 0.089 g/L [6]. Because of this, it can easily penetrate biological membranes and spread throughout the body, including the brain. Commercially, H2 is primarily generated by electrolysis for industrial and environmental fuel applications. Hydrogen enriched water is produced with specialized H2 generating machines and H2 water enrichment products such as magnesium effervescent tablets are now sold worldwide and marketed with health benefits. The global hydrogen production market size was estimated at USD 155.35 billion in 2022 [9]. Yet its medical utility remains a fraction of that figure.

2. Methods

Published scientific literature related to hydrogen therapy was identified by specific searches using the terms “hydrogen therapy,” “medical use of hydrogen,” and “hydrogen gas” in combination with “human study” and “clinical trial” in several databases with easily searchable publications including the PubMed platform. Scientific articles written in a language other than English and those studying the effects of alkaline ionized water on humans were excluded. An overview of clinical trials was collected from the International Clinical Trial Registry of the US Department of Health and Human Services (National Institutes of Health, National Library of Medicine), the Japanese Pre-Registration System for Approved Clinical Trials (UMIN, University Hospital Medical Information Network ). Relevant clinical trials were found by searching for 'hydrogen', 'hydrogen gas' and 'H2' (studies on 'hydrogen peroxide' and 'hydrogen breath test' were excluded). Publications related to clinical trials were also included in the present review. This research resulted in 47 and 34 clinical trials, from clinicaltrials.gov and UMIN, respectively, and 64 publications on human studies (in addition to several relevant animal and in vitro studies). A review article published in 2015 summarized the clinical trials up to that year, and therefore the present summary focuses mainly on the clinical data obtained after 2015 [10]. Inhalation was the dominant method of administration, followed by ingestion of fortified water. with H2 (hydrogen water), infusion of H2-enriched saline. Hydrogen bath/eye drops and H2-dialysis have also been used in several studies.

3. Human safety when applying H2

Ensuring safety is the most important consideration when the goal is clinical translation of a new drug substance. Unlike other medical gases such as carbon dioxide, nitrous oxide, and hydrogen sulfide, H2 does not bind to hemoglobin in the bloodstream, so it does not cause heme-related toxic effects. Extensive animal studies have shown that the administration of H2 is safe. A mixture of H2:O2 or H2:O2:He gas has been used by deep-sea divers to prevent decompression sickness for a long time, thus also confirming the safety for humans of inhaling H2. Two studies from 1988 and 1994 concluded that breathing mixtures containing 49–56% H2 during dives to 450–500 m below sea level can relieve some symptoms of high pressure nervous syndrome and confirm the safety of use [11,12].

4. Efficacy results of H2 administration in human studies

The efficacy of H2 administration has been reported in at least 64 peer-reviewed scientific publications, which are qualitatively reviewed below; many, but not all, are the result of clinical trials. In the following presentation, the articles are categorized into sections according to the main research areas of the disease. These categories include cardiovascular, cancer, respiratory, CNS, lifestyle-related infections, and other diseases and quantitatively discuss findings from human studies.

5.1. Cardiovascular diseases

Cardiovascular diseases are a leading cause of death worldwide [14] and need new therapies. Several clinical studies have concluded that inhaling or drinking H2 can improve cardiovascular disease outcomes, most in combination with standard treatments. An early phase/initial clinical trial evaluated the effect of inhalation of 2% H2 gas, combined with target temperature control, in a total of ten patients with post-myocardial infarction syndrome. Inhalation of H2 has been found to maintain a favorable neurological outcome in patients. However, 90-day follow-up was significantly better in the hydrogen group compared to the control [18]. In another study involving five patients with post-cardiac arrest syndrome who were given the same treatment as above, arterial H2 concentration was measurable and indications of reduced levels of oxidative stress and cytokines were found [19]. A slightly larger study involving 20 patients found beneficial effects of hydrogen therapy on adverse left ventricular remodeling after percutaneous coronary intervention in post-myocardial infarction patients. At 6-month follow-up after initiation of treatment with inhalation of 1.3% hydrogen, the improvement in left ventricular stroke volume index and ejection fraction was numerically greater than in the control group. H2 has also been shown to be a beneficial modulator of blood vessel function. Flow-mediated dilation was significantly improved in patients who ingested hydrogen water (concentration 7 ppm = 7 mg/L) compared to the placebo water group [21]. These studies show that inhaling gas with a low concentration of H2 and drinking water rich in H2 may be beneficial in treating heart and vascular diseases, respectively.

5.2. Cancer

Cancer is the second leading cause of death in the world today [14]. H2 is administered to cancer patients to control tumor progression, for combination therapy, and to alleviate the side effects and adverse effects of standard cancer treatment for a variety of cancers. In addition, administration of H2 has been shown to promote antitumor immune responses. Figure 3 summarizes the benefits of hydrogen therapy in cancer patients. Two separate case studies in patients with cancer and multiple metastases show tremendous effects of hydrogen inhalation therapy. One of the patients suffered from recurrent carcinoma of the gallbladder and received daily inhaled H2 therapy. During the first month, the tumors continued to progress after a gradual decrease in tumor size and tumor marker levels that eventually returned to normal. After about two and a half months, the patient resumed his normal life and recovery was reported after 10 months. A pseudoprogressive remission was observed after H2 therapy, which may resemble the pattern that occurs after PD-1 antibody treatment. This suggests that H2 may influence the immune system [22,23]. The other case was a patient with non-small cell lung cancer who underwent hydrogen gas inhalation as monotherapy after oral and surgical treatment had stabilized the first lesions. Brain metastases decreased in size after four months of H2 treatment and completely disappeared after one year. Liver and lung metastases were also stabilized after one year and survival was prolonged [24]. These case studies are important clinical observations and show that H2 induced significant tumor control after standard cancer treatments had failed.

A clinical trial involving 58 patients with advanced non-small cell lung cancer reported in 2020 that hydrogen therapy alleviated lung symptoms compared to a control group that did not receive H2 treatment. The hydrogen group was administered H2 by inhalation for 4–5 hours per day for 5 months. The same hydrogen treatment is also given to patients with non-small cell lung cancer in combination with chemotherapy, targeted therapy or immunotherapy. After 16 months, progression-free survival was higher for the hydrogen-only treatment group and significantly higher for all combined treatment groups (hydrogen + chemistry) compared to the control group [25]. Another study reported benefits of H2 treatment in 42 lung cancer patients treated with Nivolumab. A significantly longer overall survival was found with the combination treatment with H2 gas compared to those treated with Nivolumab alone. It has been suggested that the two therapeutic agents may exhibit synergistic effects as mitochondrial activators [26]. It is reasonable to treat lung cancer with H2 inhalation to target the site of disease, although systemic effects have been observed. Other cancers that have shown positive results from H2 therapy by inhaling H2 saline or drinking hydrogen water include liver, nasopharyngeal, and colorectal cancers [27,28,29], as well as head and neck cancers (see Table 1).

Interesting immunomodulatory effects of H2 administration have been observed in cancer patients. A high proportion of immune cells of the CD8+ T cell type expressing the programmed cell death-1 (PD-1) protein is often observed in cancer patients and may be associated with a poor cancer prognosis. PD-1 is an immune checkpoint receptor that protects against autoimmunity and is often involved in immunotherapy treatment (PD-1 inhibitors) because it causes the immune system to "surveill" cancer cells. Administration of H2 has been shown to reduce the proportion of PD-1+ CD8+ T cells in the blood of cancer patients. This has been observed in both late-stage colorectal carcinoma patients and lung cancer patients in separate clinical trials, and H2 has been shown to improve cancer prognosis in both patient groups [26,29]. Furthermore, H2 may improve the efficacy of Nivolumab treatment in cancer patients with high levels of PD-1+ CD8+ T cells who previously had a poor response to Nivolumab [26]. A significant decrease in the proportion of PD-1+ CD8+ T-cells after treatment with H2 inhalation was also observed in a case study of a patient with gallbladder carcinoma [22]. Loss of immunological activity in CD8+ T cells may be due to mitochondrial dysfunction, in which H2 has been found to be an important factor in its recovery. Colorectal carcinoma patients treated with combined hydrogen therapy and "Nivolumab" showed significantly longer overall survival compared to patients treated with "Nivolumab" alone [30]. Another study found that patients with non-small cell lung cancer who inhaled H2:O2 (2:1) without other treatments led to the restoration of normal levels of six subsets of cells involved in our immune system, including cytotoxic T cells, T helper cells and natural killer cells [31]. From these positive results, the use of H2 may be interesting in combination with immunotherapy to modulate immune responses to cancer cells.

In addition to the direct effects of H2 therapy in controlling tumor progression, several cell and animal studies [32,33,34,35] have shown that H2 can be effective in alleviating side effects without reducing the antitumor activity of the standard cancer treatment. The multiple side effects can be perceived as devastating to the quality of life of both cancer patients and survivors. Therefore, clinical studies have investigated the effect of H2 on damage induced by chemotherapy and radiotherapy. A study of 134 patients with colorectal cancer found that hydrogen-enriched water (hydrogen water) alleviated liver damage induced by mFOLFOX6 chemotherapy [36]. Patients with non-small cell lung cancer undergoing chemotherapy, targeted therapy, or immunotherapy treatment experienced a reduction in side effects after administration of H2, and in some even disappeared [25].

Radiation therapy is an important treatment for several cancers. Side effects of radiotherapy are often associated with increased generation of ROS free radicals, which can potentially be reduced with hydrogen therapy. One study tested whether six weeks of hydrogen water intake improved the quality of life of 49 patients with liver tumors who had received radiotherapy. Consumption of H2-enriched water has been shown to reduce radiation-induced oxidative stress without implicating the antitumor effects of radiotherapy. Quality of life scores were significantly improved in patients receiving hydrogen therapy in combination with radiotherapy compared to patients receiving placebo water [27]. An observational study found that inhaled H2 treatment could significantly alleviate radiation-induced bone marrow damage by reducing white blood cell and platelet levels without compromising antitumor effects [37]. Adverse reactions such as difficulty swallowing, brain damage and hearing loss are often seen after radiotherapy for nasopharyngeal cancer. Three patients with nasopharyngeal cancer were reported to have moderate to extremely severe hearing loss and required hearing aids after radiotherapy. Patients received H2 administered by inhalation for four hours each day (2:1 = H2:O2). After 1-2 months, the patient's binaural hearing had improved significantly and one of the patients no longer needed a hearing aid [28]. These findings are promising, but more research is needed to reach definitive conclusions.

5.3. Respiratory diseases

When the leading causes of death are listed worldwide, respiratory diseases are in third place [14] and they still need new pharmaceutical solutions. A helium-oxygen gas mixture has been used for decades to treat obstructive pulmonary disease due to its lower density, higher viscosity, and reduced airway resistance compared to conventional nitrogen-oxygen mixtures [38]. Using an oxygen-hydrogen mixture has similar effects, in addition to the therapeutic antioxidant effects of H2.

In 2020, a study that investigated the acute effects of inhaling a gas mixture containing hydrogen found that the inflammatory status in patients with asthma and COPD was attenuated by the treatment. The trial included 20 patients with asthma and COPD who inhaled a 2.4% H2-containing vapor mixture over a single inhalation period of 45 minutes. This treatment significantly reduced inflammatory markers such as monocyte chemotactic protein 1, IL-4 and IL-6 levels in patients with COPD and asthma [39]. In 2021, a larger clinical trial was conducted with 108 patients with acute exacerbation of COPD receiving H2:O2 or O2 therapy. They showed an impressive improvement in symptoms in the H2:O2 group with significant results in certain test scores [40], indicating that COPD is an interesting indication for hydrogen therapy. Another 2018 clinical trial evaluated the efficacy and safety of H2 inhalation in patients with acute severe tracheal stenosis. Thirty-five patients were administered a H2:O2 (2:1) gas mixture for 15 min and 120 min (6 L/min) in two consecutive breath steps. All measured endpoints, except vital signs, improved after H2 inhalation, including inspiratory effort assessed by electromyography of the diaphragm (EMGdi), transdiaphragmatic pressure (Pdi), Borg score and impulse oscillometry (IOS) [41]. These clinical studies show that H2 inhalation is a promising option for the treatment of respiratory diseases, which is a suitable method of application, both to the damaged tissue and for patient convenience, since breathing devices are often used by patients with respiratory diseases. In addition, inhalation of H2 has also been tested in patients infected with COVID-19 for the treatment of respiratory symptoms, with very promising results (see section 6.5).

5.4. Diseases of the central nervous system

Conditions affecting the central nervous system (CNS) represent one of the major public health challenges today. Dementia and other diseases causing cognitive decline are associated with an aging population, which is a growing problem, and new drugs to treat these diseases are urgently needed. Molecular hydrogen is the smallest molecule and its very small size and non-polar nature make it highly diffusible. It can even cross the blood-brain barrier, which is a major obstacle for medical treatment of the brain [8].

Several clinical studies have investigated the effects of hydrogen therapy on acute brain damage caused by heart problems, all of which have shown benefits from H2 administration. In one study, thirty-seven patients with low-grade subarachnoid hemorrhage were given H2-enriched solution by infusion for 14 days along with intracisternal magnesium sulfate infusion or intracisternal magnesium sulfate infusion alone. The incidences of cerebral vasospasm and delayed cerebral ischemia were significantly lower in the hydrogen therapy treatment groups. It also had additional effects by reducing serum malondialdehyde, a marker of oxidative stress, reduced biomarkers of neuronal damage, and improved physical therapy through the Barthel index [42]. In another study, 25 patients with cerebral infarction were given hydrogen inhalation treatment (3% H2 gas) for one hour twice a day. The H2 inhalation group, compared to the placebo control group, showed significant effects on lower relative MRI signal, indicating reduced impairment, neurological improvement as observed by NIHSS scores, and improved Barthel index scores [43].

Clinical trials with hydrogen therapy have also been conducted in patients with cognitive disorders, including Alzheimer's and Parkinson's disease, as reduced neurodegeneration has been observed in several animal studies with H2 [46,47,48]. In one study, 73 patients with mild cognitive impairment who drank 300 mL of hydrogen water or placebo water daily for one year and then measured their scores on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog ). The study found that carriers of the apolipoprotein E4 (APOE4) genotype significantly improved their overall ADAS-cog scores after drinking hydrogenated water compared to a control group drinking plain water. This shows that genetic variation can affect how subjects respond to hydrogen treatment. Another study involving eight patients diagnosed with Alzheimer's disease showed that inhalation of 3% hydrogen alleviated symptoms and had disease-modifying effects. Improvements in ADAS-cog scores and neuronal integrity monitored by diffusion tensor imaging (DTI) were significant at 6-month follow-up, but non-significant at one year, compared to untreated patients [50].

5.5. Infections

The rise of hydrogen therapy came when the coronavirus pandemic began in 2019 (COVID-19) and spread globally. Inhalation of hydrogen (H2) has been used to treat respiratory-related symptoms of COVID-19 in several clinical trials, primarily for the same reasons as its use in other respiratory conditions, namely reducing gas density and airflow resistance. However, the studies do not rule out the possible beneficial antioxidant effects of H2.

A pioneering clinical study conducted with 100 patients in seven different Chinese hospitals found overwhelmingly positive results of continuous inhalation of a 2:1 H2:O2 gas mixture (3 L/min) in all endpoints compared to standard oxygen treatment. The primary endpoint was disease severity, and the secondary endpoints were dyspnea, cough, chest distress, chest pain, and oxygen saturation, and all were significantly improved after only two days of treatment compared to the control group [55]. These excellent results led to the inclusion of this specific treatment (H2:O2 inhalation of 2:1 hydrogen oxyhydrogen) as a recommendation by the Chinese National Health Commission in the Chinese Clinical Guideline for the Diagnosis and Treatment of COVID-19 Pneumonia (7th Edition )' [56 ], in addition to standard oxygen therapy. This practice did not appear to have gained worldwide attention in the fight against COVID-19, and additional clinical trials were conducted. A study published in 2022 investigated the use of hydrogen therapy in the rehabilitation of 50 patients with acute post-COVID-19 syndrome. They found significant improvements in 6-minute walk test distance, forced vital capacity, and expiratory volume when hydrogen was administered by inhalation. The protocol describes home inhalation of 100% H2 at a low flow rate (250 mL/min) for 60 minutes twice a day for two weeks [57].

5.6. Lifestyle conditions and exercises

Hydrogen therapy is also used in the treatment of lifestyle and metabolic conditions, which is a growing problem in the increasing percentage of the population who are overweight. Many studies have indicated the beneficial effects of hydrogen therapy in relation to sports performance and impairment, including forms of administration such as inhalation of H2, drinking of hydrogen water, and topical application of H2. A pilot study found that oral ingestion of hydrogen water prevented the rise in blood lactate and reduced muscle fatigue during heavy exercise in ten elite male soccer players and showed that it may be an appropriate means of hydration in athletes [63]. Another study involving eight male cyclists found similar results, oral hydrogen water intake improved performance in intermittent cycling exercise when the duration was greater than 30 minutes (anaerobic) [64]. A clinical trial involving ten men and ten women found an increase in peak running speed of up to 4.2% in the run time test to exhaustion after seven days of inhalation of 4% H2 for 20 min each day [65]. One study showed that drinking hydrogen water before and after strenuous exercise reduced the exercise-induced increase in ROS levels in eight male volunteers. This may help prevent accumulative muscle fatigue, although exercise performance was not significantly different over the two 3-day back-to-back exercise tests compared to placebo water [66]. A larger study examined the effects of drinking H2-fortified water immediately prior to exercise on an ergometer in healthy untrained (n = 99) and trained (n = 60) participants. They found that hydrogen water, compared to placebo water, increased endurance and alleviated psychometric fatigue as measured by maximal oxygen consumption and the Borg and visual analog scales, respectively [67]. Furthermore, healing of acute sports-related soft tissue injuries was positively affected by both oral and topical H2 treatment for 2 weeks, in addition to standard care [68]. Tossing the coin of high-level exercise, hydrogen therapy has also been studied for the management of lifestyle-related disease conditions. Intake of 1–2 L of hydrogen water per day has been shown to reduce ROS levels and contribute to the reduction of body fat in obese individuals [69] as well as the management of lipid and glucose metabolism in patients with type 2 diabetes [70] and metabolic syndrome [71,72,73,74].

6.7. Other diseases and conditions

Outside of the major disease areas discussed here, several clinical studies examining H2 in other indications associated with high levels of oxidative stress have been reported. Rheumatoid arthritis is an autoimmune disease characterized by chronic inflammation and destruction of bones and cartilage. Increased levels of hydroxyl radicals are believed to be involved in the pathogenesis for which hydrogen therapy has a selective scavenging effect. Both drinking hydrogen water and injecting H2-enriched saline have been tested for the treatment of rheumatoid arthritis in separate clinical trials. In one study, twenty patients took 530 ml of hydrogen water per day for 4 weeks in two separate periods. In another study, 24 patients were randomly assigned to H2-saline or placebo-saline, which was administered intravenously by drip infusion at 500 ml daily for 5 days. The results of both studies showed that hydrogen significantly reduced biomarkers of oxidative stress (eg, urinary 8-hydroxydeoxyguanine) and the Disease Activity Score in 28 joints (DAS28), via C-reactive protein levels. This was accompanied by significant improvements in rheumatoid arthritis symptoms [75,76]. Chronic graft-versus-host disease can also be considered an autoimmune disease. A longer-term study over 12 months found therapeutic effects of daily drinking of H2-rich water at a dose of 12 ml/kg. Of the 24 enrolled patients, 18 had an objective response measured in seven sites (skin, mouth, gastrointestinal tract, liver, eyes, lungs, and joints and fascia) using the National Institutes of Health Consensus Form ( NIH) to measure therapeutic response for chronic graft-versus-host disease. Survival time and survival rate at 4 years were significantly prolonged in the responder group compared to the non-responder group. There is currently no standard therapy for patients with chronic graft-versus-host disease refractory or dependent on corticosteroid treatment, and therefore H2 may be a good option [77].

Another global health problem without any approved drugs is non-alcoholic fatty liver disease (NAFLD), causing liver dysfunction. Metabolic damage plays a major role in the pathogenesis of NAFLD, so pharmaceuticals that accelerate lipid and glucose metabolism are of interest for the treatment of this disease. Hydrogen probably has these properties, as evidenced by the results of clinical trials in patients with diabetes and metabolic syndrome. NAFLD may also be associated with inflammation, excessive oxidative stress, and abnormal cell signaling. Two separate clinical trials investigated the effect of oral hydrogen water intake at a dose of 1 L/day. One included 12 subjects and found that after one month, hydrogen therapy significantly reduced liver fat accumulation compared to a placebo group, with no significant differences in body weight and composition [78]. The second study included 30 subjects and lasted 2 months, finding nonsignificant decreases in levels of NAFLD disease markers, as well as weight and body mass index. Interestingly, non-significant trends towards increases in markers of oxidative stress (8-hydroxy-2'-deoxyguanosine and malondialdehyde) were also found, which was explained by the hormetic effects of H2 occurring before significant clinical improvements in the long term [79]. ]. Another study tested 13-week inhalation of a H2:O2 (2:1) gas mixture at a rate of 3 L/min for 1 h/day in 43 NAFLD patients with moderate-severe cases. Improvements in serum lipids and liver enzymes and significantly improved liver fat content were found. Further studies in mouse models revealed that this effect of H2 is likely caused by promoting hepatic autophagy [80].

Some specific conditions have been studied for the effect of hydrogen through other forms of administration such as dialysis solutions and through the eyes. One study demonstrated significant effects of using H2 solutions during cataract surgery (phacoemulsification) to restore vision. The procedure uses ultrasound, which produces free radicals that can potentially be neutralized with H2-enriched solutions. Thirty-two patients with cataracts in both eyes were treated with the conventional method in one eye and using H2-enriched solution in the other eye. Rates of decline in endothelial cell density, the primary endpoint, were significantly lower in the H2 group at all time points measured [81].

Hemodialysis patients suffering from chronic inflammation have poor prognoses and therapeutic approaches are limited. Therefore, the anti-inflammatory properties of H2 can be used in the dialysis solution for these patients. Two studies performed by the same research group, published in 2010 and 2018, investigated the effects of H2-enriched dialysate, with H2 from water electrolysis, in the treatment of hemodialysis patients. In the 2010 study, 21 patients were switched to H2-enriched dialysis solution for 6 months, resulting in a significant reduction in systolic blood pressure compared to before the test period. A significant reduction in plasma markers of inflammation was also found [82]. The 2018 study was longer-term and included a larger test group of 161 and 148 patients who received H2-enriched and conventional dialysis solutions, respectively, over a 3.3-year observation period. In both studies, H2 caused minimal changes in dialysis parameters, but positive outcomes, including improved blood pressure control and reduced inflammatory responses, may improve prognosis in chronic hemodialysis patients.

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