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A. Magnesium stick and the methods to generate hydrogen water in 500 ml bottles of drinking water. A plastic shelled product consisting of metallic magnesium (99.9% pure) and natural stones in the polypropylene containers combined with ceramics (Doctor SUISOSUI ® , Friendear, Tokyo, Japan) was used to produce hydrogen. The product was capable of generating hydrogen when placed in drinking water by the following chemical reaction; Mg + 2H2O → Mg (OH)2 + H2. B. Hydrogen concentrations in the water bottle (n = 3). The hydrogen concentration in a water bottle was maintained between 0.55 and 0.65 mM over an 8 week period.
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Metabolic syndrome is characterized by cardiometabolic risk factors that include obesity, insulin resistance, hypertension and dyslipidemia. Oxidative stress is known to play a major role in the pathogenesis of metabolic syndrome. The objective of this study was to examine the effectiveness of hydrogen rich water (1.5-2 L/day) in an open label, 8-w...
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Context 1
... product consisting of metallic magne- sium (99.9% pure) and natural stones in the polypropylene containers combined with ceramics (Doctor SUISOSUI ® , Friendear, Tokyo, Japan) was used to produce hydrogen. The product was capable of generating hydrogen when placed in drinking water by the following chemical reaction; Mg + 2H2O → Mg (OH)2 + H2 (Fig. 1). Hydrogen water sticks were dispensed at baseline and week 4 and used sticks were collected at week 4 and week 8 and compliance ...
Context 2
... is a possibility that the higher bilirubin levels are associated with the degradation of heme by heme oxygenase into equimolar quantities of biliverdin (bilirubin) and carbon monoxide (CO), while the central iron is released [28]. The induction of heme oxygenase (HO-1), which is the rate-limiting enzyme, catalyzes the degradation of heme [29]. Further studies are required to determine if hydrogen can induce HO-1. ...
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Citations
... On the other hand, molecular hydrogen (H2) is now recognized as a therapeutic gas for the treatment of many diseases [7,17]. Hydrogen rich water is used in clinical medicine to correct metabolic disorders and inflammation [3,9,20,27,28,32,45]. ...
Background and aim. The “Truskavetska” bottled water (TW) is officially classified as table water and is not considered medicinal. Recently, it rats experiment we found that enrichment of TW with Hydrogen generally has a favorable effect on its stress-limiting capacity, associated with antioxidant activity. We hypothesized that enrichment of TW with Hydrogen may increase its physiological/therapeutical activity, in particular in relation to patients with chronic pyelonephritis. Testing this hypothesis was the aim of this study. Material and methods. The object of observation were 22 men with chronic pyelonephritis. We determined the leukocyturia and bacteriuria levels and recorded EEG, HRV, phagocytosis, lipids peroxidation as well as routine hematological and biochemical blood parameters. The survey was conducted twice: on admission and after week of drinking of Naftussya bioactive water (NW) or TW by 200 mL for 1 hour before meals three times a day, or TW by 100 mL, mixed before use with 100 mL of regular water, but enriched with Hydrogen. Results. It was found that TW does not affect catalase activity and blood levels of α2-globulines and sialic acids, while NW significantly increases them; after enrichment of TW with Hydrogen, it partially acquires the properties of NW, although it is still significantly inferior to it. On the other hand, Hydrogen gives TW the ability to reduce blood levels of MDA, bilirubin, prothrombin and eosinophils, which also brings it closer to NW. Instead, hydrogen-enriched TW even slightly outperforms NW in terms of enhancing the intensity of blood neutrophils phagocytosis, increasing serum lysozyme activity and urinary amylase excretion, on the one hand, and reducing leukocyturia and bacteriuria, blood levels of CIC and HDLP cholesterol, as well as vagal tone, on the other hand. In addition, enrichment of TW with Hydrogen eliminates caused by it the decrease in the blood content of erythrocytes and hemoglobin and even reverses the decrease in the entropy of EEG and HRV as well as PSD of theta-rhythm in occipital loci. Conclusion. Enriching the low-activity "Truskavetska" bottled water with Hydrogen significantly increases its physiological activity to a level comparable to those of therapeutic Naftussya water, which is manifested in a favorable effect on leukocyturia and bacteriuria as well as phagocytosis, metabolism, and erythron in patients with chronic pyelonephritis.
... Redox refers to the chemical reactions in which the oxidation states of molecules are altered, often producing reactive species that influence cellular functions. In the context of the immunoredox model, the redox processes affect the body's microenvironment-referred to as the 'Field'which plays a pivotal role in regulating immune responses independently or in conjunction with immune cells ( (Zhang et al. 2021), and medical adoption of light (Kwasny 2022), gas (Li et al. 2023), and liquid (Nakao 2010). Under these conditions, the immune response varies from the normal milieu. ...
Human diseases may be a result of disruptions in homeostasis. Our previous studies suggest that, among several kinds of homeostasis, immune and redox homeostasis may be the most essential axis. Despite our cumulative reports to support the immunoredox model, still there has been neither theory nor review to explain the immunoredox model.
To address this, this review introduces the limitations of the existent immune recognition model, and enlighten the necessity, construction, and rationale of the new immunoredox model, as well as its application and implications for human disease and toxicology. Specifically, for the application to disease, comparison between immunoscore and immunoredox profiling was discussed as the first note.
Model-based Immunoredox profiling offers a comprehensive quantitative and qualitative analysis of immunokine and redox molecule interactions, focusing on the balance between immune and redox systems. This method facilitates the detection of subtle imbalances and abnormalities, enhancing the understanding, prediction, and evaluation of health issues arising from environmental toxins and inherent diseases. As a significant advancement in immunotoxicology, it provides critical insights into immune-toxicity interactions, supporting risk assessment and health mitigation strategies.
... Furthermore, participants experienced a 13 % decrease in total cholesterol/HDL cholesterol from baseline to week 4, and an 8 % increase in HDL cholesterol was observed. The study concluded that HRW drinking may be a preventive and therapeutic method for metabolic syndrome [78]. ...
Oxidative stress is responsible for the pathogenesis of many diseases, and antioxidants are commonly included in their treatment protocols. Over the past two decades, numerous biomedical reports have revealed the therapeutic benefits of molecular hydrogen (H 2) in relieving oxidation-related diseases. H 2 has been found to have selective antioxidant properties against the most dangerous oxidants (hydroxyl radicals and peroxynitrite). H 2 demonstrates numerous biologically therapeutic properties, including anti-inflammatory, antioxidant, anti-cancer, anti-stress, anti-apoptotic, anti-allergic effects, signaling molecule functions, regulation of redox balance, modulation of antioxidant enzyme gene expression, improvement of blood vessel function, down-regulation of pro-inflammatory cytokines, stimulation of energy metabolism, and protection of the nervous system. Experimental and clinical studies have shown the potential use of hydrogen nutrition therapy for ameliorating various diseases, including cardiovascular, respiratory, and metabolic disorders, as well as obesity, gastrointestinal disorders, and brain and nervous system disorders. The administration methods of hydrogen include inhalation, hydrogen-rich water, hydrogen-rich saline, hydrogen-rich eye drops, and hydrogen-rich bathing. Hydrogen nutritional therapy can be applied to different diseases, and it offers a natural alternative to chemical and radiation therapies. This review covers the different administration methods and the latest experimental and clinical research on the potential applications of H 2 in nutritional therapy for different diseases.
... When these metals react with water, they release hydrogen gas, which can then dissolve in the water. This chemical reaction that can be described by the chemical equation Mg + 2H2O → Mg(OH)2 + H2 (Nakao et al., 2010). This method is less common for consumer applications but is effective in controlled environments. ...
... HW has been shown to increase serum levels of the hormone ghrelin , which stimulates metabolism. In another study, in patients with metabolic syndrome, consumption of 1.5 to 2 liters of HW increased the antioxidant superoxide dismutase by 39%, reduced urinary thiobarbituric acid by 43%, increased high-density lipoprotein cholesterol by 8% and reduced total cholesterol by 13% (Nakao et al., 2010). Consumption of HW of a high concentration has been shown to significantly reduce blood cholesterol and glucose levels, improve biomarkers of inflammation and redox homeostasis (biomarkers). ...
Hydrogen-enriched water has been attracting growing attention due to its potential health benefits, although a consensus on its effects has yet to be reached. The aim of this study is to assess the scientific literature regarding the advantages, effects on diseases, and possible risks associated with the consumption of hydrogen-enriched water. This review involved searches through the PubMed, Taylor & Francis, and Google Scholar databases, focusing on 69 scientific articles published in English since 2010. These articles underwent a descriptive analysis to evaluate their content and conclusions. Recent studies have provided substantial evidence confirming the health benefits of hydrogen-enriched water. Significant improvements have been reported in patients with conditions such as myocardial infarction, various cancers (including lung, liver, colorectal, and gallbladder), asthma, chronic obstructive pulmonary disease, cerebral ischemia, rheumatoid arthritis, and non-alcoholic fatty liver disease. Furthermore, hydrogen-enriched water has been shown to enhance the well-being of haemodialysis patients and positively affect lifestyle-related diseases like type 2 diabetes and obesity by lowering blood glucose levels and improving metabolic function and nutrient absorption. Hydrogen can help manage immunity and even alleviate symptoms of COVID-19. Hydrogen-enriched water has also been associated with enhanced endurance, accelerated muscle recovery following exercise, and, to a lesser extent, improved athletic performance. Regular consumption of hydrogen-rich water has been linked to delayed cellular aging, improvements in skin health, and reduced ultraviolet (UV) damage, primarily through its antioxidative properties and the stimulation of type I collagen synthesis in the skin. The analysis of available data confirms that hydrogen-enriched water is safe for consumption in healthy individuals and is legally approved for use. However, individuals with underlying health conditions are advised to consult a healthcare professional before incorporating hydrogen-enriched water into their routine.
... The study demonstrates that hydrogen-rich water enhances stress resistance and physical endurance in rats, corroborating previous research on hydrogen's applications in sports medicine (Botek et al., 2021;Botek et al., 2019). The strong correlation between antioxidant enzyme activity and metabolic-endocrine and immune parameters indicates that hydrogen's primary mechanism of action operates through antioxidant pathways, explaining a substantial portion of the physiological changes observed (Nakao et al., 2010;Gao et al., 2017). This suggests that the antioxidant properties of hydrogen are central to its role in stress protection and performance enhancement, aligning with findings that hydrogen-rich water can increase antioxidant enzyme levels and reduce oxidative stress markers Dobashi et al., 2020). ...
... The study highlights the significant role of hydrogen-enriched water in mitigating stress-induced neuroendocrine changes, particularly by minimizing sympathetic tone and maintaining normal levels of corticosterone and catecholamines. This suggests that hydrogen enrichment contributes to homeostatic balance under stress conditions, extending beyond metabolic parameters to include immune system factors (Nakao et al., 2010;Hrytsak et al., 2022). The unexpected positive correlation between swimming duration and lipid peroxidation products, alongside a negative correlation with corticosterone levels, indicates complex interactions within stress response systems, challenging simplistic interpretations of antioxidant mechanisms (Nakao et al., 2010;Melnyk et al., 2021). ...
... This suggests that hydrogen enrichment contributes to homeostatic balance under stress conditions, extending beyond metabolic parameters to include immune system factors (Nakao et al., 2010;Hrytsak et al., 2022). The unexpected positive correlation between swimming duration and lipid peroxidation products, alongside a negative correlation with corticosterone levels, indicates complex interactions within stress response systems, challenging simplistic interpretations of antioxidant mechanisms (Nakao et al., 2010;Melnyk et al., 2021). Furthermore, the synergistic effects observed with "Truskavetska" mineral water imply that hydrogen enrichment can enhance the therapeutic properties of existing treatments, suggesting promising applications in balneotherapy and sports medicine (Hrytsak et al., 2022;Badiuk et al., 2021). ...
Background and aim. Despite the use of drinking hydrogen rich water both in clinical and sports medicine, further research into the mechanisms of its beneficial effect remains relevant. We found that both Naftussya bioactive water per se and combined balneotherapy have an ambiguous effect on physical performance. It was also found that the preventive use of “Truskavetska” bottled water, the chemical composition of which is somewhat similar to that of Naftussya bioactive water, has both similar and different effects on the post-stress parameters of rats. We set ourselves the goal of finding out the possibility of correcting the effect of "Truskavetska" bottled water on the post-stressor state of the neuro-endocrine-immune complex, as well as the endurance of rats by enriching it with hydrogen. Material and methods. The experiment is at 26 female Wistar rats purposefully divided into three homogeneous (according to the swimming test and HRV parameters) groups. 5 animals remained intact with free access to regular daily water. Rats of the control group (n=4) for 7 days loaded through a tube with “Truskavetska” bottled table water (2 mL once), while the animals of main group (n=17) received the same water, but enriched with Hydrogen. After completing the preconditioning course, a repeated swimming stress test was performed. The next day after stressing, a number of parameters of the neuro-endocrine-immune complex and metabolism were recorded. Results. Hydrogen rich water (HRW) minimizes the post-stressor increase in sympathetic tone and adrenal mass, and prevents the increase in catecholamines and corticosterone as well as plasma cells in the blood and rod-shaped neutrophils in the spleen. On the other hand, HRW prevents a post-stressor decrease in the intensity of macrophage phagocytosis and the bactericidal capacity of blood microphages, the content of lymphoblasts in the thymus, the activity of both antioxidant enzymes and vagal tone, and also minimizes the decrease in the content of eosinophils in the blood, non-alpha-lipoprotein cholesterol in the serum, and the mass of the spleen, in addition, the reduced content of plasma cells in the spleen reverses to an excess. Finally, the non-stress-responsive parameters of the control animals: the activity of AlT, CPhK, AsT and diene conjugates of the serum, the content of reticulocytes and Hassal’s bodies in the thymus - under the influence of HRW increase to one degree or another. Importantly, this also applies to the duration of swimming until exhaustion. A strong canonical correlation was found between the activity of antioxidant enzymes, on the one hand, and metabolic-endocrine (R=0.959) and immune (R=0.959) sets, on the other hand. Conclusion. Enrichment of "Truskavetska" bottled table water with hydrogen generally has a favorable effect on its stress-limiting and actotropic capacity, associated with antioxidant activity.
... The chemical reaction for hydrogen-rich water is [35]: ...
The present study investigated the 1H Nuclear Magnetic Resonance (NMR) spectra of hydrogen-rich water (HRW) produced using the EVObooster device. The analyzed HRW has pH = 7.1 ± 0.11, oxidation–reduction potential (ORP) of (−450 ± 11) mV, and a dissolved hydrogen concentration of 1.2 ppm. The control sample was tap water filtered by patented technology. A 600 NMR spectrometer was used to measure NMR spectra. Isotropic 1H nuclear magnetic shielding constants of the most stable clusters (H2O)n with n from 3 to 28 have been calculated by employing the gauge-including-atomic-orbital (GIAO) method at the MPW1PW91/6-311+G(2d,p) density function level of theory (DFT). The HRW chemical shift is downfield (higher chemical shifts) due to increased hydrogen bonding. More extensive formations were formed in HRW than in control filtered tap water. The exchange of protons between water molecules is rapid in HRW, and the 1H NMR spectra are in fast exchange mode. Therefore, we averaged the calculated chemical shifts of the investigated water clusters. As the size of the clusters increases, the number of hydrogen bonds increases, which leads to an increase in the chemical shift. The dependence is an exponential saturation that occurs at about N = 10. The modeled clusters in HRW are structurally stabilized, suggesting well-ordered hydrogen bonds. In the article, different processes are described for the transport of water molecules and clusters. These processes are with aquaporins, fusion pores, gap-junction channels, and WAT FOUR model. The exponential trend of saturation shows the dynamics of water molecules in clusters. In our research, the chemical shift of 4.257 ppm indicates stable water clusters of 4–5 water molecules. The pentagonal rings in dodecahedron cage H3O+(H2O)20 allow for an optimal arrangement of hydrogen bonds that minimizes the potential energy.
... Recent studies have shown that H 2 can be applied in the treatment of a variety of diseases including cancer, metabolic diseases and organ ischemia/reperfusion injury. [206][207][208] Numerous studies also suggest that H 2 impedes tumor cell activity, proliferation, invasion and migration dose-and time-dependently and promotes apoptosis in cervical, breast and cutaneous melanoma. [209][210][211] Further evidence also indicates that H 2 can significantly alleviate the progression of lung cancer, colon cancer, ovarian cancer, thymic lymphoma, Ehrlich ascites tumor cells, oral squamous cell carcinoma (OSCC) and fibrosarcoma cells, reduce tumor volume and weight and suppress tumor growth in xenografted mice. ...
Pyroptosis is an inflammatory cell death induced by inflammasomes that release several pro-inflammatory mediators such as interleukin-18 (IL-18) and interleukin-1β (IL-1β). Pyroptosis, a type of programmed cell death, has recently received increased interest both as a therapeutic and immunological mechanism. Numerous studies have provided substantial evidence supporting the involvement of inflammasomes and pyroptosis in a variety of pathological conditions including cancers, nerve damage, inflammatory diseases and metabolic conditions. Researchers have demonstrated that dysregulation of pyroptosis and inflammasomes contribute to the progression of endometriosis and gynecological malignancies. Current research also indicates that inflammasome and pyroptosis-dependent signaling pathways may further induce the progression of endometrial cancer (EC). More specifically, dysregulation of NLR family pyrin domain 3 (NLRP3) and caspase-1-dependent pyroptosis play a contributory role in the pathogenesis and development of EC. Therefore, pyroptosis-regulated protein gasdermin D (GSDMD) may be an independent prognostic biomarker for the detection of EC. This review presents the molecular mechanisms of pyroptosis-dependent signaling pathways and their contributory role and function in advancing EC. Moreover, this review offers new insights into potential future applications and innovative approaches in utilizing pyroptosis to develop effective anti-cancer therapies.
... Hydrogen-rich water demonstrated an increase in systemic antioxidant activity, although blinding was not present in this study [41]. Similar findings for hydrogen-rich water have been observed in other domains, notably increasing antioxidant activity to induce beneficial lipid profiles in subjects at risk of metabolic syndrome which were also seen in people with type 2 diabetes or impaired glucose tolerance [44,45]. To a lesser degree curcumin also increased antioxidant capacity with a moderate effect size (Figure 3) [32]. ...
... • C: No pharmaceutical supplementation with the same exposure to ionizing radiation[38][39][40][41][42][43][44][45][46][47].• O: Functional, biochemical or clinical outcomes to ionizing radiation[48][49][50][51][52][53][54][55][56][57]. ...
The negative effects of ionizing radiation on healthy tissue pose a medical challenge for both human space exploration as well as terrestrial medicine. Therefore, understanding the effectiveness of current treatments is important both in the application of current medicine and the development of new therapeutics. Health supplements are used widely in or by consumers to prevent the occurrence of symptoms following radiotherapy. To evaluate the possible efficacy of health supplements and their potential for use during deep space exploration, a systematic literature review was conducted. A search of PubMed, Cochrane Library and OVID (Medline) databases was conducted, identifying 77 studies that examined therapeutic effects of health supplements on ionizing radiation, of which 15 were eligible for inclusion in the analysis. Health supplements provided no beneficial effects to either functional or biochemical physiological outcomes. However, symptomatic relief was found in a range of irradiated areas of the body from a variety of health supplements following irradiation. The localized actions of both the radiotherapy and the health supplement means further investigations would be required before using these health supplements to protect against whole-body radiation exposure. Further investigations should also focus on the health supplements shown to have the greatest positive effects to address the lack of clinical consensus.
... Due to the transmission route of H2 through ingestion of HRW, the most pronounced effects have been described in conditions that affect the gastrointestinal tract and supporting organs such as GERD (Franceschelli et al., 2018), IBD (Chen et al., 2013) and metabolic syndrome (Nakao et al., 2010). To illustrate the favourable effects HRW imbibition has on the digestive system, an eight-week open-label pilot study reports that ingestion of 1. 5L of H2 (55-65mM) increases endogenous levels of SOD and reduces the excreted levels of MDA in patients with metabolic syndrome (Nakao et al., 2010). ...
... Due to the transmission route of H2 through ingestion of HRW, the most pronounced effects have been described in conditions that affect the gastrointestinal tract and supporting organs such as GERD (Franceschelli et al., 2018), IBD (Chen et al., 2013) and metabolic syndrome (Nakao et al., 2010). To illustrate the favourable effects HRW imbibition has on the digestive system, an eight-week open-label pilot study reports that ingestion of 1. 5L of H2 (55-65mM) increases endogenous levels of SOD and reduces the excreted levels of MDA in patients with metabolic syndrome (Nakao et al., 2010). During an empirical study assessing the effect of hydrogen on the peristaltic movement of the intestinal tract, a reduction in the strength of muscular contraction was observed, signifying reduced colonic transit (Chen et al., 2011). ...
Molecular hydrogen (H2) and oxyhydrogen (66% H2/ 33% O2) gases can remediate the effects of numerous diseases in adults. By acting as an anti-inflammatory and antioxidative agent, it is reported that H2 administration can improve recovery through mitigating the hyperinflammatory response and reducing oxidative stress. As the precise mechanisms of H2 activity are currently undefined, the lack of primary target identification, coupled with difficulties regarding administration methods (e.g., dosage and dosage frequencies, and long-term effects of treatments), there is a requirement for H2 research to evidence whether it should, and how it can reasonably and effectively, be incorporated into healthcare. To better understand the molecular mechanism(s) behind the activity of H2, and to ascertain whether H2 can be utilised as an effective nutraceutical, this treatise investigates the modality of action, and effects of H2, using a range of bioinformatical, theoretical and empirical approaches. The question of how H2 may reach distal somatic sites, and the subsequent cellular effects are also discussed. Before using oxyhydrogen gas to assess the effects of H2 on immortalised B-lymphocytes, nematodes and seeds; the gas-purity, flow-rate, and infusion limits of the HydroVitality™ alkaline water electrolyser were evaluated. Exposing cells to dissolved oxyhydrogen gas in cell media identified a trend of replicative inhibition of TK6-malignant cells with a single infusion. Further analysis detailed a significant increase in DNA in the Sub G1 phase, indicating increased apoptosis. Additionally, evidence described in this thesis identifies a possible evolutionary relationship between subunits of Complex 1 (mitochondria) and hydrogenase enzymes of ancient archaeal and bacterial species. In conclusion, this study encompasses a range of theories incorporating the evolutionary requirement of H2, how H2 may interact at a molecular level in plants and humans, and the effect of H2 administration on malignant cells, by providing novel experimental protocols and innovative theories into the biological activity of H2.
... Several studies suggest that hydrogen might directly impact the signaling pathways that activate AMPK. For example, it has been demonstrated that hydrogen influences upstream kinases that activate AMPK, such as liver kinase B1 (LKB1) and calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) [32,33]. Hydrogen may facilitate the activation of AMPK and enhance its role in regulating cellular energy by modulating these kinases. ...
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by excessive fat accumulation in the liver. Intracellular oxidative stress induced by lipid accumulation leads to various hepatocellular injuries including fibrosis. However, no effective method for mitigating MASLD without substantial side effects currently exists. Molecular hydrogen (H2) has garnered attention due to its efficiency in neutralizing harmful reactive oxygen species (ROS) and its ability to penetrate cell membranes. Some clinical evidence suggests that H2 may alleviate fatty liver disease, but the precise molecular mechanisms, particularly the regulation of lipid droplet (LD) metabolism, remain unclear. This study utilized an in vitro model of hepatocyte lipid accumulation induced by free fatty acids (FFAs) to replicate MASLD in HepG2 cells. The results demonstrated a significant increase in LD accumulation due to elevated FFA levels. However, the addition of hydrogen-rich water (HRW) effectively reduced LD accumulation. HRW decreased the diameter of LDs and reduced lipid peroxidation and FFA-induced oxidative stress by activating the AMPK/Nrf2/HO-1 pathway. Overall, our findings suggest that HRW has potential as an adjunctive supplement in managing fatty liver disease by reducing LD accumulation and enhancing antioxidant pathways, presenting a novel strategy for impeding MASLD progression.
