Clinical Effects of Hydrogen Administration: From Animal and Human Diseases to Exercise Medicine

Nicolson, Garth L.; Ferreira, Gonzalo; Settineri, Robert; Costa, Carlos Henrique Nery; Ellithorpe, Rita R.; Rosenblatt, Steven; Valle, James La; Jiménez, Antonio; Ohta, Shigeo

doi:10.4236/ijcm.2016.71005

Cited by 55 publications

(63 citation statements)

References 310 publications

(468 reference statements)

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“…Molecular hydrogen has been shown to be useful in the treatment of various medical conditions and as an antiaging supplement [22,23]. Here we examined the effects of a commercial source of hydrogenized water on cultured human brain cells.…”

Section: Resultsmentioning

confidence: 99%

“…Hydrogenized water has been shown to act as a cellular antioxidant and gene regulator [22,23]. Previously we found that hydrogenized water was an effective cellular antioxidant and could decrease transport of glucose in a dose-and time-dependent manner and elevate the levels of phosphorylation of Akt, a protein kinase B biomarker for insulin signaling [24].…”

Section: Introductionmentioning

confidence: 99%

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Hydrogenized Water Effects on Protection of Brain Cells from Oxidative Stress and Glutamate Toxicity

Settineri¹,

Zhou²,

Jin³

et al. 2019

AJFN

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Hydrogenized water is known to have protective effects on cells and tissues, mainly through its antioxidant activities. Here we examined the protective effects of a commercial source of hydrogenized water on cultured human brain cells. Hydrogenized water was able to protect brain cells from oxidative stress and glutamate toxicity. At H 2 concentrations above 0.01 mM the glutathione levels increased in cultured brain cells. The level of glutathione rose from approximately 500 to approximately 850 μM at the maximum dose of hydrogenized water with an EC 50 of approximately 0.030 mM. Hydrogenized water was also able to enhance the signaling pathway for oxidative stress response mediated by Nrf2 (Nuclear factor erythroid 2 like factor). Treatment of cells with hydrogenized water at concentrations above 0.01 mM H 2 induced activation of Nrf2 (EC 50 approximately 0.05 mM). Hydrogenized water was also able to protect brain cells against glutamate toxicity. Using a DNA damage response element, (γH2AX, to monitor the damage of glutamate toxicity we found that concentrations of H 2 above 0.01 mM protected cells from glutamate damage with an EC 50 of approximately 0.05 mM H 2 . These in vitro results demonstrated that hydrogenized water can protect brain cells against common types of damage from oxidative stress and glutamate toxicity.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hydrogenized Water Effects on Protection of Brain Cells from Oxidative Stress and Glutamate Toxicity

Settineri¹,

Zhou²,

Jin³

et al. 2019

AJFN

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“…A very safe and effective method to control oxidative stress and reduce inflammation during mycoplasma treatment is the use of hydrogenized water [160]. Molecular hydrogen reduces oxidative stress and cytotoxic oxygen radicals by a gene regulation mechanism not by direct interactions [161].…”

Section: Modifying Mycoplasma Microenvironmentsmentioning

confidence: 99%

“…Hydrogenized water does not interfere with conventional or integrative therapies against mycoplasmas. It can be easily consumed orally without need to worry about contraindications [160].…”

Section: Modifying Mycoplasma Microenvironmentsmentioning

confidence: 99%

Pathogenic Mycoplasma Infections in Chronic Illnesses: General Considerations in Selecting Conventional and Integrative Treatments

Nicolson¹

2019

IJCM

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The presence of pathogenic mycoplasmas in various chronic illnesses and their successful suppression using conventional and integrative medicine approaches are reviewed. Evidence gathered over the last three decades has demonstrated the presence of pathogenic mycoplasma species in the blood, body fluids and tissues from patients with a variety of chronic clinical conditions: atypical pneumonia, asthma and other respiratory conditions; oral cavity infections; urogenital conditions; neurodegenerative and neurobehavioral diseases; autoimmune diseases; immunosuppressive diseases; inflammatory diseases; and illnesses and syndromes of unknown origin, such as fatiguing illnesses. Only recently have these small intracellular bacteria received attention as possible causative agents, cofactors or opportunistic infections or co-infections in these and other conditions. Their clinical management is often inadequate, primarily because of missed diagnosis, underand inadequate treatment and the presence of persister or dormant microorganisms due to biofilm, resistence and other mechanisms. Pathogenic Mycoplasma species infections have been suppressed slowly by anti-microbial and integrative treatments, resulting in gradual reductions in morbidity, but not in every patient. Even if mycoplasmas are not a cause or an initial trigger for many chronic illnesses, they appear to play important roles in the inception, progression, morbidity and relapse of chronic illnesses in rather large patient subsets. Ignoring such infections can result in failure to achieve eventual patient recovery, even with application of potentially curative treatments.

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“…It has also been demonstrated that H 2 rapidly diffuses across cell membranes and is an effective ·OH radical scavenger in cultured cells and this has been related to its ability to rapidly diffuse across cell membranes. Since then, numerous studies have focused on understanding the potential therapeutic value of hydrogen and hydrogen-rich water in various disease models [12,13].…”

Section: Introductionmentioning

confidence: 99%

Effects of Hydrogenized Water on Intracellular Biomarkers for Antioxidants, Glucose Uptake, Insulin Signaling and SIRT 1 and Telomerase Activity

Settineri¹,

Jin²,

Luo³

et al. 2019

AJFN

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Hydrogen has been shown in several clinical trials to be completely safe without adverse events and there are no warnings in the literature of its toxicity or adverse effects during long-term exposure. Molecular hydrogen has proven useful and convenient as a novel antioxidant and modifier of gene expression in many conditions where oxidative stress and changes in gene expression result in cellular damage. Our intracellular biomarker studies have shown that a hydrogenized water drink formula containing 2.6 ppm dissolved hydrogen was able to penetrate cellular membranes and function as an antioxidant in human liver cells (HePG2) utilizing the Cellular Antioxidant Assay (CAA). This assay uses the protection of a florescent probe as a marker for cellular damage by reactive oxygen species (ROS), such as peroxyl radical, and compares this to the known antioxidant standard, Quercetin. Using this system oxidative damage was reduced in a dose-dependent manner. One ml of hydrogenized water was found to possess antioxidant capacity equivalent to 0.05 µmole of quercetin. When examined in a human colon cell line (Caco-2 cells), hydrogenized water demonstrated a dose-and time-dependent permeability inhibition of an intracellular fluorescent glucose derivative (2-NBDG), indicating decreased glucose uptake. In another study, the impact of hydrogenized water on Akt phosphorylation (Ser473), a biomarker for insulin signaling, was monitored in human skeletal muscle cells. The hydrogenized water treatment markedly elevated the level of phosphorylation of Akt (Ser473) in a dose-dependent manner. The anti-aging effects of hydrogenized water were examined utilizing SIRT1 expression as a biomarker of aging in human umbilical cells (HUVECs). Hydrogenized water increased dose-dependent SIRT1 gene expression. Hydrogenized water also increased telomerase activity (an anti-aging biomarker in HUVEC cells) up to 148% when cells were treated with media containing 25% hydrogenized water formula. Increased telomerase activity caused by hydrogenized water may be able to protect telomeres from degradation, suggesting the possible use of hydrogenized water in therapeutic interventions of age-related diseases. These studies show that commercial hydrogenized water improved the levels or activities of a few intracellular biomarkers specific for antioxidant activity, glucose uptake, insulin signaling and SIRT 1 and telomerase activities. Industrial Relevance: The molecular hydrogen used in this study indicates that certain commercial sources of hydrogenized water can provide similar antioxidant and gene expression modifications seen in other sources of molecular hydrogen. The biomarkers evaluated here lend well to hydrogenized water's biological activity relating to health conditions and aging.

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Clinical Effects of Hydrogen Administration: From Animal and Human Diseases to Exercise Medicine

Cited by 55 publications

References 310 publications

Hydrogenized Water Effects on Protection of Brain Cells from Oxidative Stress and Glutamate Toxicity

Hydrogenized Water Effects on Protection of Brain Cells from Oxidative Stress and Glutamate Toxicity

Pathogenic Mycoplasma Infections in Chronic Illnesses: General Considerations in Selecting Conventional and Integrative Treatments

Effects of Hydrogenized Water on Intracellular Biomarkers for Antioxidants, Glucose Uptake, Insulin Signaling and SIRT 1 and Telomerase Activity

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