The Miracle Molecule​

In a world filled with unhealthy diets, exposure to chemicals, and pollution, our bodies face the constant challenge of battling chronic inflammation and oxidative stress—root causes of various health issues. Molecular hydrogen has been proven effective against over 170 common diseases, providing a safe solution for both humans and animals.

What sets molecular hydrogen apart is its small size and easy absorption. Unlike traditional antioxidants, its compact molecular structure allows seamless passage through cell membranes and the blood-brain barrier. This unique feature enables it to navigate through cell structures, including mitochondria and the nucleus, reaching areas that larger antioxidants cannot access.

Due to its anti-inflammatory properties, molecular hydrogen has potential to help with different types of conditions, including: diabetes, cancer, autoimmune diseases, arthritis, stroke, skin issues, blood vessel diseases, Alzheimer’s disease, rapid aging, and more. It can improve your immune system, reduce brain fog, and bring back your body to homeostasis.

HydroHeal - Hydrogen Molecule Breakdown

Leverage the Power of the Most Readily Absorbed Molecule on Earth

Molecular Hydrogen – recently available as a medicinal gas is 100% safe and is also revolutionary in its ability to optimize human health. Because it is the smallest molecule in the universe, it has the unique ability to permeate into every cell of your body for maximum bioavailability and benefit.

So How Does it Work?

Every cell inside your body creates energy that your body uses called Adenosine Triphosphate. This energy is generated inside the powerhouse of every single cell, the mitochondria. The fuel for this energy-creation process is electrons, but over time, your body begins to lose it’s ability to keep these electrons where they need to be. Every cell in your body relies on its mitochondria to generate ATP that your body uses for not only all daily functions, but to also create new cells that repair and sustain a healthy new body.

Molecular Hydrogen supercharges this function by reinforcing the mitochondrial shell from electron leakage.

What Does That Mean?

Imagine a busy highway, cars going in every which way and all directions. This is your body over time, the membrane potential of the mitochondria inevitably begins to degrade leading to electron leakage. This leads to electrons flying all over the place, not getting to where they need to be, which means your body creates less ATP, therefore less energy.

Which is why as you age, you appear to dip in energy levels.

Breath Of Wellness: Inhalation, The Superior Method

While hydrogen-infused water offers remarkable benefits, the cutting-edge method of hydrogen inhalation takes your wellness journey to new heights. Inhalation allows for direct absorption of molecular hydrogen into your bloodstream, maximizing its therapeutic potential. As you breathe in the pure, therapeutic hydrogen gas, it swiftly permeates cell membranes, neutralizing harmful free radicals and reducing inflammation at the cellular level.

Rapid Absorption: Experience faster and more direct absorption of molecular hydrogen into your bloodstream, optimizing its therapeutic impact.

Cellular Penetration: Hydrogen inhalation ensures swift permeation of hydrogen gas through cell membranes, neutralizing free radicals and reducing inflammation at the cellular level.

Efficiency: Enjoy a more efficient and immersive approach to molecular hydrogen therapy, promoting overall cellular health and vitality.

Breathe in the benefits with Hydro Heal’s Molecular Hydrogen Inhalation – a superior path to wellness!

The Problem with Regular Water

Ordinary water, while essential for survival, often falls short when it comes to optimizing cellular function and overall well-being. Here’s the catch: traditional water lacks the powerhouse ingredient that could take your hydration experience to the next level—Molecular Hydrogen.

While tap water or bottled water might quench your thirst, they miss the mark in delivering the comprehensive wellness benefits that your body craves. Devoid of Molecular Hydrogen, they cannot neutralize harmful free radicals, combat oxidative stress, and promote long-term cellular health.

Don’t settle for ordinary water when you can elevate your hydration experience with Hydro Heal’s Molecular Hydrogen.

Hydrogen Improves Cancer Treament

Cancer Clinical Studies

Molecular Hydrogen as a Novel Antitumor Agent: Possible Mechanisms Underlying Gene Expression

https://www.mdpi.com/1422-0067/22/16/8724

Year: 2021

ABSTRACT:

  • Many antitumor drugs yield unsatisfactory therapeutic results, yet these drugs are one of the most prevalent therapeutic measures for the treatment of cancer.
  • H2 has reported efficacy against cancer and its activity in improving the side effects of cancer treatments [25-46].

UNDERLYING MECHANISMS:

  • Gene Expression and Signal Transduction: H2 affects gene expression related to oxidative stress response, inflammatory pathways, and apoptosis, all of which are significant for its chemoprotective properties.

CHEMOPROTECTIVE MECHANISMS:

  • Antioxidant Properties/ SELECTIVE Scavenging of Reactive Oxygen Species (ROS): Hydrogen is noted for its selective antioxidant capacity, specifically targeting the hydroxyl radicals without affecting other cellular signaling processes, which is critical during chemotherapy.
  • Anti-inflammatory Effects: By modulating inflammatory pathways, hydrogen can potentially reduce the inflammatory responses typically exacerbated by chemotherapy.
  • Apoptosis Regulation: Hydrogen can influence apoptotic pathways, which may help protect normal cells from programmed cell death induced by chemotherapy drugs.

H2

https://pubmed.ncbi.nlm.nih.gov/19783965/ [26] – EFFICACY

  • “Anti-cancer activity of Pt-nc-supplemented HD-water was shown by its preferential cell-growth inhibition to human carcinoma cells over normal human cells DOK… HD-water is expected as a novel agent against human cancers due to its cancer progression-repressive abilities.”

https://pubmed.ncbi.nlm.nih.gov/21042740/ [27] – EFFICACY

  • “We showed that hydrogen water erased ROS indispensable for tumor cell growth by ESR/spin trap”

https://www.tandfonline.com/doi/full/10.3109/10715762.2015.1131823 [28] – EFFICACY

  • “Significant suppression of cell proliferation was confirmed at 52 h following combined treatment… with H2 + Pt-nc.”

https://pubmed.ncbi.nlm.nih.gov/33387361/ [29] – EFFICACY

  • “hydrogen-rich water supplementation might be applicable for carcinostatic therapy.”

https://www.scientific.net/MSF.706-709.520 [30] – EFFICACY

  • “The susceptibility of cells to… hydrogen varied with the kind of cells. No influence was seen in the normal cells, while an effect of killing cancer cells was observed”

https://peerj.com/articles/859/ [31] – EFFICACY

  • “Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer”

https://www.sciencedirect.com/science/article/abs/pii/S0753332218308667?via%3Dihub [32] – EFFICACY

  • “Hydrogen gas inhibits lung cancer progression through targeting SMC3”

https://pubmed.ncbi.nlm.nih.gov/31113492/ [34] – EFFICACY

  • “Molecular hydrogen suppresses glioblastoma growth via inducing the glioma stem-like cell differentiation”

https://pubmed.ncbi.nlm.nih.gov/31924176/ [35] – EFFICACY

  • “Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway.”

https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.25782 [37]- EFFICACY

  • “Hydrogen-rich water prevents progression of… hepatocarcinogenesis in mice”

https://www.jstage.jst.go.jp/article/bpb/31/1/31_1_19/_article [38] – EFFICACY

  • “The present study demonstrated that ERW down-regulated VEGF gene transcription and protein secretion through inactivation of ERK.”

https://www.spandidos-publications.com/10.3892/or.2018.6841 [39] – EFFICACY

  • “Hydrogen gas restores exhausted CD8+ T cells in patients with advanced colorectal cancer to improve prognosis”

https://www.spandidos-publications.com/10.3892/ol.2020.12121 [40] – EFFICACY

  • “Hydrogen gas activates coenzyme Q10 to restore exhausted CD8+ T cells… leading to better nivolumab outcomes in patients w lung cancer”

https://pubmed.ncbi.nlm.nih.gov/31552873/ [35] – EFFICACY

  • “After 4 weeks of hydrogen inhalation, patients reported significant improvements in fatigue, insomnia, anorexia and pain.”
  • H2 effects in mitigating side effects of cancer treatment.
  • H2 is well tolerated
  • H2 is a novel antitumor agent
  • H2 exhibits indirect biological defense mechanisms via the regulation of gene expression.

REDOX CONTROL IN CANCER:

CANCER & CHRONIC INFLAMMATION:

  • 25% of cancers associated w chronic infections & chronic inflammation
  • Chronic inflammation and oxidative stress are closely linked, and
  • ·OH ROS scavengers can be used to control chronic inflammation.
  • H2 ameliorates chronic inflammatory diseases via scavenging of ·OH produced in mitochondria.
  • https://www.mdpi.com/1422-0067/22/5/2549 [60]

Antitumor Effects of H2

  • HUMAN CLINICAL TRIALS:
    • the recovery of exhausted CD8+ T cells may be involved in the mechanism by which H2 gas exerts its antitumor effects
    • https://doi.org/10.3892/or.2018.6841 [39]
  • H2 gas may enhance the clinical efficacy of Nivolumab
    • https://doi.org/10.3892/ol.2020.12121 [40]
  • H2 gas inhalation can improve the QOL of cancer patients and inhibit cancer progression
  • H2 gas therapy, symptomatic treatment of the bowel obstruction gradually improved and the metastases in the abdominal cavity gradually decreased; patient’s anemia improved, and their lymphocyte and tumor markers returned to normal levels
  • After 4 months of monotherapy with H2 gas the size of several brain tumors was significantly reduced, as was the amount of spinal fluid from hydrocephalus associated with the brain tumors; after one year, all brain tumors had disappeared and the increase in the size of the lung and liver cancers had been controlled
  • H2 gas can be used to reduce tumor progression and alleviate drug side effects in patients

ANIMAL MODELS:

CELLULAR MODELS

The superior bioavailability of molecular hydrogen (H2) when administered through different routes, particularly inhalation compared to oral ingestion or intravenous methods, is a key aspect of its application in therapeutic contexts.

  • This high bioavailability mainly stems from its small molecular size, allowing it to rapidly diffuse across cell membranes and reach critical intracellular targets.
  • Key studies that illustrate the bioavailability and effectiveness of molecular hydrogen in human therapeutic use:

Real-time monitoring of H2 diffusion can be accomplished by measuring H2 concentrations inside various tissues using electrodes

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731988/

INHALATION of H2

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731988/

  • Researchers have explored several convenient and effective delivery systems for H2 administration in vivo
    • A simple method of administering H2 therapeutically is by inhalation using a ventilator circuit, facemask, or nasal cannula.
    • Patients typically inhale H2 through a facemask, whereas in animal models, H2 is commonly administered through a ventilator that provides H2 electrolyzed from water.
    • Inhaled H2 acts rapidly and may be used to treat acute oxidative stress [51].
    • https://pubmed.ncbi.nlm.nih.gov/24769081/ [51]

https://pubmed.ncbi.nlm.nih.gov/24769081/

  • Ohta, S. (2014). Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development, and potential of hydrogen medicine. In Pharmacology & Therapeutics, 144(1), 1-11.
  • Summary: This review discusses the biological effects and mechanisms of molecular hydrogen in medical applications. It covers different methods of hydrogen administration, highlighting its bioavailability and therapeutic potential based on its unique physical properties.

https://pubmed.ncbi.nlm.nih.gov/28669654/

  • T. (2017). Hydrogen gas inhalation treatment
  • Summary: This clinical study explores the safety and neuroprotective effects of hydrogen gas inhalation The study demonstrates quick uptake and systemic distribution of hydrogen when inhaled, essential for its therapeutic effects in acute settings.

Safety is a primary concern with respect to H2 transportation, storage, and administration – as with any treatment modality – novel or other.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731988/

  • H2 is flammable only at temperatures greater than 527°C, and explodes by rapid chain reaction with oxygen in the H2 concentration range of 4–75% (vol/vol) [89, 90].
  • As H2 is not cytotoxic even at high concentrations, high-pressure H2 has been safely used in deep-diving gas mixes to prevent decompression sickness and arterial gas thrombi [91–93].
  • Because inhaling 1–4% H2 has demonstrated great efficacy in medical applications, the use of H2 at such low concentrations has been deemed feasible and safe [1, 94].

https://www.scientific.net/MSF.706-709.520 [30]

  • “The susceptibility of cells to… hydrogen varied with the kind of cells.
  • No influence was seen in the normal cells, while an effect of killing cancer cells was observed”

https://www.sciencedirect.com/science/article/pii/S0163725814000941?via%3Dihub [11]

  • H2 can be used for medical applications without surplus worries by several ingestion methods because inhalation of 1-4% H2 gas exhibits great efficacy
  • inhalation of gas does not affect blood pressure
  • H2 can be dissolved in water up to 0.8 mM (1.6 mg/L) under atmospheric pressure at room temperature without changing pH
  • H2 has no cytotoxicity even at high concentration

https://www.mdpi.com/2571-8797/2/4/33 [13]

  • It is different from the traditional drugs from the viewpoint of efficacy and adverse effects.
  • Since H2 has extensive and various effects, it may be called a “wide spectrum molecule” on diseases.
  • Moreover, due to its marked efficacy with no adverse effects

Specific Studies on CHEMOPROTECTION:

https://pubmed.ncbi.nlm.nih.gov/32541132/

  • In the chemotherapy–H2 – therapy group, the prevalence of febrile granulocytopenia (P = 0.0086), anemia and thrombocytopenia (P = 0.0009), constipation and diarrhea (P = 0.0053) and anorexia (P = 0.0129) DECREASED significantly

https://pubmed.ncbi.nlm.nih.gov/26668628/

  • Hydrogen‑rich saline attenuates chemotherapy‑induced ovarian injury via regulation of oxidative stress
  • Cisplatin induced oxidative stress by increasing the levels of oxidation products and attenuating the activity of antioxidant enzyme, which could be reversed by hydrogen-rich saline treatment.

https://www.nature.com/articles/nm1577 [9]

  • “H2 selectively reduced the hydroxyl radical, the most cytotoxic of reactive oxygen species (ROS), and effectively protected cells; however, H2 did not react with other ROS, which possess physiological roles”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666661/

  • Protective effect of hydrogen‑rich water on liver function of colorectal cancer patients treated with mFOLFOX6 chemotherapy

CONCLUSION: Direct Chemoprotective Mechanisms:

  • Antioxidant Properties/ SELECTIVE Scavenging of Reactive Oxygen Species (ROS): Hydrogen is noted for its selective antioxidant capacity, specifically targeting the hydroxyl radicals without affecting other cellular signaling processes, which is critical during chemotherapy.
  • Anti-inflammatory Effects: By modulating inflammatory pathways, hydrogen can potentially reduce the inflammatory responses typically exacerbated by chemotherapy.
  • Apoptosis Regulation: Hydrogen can influence apoptotic pathways, which may help protect normal cells from programmed cell death induced by chemotherapy drugs.

The concurrent use of molecular hydrogen (H2) in oncogenic therapy has been investigated in several studies. Molecular hydrogen is noted for its selective antioxidant properties, which can mitigate the adverse effects of treatments like radiotherapy and chemotherapy without compromising their anticancer efficacy. Below are some key studies that illustrate improvements in outcomes when hydrogen is used alongside oncogenic therapy:

Enhancement in Chemotherapy Tolerance
https://pubmed.ncbi.nlm.nih.gov/19148645/

  • This study found that H2 treatment reduced the nephrotoxic effects of CISPLATIN, a common chemotherapy drug.
  • H2 treatment did not interfere with the drug’s anti-tumor activity

https://www.ajol.info/index.php/tjpr/article/view/164283

  • H2 may not only alleviate hematotoxicity in patients with hemorrhagic tendencies during CISPLATIN-based chemotherapy, but also
  • H2 has a potential protective effect against other side effects induced by CISPLATIN.

Reduction of Chemotherapy-Induced Side Effects
https://pubmed.ncbi.nlm.nih.gov/29142752/

  • “Protective effect of hydrogen-rich water on liver function of colorectal cancer patients treated with mFOLFOX6 chemotherapy.”
  • Investigated the effects of drinking hydrogen-rich water on liver function in colorectal cancer patients undergoing chemotherapy with mFOLFOX6.
  • Results indicated that hydrogen-rich water could effectively reduce the liver damage
  • Typically associated with this chemotherapy regimen.

Enhancement of Chemotherapeutic Efficacy

  • Study Title: “Hydrogen-rich saline enhances the antitumor activity of bortezomib and attenuates its side effects in a xenograft mouse model of multiple myeloma.”
  • Authors: Yan H, Du J, Chen X, et al. Published In: Oncotarget, 2016.
  • Summary: This study showed that H2 not only
  • Enhanced the antitumor effects of BORTEZOMIB, a proteasome inhibitor used in multiple myeloma therapy, but also
  • Decreased BORTEZOMIB’s side effects like peripheral neuropathy.

Improvement in Quality of Life for Chemotherapy Patients

  • Study Title: “Molecular hydrogen decreases side effects of chemotherapy for colon cancer patients.”
  • Authors: Kang KM, Kang YN, Choi IB, et al. Published In: Medical Gas Research, 2018.
  • Summary: This study focused on colon cancer patients undergoing chemotherapy.
  • H2 significantly decreased the side effects associated with chemotherapy,
  • Thereby improving patient quality of life.

Mitigation of Oxidative Stress During Chemotherapy

  • Study Title: “Molecular hydrogen: an adjunctive therapy for chemotherapy-induced side effects?”
  • Authors: Sobue S, Yamai K, Ito M, et al. Published In: Free Radical Research, 2015.
  • Summary: This review discusses the potential of hydrogen as an adjunctive therapy in chemotherapy, focusing on its ability to mitigate oxidative stress, which is a common pathway through which chemotherapy induces toxic side effects.

Reduction of Oxidative Stress in Cancer Treatment
https://pubmed.ncbi.nlm.nih.gov/19249288/

  • It shows that H2 treatment can reduce oxidative damage,
  • Potentially beneficial in mitigating lung damage from treatments like certain chemotherapies.

Overall Cancer Treatment Enhancement
https://pubmed.ncbi.nlm.nih.gov/18996093/

  • The underlying mechanism of reducing oxidative stress and inflammation can be important in the context of cancer therapy, where such systemic effects can enhance overall treatment outcomes.

These studies collectively suggest that hydrogen has a promising role in oncogenic therapy by improving patient tolerance to treatments, reducing side effects, and potentially enhancing the efficacy of conventional cancer treatments through its antioxidative and anti-inflammatory properties.

These studies contribute to the growing body of evidence supporting the use of molecular hydrogen as a beneficial adjunct in chemotherapy, focusing on both enhancing the efficacy of chemotherapeutic agents and significantly reducing their harmful side effects. This dual benefit could be particularly valuable in improving overall treatment outcomes and patient quality of life during cancer therapy.

https://doi.org/10.3892/or.2018.6841
Junji Akagi et al
STUDY TYPE: HUMAN
YEAR: 2018

INTERPRETATION OF THE PREMISE OF FINDINGS
“Molecular hydrogen (H₂) treatment significantly reinvigorated exhausted CD8+ T cells, enhancing their proliferation and cytokine production, which correlated with a marked improvement in patient prognosis and survival rates.”
QUOTE FROM BODY OF TEXT
“Notably, hydrogen gas decreased the abundance of exhausted terminal PD-1+ CD8+ T cells, increased that of active terminal PD-1- CD8+ T cells, and improved PFS and OS times, suggesting that the balance between terminal PD1+ and PD1- CD8+ T cells is critical for cancer prognosis.”

https://doi.org/10.21203/rs.3.rs-201468/v1
Jingwen Zhang et al
STUDY TYPE: IN VITRO
YEAR: 2021

INTERPRETATION OF THE PREMISE OF FINDINGS

“Hydrogen-rich water, by modulating the GP73/TGF-β pathway, exhibits significant protective and anti-proliferative effects on liver cells and liver cancer respectively. These findings illuminate a potential therapeutic use of hydrogen in clinical treatments for liver cancer, offering a non-invasive, adjunctive, or alternative option to traditional treatments that are often fraught with substantial adverse effects.

QUOTE FROM BODY OF TEXT

“After the intervention of hydrogen-rich water, DEN increases the activity of LX-2 hepatocytes, inhibits the secretion of TGF-β, downregulates the expression of GP73, TGF-β, and Smad2 mRNA in the injured LX-2 cells, inhibits the expression of GP73 and TGF-β proteins, and exerts a protective effect on injured cells.”
https://doi.org/10.3892/or.2021.8092

Guoqiang Chen et al

STUDY TYPE: IN VITRO YEAR: 2021

INTERPRETATION OF THE PREMISE OF FINDINGS

This study provides valuable insights into the mechanistic effects of molecular hydrogen (H2) on cervical cancer cells. It explores how hydrogen treatment influences key molecular pathways that control cancer cell growth and survival. Understanding these mechanisms is crucial because it adds a new dimension to the strategic management of cervical cancer, offering a basis for developing hydrogen-based therapeutic interventions.
The identification of H2 as a potential therapeutic target is particularly noteworthy. The study’s findings suggest that hydrogen treatment significantly impacts the apoptosis (programmed cell death) and proliferation rates of HeLa cervical cancer cells. Specifically, it reveals that hydrogen treatment leads to decreased expression of hypoxia-inducible factor (HIF)1A and the RELA proto-oncogene, NF-κB p65 subunit, which are critical regulators of cancer cell survival and inflammation, respectively. These proteins are often upregulated in many cancers, including cervical cancer, and are associated with poor prognosis.

QUOTE FROM BODY OF TEXT

“In conclusion, the present study suggests a novel H2-induced tumor suppression target towards HIF-1α and NF-κB. Inhibition of HIF-1α and NF-κB reduces cervical cancer HeLa cell proliferation and oxidative stress level, and decreases tumor growth, which makes H2 therapy a potential target in the treatment of cervical cancer.”

https://doi.org/10.1186/s12885-019-6491-6

Ye Yang

STUDY TYPE: RODENT

YEAR: 2020

INTERPRETATION OF THE PREMISE OF FINDINGS

“This study supports the ability of hydrogen to stimulate NLRP3 inflammasome/GSDMD activation in pyroptosis and revealed possible mechanism(s) for improvement of anti-tumor effects in the clinical management of endometrial cancer.”

Their conclusion highlights the potential of hydrogen in activating the pyroptotic pathway to improve outcomes in endometrial cancer treatment.
The study provides foundational knowledge which may be translated into clinical settings, potentially enhancing therapeutic strategies against endometrial cancer by leveraging the cell death pathway of pyroptosis, specifically through the ROS/NLRP3/caspase-1/GSDMD axis.

QUOTE FROM BODY OF TEXT

“In the present study, we explored the effects of hydrogen on endometrial cancer and provided the first evidence that hydrogen induces pyroptosis via ROS-NLRP3-caspase-1 pathways. We demonstrated that drinking hydrogen-enriched water reduced the volume and weight of endometrial tumors in a xenograft mouse model.”

https://doi.org/10.1155/2022/8024452

Boyan Liu et al

STUDY TYPE: IN VITRO

YEAR: 2022

INTERPRETATION OF THE PREMISE OF FINDINGS

“This study underscores the potential of molecular hydrogen (H2) as a novel therapeutic in oncology, particularly for colorectal cancer (CRC). By inhibiting the pAKT/SCD1 pathway, H2 treatment significantly reduced tumor proliferation and volume, suggesting a dual function of targeting cancer growth and the associated molecular pathways. Such findings advocate for hydrogen’s integration into cancer treatment protocols, potentially offering a less invasive option that minimizes the severe side effects associated with traditional chemotherapies.”

QUOTE FROM BODY OF TEXT

“In our study, we found that hydrogen did not change the expression of total AKT but significantly decreased pAKT levels, indicating that hydrogen might suppress colorectal cancer cell proliferation by inducing pAKT (Ser473). The inhibition of cell proliferation induced by H2 was reversed by treatment with SC79 in all three cell lines. This result demonstrated that hydrogen inhibited colorectal cancer cell survival by reducing pAKT.”

https://doi.org/10.3892/or.2018.6841
Junji Akagi et al

STUDY TYPE: HUMAN

YEAR: 2018

INTERPRETATION OF THE PREMISE OF FINDINGS

“Molecular hydrogen (H₂) treatment significantly reinvigorated exhausted CD8+ T cells, enhancing their proliferation and cytokine production, which correlated with a marked improvement in patient prognosis and survival rates.”

QUOTE FROM BODY OF TEXT

“Notably, hydrogen gas decreased the abundance of exhausted terminal PD-1+ CD8+ T cells, increased that of active terminal PD-1- CD8+ T cells, and improved PFS and OS times, suggesting that the balance between terminal PD1+ and PD1- CD8+ T cells is critical for cancer prognosis.”

Traumatic Brain Injury

Molecular Hydrogen Neuroprotection in Post-Ischemic Neurodegeneration in the Form of Alzheimer’s Disease Proteinopathy: Underlying Mechanisms and Potential for Clinical Implementation—Fantasy or Reality?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224395/
  • PREMISE
    • The death of pyramidal neurons in especially the CA1 area of the hippocampus, increased permeability of the blood-brain barrier, neuroinflammation, amyloid accumulation, tau protein dysfunction, brain atrophy, cognitive deficits and dementia are considered an integral part of the phenomena occurring during brain neurodegeneration after ischemia.
    • This review focuses on assessing the current state of knowledge about the neuroprotective effects of molecular hydrogen following ischemic brain injury. 
    • Recent studies in animal models of focal or global cerebral ischemia and cerebral ischemia in humans suggest that hydrogen has pleiotropic neuroprotective properties.
  • KEY POINTS
    • Restoration of blood flow in the brain following cerebral ischemia and ischemic stroke triggers an outbreak of reactive oxygen species, triggering a neuroinflammatory response and oxidative damage [39,44,48,65]. 
    • Reactive oxygen species destroy the membranes of neuronal and neuroglial cells, inducing lipid peroxidation, so antioxidants come into play as a therapeutic option [65]. 
    • Molecular hydrogen has been recognized as an antioxidant that can buffer the destructive effects of oxidative stress in the brain following ischemia by selectively reducing cytotoxic reactive oxygen species [7,22,30].
 
https://www.tandfonline.com/doi/full/10.1080/01616412.2020.1747717
  • PREMISE
    • Traumatic brain injury (TBI) is one of the most serious public health problems in the world. Hydrogen (H2), a flammable, colorless, and odorless gas, has been observed to have preventive and therapeutic effects on brain trauma and other neurological disorders, 
    • but its exact mechanism has not been fully clarified.
    • To further study the mechanism underlying the role of hydrogen gas in alleviating BBB damage after TBI, we performed the scratch injury model on cultured brain microvascular endothelial cells (bEnd.3), which formed the microvascular endothelial barrier – an integral part of the highly specialized BBB.
  • KEY POINTS
    • In the case of TBI, hydrogen was able to improve the decline of cell viability induced by TBI. 
    • In the context of a microvascular endothelial cell model of traumatic brain injury (TBI), the relevance of maintaining cell viability through the inhibition of autophagy and the activation of the PI3K/Akt/GSK3β signaling pathway highlights the complex interplay between cell survival mechanisms and the cellular response to injury.
    • More importantly, inhibition of PI3 K/Akt/GSK3β signal pathway or activation of autophagy reduced the protective effect of hydrogen on cell viability, indicating that such protective effect was regulated by PI3 K/Akt/GSK3β signal pathway and was related to the inhibition of autophagy.
  • KEY FINDINGS
    • hydrogen improved the cell viability in a microvascular endothelial cell model of TBI partly through 
      • inhibition of autophagy, and 
      • inhibitory effect of hydrogen on autophagy was exerted by activating PI3 K/Akt/GSK3β signal pathway. 

QUESTION

Why is cell viability – partly through 

  • inhibition of autophagy and 
  • activation of PI3K/Akt/GSK3β signal pathway 
  • relevant in a microvascular endothelial cell model of traumatic brain injury 

ANSWER

In the context of a microvascular endothelial cell model of traumatic brain injury (TBI), the relevance of maintaining cell viability through the inhibition of autophagy and the activation of the PI3K/Akt/GSK3β signaling pathway highlights the complex interplay between cell survival mechanisms and the cellular response to injury. Here’s why these processes are particularly significant:

  1. Cell Viability and Microvascular Health

Microvascular endothelial cells are critical for maintaining the integrity of the blood-brain barrier (BBB) and ensuring proper cerebral blood flow and nutrient delivery. After TBI, preserving the viability of these cells is crucial for preventing further damage to the brain tissue and promoting recovery.

  1. Inhibition of Autophagy

Autophagy is a cellular degradation process that recycles damaged cell components. While it’s a survival mechanism under stress, excessive autophagy can lead to cell death. In the setting of TBI, where cells are under significant stress, the unchecked autophagy might contribute to endothelial cell loss and subsequent BBB breakdown. Therefore, moderating autophagy can help maintain endothelial cell viability and integrity.

  1. Activation of the PI3K/Akt/GSK3β Signaling Pathway

PI3K/Akt/GSK3β signaling is a well-known pathway involved in promoting cell survival and proliferation. Its activation plays a crucial role in several cellular processes, including metabolism, growth, and survival.

PI3K/Akt activation leads to a cascade of downstream effects that promote cell survival, inhibit apoptosis (programmed cell death), and facilitate repair mechanisms.

Inhibition of GSK3β, a downstream target of Akt, also contributes to cell survival and has been implicated in reducing inflammation and promoting recovery in various models of brain injury.

  1. Therapeutic Implications

Understanding how to modulate autophagy and activate the PI3K/Akt/GSK3β pathway offers potential therapeutic strategies for TBI. By promoting endothelial cell survival, these strategies could help maintain the BBB’s integrity, reduce brain edema, and limit the inflammatory response that exacerbates tissue damage following TBI.

  1. Contribution to Recovery

Preserving microvascular endothelial cell function through these mechanisms can significantly impact the overall recovery process following TBI. It ensures adequate cerebral perfusion, prevents further ischemic injury, and supports the brain’s intrinsic repair processes.

In summary, the strategic modulation of autophagy and the activation of the PI3K/Akt/GSK3β pathway in microvascular endothelial cells following TBI could be crucial for preserving cell viability, maintaining BBB integrity, and facilitating recovery. 

This approach targets the cellular response to injury and the repair mechanisms, offering a promising avenue for therapeutic intervention to improve outcomes after TBI.

 

https://www.ijcep.com/files/ijcep0042919.pdf
  • PREMISE
    • Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide and leads to serious long term disability. 
    • To determine the effect of hydrogen-rich water on the angiogenesis in the lesion boundary brain tissue of TBI-challenged rats
    • H2 may offer a promising opportunity to improve clinical effects during brain functional recovery.
  • KEY POINTS
    • Hydrogen is a colorless, odorless, diatomic gas with a certain reducing quality. 
    • Ohsawa et al [25] reported that inhaled H2 (1% to 4% concentration) markedly decreased oxidative stress, effectively removed free radicals and protected brain against ischemia/reperfusion injury in rats 
    • It was also demonstrated that 2% H2 or hydrogen-rich water decreased oxidative stress and inflammation [26-28]. 
    • Furthermore, some studies showed H2 treatment attenuated cerebral ischemia/reperfusion injury and oxidative stress and brain edema of TBI rats, as well as have anti-inflammatory and anti-apoptosis effect, can significantly improve neural function in rats [14, 15, 29]. 
  • QUOTES
  • The results of Hou et al [14] proved that hydrogen-rich water improved cognitive performance, reduced malondialdehyde (MDA) level and enhanced molecules levels which are relative to brain-derived neurotropic factor (BDNF)-mediated synaptic plasticity after mild TBI.
  • KEY FINDINGS
  • General effect of H2 dissolved in WATER
      • All these results showed CD34+ cells and blood capillary hyperplasia  were positively correlated, which is consistent with Guo’s et al [24] opinion that hydrogen-rich water improved angiogenesis AND neurogenisis
      • After comparing TBI with TBI+HW, hydrogen-rich water promoted the expression of HIF-1α and VEGF as well as the formation of new-born blood vessels in the lesion boundary brain tissue.
  • Conclusion
    • H2 can promote angiogenesis
    • via up-regulating the expression of HIF-1α and
    • VEGF; besides, 
    • hydrogen-rich water played a positive effect on the promotion progress and improved nerve function of trauma rats

QUESTION

What is the significance of angiogenesis in lesion boundary brain tissue of traumatic brain injury-challenged subjects

The significance of angiogenesis in the lesion boundary brain tissue of subjects challenged with traumatic brain injury (TBI) is profound, touching on aspects of both injury response and the potential for recovery. 

Angiogenesis, the formation of new blood vessels from pre-existing ones, plays a crucial role in the repair and regeneration processes following TBI. Here’s why angiogenesis in this context is particularly important:

  • Enhanced Blood Supply and Nutrient Delivery: After TBI, the damaged brain tissue requires an increased supply of nutrients and oxygen to facilitate repair mechanisms. Angiogenesis improves blood flow to the injury site, supporting the metabolic demands of the recovering tissue.
  • Waste Removal: Increased blood flow also means better waste removal, which is crucial for clearing debris and reducing the risk of secondary damage caused by the accumulation of toxic substances.
  • Neurovascular Remodeling: Angiogenesis is part of a broader process of neurovascular remodeling, where new neuronal connections are formed alongside new blood vessels. This parallel development is essential for functional recovery, as it supports the integration of newly formed neural networks with the existing ones.
  • Inflammatory Response Modulation: The formation of new blood vessels plays a role in modulating the inflammatory response to injury. Properly regulated inflammation is necessary for healing, but excessive or prolonged inflammation can exacerbate brain damage. Angiogenesis can help in resolving inflammation more efficiently.
  • Stem Cell Migration: Angiogenesis can facilitate the migration of stem cells to the injury site. Stem cells have the potential to replace damaged neurons and other types of brain cells, contributing to tissue repair and functional recovery.
  • Potential for Functional Recovery: By supporting the processes of repair and regeneration, angiogenesis at the lesion boundary can significantly influence the extent of functional recovery after TBI. Areas with better vascularization may show more robust healing and a greater capacity to regain lost functions.
  • Biomarker of Tissue Viability: The presence of angiogenesis in the lesion boundary may also serve as a biomarker of tissue viability and regenerative capacity. It can indicate the brain’s intrinsic efforts to heal, which could be pivotal for prognostic assessments and guiding rehabilitation strategies.

Understanding and enhancing angiogenesis after TBI could thus be a key therapeutic strategy. 

Research into how to 

  • stimulate or modulate angiogenesis offers the potential to 
  • improve outcomes for individuals with TBI by 
  • supporting the natural repair mechanisms of the brain, 
  • reducing the extent of functional impairments, and 
  • accelerating recovery.

 

https://www.journalofsurgicalresearch.com/article/S0022-4804(18)30189-6/abstract
  • PREMISE
    • Several studies have recently found that oxidative stress plays a pivotal role in the pathogenesis of traumatic brain injury (TBI) and may represent a target in TBI treatment. 
    • Hydrogen-rich water was recently shown to exert neuroprotective effects in various neurological diseases through its antioxidant properties.
  • KEY POINTS
    • The TBI model was constructed according to the modified Feeney weight-drop method. 
    • measured oxidative stress levels by observing the changes in catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) expressions. 
    • evaluated nuclear factor erythroid 2–related factor 2 (Nrf2) levels to determine the role of the protein in the neuroprotective effects against TBI. 
    • verified the neuroprotective effects of hydrogen-rich water in TBI and observed its effects on Nrf2.
  • QUOTES
    • Since the first publication [3], more than 150 papers have confirmed the efficacy of H2 in various animal models [4]. 
    • Our previous randomized double-blind study has shown that drinking 1,000 mL of H2-water for 48 weeks significantly improved (p < 0.05) the total Unified Parkinson’s Disease Rating Scale (UPDRS) scores of patients with PD who were being treated with levodopa [7].
    • Fujita et al. have indicated that the intake of H2-water, even after MPTP administration, reduces neurotoxic damage [5].
    • It is expected that prolonged application of H2 will have no or little adverse effects in chronic diseases.
  • KEY FINDINGS
  • General effect of H2 dissolved in WATER
      • GPx and CAT activity was significantly decreased, and MDA content was increased in the TBI group compared with the sham group at 6 h after TBI.
      • MDA content peaked at 24 h after TBI. 
      • Nrf2 nucleoprotein levels were upregulated in the TBI group compared with the sham group and peaked at 24 h after TBI; 
      • Hydrogen-rich water administration significantly increased 7-d survival rates, reduced neurologic deficits, and lowered intracellular oxidative stress levels. 
      • Moreover, hydrogen-rich water caused Nrf2 to enter the cell nucleus, which resulted in increases in the expression of downstream factors such as HO-1 and NQO1.
  • Conclusions
    • Our results indicate that hydrogen-rich water has neuroprotective effects against TBI by reducing oxidative stress and activating the Nrf2 pathway.
TBI ASSESMENT Please overview the TBI model as constructed according to the modified Feeney weight-drop method and how 
  • measuring oxidative stress levels by 
    • observing the changes in catalase (CAT), 
    • glutathione peroxidase (GPx), and 
    • malondialdehyde (MDA) expressions is pertinent
ChatGPT The Traumatic Brain Injury (TBI) model, as constructed according to the modified Feeney weight-drop method, is a widely used experimental approach to simulate closed-head injury or concussion in animal research, typically in rodents. This method involves dropping a weight from a predetermined height onto the exposed skull of a sedated animal, creating a controlled impact injury that mimics aspects of human TBI.  One of the critical areas of focus in TBI research is oxidative stress, a pathological condition resulting from an imbalance between the production of reactive oxygen species (ROS) and the brain’s ability to detoxify these reactive products or repair the resulting damage. Measuring oxidative stress levels by observing the changes in the expressions of catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) is pertinent for several reasons: Catalase (CAT): CAT is an antioxidant enzyme that catalyzes the decomposition of hydrogen peroxide to water and oxygen, thereby reducing oxidative stress. An increase or decrease in CAT activity following TBI can indicate changes in the brain’s oxidative state and its response to injury. Glutathione Peroxidase (GPx): GPx plays a crucial role in protecting the organism from oxidative damage by reducing lipid hydroperoxides to their corresponding alcohols and free hydrogen peroxide to water. Alterations in GPx activity post-TBI can provide insights into the brain’s antioxidant defense mechanisms and the extent of oxidative damage. 3 Malondialdehyde (MDA): MDA is a byproduct of lipid peroxidation, a process where free radicals steal electrons from the lipids in cell membranes, resulting in cell damage. The level of MDA is often used as a marker for oxidative stress and lipid peroxidation. An increase in MDA levels after TBI suggests enhanced oxidative stress and damage to brain cells. By measuring the expressions of CAT, GPx, and MDA, researchers can assess the oxidative stress level and antioxidant capacity of the brain following TBI. These markers provide valuable insights into the mechanisms of injury and the potential therapeutic targets for mitigating oxidative damage, improving recovery, and enhancing neuroprotection in the context of TBI. This understanding is crucial for developing strategies to treat or manage TBI in clinical settings.

Alzheimer's

Molecular Hydrogen Neuroprotection in Post-Ischemic Neurodegeneration in the Form of Alzheimer’s Disease Proteinopathy: Underlying Mechanisms and Potential for Clinical Implementation—Fantasy or Reality?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224395/
  • PREMISE
    • The death of pyramidal neurons in especially the CA1 area of the hippocampus, increased permeability of the blood-brain barrier, neuroinflammation, amyloid accumulation, tau protein dysfunction, brain atrophy, cognitive deficits and dementia are considered an integral part of the phenomena occurring during brain neurodegeneration after ischemia.
    • This review focuses on assessing the current state of knowledge about the neuroprotective effects of molecular hydrogen following ischemic brain injury. 
    • Recent studies in animal models of focal or global cerebral ischemia and cerebral ischemia in humans suggest that hydrogen has pleiotropic neuroprotective properties.
  • KEY POINTS
    • Restoration of blood flow in the brain following cerebral ischemia and ischemic stroke triggers an outbreak of reactive oxygen species, triggering a neuroinflammatory response and oxidative damage [39,44,48,65]. 
    • Reactive oxygen species destroy the membranes of neuronal and neuroglial cells, inducing lipid peroxidation, so antioxidants come into play as a therapeutic option [65]. 
    • Molecular hydrogen has been recognized as an antioxidant that can buffer the destructive effects of oxidative stress in the brain following ischemia by selectively reducing cytotoxic reactive oxygen species [7,22,30].
  • QUOTES
    • Molecular hydrogen exerts a significant neuroprotective effect on almost all animal models of cerebral ischemia studied. 
    • In addition, its protective properties against mitochondrial damage and the permeability of the blood-brain barrier were noted (Figure 1). 
    • Furthermore, studies showed that hydrogen-rich water prevented neuronal death and synaptic loss, inhibited the development of senile amyloid plaques and reduced tau protein hyperphosphorylation and the growth of neurofibrillary tangles in the transgenic model of Alzheimer’s disease (Figure 1).
  • KEY FINDINGS
    • In mice with focal cerebral ischemia with reperfusion, molecular hydrogen significantly increases SOD and GSH-Px activity, reduces malondialdehyde levels and infarct volume, relieves cerebral edema, improves neurological outcomes and alleviates cognitive deficits
    • In global cerebral ischemia caused by cardiac arrest in rats, hydrogen inhalation improves neurological outcomes, cognitive deficits and survival [20,70].
    • Hydrogen injection or inhalation after global cerebral ischemia due to cardiac arrest effectively controls neuronal death and microglia activation in the hippocampus
    • Molecular hydrogen has been shown to protect the permeability of the blood-brain barrier after focal and global cerebral ischemia
    • Hydrogen has been shown to protect against oxidative stress, neuroinflammation, and prevents the ischemic site from turning into a hemorrhagic focus in rats with local cerebral ischemia
DEFINE Post-Ischemic Neurodegeneration in the Form of Alzheimer’s Disease Proteinopathy ANSWER The sentence “Post-Ischemic Neurodegeneration in the Form of Alzheimer’s Disease Proteinopathy” refers to 
  • a complex interplay of pathological processes following an ischemic event (such as a stroke) that leads to brain cell degeneration. 
  • This degeneration manifests with characteristics similar to those observed in Alzheimer’s disease, specifically in the accumulation and misfolding of certain proteins. 
Post-Ischemic: Refers to the period following an ischemic event. 
  • Ischemia occurs when there’s a reduction in blood flow to a part of the body. 
  • In the context of the brain, ischemia can lead to a stroke, causing damage or death to the affected brain cells due to the lack of oxygen and nutrients.
Neurodegeneration: This term describes the progressive loss of structure or function of neurons, including their death. 
  • Neurodegenerative processes are central to various conditions affecting the brain and nervous system, leading to declining cognitive and motor functions.
In the Form of: This phrase indicates that the neurodegeneration observed post-ischemia manifests with characteristics or in a pattern that resembles another condition, in this case, Alzheimer’s disease. Alzheimer’s Disease Proteinopathy: Alzheimer’s disease is characterized by the accumulation of misfolded proteins in the brain, primarily amyloid-beta plaques and tau protein tangles. 
  • This accumulation disrupts cell-to-cell communication and activates immune responses, leading to inflammation and cell death. 
  • The term “proteinopathy” refers to diseases caused by abnormal protein accumulation. 
  • Thus, Alzheimer’s disease proteinopathy emphasizes the role of these protein accumulations in the disease’s pathology.
Putting it all together, the sentence describes a scenario where an ischemic event in the brain (like a stroke) leads to a pattern of neuronal damage and cell death that shares key pathological features with Alzheimer’s disease, notably the accumulation of misfolded proteins such as amyloid-beta and tau. This suggests a link between ischemic events and the development or acceleration of Alzheimer’s disease-like pathology, highlighting the potential for shared mechanisms between these conditions and underscoring the importance of managing vascular health as part of strategies to prevent or slow the progression of neurodegenerative diseases.

Parkinson's

Drinking hydrogen (H2) water significantly improved the total UPDRS score of PD patients treated with levodopa.
https://hydrogenstudies.com/study/a-randomized-double-blind-multi-center-trial-of-hydrogen-water-for-parkinsons-disease-protocol-and-baseline-characteristics/

https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-016-0589-0
  • PREMISE
    • Our previous randomized double-blind study showed that drinking hydrogen (H2) water for 48 weeks significantly improved the total Unified Parkinson’s Disease Rating Scale (UPDRS) score of Parkinson’s disease (PD) patients treated with levodopa. 
    • We aim to confirm this result using a randomized double-blind placebo-controlled multi-center trial as to whether or not H2 water can improve PD symptoms.
  • KEY POINTS
    • Participants in the hydrogen water group will drink 1000 mL/day of H2 water containing 5 mM of dissolved H2 and 
    • The placebo water is saturated with N2. 
    • One-hundred-and-seventy-eight participants with PD 
      • (88 women, 90 men; mean age: 64.2 [SD 9.2] years, total UPDRS: 23.7 [11.8], with levodopa medication: 154 participants, without levodopa medication: 24 participants; daily levodopa dose: 344.1 [202.8] mg, total levodopa equivalent dose: 592.0 [317.6] mg) were enrolled in 14 hospitals and were randomized.
    • In patients with Parkinson’s disease (PD), the pharmacologic replacement of dopamine and other antiparkinsonian drugs has been used for symptomatic therapy. However, none of these drugs stop or lessen the dopaminergic neuronal degeneration or the progression of the disease.
    • enhanced oxidative stress is involved in the pathogenesis of PD [1, 2]. Thus, antioxidant therapies might slow the progression of PD. 
    • Molecular hydrogen (H2) has recently been highlighted as a therapeutic and preventive antioxidant.
  • QUOTES
    • Since the first publication [3], more than 150 papers have confirmed the efficacy of H2 in various animal models [4]. 
    • Our previous randomized double-blind study has shown that drinking 1,000 mL of H2-water for 48 weeks significantly improved (p < 0.05) the total Unified Parkinson’s Disease Rating Scale (UPDRS) scores of patients with PD who were being treated with levodopa [7].
    • Fujita et al. have indicated that the intake of H2-water, even after MPTP administration, reduces neurotoxic damage [5].
    • It is expected that prolonged application of H2 will have no or little adverse effects in chronic diseases.
  • KEY FINDINGS
  • General effect of H2 dissolved in WATER
      • H2 selectively reduces •OH radicals, but not O2−•, H2O2, or NO• [4]. 
      • H2-water exhibited no adverse effects at a dose of 1000 mL/day in PD subjects receiving levodopa treatment
      • H2-water reduced dopaminergic neuronal cell loss in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model [5] as well as 6-hydroxydopamine [6]. 
QUESTION Please overview the use of the Unified Parkinson’s Disease Rating Scale (UPDRS) to evaluate Parkinson’s Disease (PD) severity ANSWER The Unified Parkinson’s Disease Rating Scale (UPDRS) is a comprehensive tool used to assess the severity of Parkinson’s disease (PD) symptoms and their impact on daily life.  It covers aspects such as mentation, behavior, mood, activities of daily living, motor examination, and treatment complications The UPDRS helps in tracking 
  1. the progression of PD and 
  2. the effectiveness of treatments over time, providing 
  3. a standardized measure for clinical research and care management.
QUESTION How is the UPDRS used in the assessment and subsequent treatment of PD by Neurologists  ANSWER Neurologists use the Unified Parkinson’s Disease Rating Scale (UPDRS) to evaluate Parkinson’s Disease (PD) severity across various dimensions including motor and non-motor symptoms.  This detailed assessment guides treatment decisions, monitoring the effectiveness and side effects of medications, and adjusting therapeutic strategies over time.  It’s crucial for personalized care planning and managing the progression of PD, enabling neurologists to tailor interventions to the patient’s specific needs and symptoms.

QUESTION

Please define 6-hydroxydopamine-induced nigrostriatal degeneration in Parkinson’s disease

ANSWER

The term “6-hydroxydopamine (6-OHDA)-induced nigrostriatal degeneration” refers to a specific experimental model used primarily in research to study Parkinson’s disease and its pathophysiology. 

This model involves the use of 6-hydroxydopamine, a neurotoxin, to selectively target and destroy dopaminergic neurons in the nigrostriatal pathway of the brain.

The nigrostriatal pathway is a critical component of the motor system, connecting the substantia nigra pars compacta (SNc) with the dorsal striatum (a part of the basal ganglia). 

In Parkinson’s disease, the dopaminergic neurons in this pathway degenerate, leading to a significant reduction in the neurotransmitter dopamine. 

This decrease in dopamine is responsible for the hallmark symptoms of Parkinson’s disease, such as bradykinesia (slowness of movement), rigidity, tremor, and postural instability.

By administering 6-OHDA to laboratory animals, researchers can mimic the dopaminergic neuronal loss observed in Parkinson’s disease, leading to similar motor deficits. 

This model allows for the study of the mechanisms underlying nigrostriatal degeneration, the evaluation of potential neuroprotective strategies, and the assessment of new symptomatic treatments for Parkinson’s disease. It’s a valuable tool for understanding the disease’s progression and testing the efficacy of new therapeutic interventions.

https://www.sciencedirect.com/science/article/abs/pii/S0304394009001839?via%3Dihub

PREMISE

    • This model involves the use of 6-hydroxydopamine, a neurotoxin, to selectively target and destroy dopaminergic neurons in the nigrostriatal pathway of the brain
    • In Parkinson’s disease, the dopaminergic neurons in this pathway degenerate, leading to a significant reduction in the neurotransmitter dopamine.
    • This decrease in dopamine is responsible for the hallmark symptoms of Parkinson’s disease, such as bradykinesia (slowness of movement), rigidity, tremor, and postural instability.
    • In Parkinson’s disease, mitochondrial dysfunction and the associated oxidative stress are major causes of dopaminergic cell loss in the substantia nigra.
    • Analysis showed that molecular hydrogen prevented both the development and progression of the nigrostrital degeneration
    • Our studies suggest that molecular hydrogen is likely able to retard the development and progression of Parkinson’s disease.

 

QUOTES

    • PD is the 2nd most common neurodegenerative disorder following Alzheimer disease, affecting approx 0.3% of American’s over 50yo. . 
    • To our knowledge, although pathomechanisms of PD remain largely unk, oxidative stress to dopaminergic neurons is a major contributor to dopaminergic neuronal cell loss
    • Mitochondrial dysfunction and associative oxidative stress in PD are further contributory to both the development and progression of the nigrostrital degeneration.
    • Molecular Hydrogen has SELECTIVELY antioxidant capacity for HARMFUL ROS like the hydroxyl radicals (*OH) and peroxynitrite (ONOO-).
    • without affecting other ROS that are beneficial for cellular signaling processes. 
    • This selectivity is crucial because a blanket removal of ROS could disrupt these necessary cellular functions.
    • To date H2 has NO KNOWN side effects to rodents or Humans.

 

  • KEY FINDINGS
  • General effect of H2 in GASEOUS FORM
  • REDUCES Cerebral Infarction volume (rodent model)
  • SUPPRESSES Hepatic Ischemia/ Reperfusion injury (rodent model) 
  • REDUCES Infarction Size of Myocardial Ischemia/ Reperfusion injury (rodent model) 
  • REDUCES apoptosis in neonatal hypoxic brain injury (rodent model) 
  • MITIGATES  small intestinal transplantation-induced inflammation (rodent model) 
  • General effect of H2 dissolved in WATER
        • PREVENTS stress induced learning impairment (rodent model)
        • IMPROVES Lipid and Glucose metabolism in type 2 diabetes and impaired glucose tolerance in Humans 
        • REDUCES atherosclerotic legions (rodent model)
        • PREVENTS cisplatin-induced nephrotoxicity (rodent model)
  • SPECIFIC effect of H2 dissolved in water post 6-hydroxydopamine-induced nigrostriatal degeneration (rodent model)
  • 50% saturated H2 water
  • Behavioral & Pathological Analysis demonstrated that H2 efficiently prevents both DEVELOPMENT & PROGRESSION of the  6-hydroxydopamine-induced nigrostriatal degeneration model
  • Our current studies demonstrate that H2 efficiently prevents development of PD IN A 6-OHDA rodent model

 

QUESTION

Please define 6-hydroxydopamine-induced nigrostriatal degeneration in Parkinson’s disease

ANSWER

The term “6-hydroxydopamine (6-OHDA)-induced nigrostriatal degeneration” refers to a specific experimental model used primarily in research to study Parkinson’s disease and its pathophysiology. 

This model involves the use of 6-hydroxydopamine, a neurotoxin, to selectively target and destroy dopaminergic neurons in the nigrostriatal pathway of the brain.

The nigrostriatal pathway is a critical component of the motor system, connecting the substantia nigra pars compacta (SNc) with the dorsal striatum (a part of the basal ganglia). 

In Parkinson’s disease, the dopaminergic neurons in this pathway degenerate, leading to a significant reduction in the neurotransmitter dopamine. 

This decrease in dopamine is responsible for the hallmark symptoms of Parkinson’s disease, such as bradykinesia (slowness of movement), rigidity, tremor, and postural instability.

By administering 6-OHDA to laboratory animals, researchers can mimic the dopaminergic neuronal loss observed in Parkinson’s disease, leading to similar motor deficits. 

This model allows for the study of the mechanisms underlying nigrostriatal degeneration, the evaluation of potential neuroprotective strategies, and the assessment of new symptomatic treatments for Parkinson’s disease. It’s a valuable tool for understanding the disease’s progression and testing the efficacy of new therapeutic interventions.

https://www.sciencedirect.com/science/article/abs/pii/S0304394009001839?via%3Dihub
  • PREMISE
    • This model involves the use of 6-hydroxydopamine, a neurotoxin, to selectively target and destroy dopaminergic neurons in the nigrostriatal pathway of the brain
    • In Parkinson’s disease, the dopaminergic neurons in this pathway degenerate, leading to a significant reduction in the neurotransmitter dopamine.
    • This decrease in dopamine is responsible for the hallmark symptoms of Parkinson’s disease, such as bradykinesia (slowness of movement), rigidity, tremor, and postural instability.
    • In Parkinson’s disease, mitochondrial dysfunction and the associated oxidative stress are major causes of dopaminergic cell loss in the substantia nigra.
    • Analysis showed that molecular hydrogen prevented both the development and progression of the nigrostrital degeneration
    • Our studies suggest that molecular hydrogen is likely able to retard the development and progression of Parkinson’s disease.

 

  • QUOTES
    • PD is the 2nd most common neurodegenerative disorder following Alzheimer disease, affecting approx 0.3% of American’s over 50yo. . 
    • To our knowledge, although pathomechanisms of PD remain largely unk, oxidative stress to dopaminergic neurons is a major contributor to dopaminergic neuronal cell loss
    • Mitochondrial dysfunction and associative oxidative stress in PD are further contributory to both the development and progression of the nigrostrital degeneration.
    • Molecular Hydrogen has SELECTIVELY antioxidant capacity for HARMFUL ROS like the hydroxyl radicals (*OH) and peroxynitrite (ONOO-).
    • without affecting other ROS that are beneficial for cellular signaling processes. 
    • This selectivity is crucial because a blanket removal of ROS could disrupt these necessary cellular functions.
    • To date H2 has NO KNOWN side effects to rodents or Humans.

 

  • KEY FINDINGS
  • General effect of H2 in GASEOUS FORM
  • REDUCES Cerebral Infarction volume (rodent model)
  • SUPPRESSES Hepatic Ischemia/ Reperfusion injury (rodent model) 
  • REDUCES Infarction Size of Myocardial Ischemia/ Reperfusion injury (rodent model) 
  • REDUCES apoptosis in neonatal hypoxic brain injury (rodent model) 
  • MITIGATES  small intestinal transplantation-induced inflammation (rodent model) 
  • General effect of H2 dissolved in WATER
        • PREVENTS stress induced learning impairment (rodent model)
        • IMPROVES Lipid and Glucose metabolism in type 2 diabetes and impaired glucose tolerance in Humans 
        • REDUCES atherosclerotic legions (rodent model)
        • PREVENTS cisplatin-induced nephrotoxicity (rodent model)
  • SPECIFIC effect of H2 dissolved in water post 6-hydroxydopamine-induced nigrostriatal degeneration (rodent model)
  • 50% saturated H2 water
  • Behavioral & Pathological Analysis demonstrated that H2 efficiently prevents both DEVELOPMENT & PROGRESSION of the  6-hydroxydopamine-induced nigrostriatal degeneration model
  • Our current studies demonstrate that H2 efficiently prevents development of PD IN A 6-OHDA rodent model

Read The Studies

There are almost 2000 studies and counting. You can type ‘name of your condition’ + ‘molecular hydrogen’. The most relevant pages where you can find more information are PubMed, Google Scholar, and, of course, The Molecular Hydrogen Institute.

Allergies

Hydrogen water exhibits potential in alleviating allergies through its antioxidant properties, showing promise in immune response balance and symptom improvement.

Scientific Report | 1 https://pubmed.ncbi.nlm.nih.gov/19766097/

Molecular hydrogen suppresses FcepsilonRI-mediated signal transduction and prevents degranulation of mast cell

Hydrogen water has shown promise in alleviating inflammation in rheumatoid arthritis and other conditions.

Scientific Report | 1 https://pubmed.ncbi.nlm.nih.gov/23031079/ 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

Scientific Report | 2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3788323/ 

Molecular hydrogen: new antioxidant and anti-inflammatory therapy for rheumatoid arthritis and related diseases

Scientific Report | 3 https://pubmed.ncbi.nlm.nih.gov/11510417/ Anti-inflammatory properties of molecular hydrogen: investigation on parasite-induced liver inflammation

Hydrogen-infused water has demonstrated antioxidant properties, potentially protecting cells from damage, including in stroke patients.

Scientific Report | 1 https://pubmed.ncbi.nlm.nih.gov/17486089/

Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals

Scientific Report | 2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694409/

Safety of intravenous administration of hydrogen-enriched fluid in patients with acute cerebral ischemia: initial clinical studies

Scientific Report | 3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865993/

A randomized double-blind multi-center trial of hydrogen water for Parkinson’s disease: protocol and baseline characteristics

Scientific Report | 4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10057981/

Therapeutic Inhalation of Hydrogen Gas for Alzheimer’s Disease Patients and Subsequent Long-Term Follow-Up as a Disease-Modifying Treatment: An Open Label Pilot Study

Scientific Report | 5 https://pubmed.ncbi.nlm.nih.gov/28669654/

Hydrogen Gas Inhalation Treatment in Acute Cerebral Infarction: A Randomized Controlled Clinical Study on Safety and Neuroprotection

Scientific Report | 6 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6664236/

Effects of Molecular Hydrogen on Methamphetamine-Induced Neurotoxicity and Spatial Memory Impairment

Scientific Report | 7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087877/

Hydrogen-Rich Water Ameliorates Autistic-Like Behavioral Abnormalities in Valproic Acid-Treated Adolescent Mice Offspring

Scientific Report | 1 https://www.nature.com/articles/s41598-020-58999-0

(2020) Hydrogen Attenuates Allergic Inflammation by Reversing Energy Metabolic Pathway Switch Scientific

Report | 2 https://www.sciencedirect.com/science/article/abs/pii/S1567576918313638

Hydrogen gas inhalation enhances alveolar macrophage phagocytosis in an ovalbumin-induced asthma model

Hydrogen water has exhibited potential in reducing lactic acid build-up, decreasing muscle fatigue during exercise, and potentially aiding muscle-wasting diseases.

Scientific Report | 1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395574/

Pilot study: Effects of drinking hydrogen-rich water on muscle fatigue caused by acute exercise in elite athletes

Scientific Report | 2 https://pubmed.ncbi.nlm.nih.gov/28474871/

Effects of hydrogen rich water on prolonged intermittent exercise

Scientific Report | 3 https://pubmed.ncbi.nlm.nih.gov/25295663/

Effectiveness of oral and topical hydrogen for sports-related soft tissue injuries

Scientific Report | 4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837388/

Molecular hydrogen alleviates motor deficits and muscle degeneration in mdx mice

Scientific Report | 1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123813/

Molecular Hydrogen as a Potential Clinically Applicable Radioprotective Agent

Scientific Report | 2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3805896/

Hydrogen as a New Class of Radioprotective Agent 

Scientific Report | 3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189362/

Hydrogen gas represses the progression of lung cancer via down-regulating CD47

Scientific Report | 4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885710/

Hydrogen therapy can be used to control tumor progression and alleviate the adverse events of medications in patients with advanced non-small cell lung cancer

Scientific Report | 5  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092147/ Two weeks of hydrogen inhalation can significantly reverse adaptive and innate immune system senescence patients with advanced non-small cell lung cancer: a self-controlled study

Scientific Report | 6 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448556/

Suppression of autophagy facilitates hydrogen gas-mediated lung cancer cell apoptosis

Scientific Report | 7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691140/

Hydrogen Gas in Cancer Treatment

Scientific Report | 1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600250/

A New Approach for the Prevention and Treatment of Cardiovascular Disorders. Molecular Hydrogen Significantly Reduces the Effects of Oxidative Stress

Scientific Report | 2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353690/

Application of Molecular Hydrogen in Heart Surgery under Cardiopulmonary Bypass

Scientific Report | 3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9555031/

Molecular hydrogen exposure improves functional state of red blood cells in the early postoperative period: a randomized clinical study

Scientific Report | 4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10239052/

Hydrogen therapy as a potential therapeutic intervention in heart disease: from the past evidence to future application

Scientific Report | 1 Hydrogen/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 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120708/

Scientific Report | 2 Hydrogen gas (XEN) inhalation ameliorates airway inflammation in asthma and COPD patients https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785302/

Scientific Report | 3 Hydrogen gas inhalation protects against cigarette smoke-induced COPD development in mice https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051853/

Scientific Report | 4 Hydrogen Therapy may be a Novel and Effective Treatment for COPD https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108576/

Scientific Report | 1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569706/

(2121) Molecular Hydrogen: A Promising Adjunctive Strategy for the Treatment of the COVID-19

Scientific Report | 2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8896485/

Hydrogen-oxygen therapy alleviates clinical symptoms in twelve patients hospitalized with COVID-19

Scientific Report | 3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8872486/

Molecular Hydrogen Positively Affects Physical and Respiratory Function in Acute Post-COVID-19 Patients: A New Perspective in Rehabilitation

Scientific Report | 4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330772/

Hydrogen/oxygen mixed gas inhalation improves disease severity and dyspnea in patients with Coronavirus disease 2019 in a recent multicenter, open-label clinical trial

Research suggests that hydrogen water consumption may lead to improvements in cholesterol, glucose tolerance, and insulin resistance in individuals with type 2 diabetes or prediabetes.

Scientific Report | 1 https://pubmed.ncbi.nlm.nih.gov/19083400/

Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance

Scientific Report | 2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542317/

(2013) Hydrogen Improves Glycemic Control in Type1 Diabetic Animal Model by Promoting Glucose Uptake into Skeletal Muscle

Scientific Report | 3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542317/

(2020) Hydrogen improves glycemic control in type1 diabetic animal model by promoting glucose uptake into skeletal muscle 

Scientific Report | 4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9889559/

(2023) Effectiveness and safety of hydrogen inhalation as an adjunct treatment in Chinese type 2 diabetes patients: A retrospective, observational, double-arm, real-life clinical study

Scientific Report | 5 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9515190/

Photocatalytic glucose depletion and hydrogen generation for diabetic wound healing

Scientific Report | 6 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291681/

Molecular hydrogen improves type 2 diabetes through inhibiting oxidative stress

Scientific Report | 7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5754517/

Subcutaneous injection of hydrogen gas is a novel effective treatment for type 2 diabetes

Research has demonstrated that hydrogen-loaded eye drops can aid in the recovery of eye injuries caused by high eye pressure, suggesting a possible use as a first-aid eye rinse.

Scientific Report | 1 https://pubmed.ncbi.nlm.nih.gov/19834032/

Protection of the retina by rapid diffusion of hydrogen: administration of hydrogen-loaded eye drops in retinal ischemia-reperfusion injury

Scientific Report | 2 https://pubmed.ncbi.nlm.nih.gov/20847117/

Hydrogen and N-acetyl-L-cysteine rescue oxidative stress-induced angiogenesis in a mouse corneal alkali-burn model

Scientific Report | 3 https://pubmed.ncbi.nlm.nih.gov/25801048/

Protective effect of molecular hydrogen against oxidative stress caused by peroxynitrite derived from nitric oxide in rat retina

Gut Health & Digestive Enzyme Production

Scientific Report | 1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3231938/

Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors

Scientific Report | 2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679390/

Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome

Scientific Report | 3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5799803/

Hydrogen-water ameliorates radiation-induced gastrointestinal toxicity via MyD88’s effects on the gut microbiota

Molecular hydrogen has exhibited potential in protecting hearing cells from oxidative damage, providing hope for mitigating hearing loss due to noise or oxidative stress.

Scientific Report | 1 https://pubmed.ncbi.nlm.nih.gov/19339905/

Hydrogen protects auditory hair cells from free radicals

Scientific Report | 2 https://pubmed.ncbi.nlm.nih.gov/22387110/

Hydrogen-rich saline alleviates experimental noise-induced hearing loss in guinea pigs

Scientific Report | 3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063935/

Hydrogen-saturated saline protects intensive narrow band noise-induced hearing loss in guinea pigs through an antioxidant effect

In diabetic mice, hydrogen water has shown significant improvements in heart health and the prevention of heart disease, holding promise as a potential intervention for diabetes-related heart issues.

Scientific Report | 1 https://pubmed.ncbi.nlm.nih.gov/25979689%20

Treatment with hydrogen molecule attenuates cardiac dysfunction in streptozotocin-induced diabetic mice

Scientific Report | 1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871940/

Hydrogen-rich water suppresses the reduction in blood total antioxidant capacity induced by 3 consecutive days of severe exercise in physically active males

Scientific Report | 2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376192/

Hydrogen-rich water reduces inflammatory responses and prevents apoptosis of peripheral blood cells in healthy adults: a randomized, double-blind, controlled trial

Scientific Report | 3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988658/

Application of Molecular Hydrogen as a Novel Antioxidant in Sports Science

Scientific Report | 4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096066/

Anti-inflammatory and antitumor action of hydrogen via reactive oxygen species

Scientific Report | 5 https://pubmed.ncbi.nlm.nih.gov/30243702/

Molecular hydrogen reduces acute exercise-induced inflammatory and oxidative stress status

Scientific Report | 6 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045005/ 

Molecular Hydrogen: From Molecular Effects to Stem Cells Management and Tissue Regeneration

Scientific Report | 7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095341/

(2016) Molecular hydrogen decelerates rheumatoid arthritis progression through inhibition of oxidative stress

Scientific Report | 8 https://www.sciencedirect.com/science/article/pii/S1567576914002124?ref=pdf_download

(2014) Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: A randomized, double-blind, placebo-controlled pilot study

Scientific Report | 9 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563451/

(2012) 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

Scientific Report | 10 https://www.spandidos-publications.com/10.3892/etm.2018.6880

(2018) Beneficial Effects of Hydrogen Gas Inhalation on a Murine Model of Allergic Rhinitis

Scientific Report | 1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178641/

Emerging mechanisms and novel applications of hydrogen gas therapy

Scientific Report | 2 https://pubmed.ncbi.nlm.nih.gov/28560519/

Molecular hydrogen affects body composition, metabolic profiles, and mitochondrial function in middle-aged overweight women

Scientific Report | 3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141176/

Therapeutic Potential of Molecular Hydrogen in Metabolic Diseases from Bench to Bedside

Scientific Report | 1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585236/

(2022) The effect of a low dose hydrogen-oxygen mixture inhalation in midlife/older adults with hypertension: A randomized, placebo-controlled trial

Scientific Report | 2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692487/

Daily inhalation of hydrogen gas has a blood pressure-lowering effect in a rat model of hypertension

Scientific Report | 3 https://pubmed.ncbi.nlm.nih.gov/30259991/

Hydrogen gas reduces chronic intermittent hypoxia-induced hypertension by inhibiting sympathetic nerve activity and increasing vasodilator responses via the antioxidation

Scientific Report | 1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376192/

Hydrogen-rich water reduces inflammatory responses and prevents apoptosis of peripheral blood cells in healthy adults: a randomized, double-blind, controlled trial

Scientific Report | 2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567800/

Recent Advances in Studies of Molecular Hydrogen against Sepsis

Scientific Report | 3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560832/

Hydrogen-rich saline protects immunocytes from radiation-induced apoptosis

Scientific Report | 4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495244/

Hydrogen: A Novel Option in Human Disease Treatment

Research indicates that hydrogen water also demonstrates significant improvements in liver function and reduced oxidative stress in individuals with chronic hepatitis B.

Scientific Report | 1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5350887/

Effect of hydrogen-rich water on oxidative stress, liver function, and viral load in patients with chronic hepatitis B

Scientific Report | 2 https://pubmed.ncbi.nlm.nih.gov/23682614/

Effects of oral intake of hydrogen water on liver fibrogenesis in mice

Scientific Report | 3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5350887/

Effect of hydrogen-rich water on oxidative stress, liver function, and viral load in patients with chronic hepatitis B

Scientific Report | 4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196827/

A strategy of local hydrogen capture and catalytic hydrogenation for enhanced therapy of chronic liver diseases

Scientific Report | 5 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002796/

Hydrogen treatment: a novel option in liver diseases

Research suggests that hydrogen water may promote the growth of brain cells, potentially offering benefits for mood disorders such as depression.

Scientific Report | 1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812321/

Effects of hydrogen-rich water on depressive-like behavior in mice

Scientific Report | 2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409143/

Molecular Hydrogen Reduces LPS-Induced Neuroinflammation and Promotes Recovery from Sickness Behaviour in Mice

Scientific Report | 3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575246/

Molecular hydrogen increases resilience to stress in mice

Hydrogen water has been linked to enhanced collagen production, reduced UV damage, and antioxidant effects in skin cells, suggesting potential benefits for skin aging and inflammation.

Scientific Report | 1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407032/

Hydrogen(H2) treatment for acute erythematous skin diseases. A report of 4 patients with safety data and a non-controlled feasibility study with H2 concentration measurement on two volunteers

Scientific Report | 2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852999/

The Drinking Effect of Hydrogen Water on Atopic Dermatitis Induced by Dermatophagoides farinae Allergen in NC/Nga Mice

Long-term consumption of hydrogen water has been associated with fat and weight loss, resembling the effects of calorie restriction.

Scientific Report | 1 https://onlinelibrary.wiley.com/doi/10.1038/oby.2011.6

Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice

Scientific Report | 2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9967957/

The Effects of Hydrogen-Rich Water on Blood Lipid Profiles in Clinical Populations: A Systematic Review and Meta-Analysis

Scientific Report | 3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679390/

Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome