Hydrogen - Clinical use and future prospects
In this presentation we will show how hydrogen can have a positive effect on: Cancer Inflammation/pain killer Diabetes Atopic dermatitis
The Problem Everyday we are exposed to cell-damaging free radicals Every single day we are exposed to the harmful effect of our environment. Pollution, sun exposure and various toxins from a broad range of sources damage our cells. Science is starting to understand the biology behind this damage. One of the main reasons is caused by the molecules known as ‘free radicals’ or Reactive Oxidative Species ( ROS ). Typically, molecules have two electrons to keep them stable. The free radicals, however, only have one electron due to the harmful environmental impact, which makes them unstable and a contributing factor to the breakdown of our bodies. The unstable free radical are always seeking to become stabilised by pulling in an additional electron from healthy molecules. This process sets off a chain reaction and more molecules become imbalanced and thus unhealthy. A damaging process known as oxidative stress. Persistent oxidative stress is one of the major causes of most lifestyle-related diseases, cancer and the ageing process.
The Solution Molecular Hydrogen eliminates free radicals. Antioxidants are substances that protect your cells from oxidative stress and inflammation by removing the harmful free radicals. The amount of free radicals in the body must be in balance to maintain a good health. Certain vitamins are known as antioxidants and are believed to counteract oxidative stress by reducing the formation of free radicals. Nevertheless, vitamins and nutrients are linked to a limited therapeutic success. On the other hand, molecular hydrogen has potential as a novel antioxidant in preventative and therapeutic applications. Hydrogen readily gives up electrons to ROS , which stabilises them and stops them in their tracks. Hydrogen shows not only effects against oxidative stress, but also various anti-inflammatory and anti-allergic effects. Hydrogen holds advantages over other antioxidants because it is such a tiny molecule: it is able to penetrate cell membranes, and can easily enter deep into cell components, where other antioxidants are not able to reach. Also, hydrogen boosts the body’s defences by increasing production of natural antioxidants. No adverse effects of consuming hydrogen exist.
ROS and their potential implications Cancer Proliferation / metastasis DNA Oxidation Cell ageing ROS Protein oxidation Intracellular organ degeneration Lipid oxidation Disease/ageing Tissue ageing/dedegeneration
Two types of ROS Cytotoxic Action Physiological Activity Intracellular progression Oxidative deterioration Immune system cell growth AGE production ROS Growth factor stimulus Acidification Enzyme Synthesis Inflammation promotion Osteoclasts promote
Hydrogen as a selective antioxidant Selective, clean, and safe. While taking high doses of supplemental antioxidants has negative health effects, it is impossible to take too much H2. Molecular Hydrogen ONLY scavenges and neutralises the harmful free radicals, leaving the beneficial ones alone. Many antioxidants leave behind toxic byproducts, but the only byproduct of H2 is water.
��� ��� ROS activity and physiological activity/cytotoxicity stimulation Strong TROS Toxic ROS Cytotoxic activity: high Therapeutic target BROS Biological ROS Physiological activity: Low Adverse effects due to removal weak Target selectivity is important for antioxidant therapy
Scientific? The wide-ranging therapeutic and preventative benefits of molecular hydrogen have been evidenced in over 850 peer-reviewed, scientific articles, encompassing over 170 disease models including: type 2 diabetes, rheumatoid arthritis and other autoimmune diseases, metabolic syndrome, Parkinson’s & Alzheimer’s disease, heart disease, numerous forms of cancer
Major papers/clinical trials since 2007
2013: hydrogen molecule suppresses TNF α induced cell damage Immune activation / inflammation and ROS • Block TNF α induction in the NF κ B pathwa • NO suppression by inhibition of iNOS activity • Suppress IL-6 mRNA expression • Suppression of ICAM-1 mRNA expression • Maintaining mitochondrial function ROS TNF α NF κ B Cytokine TNF α Cytotoxicity iNOS COX
2014: Effect of inhalation of hydrogen gas after cardiac arrest · Suppression of decline in behaviour/cognitive function. · Neuronal cell death/inflammatory response decreased markedly. By hydrogen inhalation · Neuronal cell necrosis decreases. · Suppress hippocampal / cerebral cortex microglial activity.
2015: Hydrogen drip suppressed intestinal mucosal damage due to hemorrhagic shock · Administration of hydrogen to the ischemic injury of the digestive tract mucosa caused by hemorrhagic shock · Histologically, reduction of intestinal villous damage, reduction of neutrophil infiltration · Reduction of MDA, MPO, IL-6, TNF α (increase of inflammatory cytokines) in the hydrogen administration group · Increase in SOD, IL-10 (antiinflammatory cytokine / increase in antioxidant substance) in hydrogen administration group
Appendix 2016: Onset of Parkinson's disease by mutation of DJ-1 gene O 2 O 2 Oxidative damage Mitochondria Cell/DNA Mitochondria Cell/DNA H 2 ? ROS ROS ROS ROS Stress Signal Oxidative damage: Acquired DJ-1 Antioxidant DJ-1 Antioxidant Genetic mutation: Familiar
2016: Multi-center double-blind study on Parkinson's disease Confirm effectiveness with large-scale double-blind trial conducted on Parkinson's disease • H 2 Hydrogen water containing 5 mM 1 L / day 8 weeks Evaluation: • UPDRS (unified Parkinson 's disease rating scale) Confirmed effect in: Hydrogen administration can inhibit the progression of Parkinson's disease
Clinical Use From basic medicine to clinical medicine
Exploring administration methods considered from previous papers 1: Dissolved in liquid before administration * Water (digestive tube) * drip * injection * 2: Gas administered, dissolving in the body * Inhalation (lung) * Dermal Injection* 3: Generated in the gastrointestinal tract, dissolved in the body * Hydrogen body occlusion (oral administration) * Acceleration of development by intestinal bacteria (Acarbose etc.)
Drip Injection
Infusion/injection solution Hydrogenated physiological saline Hydrogen dissolution • Henry's law • Boyle/Charles' law • Intermolecular force of hydrogen gas Dissolution • Intermolecular force of liquid limit ≒ 1.57ppm • Presence in the nano bubble state (Ppm measurement) Gas concentration in cylinder : >99.999% Filled gas concentration : 99.9999% Humidity : 0% Filling pressure : 0~100kPa
Dissolved hydrogen concentration in drip bag Dissolution limit (1.57 ppm) hyper phenomena due to pressurised dissolution 3.0 ppm 2.4 2.4 2.2 2.1 2.1 1.9 1.9 1.8 1.8 1.7 1.7 1.6 1.6 1.6 1.5 1.5 1.5 1.4 1.4 1.3 1.3 1.3 1.2 1.2 1.2 1.1 1 0.7 0.6 0.5 0.4 0 0 0 0.0 Fill straight up Immediately after Shake After 5 minutes After 10 minutes After 15 minutes After 20 minutes After 50 minutes After 60 minutes After 24 hours After 48 hours Atmospheric pressure filling shake 10 seconds 90kpa filling - Shake 10 seconds 90 kpa filling - shake 15 seconds
Water drip Perform various inspections before and after Hydrogen gas injection
What is 8-OHdG? Steady-state levels of DNA damages represent the balance between formation and repair. Average frequencies of steady state endogenous DNA damages in mammalian cells. The most frequent oxidative DNA damage normally present in DNA is 8-oxo-dG, occurring at an average frequency of 2,400 per cell. When 8-oxo-dG is induced by a DNA damaging agent it is rapidly repaired. Increased levels of 8-oxo-dG in a tissue can serve as a biomarker of oxidative stress. Oxidative DNA damage, such as 8-oxo-dG, likely contributes to carcinogenesis (cancer) The contribution happens via two different mechanisms. The first mechanism involves modulation of gene expression, whereas the second is through the induction of mutations.Thus 8-oxo-dG, if not repaired, can directly cause frequent mutations, some of which may contribute to cancer.
Oxidative stress and 8-OHdG · Genetic damage is 5 to 500,000 per day ( × 60 trillion) per cell · Detect damage due to oxidation · 8-OHdG test ≈ oxidative stress speed to genes 8-OHdG 8-hydroxy-2’-deoxyguanosine Normal deoxyguanosine (dG) HO Urine Elimination by repairing enzymes Oxidative stress This process is constantly occurring tens of thousands of times per cell/day
Relationship between administration and 8-OHdG H 2 Reduction of 8-OHdG by administration In the blood ≈ nuclear migration of hydrogen molecules ≈ Protection action of DNA H 2 Interstitial repair H 2 Cell ageing in the cell In the nucleus damage DNA OH � Cancer H 2 O Nuclear membrane Apoptosis Cell membrane 8-OHdG Cell death / destruction Regeneration by stem cells
Changes of 8-OHdG by hydrogenated physiological saline infusion Reference value 4~13 • 32 patients treated with hydrogen saline infusion • In nearly all cases, a decrease in 8-OHdG is observed • Braking the oxidation damage speed of DNA
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