I was surprised to see that the only discussions of hydrogen are on ghrelin. It is such a small and relatively insignificant benefit of hydrogen therapy when considering the body of evidence. This write up has a section focused on magnesium for the tablets creating high dose h2 saturation in water. I won't mention any brands, but there are only two manufacturers world wide with competing IP. One tablet optimizes use in an open container, the other requires external pressurization for hours to hit super saturation.
This is a brief review full of necessary citations with an overview of what it means for health and longevity. Confidential data yet to be published or make it through peer review will change some of this in the coming months, both elucidating on more mechanisms of action, proper dosing protocols and also correcting conclusions based on erroneously attributed mechanisms.
Gene Signalling
Inflammation
Excessive levels of inflammation is believed to be one of the three most common precursors and driving forces of disease and premature death along with insulin resistance and oxidative stress. These three factors lead to a myriad of disease models, and contribute to premature aging at a cellular level. These stresses accelerate the shortening of our telomeres (needed for cell division) by either reducing our levels of telomerase, the enzyme required to extend our telomeres, or by causing a cascade of signals which reduce telomerase efficiency. [i][ii][iii][iv][v][vi][vii][viii][ix][x][xi]
While hydrogen administration does not directly eliminate inflammation it will down-regulate the production of pro inflammatory cytokines through various pathways when excess inflammation occurs which can promote a normal level of inflammation[xii][xiii][xiv][xv][xvi][xvii][xviii][xix][xx][xxi][xxii][xxiii][xxiv][xxv][xxvi] Non steroidal anti inflammatorys (NSAIDS) typically used as a treatment for inflammation treat the symptoms of inflammation but not the underlying cause. In addition they also have unwanted side effects including nephrotoxity (kidney damage) and GI trauma (ulcers). Other more powerful (prescription only) COX inhibitors and corticosteroids will completely eliminate inflammation which can be as hazardous as excess inflammation. Hydrogen can promote a healthy level of inflammation through regulation of our pro inflammatory cytokines.
Oxidative Stress
As one of the ‘main issues in disease indicators along with inflammation and insulin resistance, an imbalance of oxidative stress is a primary marker in the vast majority of diseases. Exogeneous antioxidant supplementation has shown to lack efficacy at best in a recent meta analysis[xxvii], and in some cases may prove harmful due to indiscriminately reducing necessary oxidative species while down regulating our endogenous production of antioxidants[xxviii], even leading to an increase in prevalence of cancer.[xxix] Understandably, the ground breaking seminal article in Nature Med showing hydrogen acts as a selective antioxidant in only reducing the most cytotoxic hydroxyl radicals, the ‘bad oxidative species’ was met with considerable interest and an explosion in research.[xxx] Since this article, the exact mechanisms in which hydrogen works as an antioxidant have been further explored, with the realization that the most profound benefit is its ability to activate the Nrf2 pathway, regulating our bodies endogenous antioxidant productions of glutathione, catalase, super oxide dismutase, etc. protecting against oxidative damages and promoting a homeostatic antioxidant/oxidative stress balance.[xxxi][xxxii][xxxiii][xxxiv][xxxv][xxxvi] While other potent Nrf2 activators have come under criticism with the potential that the increased cholesterol levels in the liver associated with their administration may overshadow the benefits of increased antioxidant production[xxxvii], and perhaps more disturbing the evidence suggesting in some instances Nrf2 activation [r1] beyond homeostatic levels can promote cancerous tumours and decrease the effectiveness of chemotherapy[xxxviii][xxxix]. In constrast, hydrogen stands alone as a solution as it only promotes Nrf2 activation towards homeostatic balance of our ROS/Antioxidant system. It has also shown to lower our LDL or ‘bad’ cholesterols while promoting our HDL or ‘good’ cholesterol[xl][xli][xlii] , and also as both suppression of tumor growth [xliii][xliv] while suppressing the negative side effects of cancer treatments without interfering with efficacy[xlv][xlvi][xlvii]. Through its attenuation of oxidative stress, hydrogen has shown to be an effective treatment in human studies of rheumatoid arthritis[xlviii][xlix], Hepatitis B[l], Parkinson’s Disease[li], and many more.
Glucose Homeostasis and Insulin Sensitivity
In a tragic cyclical relationship that leads to, or dramatically increases the risk of, a plethora of diseases such as metabolic syndrome, diabetes, Alzheimer’s, cardiovascular disease, shortening of the telomeres and more, increased blood glucose leads to the formation of advanced glycation end products (AGEs) and insulin resistance. Insulin resistance and AGE crosslink formation further exacerbate the issue of blood glucose levels by decreased glucose absorption, leading to higher blood glucose levels, increased insulin resistance and further formations of AGEs.[lii] Hydrogen has shown incredible promise in assisting both in healthy glucose levels as well as increasing insulin sensitivity in both animals and human studies of metabolic syndrome and diabetes- both types I and II.[liii][liv][lv][lvi][lvii][lviii][lix][lx] While not a substitute for a healthy diet, H2 acts as a protective shield to mitigate the damages and prevent this avalanche of symptoms from developing into chronic illness. While also profound for its’ neuroprotection, hydrogen has also shown to increase ghrelin secretion in mice[lxi], which is also needed for glucose metabolism.[lxii] Additionally, the highly bioavailable magnesium found in our tablets further adds to this protection. Magnesium is a cofactor of many enzymes involved in glucose metabolism such as its role in insulin action, and insulin stimulates magnesium uptake in insulin-sensitive tissues[lxiii].
Neuroprotection
One of hydrogens largest potentials is its exciting findings as a potential prophylactic neurodegenerative agent. Hydrogen has gathered considerable evidence demonstrating results in neurodegenerative diseases such as Alzheimer’s[lxiv][lxv] and Parkinson’s[lxvi][lxvii][lxviii], benefits in protection from cognitive impairment/decline[lxix][lxx][lxxi][lxxii][lxxiii][lxxiv][lxxv][lxxvi][lxxvii], rodent models on central nervous system diseases such as ALS[lxxviii] and MS[lxxix], reduction of neuroinflammation[lxxx][lxxxi]. Hydrogen has also shown to induce secretion of ghrelin[lxxxii] which has demonstrated neuroprotective capabilities.[lxxxiii][lxxxiv]
Senescent Cells, Anti-Apoptosis, telomerase and the Mitochondria
Along with the vast list of benefits being explored for various markers associated with disease progression, hydrogen also has shown promise in protecting our cells and DNA from damage and aging at a fundamental level. The mitochondria function as our cells power plants, releasing ATP (adenosine triphosphate) for a source of chemical energy. When mitochondria ‘die’ or stop functioning, our lysosome is tasked with breaking them down. A challenge facing our evolved system is when mitochondria mutate internally and are able to escape detection from the lysosome. Internally mutated mitochondria escape lysosomal detection and releases damaging oxidative molecules, which are linked to apoptosis, or cellular death[lxxxv]. Molecular hydrogen is a small enough molecule to pass right into the mitochondria and decrease hydroxyl radicals at the source, and has shown to be protective towards mitochondrial health and function[lxxxvi][lxxxvii][lxxxviii][lxxxix] while protecting against mitochondrial damaged and other damage induced cell apoptosis.[xc][xci][xcii][xciii][xciv][xcv][xcvi][xcvii][xcviii][xcix][c][ci][cii][ciii] Hydrogen has also shown to be able to prevent cellular senescence[civ][cv], which is the phenomenon where cells stop dividing, increase telomerase activity[cvi], the RNA containing protein that extends our telomeres and activate Sirt194[cvii][cviii] which is linked to extending lifespan in rodents[cix][cx].
Athletic Performance & Recovery
Hydrogen has received a considerable amount of research regarding its’ benefits for athletes. Studies have focused on decreasing healing time by speeding up healing of soft tissue injury, decreasing inflammation, and plasma viscosity[cxi], or rather proteins in our blood which coincide with inflammation. Hydrogen also helps by decreasing blood lactate levels leading to increased work completed before fatigue[cxii][cxiii][cxiv], over all peak performance[cxv] as well as potentially decreasing time needed for recovery[cxvi].
Skin Health
While only a few articles exist on the potential benefits for H2 and skin health, these benefits include wrinkle reduction[cxvii], atopic dermatitis[cxviii][cxix], burn wounds[cxx], psoriasis and skin lesions,[cxxi] pressure ulcers[cxxii], as well as UV damage[cxxiii]. Additionally, the tablet delivers ionic magnesium which has shown to be bioavailable through the skin not just for skin health, but absorption for whole body supplementation[cxxiv]. While the tablet remains stoichiometrically alkaline due to the magnesium content, the momentary pH upon topical application falls in the 4.6-5pH range. This range is the precise range in which our skin naturally operates, and is optimal for our skins resident flora.[cxxv]
Acts as a Selective Antioxidant
One of the chronic challenges humanity is dealing with in longevity research is oxidative stress. Oxygen, so critical for life as we know it, wreaks havoc on our cells through certain oxygen free radicals. As our bodies age or become sick, these oxygen radicals increase and our health plummets into a downward spiral. In the beginning the Universe began with Hydrogen, so the realization that hydrogen is capable of supressing the most damaging oxidative radical, which if the suppression is done by reaction, the product becomes the essence of life, water, was not only a profound revelation which lead to an avalanche of research but truly poetic.
Magnesium
Magnesium is perhaps the most important- and the most deficient macro mineral in the human body, necessary in over 300 biological functions. It is estimated that nearly 90% of North Americans do not receive adequate magnesium from their diets, with an annual 4.5 million preventable deaths attributed to heart disease and stroke that may have been avoided through adequate magnesium intake through water source.[cxxvi] Many magnesium supplements offer poor bioavailability, such as the most common supplemental form magnesium oxide. One study suggests the average availability of magnesium oxide to be as low as 4%[cxxvii]. In reality, depending on the strength of each individuals stomach acid, the bioavailability could be higher or even as low as zero. One of the results of our reaction is a powerful secondary benefit. The elemental magnesium first reacts creating with water creating magnesium hydroxide. Since hydroxide is a function of pH, our buffering acids are able to reduce the hydroxide dissociating it from the magnesium and leaving free magnesium ions in suspension. These magnesium ions will in turn be highly bioavailable, offering a fantastic source for this critical mineral.
[i] Kordinas V, Ioannidis A, Chatzipanagiotou S. The Telomere/Telomerase System in Chronic Inflammatory Diseases. Cause or Effect? Saretzki G, ed. Genes. 2016;7(9):60. doi:10.3390/genes7090060.
[ii] Arai Y, Martin-Ruiz CM, Takayama M, et al. Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians. EBioMedicine. 2015;2(10):1549-1558. doi:10.1016/j.ebiom.2015.07.029.
[iii] Kordinas, V., Tsirpanlis, G., Nicolaou, C., et al. (2015). Is there a connection between inflammation, telomerase activity and the transcriptional status of telomerase reverse transcriptase in renal failure?. Cellular and Molecular Biology Letters, 20(2), pp. 222-236. Retrieved 10 Dec. 2017, from doi:10.1515/cmble-2015-0016
[iv] Najib Nassani, Georges Khayat, Issam Raad, Ying Jiang, Nada Alaaeddine, George Hilal, Telomerase as a potential marker for inflammation and cancer detection in bronchial washing: A prospective study, In Clinical Biochemistry, Volume 46, Issues 16–17, 2013, Pages 1701-1704, ISSN 0009-9120, https://doi.org/10.1...em.2013.07.018.
(http://www.sciencedi...009912013003512)
Keywords: Bronchial aspiration; Lung cancer; Telomerase; Inflammation
[v] Jurk, D., Wilson, C., Passos, J. F., Oakley, F., Correia-Melo, C., Greaves, L., ... von Zglinicki, T. (2014). Chronic inflammation induces telomere dysfunction and accelerates ageing in mice. Nature Communications, 5, [4172]. DOI: 10.1038/ncomms5172
[vi] -von Zglinicki T. Oxidative stress shortens telomeres. Trends Biochem Sci 2002;27(7):339–344.
[vii] Oikawa S, Kawanishi S. Site-specific DNA damage at GGG sequence by oxidative stress may accelerate telomere shortening. FEBS Lett 1999;453(3):365-8
[viii] Kurz DJ, Decary S, Hong Y, Trivier E, Akhmedov A,Erusalimsky JD. Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells. J Cell Sci 2004;117(Pt 11):2417-26
[ix] Fulsen Bozkus. Could serum levels of telomerase be considered as an oxidative stress marker in COPD?
Telomere Telomerase 2016; 3: e1258. doi: 10.14800/tt.1258.
[x] Ping F, Li Z, Lv K, et al. Deoxyribonucleic acid telomere length shortening can predict the incidence of non‐alcoholic fatty liver disease in patients with type 2 diabetes mellitus. Journal of Diabetes Investigation. 2017;8(2):174-180. doi:10.1111/jdi.12555.
[xi] E.V. Plokhova, O.N. Tkacheva, D.U. Akasheva, I.D. Strazhesko, E.N. Dudinskaya, S.A. Boytsov; P3995
Advanced glycation end-products and telomere shortening contribute to cardiac aging: the relationship with myocardial strain, European Heart Journal, Volume 38, Issue suppl_1, 1 August 2017, ehx504.P3995, https://doi.org/10.1093/eurheartj/ehx504.P3995
[xii] Chen Y, Chen H, Xie K, et al (2015): H2 Treatment attenuated pain behavior and cytokine release through the HO-1/CO pathway in a rat model of neuropathic pain. Inflammation. 38:1835-1846
[xiii] Gao Y, Yang H, Fan Y, et al (2016): Hydrogen-rich saline attenuates cardiac and hepatic injury in doxorubicin rat model by inhibiting inflammation and apoptosis. Mediators Inflamm, 2016; 2016: 1320365. doi: 10. 1155/2016/1320365. [Epub ahead of print].
[xiv] Gharib B, Hanna S, Abdallahi OMS, et al (2001): Anti-inflammatory properties of molecular hydrogen: investigation on parasiteinduced liver inflammation. C R Acad Sci III,.324: 719-724.
[xv] Guo SX, Fang Q, You CG, et al (2015): Effects of hydrogen-rich saline on early acute kidney injury in severely burned rats by suppressing oxidative stress induced apoptosis and inflammation. J Transl Med, 13: 183.
[xvi][xvi][xvi] Kajiya M, Silva MJ, Sato K, et al (2009b): Hydrogen mediates suppression of colon inflammation induced by dextran sodium sulfate. Biochem Biophys Res Commun 386: 11-15.
[xvii] Li J, Hong Z, Liu H, et al (2016a): Hydrogen-rich saline promotes the recovery of renal function after ischemia/reperfusion injury in rats via anti-apoptosis and anti-inflammation. Front Pharmacol, 2016 Apr 22;7; 106. doi; 10. 00106. eCollection 2016.
[xviii] Liu L, Xie K, Chen H, et al (2014a): Inhalation of hydrogen gas attenuates brain injury in mice with cecal ligation and puncture via inhibiting neuroinflammation, oxidative stress and neuronal apoptosis. Brain Res, 2014 Sep 22. pii: S0006-8993(14)01251-7. doi: 10.1016/j.brainres. 2014. 09. 030. [Epub ahead of print].
[xix] Noda K, Tanaka Y, Shigemura N, et al (2012): Hydrogen-supplemented drinking water protects cardiac allografts from inflammationassociated deterioration. Transpl Int, 2012 Aug 14. doi: 10. 1111/j. 1432-2227. 2012. 01542. x.
[xx] Shi Q, Chen C, Deng WH, et al (2016): Hydrogen-rich saline attenuates acute hepatic injury in acute necrotizing pancreatitis by inhibiting inflammation and apoptosis, involving JNK and p38 mitogen-activated protein kinase-dependent reactive oxygen species. Pancreas, 45: 1424-1431.
[xxi] Spulber S, Edoff K, Hong L, et al (2012): Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice. PLoS One, 7: e42078.
[xxii] Tian R, Hou Z, Hao S, et al (2016): Hydrogen-rich water attenuates brain damage and inflammation after traumatic brain injury in rats. Brain Res, 1637: 1-13.
[xxiii] Wang C, Li J, Liu Q, et al (2011a): Hydrogen-rich saline reduces oxidative stress and inflammation by inhibit of JNK and NF-κB activation in a rat model of amyloid-beta-induced Alzheimer's disease. Neurosci Lett. 491: 127-132.
[xxiv] Wang X, Yu P, Yong Y, et al (2015): Hydrogen-rich saline resuscitation alleviates inflammation induced by severe burn with delayed resuscitation. Burns, 41: 379-85.
[xxv] Xie K, Yu Y, Zhang Z, et al (2010b): Hydrogen gas improves survival rate and organ damage in zymosan-induced generalized inflammation model. Shock, 34: 495-501.
[xxvi] Xie K, Yu Y, Huang Y, et al (2012a): Molecular hydrogen ameliorates lipopolysaccharide-induced acute lung injury in mice through reducing inflammation and apoptosis. Shock. 37: 548-55.
[xxvii] Macpherson H, Pipingas A, Pase MP Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2013 Feb; 97(2):437-44.
[xxviii]Bjelakovic G1, Nikolova D, Gluud C. Antioxidant supplements and mortality. Curr Opin Clin Nutr Metab Care. 2014 Jan;17(1):40-4. doi: 10.1097/MCO.0000000000000009.
[xxix] KRISTELL LE GAL, MOHAMED X. IBRAHIM, CLOTILDE WIEL, VOLKAN I. SAYIN, MURALI K. AKULA, CHRISTIN KARLSSON, MARTIN G. DALIN, LEVENT M. AKYÜREK, PER LINDAHL, JONAS NILSSON, MARTIN O. BERGO Antioxidants can increase melanoma metastasis in mice SCIENCE TRANSLATIONAL MEDICINE07 OCT 2015 : 308RE8 Antioxidants increase migration and invasion of human melanoma cells and accelerate metastasis in an endogenous mouse model of malignant melanoma.
[xxx] Ohsawa I1, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, Katayama Y, Asoh S, Ohta S. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007 Jun;13(6):688-94. Epub 2007 May 7.
[xxxi] Diao M, Zhang S, Wu L, et al (2016): Hydrogen gas inhalation attenuates seawater instillation-induced acute lung injury via the Nrf2 pathway in rabbits. Inflammation 2016 Sep 5
[xxxii] Kawamura T, Wakabayashi N, Shigemura N, et al (2013): Hydrogen gas reduced hyperoxic lung injury vai the Nrf2 pathway in vivo. Am J Physiol Lung Cell Mol Physiol, 304: L646-L656.
[xxxiii] Li Y, Xie K, Chen H, et al (2014): The role of Nrf2 in the hydrogen treatment for intestinal injury caused by severe sepsis. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue, 26: 415-419. (in Chinese).
[xxxiv] Liu L, Xie K, Chen H, et al (2014b): Role of Nrf2 in the protective effects of hydrogen against cerebral dysfunction in septic mice. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue, 26: 629-633. (in Chinese).
[xxxv] Tamaki N, Orihuela-Campos RC, Fukui M, et al (2016): Hydrogen-rich water intake accelerates oral palatal wound healing via activation of the Nrf2/antioxidant defense pathways in a rat model. Oxid Med Cell Long, 2016: Article ID 5679040.
[xxxvi] Yu J, Zhang W, Zhang R, et al (2015): Molecular hydrogen attenuates hypoxia/reoxygenation injury of intrahepatic cholangiocytes by activating Nrf2 expression. Toxicol Lett, 238: 11-19.
[xxxvii] Barajas B, Che N, Yin F, Rowshanrad A, Orozco LD, Gong KW, Wang X, Castellani LW, Reue K, Lusis AJ, Araujo JA (Jan 2011). "NF-E2-related factor 2 promotes atherosclerosis by effects on plasma lipoproteins and cholesterol transport that overshadow antioxidant protection". Arteriosclerosis, Thrombosis, and Vascular Biology. 31 (1): 58–66.
[xxxviii] DeNicola GM, Karreth FA, Humpton TJ, Gopinathan A, Wei C, Frese K, Mangal D, Yu KH, Yeo CJ, Calhoun ES, Scrimieri F, Winter JM, Hruban RH, Iacobuzio-Donahue C, Kern SE, Blair IA, Tuveson DA (Jul 2011). "Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis". Nature. 475 (7354): 106–9.
[xxxix] Sporn MB, Liby KT. NRF2 and cancer: the good, the bad and the importance of context. Nature reviews Cancer. 2012;12(8):10.1038/nrc3278. doi:10.1038/nrc3278.
[xl] Song G, Li M, Sang H, et al (2013): Hydrogen-rich water decrease serum low-density lipoprotein cholesterol levels and improves highdensity lipoprotein function in patients with potential metabolic syndrome. J Lipid Res, 2013 Apr 22.
[xli] Song G, Lin Q, Zhao H, et al (2015b): Hydrogen activates ATP-binding cassette transporter A1-dependent efflux ex vivo and improves high-density lipoprotein function in patients with hypercholesterolemia: A double-blinded, randomized, and placebo-controlled trial. J Clin Endocrinol Metab. 100: 2724-2733
[xlii] Zong C, Song G, Yao S, et al (2012): Administration of hydrogen-saturated saline decreases plasma low-density lipoprotein cholesterol levels and improves high-density lipoprotein function in high-fat diet-fed hamsters. Metabolism, 61: 79
[xliii] Runtuwene J, Amitani H, Amitani M, et al (2015): Hydrogen-water enhances 5-fluorouracil-induced inhibition of colon cancer. PeerJ, 3: e859; DOI 10.7717/peerj.859.
[xliv] Dole M, Wilson FR, and Fife WP (1975): Hyperbaric hydrogen therapy: A possible treatment for cancer. Science, 190: 152-154.
[xlv] Kang KM, Kang YN, Choi IB, Gu Y, Kawamura T, Toyoda Y, et al. Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors. Med Gas Res. 2011;1:11.
[xlvi] Nakashima-Kamimura N, Mori T, Ohsawa I, et al (2009): Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice. Cancer Chemother Pharmacol, 64: 753-761
[xlvii] Zhao L, Zhou C, Zhang J, et al (2011): Hydrogen protects mice from radiation induced thymic lymphoma in BALB/c mice. Int J Bio Sci, 7: 297-300.
[xlviii] Ishibashi T, Sato B, Rikitake M, et al (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. Med Gas Res, 2012
[xlix] Ishibashi T, Sato B, Shibata S, et al (2014): Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: A randomized, double-blind placebo-controlled pilot study. Int Immunopharmacol, 21: 468-473.
[l] Xia C, Liu W, Zeng D, et al (2013): Effect of hydrogen-rich water on oxidative stress, liver function, and viral load in patients with chronic hepatitis B. Clin Trans Sci, 6: 372-375.
[li] Yoritaka A, Takanashi M, Hirayama M, et al (2013): Pilot study of H2 therapy in Parkinson’s disease. A randomized double-blind placebo-controlled trial. Mov Disord, 28: 836-839
[lii] Vlassara H, Uribarri J. Advanced Glycation End Products (AGE) and Diabetes: Cause, Effect, or Both? Current diabetes reports. 2014;14(1):453. doi:10.1007/s11892-013-0453-1.
[liii] Korovljev D1, Trivic T1, Drid P1, Ostojic SM2,3,4 Molecular hydrogen affects body composition, metabolic profiles, and mitochondrial function in middle-aged overweight women. Ir J Med Sci. 2017 May 30. doi: 10.1007/s11845-017-1638-4. [Epub ahead of print]
[liv] Li Y, Hamasaki T, Nakamichi N, et al (2011): Suppressive effects of electrolyzed reduced water on alloxan-induced apoptosis and type 1 diabetes mellitus. Cytotecnol, 63: 119-131
[lv] Kamimura N, Nishimaki K, Ohsawa I, et al (2011): Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice. Obesity (Silver Spring), 19: 1396-1403
[lvi] Kajiyama S, Hasegawa G, Asano M, et al (2008): Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutr Res, 28: 137-143.
[lvii] Nakao A, Toyoda Y, Sharma P, et al (2010b): Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome: an open label pilot study. J Clin Biochem Nutr, 46: 140-149.
[lviii] Hashimoto M, Katakura M, Nabika T, et al (2011): Effects of hydrogen-rich water on abnormalities in a SHR.Cg-LeprCP/NDmcr rat – a metabolic syndrome rat model. Med Gas Res, 1: 26.
[lix] Song G, Li M, Sang H, et al (2013): Hydrogen-rich water decrease serum low-density lipoprotein cholesterol levels and improves highdensity lipoprotein function in patients with potential metabolic syndrome. J Lipid Res, 2013 Apr 22. [Epub ahead of print].
[lx] Wang QJ1, Zha XJ, Kang ZM, Xu MJ, Huang Q, Zou DJ. Therapeutic effects of hydrogen saturated saline on rat diabetic model and insulin resistant model via reduction of oxidative stress. Chin Med J (Engl). 2012 May;125(9):1633-7.
[lxi] Matsumoto A, Yamafuji M, Tachibana T, et al (2013): Oral ‘hydrogen water’ induces neuroprotective ghrelin secretion in mice. Sci Rep, 3: 3273. doi: 10. 1038. Srep03273.
[lxii] Heppner KM, Tong J (July 2014). "Mechanisms in endocrinology: regulation of glucose metabolism by the ghrelin system: multiple players and multiple actions". European Journal of Endocrinology. 171 (1): R21–32.
[lxiii] Junji Takaya, Hirohiko Higashino, Yohnosuke Kobayashi . Intracellular magnesium and insulin resistance . Magnesium Research. 2004;17(2):126-136.
Top of Form
Votre Email :
Bottom of Form
[lxiv] Li J, Wang C, Zhang JH, et al (2010): Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer’s disease by reduction of oxidative stress. Brain Res, 1328: 152-161
[lxv] Wang C, Li J, Liu Q, et al (2011a): Hydrogen-rich saline reduces oxidative stress and inflammation by inhibit of JNK and NF-κB activation in a rat model of amyloid-beta-induced Alzheimer's disease. Neurosci Lett. 491: 127-132
[lxvi] Ito M, Hirayama M, Yamai K, et al. Drinking hydrogen water and intermittent hydrogen gas exposure, but not lactulose or continuous hydrogen gas exposure, prevent 6-hydorxydopamine-induced Parkinson’s disease in rats. Medical Gas Research. 2012;2:15. doi:10.1186/2045-9912-2-15.
[lxvii] Fu Y, Ito M, Fujita Y, et al (2009): Molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson’s disease. Neurosci Lett, 453: 81-85
[lxviii] Fujita K, Seike T, Yutsudo N, et al (2009): Hydrogen in drinking water reduces dopaminergic neuronal loss in the 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. PLoS One, 4: e7247
[lxix] Gu Y, Huang C-S, Inoue T, et al. Drinking Hydrogen Water Ameliorated Cognitive Impairment in Senescence-Accelerated Mice. Journal of Clinical Biochemistry and Nutrition. 2010;46(3):269-276. doi:10.3164/jcbn.10-19.
[lxx] Ge P, Zhao J, Li S, et al (2012): Inhalation of hydrogen gas attenuates cognitive impairment in transient cerebral ischemia via inhibition of oxidative stress. Neurol Res. 34: 187-194.
[lxxi] Li C, Hou L, Chen D, et al (2017): Hydrogen-rich saline attenuates isoflurane-induced caspase-3 activation and cognitive impairment via inhibition of isoflurane-induced oxidative stress, mitochondrial dysfunction, and reduction in ATP levels. Am J Transl Res, 9: 1162- 1172.
[lxxii] Hou Z, Luo W, Sun X, et al (2012): Hydrogen-rich saline protects against oxidative damage and cognitive deficits after mild traumatic brain injury. Brain Res Bull, 88: 560-565.
[lxxiii] Liu L, Xie K, Chen H, et al (2015): Protective effects of inhaled hydrogen gas on cognitive function in mice with sepsis-associated encephalopathy. DeZhonghua Yi Xue Za Zhi, 94:3179-3183.
[lxxiv] Tian Y, Guo S, Zhang Y, et al (2016): Effects of hydrogen-rich saline on hepatectomy-induced postoperative cognitive dysfunction in old mice. Mol Neurobiol, 2016 Mar 19.
[lxxv] Zhou J, Chen Y, Huang GQ, et al (2012a): Hydrogen-rich saline reverses oxidative stress, cognitive impairment, and mortality in rats submitted to sepsis by cercal ligation and puncture. J Surg Res. 2012 Apr 1
[lxxvi] Nagata, Kazufumi & Kamimura, Naomi & Mikami, Toshio & Ohsawa, Ikuroh & Ohta, Shigeo. (2008). Consumption of Molecular Hydrogen Prevents the Stress-Induced Impairments in Hippocampus-Dependent Learning Tasks during Chronic Physical Restraint in Mice. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 34. 501-8. 10.1038/npp.2008.95.
[lxxvii] Takeuchi S, Nagatani K, Otani N, et al. Hydrogen improves neurological function through attenuation of blood–brain barrier disruption in spontaneously hypertensive stroke-prone rats. BMC Neuroscience. 2015;16:22. doi:10.1186/s12868-015-0165-3.
[lxxix]Zhao, Ming et al. Hydrogen-rich water improves neurological functional recovery in experimental autoimmune encephalomyelitis mice Journal of Neuroimmunology , Volume 294 , 6 - 13
[lxxx] Liu L, Xie K, Chen H, et al (2014a): Inhalation of hydrogen gas attenuates brain injury in mice with cecal ligation and puncture via inhibiting neuroinflammation, oxidative stress and neuronal apoptosis. Brain Res, 2014 Sep 22. pii: S0006-8993(14)01251-7. doi: 10.1016/j.brainres. 2014. 09. 030.
[lxxxi] Spulber S, Edoff K, Hong L, et al (2012): Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice. PLoS One, 7: e42078
[lxxxii] Matsumoto A, Yamafuji M, Tachibana T, Nakabeppu Y, Noda M, Nakaya H. Oral “hydrogen water” induces neuroprotective ghrelin secretion in mice. Scientific Reports. 2013;3:3273. doi:10.1038/srep03273.
[lxxxiii] Bayliss JA, Andrews ZB. Ghrelin is neuroprotective in Parkinson’s disease: molecular mechanisms of metabolic neuroprotection. Therapeutic Advances in Endocrinology and Metabolism. 2013;4(1):25-36. doi:10.1177/2042018813479645.
[lxxxiv] Dos Santos VV1, Rodrigues AL, De Lima TC, de Barioglio SR, Raisman-Vozari R, Prediger RD. Ghrelin as a neuroprotective and palliative agent in Alzheimer's and Parkinson's disease. Curr Pharm Des. 2013;19(38):6773-90.
[lxxxv] Terman A, Kurz T, Gustafsson B, Brunk UT. The Involvement of Lysosomes in Myocardial Aging and Disease . Current Cardiology Reviews. 2008;4(2):107-115. doi:10.2174/157340308784245801.
[lxxxvi] Cui Y, Zhang H, Ji M, et al (2014): Hydrogen-rich saline attenuates neuronal ischemia-reperfusion injury by protecting mitochondrial function in rats. J Sur Res, 2014 May 24. pii: S0022-4804(14)00529-0. doi: 10. 1016/j. jss. 2014. 05. 060.
[lxxxvii] Ito M, Ibi T, Sahashi K, et al (2011): Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogenenriched water for mitochondrial and inflammatory myopathies. Med Gas Res, 1: 24
[lxxxviii] Li C, Hou L, Chen D, et al (2017): Hydrogen-rich saline attenuates isoflurane-induced caspase-3 activation and cognitive impairment via inhibition of isoflurane-induced oxidative stress, mitochondrial dysfunction, and reduction in ATP levels. Am J Transl Res, 9: 1162- 1172
[lxxxix] Yoshida A, Asanuma H, Sasaki H, et al (2012): H2 mediates cardioprotection via involvements of KATP channels and permeability transition pores of mitochondria in dogs. Cardiovasc Drugs Ther, 26: 217-226
[xc] Liu Q, Li BS, Song YJ, et al (2016): Hydrogen-rich saline protects against mitochondrial dysfunction and apoptosis in mice with obstructive jaundice. Mol Med Rep, 4: 3588-3596
[xci] Cai J, Kang Z, Liu WW, et al (2008): Hydrogen therapy reduced apoptosis in neonatal hypoxia-ischemia rat model. Neurosci Lett, 441: 167-172
[xcii] Gao Y, Yang H, Fan Y, et al (2016): Hydrogen-rich saline attenuates cardiac and hepatic injury in doxorubicin rat model by inhibiting inflammation and apoptosis. Mediators Inflamm, 2016; 2016: 1320365. doi: 10. 1155/2016/1320365.
[xciii] Guo SX, Fang Q, You CG, et al (2015): Effects of hydrogen-rich saline on early acute kidney injury in severely burned rats by suppressing oxidative stress induced apoptosis and inflammation. J Transl Med, 13: 183.
[xciv] Hong Y, Shao A, Wang J, et al (2014): Neuroprotective effect of hydrogen-rich saline against neurologic damage and apoptosis in early brain injury following subarachnoid hemorrhage: Possible role of the Akt/GSK3βsignaling pathway. PLoS ONE, 9: e96212. doi. 10. 1371.
[xcv] Huang CS, kawamura T, Peng X, et al (2011a): Hydrogen inhalation reduced epithelial apoptosis in ventilator-induced lung injury via a mechanism involving nuclear factor-kappa B activation. Biochem Biophys Res Commun, 408: 253-258
[xcvi] Jiang H, Yu P, Qian DH, et al (2013): Hydrogen-rich medium suppresses the generation of reactive oxygen species, elevates the Bcl- 2/Bax ratio and inhibits advanced glycation end product-induced apoptosis. Int J Mol Med, 31: 1381-1387.
[xcvii] Li J, Hong Z, Liu H, et al (2016a): Hydrogen-rich saline promotes the recovery of renal function after ischemia/reperfusion injury in rats via anti-apoptosis and anti-inflammation. Front Pharmacol, 2016 Apr 22;7; 106. doi; 10. 00106. eCollection 2016.
[xcviii] Li J, Ge Z, Fan L, et al (2017): Protective effect of molecular hydrogen on steroid-induced osteonecrosis in rabbits via reducing oxidative stress and apoptosis. BMC Musculoskelet Disord, 18: 58
[xcix] Liu Q, Li BS, Song YJ, et al (2016): Hydrogen-rich saline protects against mitochondrial dysfunction and apoptosis in mice with obstructive jaundice. Mol Med Rep, 4: 3588-3596
[c] Liu YQ, Liu YF, Ma XM, et al (2015): Hydrogen-rich saline attenuates skin ischemia/reperfusion induced apoptosis via regulating Bax/Bcl-2 ratio and ASK-1/JNK pathway. J Plast Reconstr Aesthet Surg. 68:e147-156
[ci] Shi Q, Chen C, Deng WH, et al (2016): Hydrogen-rich saline attenuates acute hepatic injury in acute necrotizing pancreatitis by inhibiting inflammation and apoptosis, involving JNK and p38 mitogen-activated protein kinase-dependent reactive oxygen species. Pancreas, 45: 1424-1431
[cii] Yonamine R, Satoh Y, Kodama M, et al (2013): Co-administration of hydrogen gas as part of the carrier gas mixture suppresses neuronal apoptosis and subsequent behavioral deficits caused by neonatal exposure to sevoflurane in mice. Anesthesiology, 118: 105-113
[ciii] Yang Y, Li B, Liu C, et al (2012): Hydrogen-rich saline protects immunocytes from radiation-induced apoptosis. Med Sci Monit. 18: BR144-148
[civ] Hara F, Tatebe J, Watanabe I, et al (2016): Molecular hydrogen alleviates cellular senescence in endothelial cells. Cric J, 80: 2037-2046
[cv] Han AL, Park SH, and Park MS (2017): Hydrogen treatment protects against cell death and senescence induced by oxidative damage. J Microbiol Biotechnol, 27: 365-371
[cvi] Robert Settineri, Jin Ji, Chunlan Luo, Rita R. Ellithorpe, Gonzalo Ferreira de Mattos, Steven Rosenblatt, James LaValle, Antonio Jinenez, Shigeo Ohta, Garth L. Nicolson. Effects of Hydrogenized Water on Intracellular Biomarkers for Antioxidants, Glucose Uptake, Insulin Signaling and SIRT 1 and Telomerase Activity. American Journal of Food and Nutrition. Vol. 4, No. 6, 2016, pp 161-168
[cvii] Xing Z, Pan W, Zhang J, et al (2017): Hydrogen rich water attenuates renal injury and fibrosis by regulation transforming growth factor-β induced Sirt1. Biol Pharm Bull, 40: 610-615.
[cviii] Qi LS, Yao L, Liu W, et al (2015): Sirtuin type 1 mediates the retinal protective effect of hydrogen-rich saline against light-induced damage in rats. Invest Ophthalmol Vis Sci, 56: 8268-8269.
[cix] Mitchell SJ, Martin-Montalvo A, Mercken EM, et al. The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet. Cell reports. 2014;6(5):836-843. doi:10.1016/j.celrep.2014.01.031.
[cx] Mitchell SJ, Martin-Montalvo A, Mercken EM, Palacios HH, Ward TM, Abulwerdi G, Minor RK, Vlasuk GP, Ellis JL, Sinclair DA, Dawson J, Allison DB, Zhang Y, Becker KG, Bernier M, de Cabo R (2014). "The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet". Cell Rep. 6
[cxi]Sergej M. Ostojic, Boris Vukomanovic, Julio Calleja-Gonzalez & Jay R. Hoffman Effectiveness of Oral and Topical Hydrogen for Sports-Related Soft Tissue Injuries Postgraduate Medicine Vol. 126 , Iss. 5,2014
[cxii] Aoki K, Nakao A, Adachi T, Matsui Y, Miyakawa S. Pilot study: Effects of drinking hydrogen-rich water on muscle fatigue caused by acute exercise in elite athletes. Medical Gas Research. 2012;2:12. doi:10.1186/2045-9912-2-12.
[cxiii] Ostojic, Sergej M. Serum Alkalinization and Hydrogen-Rich Water in Healthy Men Mayo Clinic Proceedings , Volume 87 , Issue 5 , 501 - 502
[cxiv] Sergej M. Ostojic & Marko D. Stojanovic Hydrogen-Rich Water Affected Blood Alkalinity in Physically Active Men Research in Sports Medicine Vol. 22 , Iss. 1,2014
[cxv] Da Ponte A, Giovanelli N, Nigris D, Lazzer S. Effects of hydrogen rich water on prolonged intermittent exercise. J Sports Med Phys Fitness 2017 Apr 26. DOI: 10.23736/S0022-4707.17.06883-9
[cxvii] Shinya Kato, Yasukazu Saitoh, Keizou Iwai, Nobuhiko Miwa, Hydrogen-rich electrolyzed warm water represses wrinkle formation against UVA ray together with type-I collagen production and oxidative-stress diminishment in fibroblasts and cell-injury prevention in keratinocytes, In Journal of Photochemistry and Photobiology B: Biology, Volume 106, 2012, Pages 24-33, ISSN 1011-1344, https://doi.org/10.1...ol.2011.09.006.
(http://www.sciencedi...011134411002193)
Keywords: Hydrogen water; UV-A; Type-I collagen; Oxidative stress; Hydrogen water bathing; Wrinkle repression
[cxviii] Yoon YS, Sajo ME, Ignacio RM, et al (2014): Positive effects of hydrogen water on 2,4-dinitrochlorobenzene-induced atopic dermatitis in NC/Nga mice. Bio Pharm Bull, 2014; 37 (9): 1480-1485.
[cxix] Ignacio RM, Kwak HS, Yun YU, et al (2013b): The drinking effect of hydrogen water on atopic dermatitis induced by Dermatophagoides farina allergen in NC/Nga mice. Evid Based Complement Alternat Med, 2013, Article ID 538673, doi: 10.1155/2013/538673. Epub 2013 Nov 20.
[cxx] Guo SX, Jin YY, Fang Q, et al (2015): Beneficial effects of hydrogen-rich saline on early burn-wound progression in rats. PLoS One. 10 (4):e0124897.
[cxxi] Ishibashi T, Ichikawa M, Sato B, et al (2015): Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: A report of three cases. Mol Med Rep, 2015 Apr 30. doi: 10.3892/mmr.2015.3707
[cxxii] Li Q, Kato S, Matsuoka D, et al (2013): Hydrogen water intake via tube-feeding for patients with pressure ulcer and its reconstructive effects on normal human skin cells in vitro. Med Gas Res, 3:20.
[cxxiv] Kass L, Rosanoff A, Tanner A, Sullivan K, McAuley W, Plesset M. Effect of transdermal magnesium cream on serum and urinary magnesium levels in humans: A pilot study. Song Y, ed. PLoS ONE. 2017;12(4):e0174817. doi:10.1371/journal.pone.0174817.
[cxxv] Lambers, H., Piessens, S., Bloem, A., Pronk, H. and Finkel, P. (2006), Natural skin surface pH is on average below 5, which is beneficial for its resident flora. International Journal of Cosmetic Science, 28: 359–370. doi:10.1111/j.1467-2494.2006.00344.x
Volume 81, Issue 6, December 2013, Pages 1063-1065