Molecular Hydrogen: An Adjunctive Therapy for Conventional Cancer Care?
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Evidence suggests this unconventional antioxidant can help mitigate radiation side effects
We’ve delved into many of the basics pertaining to hydrogen (H2): what it is, its history of use, and various means of delivering it to the body. We also have discussed how it acts as a selective antioxidant and an anti-inflammatory, and as such, how it helps protect the brain. However, this is but a small nugget of the research pertaining to molecular H2 and its potential clinical uses. Herein, we take a look at the research suggesting H2 may be another tool to help mitigate side effects associated with the conventional treatment of cancer.
When highly stressed, H2 is best?
As an antioxidant, H2 has many features that make it different from the other many substances that we know to have antioxidant activity. Firstly, H2 is the smallest molecule that exists, which enables it to readily pass through biological membranes and into all cellular compartments and biological tissues. Its neutral charge, nonreactivity, and nonpolarity further supports its transport through the body. Secondly, rather than being a strong reducing agent, H2 is actually highly effective because it is a weak reducing agent., This means it reacts primarily with very reactive and toxic oxidants (such as the hydroxyl radical [•OH] and peroxynitrite [ONOO-]), leaving weaker (and biologically necessary) oxidants like nitric oxide (NO) and hydrogen peroxide (H2O2) present. However, H2 has been shown to help reduce the body’s overproduction of these necessary oxidants and proinflammatory cytokines, – a situation that underlies many chronic disease processes and occurs with treatment for malignancy. Seemingly, when the body is highly stressed, H2 may be most useful as a therapy.
Preclinical research using hydrogen as adjunctive support for cancer treatment
Numerous studies suggest molecular H2 may be a useful tool to help protect the body against damage that occurs with ionizing radiation. A significant amount of harm from radiation is caused by the •OH radicals associated with it, because •OH indiscriminately damages cellular membranes, proteins, and DNA. Although this process is necessary to kill off cancer cells, it also contributes to considerable damage of healthy cells, in particular those that reproduce at a more rapid rate such as the gastrointestinal tract.
Research suggests the damaging effects of ionizing radiation and chemotherapy on healthy cells can be mitigated, at least in part, by a higher cellular antioxidant status or pretreatment with substances having high antioxidant activity.
Research suggests the damaging effects of ionizing radiation and chemotherapy on healthy cells can be mitigated, at least in part, by a higher cellular antioxidant status or pretreatment with substances having high antioxidant activity.,,, Specifically, cellular and animal studies have shown that pretreatment with H2 decreases the damaging effects of radiation or chemotherapy on cells of the immune system, digestive tract, reproductive system, kidneys, and even the heart,,,,, and thus it may help protect against problems of these systems that commonly occur with cancer treatment. In one of these studies, although H2 was shown to be protective for healthy cells, it did not adversely affect the intended anti-tumor effects of the treatment,14 while in another study, it even enhanced the effects of the treatment. By mitigating some of the side effects of these treatments, H2 supplementation may reduce the number of patients that abandon treatment due to the high rate of adverse effects and reduced quality of life.
Hydrogen as an adjunct to radiation treatment
At this time, a single human study has investigated the effects of H2-rich water as a supplement in patients undergoing radiation treatment. In this randomized, double-blind, placebo-controlled trial, 49 individuals receiving radiotherapy for treatment of liver cancer (hepatocellular carcinoma or hepatic metastasis) were given H2-rich water or placebo during six weeks of their treatment. Participants were provided with four 500 mL bottles of H2-rich water or placebo water to drink daily, starting on the first day of radiation treatment, and instructions were provided to drink 200 to 300 mL of the water in the morning, and 100 to 200 mL every few hours throughout the day. To determine the effectiveness of the intervention, quality of life (QOL) scores were assessed weekly using a questionnaire that evaluates numerous areas of function (including cognitive, emotional, and physical health) that are often affected by malignancy and its treatment, and antioxidant power and reactive oxidant metabolite levels in the blood were assessed on day one (before radiation treatment and intervention began) and after six weeks.
Importantly, the tumor response to radiation treatment was not compromised by consumption of H2-rich water.
From week one and through the study, QOL scores were significantly better in patients receiving H2-rich water compared to placebo. The individuals consuming H2 water also had significantly less appetite loss and fewer tasting disorders. Changes in both oxidative stress and antioxidant levels were prevented by consumption of H2 water, while both markers were significantly worsened by radiation treatment in the group receiving placebo water. Other markers (liver function, red and white blood cell counts, platelet counts, and cholesterol) did not change significantly in either group. Importantly, the tumor response to radiation treatment was not compromised by consumption of H2-rich water, and 48% of the patients in the H2 water group exhibited a complete or partial response to treatment, as compared to 50% of the placebo group, and in neither group did patients experience progressive disease in the three month follow-up period.
Clearly, molecular H2 is a therapy with great potential that we are just beginning to understand. Given that research with H2 as a therapy really just got underway in 2007, when the landmark study using H2 in a manner in which it could be practically applied as a supplement therapy was published in Nature Medicine,1 the findings of these and other studies make it clear that we will continue to see an increasing amount of research in the years to come. Although there are promising findings in the studies evaluating the use of H2 as an adjunctive agent with cancer treatments, it is important to note that usage of H2 or any other supplement during treatment for malignancy should be thoroughly discussed with one’s oncologist before initiating supplementation.
Click here to see References
 Ohsawa I, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007 Jun;13(6):688-94.
 Matei N, et al. Emerging mechanisms and novel applications of hydrogen gas therapy. Med Gas Res. 2018 Sep 25;8(3):98-102.
 Sakai T, et al. Hydrogen indirectly suppresses increases in hydrogen peroxide in cytoplasmic hydroxyl radical-induced cells and suppresses cellular senescence. Int J Mol Sci. 2019 Jan 21;20(2):456.
 Zhang Y, et al. Effects of hydrogen-rich water on depressive-like behavior in mice. Sci Rep. 2016 Mar 30;6:23742.
 Chuai Y, et al. Molecular hydrogen and radiation protection. Free Radic Res. 2012 Sep;46(9):1061-7.
 Riley PA, et al. Free radicals in biology: oxidative stress and the effects of ionizing radiation. Int J Radiat Biol. 1994 Jan;65(1):27-33.
 Srinivasan M, et al. Lycopene: an antioxidant and radioprotector against gamma-radiation-induced cellular damages in cultured human lymphocytes. Toxicology. 2009 Jul 28;262(1):43-9.
 Kalpana KB, et al. Investigation of the radioprotective efficacy of hesperidin against gamma-radiation induced cellular damage in cultured human peripheral blood lymphocytes. Mutat Res. 2009 May 31;676(1-2):54-61.
 Yahyapour R, et al. Radiation protection and mitigation by natural antioxidants and flavonoids: implications to radiotherapy and radiation disasters. Curr Mol Pharmacol. 2018;11(4):285-304.
 Sheu MT, et al. Efficacy of antioxidants as a Complementary and Alternative Medicine (CAM) in combination with the chemotherapeutic agent doxorubicin. Integr Cancer Ther. 2015 Mar;14(2):184-95.
 Qian L, et al. Radioprotective effect of hydrogen in cultured cells and mice. Free Radic Res. 2010 Mar;44(3):275-82.
 Qian L, et al. The potential cardioprotective effects of hydrogen in irradiated mice. J Radiat Res. 2010;51(6):741-7.
 Chuai Y, et al. Hydrogen-rich saline attenuates radiation-induced male germ cell loss in mice through reducing hydroxyl radicals. Biochem J. 2012 Feb 15;442(1):49-56.
 Nakashima-Kamimura N, et al. Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice. Cancer Chemother Pharmacol. 2009 Sep;64(4):753-61.
 Meng X, et al. Hydrogen-rich saline attenuates chemotherapy-induced ovarian injury via regulation of oxidative stress. Exp Ther Med. 2015 Dec;10(6):2277-82.
 Runtuwene J, et al. Hydrogen-water enhances 5-fluorouracil-induced inhibition of colon cancer. PeerJ. 2015 Apr 7;3:e859.
 Kang KM, 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 Jun 7;1(1):11.
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Dr. Carrie Decker
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