Going Beyond the Hype of Hydrogen Water

New randomized, double-blind, controlled trial suggests hydrogen water can increase antioxidant capacity and reduce inflammation

By Dana G. Cohen, MD, and Karolyn A. Gazella

REFERENCE

Sim M, Kim CS, Shon WJ, Lee YK, Choi EY, Shin DM. Hydrogen-rich water reduces inflammatory responses and prevents apoptosis of peripheral blood cells in healthy adults: a randomized, double-blind, controlled trial. Sci Rep. 2020;10(1):12130.

STUDY OBJECTIVE

To determine if hydrogen water versus plain water increases antioxidant capacity, reduces oxidative stress, and improves immune function in healthy adults

PARTICIPANTS

A total of 38 healthy adults aged 20 to 59 years completed the trial and were randomly assigned to the plain water group (n=18) or the hydrogen water group (n=20). At baseline when the study began, there was no statistical difference in age, height, weight, body mass index (BMI), and daily water intake between the 2 groups (P>0.05).

DESIGN

Randomized, double-blind, controlled trial

INTERVENTION

For 4 weeks, each group drank 1.5 liters (approximately 51 ounces) of either plain or hydrogen water daily. The hydrogen water was regular water with hydrogen (H2) gas added. Researchers provided the water in 3 different bottles and directed all participants to drink the bottle of water within 1 hour of opening it to minimize the loss of dissolved hydrogen from those bottles containing it.

MEASURED OUTCOMES

Researchers measured the following outcomes: • Antioxidant capacity as indicated by serum biological antioxidant potential (BAP) • Oxidative stress via the level of serum derivatives of reactive oxygen metabolites (d-ROMs) • Apoptosis via the number of apoptotic cells in the blood • Profiles of peripheral blood mononuclear cells (PBMCs) for cell-surface markers including CD4, CD8, CD14, CD20, and CD11b • Inflammation via toll-like receptor (TLR) NF-кB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling, as well as pro-inflammatory cytokine expression. What is additionally interesting about this study is that the benefits of hydrogen water were more significant in individuals “ over age 30.”

KEY FINDINGS

The following findings were observed: • Participants in the hydrogen water group who were aged over 30 years showed a significant increase in BAP compared to the plain water group (P=0.028), but there was no significant effect on

BAP in younger individuals in the hydrogen water group compared to plain water. • A marker for DNA damage due to oxidative stress (8-Oxo-2’-deoxyguanosine) significantly decreased in both groups (Δ=−0.94±1.44 ng/ mL, P<0.05 in the plain water group;

Δ=−1.32±1.05 ng/mL, P<0.001 in the hydrogen water group). • After the 4 weeks, the hydrogen water group showed a significantly lower percentage of PBMC apoptosis compared to the plain water group (P=0.036). • The frequency of CD14+ cells increased in the hydrogen water group and decreased in the plain water group, and this difference reached statistical significance (P=0.039). • The hydrogen water group had significantly lower expression levels of several cytokines: interleukin 1 beta (IL1B), interleukin 8 (IL8), interleukin 6 receptor (IL6R), and tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) compared to the plain water group. (continued on page 16)

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PRACTICE IMPLICATIONS

Immune activation and inflammation go hand in hand as reactive oxygen species stimulate immune cells that cause the subsequent inflammatory response. Reducing underlying oxidative stress is an ongoing clinical objective with many patients, and finding safe, efficacious interventions that can do this on an ongoing basis is appealing. One such tool may be in the use of therapeutic hydrogen gas.

In addition to hydrogen-rich water, hydrogen therapies include injecting hydrogen saline, inhaling hydrogen gas, using hydrogen eye drops, and taking hydrogen-rich water baths.1 The scientific community is just now uncovering hydrogen therapy’s mechanisms of action, which are diverse. They include:2 • Increasing antioxidant activity, • Inhibiting apoptosis and inflammation, • Modulating immune regulation, and • Regulating autophagy, circadian rhythm, and mitochondria. Hydrogen gas as a therapeutic tool is being investigated for a variety of conditions in the scientific literature because of these multiple mechanisms of action. But what does the research tell us specifically about hydrogen water? Similar to therapeutic hydrogen gas, hydrogen water has been studied in diverse patient populations and has shown positive effects on antioxidant status, immunity, and inflammation.

For example, a 2017 randomized, placebo-controlled trial involving colon cancer patients undergoing chemotherapy treatment showed that hydrogen water helped protect against chemotherapy-induced liver damage compared to placebo.3 This is consistent with a 2011 randomized, placebo-controlled trial involving liver cancer patients that showed hydrogen water reduced radiation-induced oxidative stress without compromising the antitumor effects compared to placebo.4 In that study, quality-of-life scores were also significantly better in the hydrogen water group compared to placebo.

Metabolic syndrome is another area where there is growing research regarding the benefits of hydrogen water. In a 2010 pilot study involving individuals at risk of developing metabolic syndrome, the group drinking the hydrogen water had a 39% increase in the antioxidant enzyme superoxide dismutase (SOD), an 8% increase in high-density lipoprotein cholesterol, and a 13% decrease in total cholesterol.5 Similarly, a 2020 randomized, double-blind, placebo-controlled trial showed that the group drinking the hydrogen water had significantly reduced blood cholesterol, glucose, and hemoglobin A1c, and improved inflammatory markers and redox homeostasis compared to placebo.6

In a 2012 pilot study involving patients with rheumatoid arthritis (RA), hydrogen water not only reduced markers of oxidative stress, but it also improved RA symptoms.7

A 2013 randomized, controlled trial involving patients with hepatitis B showed that hydrogen water improved markers of oxidative stress and liver function compared to placebo.8

A 2017 double-blind, placebo-controlled study discovered that the anti-inflammatory and antioxidant activity of hydrogen water can also impact the central nervous system. In that study, the group drinking the hydrogen water had improvements in mood, anxiety, and overall quality of life compared to placebo.9

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Preliminary research also demonstrates that hydrogen water may positively influence the gut microbiome. In a trial involving female juvenile soccer players, 2 months of drinking hydrogen water reduced IL1, IL2, and tumor necrosis factor; increased SOD, total antioxidant capacity, and whole blood hemoglobin; and improved the diversity and abundance of gut flora.10

As this paper points out, the US Food and Drug Administration has recognized hydrogen gas as a food additive with generally recognized as safe (GRAS) status. The research confirms that hydrogen water is safe when consumed at the recommended doses.

One argument often made regarding the hydrogen water studies is that merely increasing consumption of water will confer significant health benefits and that even mild dehydration can contribute to a variety of illnesses.11 However, that argument is not valid in studies comparing hydrogen water to the same amount of plain water consumed.

This latest clinical trial adds credence to the therapeutic efficacy of hydrogen water, which has come under fire as being all hype and no substance. What is additionally interesting about this study is that the benefits of hydrogen water were more significant in individuals over age 30. Because aging is often accompanied by increased systemic oxidative stress and damage, it makes sense that as one ages, the need for enhanced antioxidant defenses would also increase and, therefore, those individuals would get more benefit from hydrogen water. This is also true for individuals dealing with dysregulated redox balance and systemic inflammation due to illness.

From a clinical perspective, the research appears to support the use of hydrogen water for a variety of conditions that require immune regulation, increased antioxidant activity, and reduced inflammation. The biggest clinical issue with hydrogen water is the cost. Individual cans or bottles range from $2.50 to $3.00 each versus about $0.60/bottle of spring water. In this particular study, the participants drank 51 ounces a day, which is more than 6 8-ounce bottles, adding up to about $15/day. Hydrogen water tablets and machines are also available, which may cut down on the cost somewhat.

Hydrogen water packaging can also be an issue. The authors of this study did not identify the type of packaging; however, they did direct participants to drink the water within an hour to reduce hydrogen loss. Hydrogen dissipates quickly, and if hydrogen water is packaged in plastic or glass, it likely will not contain much hydrogen. Special packaging is required to maintain optimal hydrogen levels.

As with any intervention, there are pros and cons. While cost may be a con, patient compliance may be a pro. After all, asking patients to drink more water is something integrative practitioners do all the time in clinical practice. Asking them to drink a certain type of water may be an easy solution for some patients who are not as compliant with dietary supplement recommendations. Assessing the individual patient to choose the proper intervention is something that integrative practitioners excel at. In some cases, hydrogen water may be worth considering.

REFERENCES

1 Shi J, Duncan B, Kuang X. Hydrogen treatment: a novel option in liver disease. Clin

Med. 2021;21(2):e223-e227. 2 Yang M, Dong Y, He Q, et al. Hydrogen: a novel option in human disease treatment.

Oxid Med Cell Longev. 2020;2020. 3 Yang Q, Ji G, Ran R, et al. Protective effect of hydrogen-rich water on liver function of colorectal cancer patients treated with mFOLFOX6 chemotherapy. Mol Clin

Oncol. 2017;7(5):891-896. 4 Kang K, Kang Y, Choi I, 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. 5 Nakao A, Toyoda Y, Sharma P, et al. Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome—an open label pilot study. J Clin Biochem Nutr. 2010;46(2):140-149. 6 LeBaron TW, Singh RB, Fatima G, et al. Effects of 24-week, high-concentration hydrogen-rich water on body composition, blood lipid profiles, and inflammation biomarkers in men and women with metabolic syndrome: a randomized controlled trial. Diabetes, Metab Syndr Obes. 2020;13:889-896. 7 Ishibashi T, Sato B, Rikitake M, et al. 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;2(27). 8 Xia C, Liu W, Zeng D, et al. Effect of hydrogen-rich water on oxidative stress, liver function, and viral load in patients with chronic hepatitis B. Clin Transl Sci. 2013;6(5):372-375. 9 Mizuno K, Sasaki AT, Ebisu K, et al. Hydrogen-rich water for improvements of mood, anxiety, and autonomic nerve function in daily life. Med Gas Res. 2017;7(4):247-255. 10 Sha J, Zhang S, Lu Y, et al. Effects of the long-term consumption of hydrogen-rich water on antioxidant activity and the gut flora in female juvenile soccer players from

Suzhou, China. Med Gas Res. 2018;8(4):135-143. 11 El-Sharkawy AM, Shota O, Lobo DN. Acute and chronic effects of hydration status on health. Nutr Rev. 2015;73(S2):97-109.