Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 7, 2018; 24(45): 5095-5108
Published online Dec 7, 2018. doi: 10.3748/wjg.v24.i45.5095
Effects of alkaline-electrolyzed and hydrogen-rich water, in a high-fat-diet nonalcoholic fatty liver disease mouse model
Karen Jackson, Noa Dressler, Rotem S Ben-Shushan, Ari Meerson, Tyler W LeBaron, Snait Tamir
Karen Jackson, Noa Dressler, Rotem S Ben-Shushan, Ari Meerson, Snait Tamir, Laboratory of Human Health and Nutrition Sciences, MIGAL-Galilee Research Institute, Kyriat Shmona 11016, Israel
Karen Jackson, Noa Dressler, Snait Tamir, Tel Hai College, Upper Galilee 12110, Israel
Tyler W LeBaron, Center of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Bratislava 84005, Slovakia
Tyler W LeBaron, Molecular Hydrogen Institute, UT 48101, United States
Author contributions: Jackson K designed and coordinated the research analyzed the data and wrote the paper; Dressler N performed the majority of experiments and analyzed the data; Ben-Shushan RS performed the perfusion, and in vitro experiments; Meerson A designed and analyzed the PCR data, LeBaron TW analyzed the data and wrote the paper; Tamir S analyzed the data and contributed to the writing of the final draft.
Supported by Tel Hai College Research funding Grant, No. 25-2-14-114.
Correspondence author to: Karen Jackson, PhD, Senior Lecturer, Senior Researcher, Laboratory of Human Health and Nutrition Sciences, MIGAL-Galilee Research Institute, POB 831, Kyriat Shmona 11016, Israel.
Telephone: +972-4-6953511 Fax: +972-4-6944980
Received: September 30, 2018
Peer-review started: September 30, 2018
First decision: October 23, 2018
Revised: October 31, 2018
Accepted: November 9, 2018
Article in press: November 9, 2018
Published online: December 7, 2018
Research background

Nonalcoholic fatty liver disease (NAFLD) is a major growing metabolic health condition. Conventional pharmaceuticals and drugs are not effective in preventing or treating this disease condition. There is a deep interest in searching for novel, safe, and effective methods to prevent and treat NAFLD. For many years there have been many claims about healthy functional waters including alkaline ionized water, also known as electrolyzed reduced water. Some of those claims suggest it is beneficial for obesity and metabolic disturbances. However, there is a paucity of scientific data on this electrolyzed water, but significant noise and claims by commercial companies marketing and selling it. There are untenable claims about the benefits of high pH, alkaline water, or the oft claimed, albeit impossible, microclustering/structuring of the water. Strong claims have also been made regarding the water’s negative oxidation-reduction potential. However, electrolysis of water does produce hydrogen gas at the cathode, and H2 gas does produce a negative oxidation-reduction potential (ORP). Interestingly, biomedical investigations of molecular hydrogen have demonstrated that this small molecule does have therapeutic potential. Perhaps electrolyzed alkaline water does have beneficial effects, but they are not due to its high alkaline pH or other impossible properties, but due to the presence of dissolved H2 gas produced during electrolysis. Additionally, molecular hydrogen may be an important molecule to combat against NAFLD.

Research motivation

We first wanted to examine if the claimed functional water, electrolyzed alkaline water, could exert therapeutic effects on a mouse model of NAFLD induced by a high-fat diet. We also wanted to compare these results to water with a similar and a greater concentration of molecular hydrogen. This would allow us to know if electrolyzed water has any beneficial effects on NAFLD, and the importance of molecular hydrogen in that water. Additionally, if molecular hydrogen was shown to be therapeutic as previous studies suggest, then it would add to the body of literature lending support for more research.

Research objectives

To determine the effects of H2 water in preventing NAFLD development under an obesogenic diet. This is the first step to understanding the efficacy of this approach for preventing and treating the disease.

Research methods

In this research mice under an obesogenic high fat diet were used for developing NAFLD. Control mice ingested regular water while the experimental consumed two types of hydrogen-rich water produced in two different ways: via electrolysis with an alkaline water ionizer or via a chemical reaction between water and metallic magnesium. General parameters as food and water consumption, body weight and composition were measured during the experiment. In the end, livers were sampled for histology and gene expression measuring by means of RT-PCR. In the in vitro experiment hepatocytes obtained from mice drinking either regular water or H2-rich water were exposed to a high-fat environment in order to check the residual protective effects of H2-rich water.

Research results

This study demonstrated the positives effects of H2-rich water on NAFLD. Mice fed a high-fat diet that were drinking H2-rich water showed less weight gain, more lean body tissue, less steatosis, and better liver histology when compared to the control group. It was also demonstrated that electrolyzed water with a high pH, -ORP, but a low H2 concentration did not result in any improvement. Hepatocytes derived from mice drinking H2-rich water were more resilient to palmitate overload in vitro when compared to hepatocytes obtained from mice drinking regular water. H2-rich water positively affected the expression of several NAFLD related genes. However, the mechanism of action of H2-rich water needs further investigation.

Research conclusions

This study demonstrated that the H2 dissolved in water is the therapeutic agent in functional waters since electrolyzed water with a high pH and a negative ORP did not show any effect on preventing the development of NAFLD. Apparently, H2 works at a molecular level since it changed the expression of specific genes related to the disease. This study also demonstrates a long-term protective effect of H2 in an in vitro experiment. Functional water rich in H2 could be a preventive agent in NAFLD. The Therapeutic aspect of H2 still need to be elucidated and the optimum dosage determined.

Research perspectives

H2-rich water is already consumed by humans without any contraindication, which makes it a good candidate for future human clinical studies on NAFLD patients.