Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jan 15, 2022; 14(1): 242-252
Published online Jan 15, 2022. doi: 10.4251/wjgo.v14.i1.242
Hydrogen-rich water exerts anti-tumor effects comparable to 5-fluorouracil in a colorectal cancer xenograft model
Fereshteh Asgharzadeh, Alex Tarnava, Asma Mostafapour, Majid Khazaei, Tyler W LeBaron
Fereshteh Asgharzadeh, Majid Khazaei, Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad 9177899191, Iran
Alex Tarnava, Drink HRW, New Westminster, BC V3j0b6 Canada
Asma Mostafapour, Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad 9177899191, Iran
Tyler W LeBaron, Centre of Experimental Medicine, Institute for Heart Research Slovak Academy of Sciences, Bratislava 984104, Slovakia
Tyler W LeBaron, Department of Kinesiology and Outdoor Recreation, Southern Utah University, UT 84720, United States
Tyler W LeBaron, Biological Research, Molecular Hydrogen Institute, UT 84721, United States
Tyler W LeBaron, Department of Physical Science, Southern Utah University, UT 84720, United States
Author contributions: All authors were involved in design of experiment; Asgharzadeh F, Mostafapour A, and Khazaei M carried out the experiments and wrote the methods and results sections; Tarnava A and LeBaron TW wrote the background, discussion and conclusion; and all authors agree to final manuscript.
Supported by the HRW Natural Health Products Inc. (dba Drink HRW), as well as by a grant from Mashhad University of Medical Sciences.
Institutional review board statement: The Mashhad University of Medical Sciences Committee on Animal Ethics has approved all animal protocols used in this research.
Institutional animal care and use committee statement: The Mashhad University of Medical Sciences Committee on Animal Ethics has approved all animal protocols used in this research. Reference Number: 991229; Date: July 10, 2020.
Conflict-of-interest statement: Tarnava A is involved in commercial entities with interest in the marketing of hydrogen-rich water; LeBaron TW has received travel reimbursement, honoraria, and speaking and consultancy fees from various academic and commercial entities regarding molecular hydrogen. All other authors report no conflict of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Tyler W LeBaron, BSc, MSc, Director, Instructor, Research Scientist, Centre of Experimental Medicine, Institute for Heart Research Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratislava, Slovak Republic, Bratislava 984104, Slovakia.
Received: May 19, 2021
Peer-review started: May 19, 2021
First decision: June 16, 2021
Revised: June 30, 2021
Accepted: December 7, 2021
Article in press: December 7, 2021
Published online: January 15, 2022
Research background

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. Surgical removal remains the first-line treatment for CRC; however, nonsurgical options remain important tools for treatment. Currently, treatments such as 5-fluorouracil (5-FU), a widely administered chemotherapeutic agent utilized in the treatment of CRC, presents known beneficial effects, but also significant side effects. Hydrogen-rich water (HRW) has demonstrated beneficial effects in numerous species, including humans, in many disease models, including various cancers. One attractive aspect of HRW is the high safety profile and low rates of side effects combined with its promising therapeutic effects.

Research motivation

New treatments with potential positive effects in CRC are desperately needed, particularly treatments with high safety profiles and low side effects. HRW may fit the criteria as a safe potential treatment for CRC, either as a stand-alone treatment or in combination with conventional treatments.

Research objectives

We aimed to evaluate the efficacy of HRW on a CRC model compared to 5-FU and control, as well as the combination treatment of HRW and 5-FU compared to 5-FU alone, HRW alone, or control. We measured tumor size, tumor weight, fibrosis, and collagen content, as well as oxidative stress (OS) and antioxidant activity (AA) in mice with induced CRC. These objectives allow us to determine the therapeutic efficacy and mechanistic insight of HRW with or without 5-FU, as well as determine if there are additive benefits in a combinational treatment to guide future clinical studies.

Research methods

Six- to eight-week-old female inbred Balb/c mice were injected with 5 × 105 CT-26 cells (100 μL) into the left rear flank (day 0). When tumor volumes reached 80-100 mm3, 24 mice bearing tumors were randomly divided into four groups. Mice were either left untreated (control) or treated with 5-FU (intraperitoneal injection, 5 mg/kg every other day), high-concentration HRW produced by magnesium tablets (ad libitum in drinking water, as well as by oral gavage 200 μL daily), or both HRW and 5-FU.

Research results

We report that molecular hydrogen dissolved in water (HRW) was as effective as 5-FU, with more preferential outcomes relating to higher AA and lower OS. Importantly, the combination of HRW and 5-FU was superior to either therapy on its own, presenting the possibility that HRW may be explored as an adjuvant therapy alongside conventional chemotherapeutics.

Research conclusions

HRW may be a novel safe adjuvant therapy for treating CRC, either as a stand-alone therapy, or preferably, alongside conventional chemotherapeutics.

Research perspectives

Clinical research to evaluate the effects of HRW as a treatment for CRC, both alone and in combination with 5-FU and other chemotherapeutics, is highly warranted.