Randomized, crossover clinical efficacy trial in humans and mice on tear secretion promotion and lacrimal gland protection by molecular hydrogen

Miyuki Kubota,Sachiko Inoue,Ryo Takemura,Shunsuke Kubota,Mitsuhiro Watanabe,Motoko Kawashima,Shigeru Nakamura,Kazuo Tsubota,Toshihiro Imada

doi:10.1038/s41598-021-85895-y

Miyuki Kubota, Sachiko Inoue + Show 7 more

Open Access

https://doi.org/10.1038/s41598-021-85895-y

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Journal: Scientific Reports	Publication Date: Mar 19, 2021
Citations: 2	License type: open-access

Affiliation: Keio University, Keio University Hospital

Abstract

The incidence of dry eye disease is increasing worldwide because of the aging population and increasing use of information technology. Dry eye disease manifests as tear-layer instability and inflammation caused by osmotic hypersensitization in tear fluids; however, to our knowledge, no agent that treats both pathologies simultaneously is available. Molecular hydrogen (H2) is known to be effective against various diseases; therefore, we aimed to elucidate the effects of H2 on tear dynamics and the treatment of dry eye disease. We revealed that administering a persistent H2-generating supplement increased the human exhaled H2 concentration (p < 0.01) and improved tear stability (p < 0.01) and dry eye symptoms (p < 0.05) significantly. Furthermore, H2 significantly increased tear secretion in healthy mice (p < 0.05) and significantly suppressed tear reduction in a murine dry eye model (p = 0.007). H2 significantly and safely improved tear stability and dry eye symptoms in a small exploratory group of 10 human subjects, a subset of whom reported dry eye symptoms prior to treatment. Furthermore, it increased tear secretion rapidly in normal mice. Therefore, H2 may be a safe and effective new treatment for dry eye disease and thus larger trials are warranted.

Highlights

The incidence of dry eye disease is increasing worldwide because of the aging population and increasing use of information technology
Since the molecular weight of H 2 is minimal, it rapidly diffuses to the site of oxidative stress and has antioxidant and anti-apoptotic p roperties11. H2 selectively reduces cytotoxic reactive oxygen species (ROS), such as hydroxyl radicals, and preserves the ROS needed by living o rganisms[11]
The purpose of this study was to elucidate the effects of H2, a safe and inexpensive therapy, on the external secretory function of the lacrimal glands and to investigate whether H 2 protects the eye from tear loss in a severe dry eye model

Summary

Introduction

The incidence of dry eye disease is increasing worldwide because of the aging population and increasing use of information technology. H2 significantly and safely improved tear stability and dry eye symptoms in a small exploratory group of 10 human subjects, a subset of whom reported dry eye symptoms prior to treatment. It increased tear secretion rapidly in normal mice. Our group previously reported on milk-producing capability of H 2, which is created by adding galacto-oligosaccharide, maltitol, and glucomannan (the active ingredients for intestinal H2 production26) to a solution comprising cow milk (50%) and skim milk (50%)[27] This milk induced the intestinal microbiota to produce H 2, preventing the decrease in tear stability that occurs when adult human participants use visual display terminals daily[27]. The purpose of this study was to elucidate the effects of H2, a safe and inexpensive therapy, on the external secretory function of the lacrimal glands and to investigate whether H 2 protects the eye from tear loss in a severe dry eye model

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