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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 (H<jats:sub>2<\/jats:sub>) is known to be effective against various diseases; therefore, we aimed to elucidate the effects of H<jats:sub>2<\/jats:sub> on tear dynamics and the treatment of dry eye disease. We revealed that administering a persistent H<jats:sub>2<\/jats:sub>-generating supplement increased the human exhaled H<jats:sub>2<\/jats:sub> concentration (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) and improved tear stability (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) and dry eye symptoms (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) significantly. Furthermore, H<jats:sub>2<\/jats:sub> significantly increased tear secretion in healthy mice (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and significantly suppressed tear reduction in a murine dry eye model (<jats:italic>p<\/jats:italic>\u2009=\u20090.007). H<jats:sub>2<\/jats:sub> 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, H<jats:sub>2<\/jats:sub> may be a safe and effective new treatment for dry eye disease and thus larger trials are warranted.<\/jats:p>","DOI":"10.1038\/s41598-021-85895-y","type":"journal-article","created":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T13:05:27Z","timestamp":1616159127000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Randomized, crossover clinical efficacy trial in humans and mice on tear secretion promotion and lacrimal gland protection by molecular hydrogen"],"prefix":"10.1038","volume":"11","author":[{"given":"Miyuki","family":"Kubota","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoko","family":"Kawashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Imada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Kubota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiro","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Takemura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Tsubota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,19]]},"reference":[{"key":"85895_CR1","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.jtos.2017.05.005","volume":"15","author":"JD Nelson","year":"2017","unstructured":"Nelson, J. 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