{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:22:12Z","timestamp":1791645732716,"version":"4.3.4"},"reference-count":57,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS Grant-in-Aid for Scientific Research","doi-asserted-by":"publisher","award":["23K26847"],"award-info":[{"award-number":["23K26847"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Fund of Sugiyama Chemical & Industrial Laboratory"},{"name":"Tohoku University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Late-onset hypogonadism (LOH) is an age-related condition characterized by a decline in testosterone (Ts) levels and associated symptoms that impair quality of life in older men. Although Ts replacement therapy is available, its clinical use is limited by adverse effects. Vitamin K (VK) is a fat-soluble vitamin that functions as a cofactor for \u03b3-glutamylcarboxylase and plays important roles in blood coagulation and bone homeostasis. Menaquinone-4 (MK-4), a VK homolog predominantly found in animal-derived foods, has been shown to enhance Ts production in healthy male rats. However, whether this effect occurs under low-Ts conditions remains unclear. In this study, we investigated the effects of VK on LOH using a leuprorelin acetate (LA)-induced low-Ts rat model. Male Sprague\u2013Dawley rats were administered sustained-release LA and fed a control diet or diets supplemented with VK1 or MK-4 (75 mg\/kg) for 4 weeks. Compared with the control group, MK-4 supplementation significantly ameliorated the reduction in serum Ts levels and seminiferous tubule diameter, whereas VK1 supplementation showed no significant effects. Furthermore, MK-4 supplementation activated the protein kinase A signaling pathway, which is directly involved in testicular Ts production. These findings suggest that MK-4 supplementation may represent a novel nutritional strategy for the management of LOH.<\/jats:p>","DOI":"10.3390\/foods15061070","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:12:26Z","timestamp":1773853946000},"page":"1070","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effect of Vitamin K Supplementation on Testosterone Production in a Rat Model of Late-Onset Hypogonadism"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4910-0270","authenticated-orcid":false,"given":"Rui","family":"Murakami","sequence":"first","affiliation":[{"name":"Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Ohsaki","sequence":"additional","affiliation":[{"name":"Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"},{"name":"International Education and Research Center for Food Agricultural Immunology, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hikaru","family":"Ito","sequence":"additional","affiliation":[{"name":"Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8421-4919","authenticated-orcid":false,"given":"Hsin-Jung","family":"Ho","sequence":"additional","affiliation":[{"name":"Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"},{"name":"Institute for Excellence in Higher Education, Tohoku University, Sendai 980-8576, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afifah Zahra","family":"Agista","sequence":"additional","affiliation":[{"name":"Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"},{"name":"International Education and Research Center for Food Agricultural Immunology, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2233-7046","authenticated-orcid":false,"given":"Yi-Fen","family":"Chiang","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Ling","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6723-0298","authenticated-orcid":false,"given":"Masamitsu","family":"Maekawa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8761-3779","authenticated-orcid":false,"given":"Takuo","family":"Hirose","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai 983-8536, Japan"},{"name":"Division of Integrative Renal Replacement Therapy, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai 983-8536, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenshiro","family":"Hara","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Reproduction and Development, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4638-5412","authenticated-orcid":false,"given":"Wan-Chun","family":"Chiu","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8245-4601","authenticated-orcid":false,"given":"Chiu-Li","family":"Yeh","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2888-2618","authenticated-orcid":false,"given":"Shih-Min","family":"Hsia","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1579-2165","authenticated-orcid":false,"given":"Suh-Ching","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nariyasu","family":"Mano","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takefumi","family":"Mori","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai 983-8536, Japan"},{"name":"Division of Integrative Renal Replacement Therapy, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai 983-8536, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4828-5274","authenticated-orcid":false,"given":"Hitoshi","family":"Shirakawa","sequence":"additional","affiliation":[{"name":"Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"},{"name":"International Education and Research Center for Food Agricultural Immunology, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"ref_1","unstructured":"United Nations (2024). 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