{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T15:07:28Z","timestamp":1780672048612,"version":"3.54.1"},"reference-count":19,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jufuku Sangyo Co., Ltd."},{"name":"Take Yakuhin Co., Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: We aimed to evaluate the efficacy and safety of a short-term dietary intervention using trigonelline-rich Sakurajima radish on vascular endothelial function in patients with metabolic syndrome (MetS). Methods: In this multicenter, open-label, randomized, three-period crossover phase IIb trial, 21 patients with MetS were assigned to three 14-day sequences (Sakurajima radish powder, Aokubi radish powder, and a usual diet), separated by 14-day washouts. The primary outcome was flow-mediated dilation (FMD). Key Secondary outcomes included blood pressure (BP), urinary nitric oxide metabolites (NOx), and the oxidative stress marker 8-hydroxy-2\u2032-deoxyguanosine (8-OHdG). Results: Sakurajima radish did not improve FMD versus the usual diet (p = 0.58) or Aokubi radish (p = 0.59), although a significant negative carryover effect following the Aokubi period likely confounded this estimation. Despite successfully stimulating NO production (elevated urinary NOx, p = 0.03), the intervention paradoxically increased oxidative stress (elevated 8-OHdG\/creatinine, p = 0.02) and significantly elevated systolic BP compared with the usual diet (+9.67 mmHg, p = 0.03) and Aokubi radish (+8.86 mmHg, p = 0.04). Conclusions: Sakurajima radish does not appear to improve endothelial function in patients with MetS within the constraints of this short-term crossover design. Importantly, the unexpected negative carryover effect inherently limits the interpretability of this primary FMD outcome, as it may have masked potential physiological benefits. Despite boosting NO production, the intervention paradoxically exacerbated systemic oxidative stress and elevated systolic BP. These findings suggest that in the pro-oxidant environment of MetS, NO-boosting functional foods may induce unintended adverse hemodynamic responses, underscoring the need for careful risk\u2013benefit evaluation and parallel-group trial designs in this specific population.<\/jats:p>","DOI":"10.3390\/nu18111801","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T13:46:48Z","timestamp":1780494408000},"page":"1801","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of Sakurajima Radish in Patients with Metabolic Syndrome: A Phase IIb Randomized, Three-Period Crossover Trial"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2942-3034","authenticated-orcid":false,"given":"Akihiro","family":"Tokushige","sequence":"first","affiliation":[{"name":"Department of Prevention and Analysis of Cardiovascular Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan"},{"name":"Department of Clinical Pharmacology and Therapeutics, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1488-310X","authenticated-orcid":false,"given":"Yuichi","family":"Akasaki","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Sakoda","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akari","family":"Tajima","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7353-1206","authenticated-orcid":false,"given":"Takashi","family":"Kajiya","sequence":"additional","affiliation":[{"name":"Tenyoukai Central Hospital, Kagoshima 892-0822, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naohiro","family":"Shirasawa","sequence":"additional","affiliation":[{"name":"Keizankai Kyoritsu Hospital, Kagoshima 890-0069, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narisato","family":"Hamada","sequence":"additional","affiliation":[{"name":"Keizankai Kyoritsu Hospital, Kagoshima 890-0069, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Jinaikai Ueyama Hospital, Kagoshima 890-0073, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Kubota","sequence":"additional","affiliation":[{"name":"Keishinkai Kubota Internal Medicine Clinic, Kagoshima 892-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuminori","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Tsuminori Internal Medicine Clinic, Kagoshima 890-0105, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenjuro","family":"Higo","sequence":"additional","affiliation":[{"name":"Jiaikai Imamura General Hospital, Kagoshima 890-0064, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuro","family":"Kubozono","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7015-4353","authenticated-orcid":false,"given":"Kouta","family":"Funakoshi","sequence":"additional","affiliation":[{"name":"Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3880-762X","authenticated-orcid":false,"given":"Ryota","family":"Kawai","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5999-5773","authenticated-orcid":false,"given":"Hisako","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumi","family":"Shintani","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9043-5515","authenticated-orcid":false,"given":"Katsuko","family":"Kajiya","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture, Kagoshima University, Kagoshima 890-0065, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Ohishi","sequence":"additional","affiliation":[{"name":"Department of Prevention and Analysis of Cardiovascular Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan"},{"name":"Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, 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