First Clinical Trial of a Newly Developed, Low Menaquinone-7, Fermented Soybean Natto in Warfarin-Dependent Patients
First Clinical Trial of a Newly Developed, Low Menaquinone-7, Fermented Soybean Natto in Warfarin-Dependent Patients
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新开发的低 Menaquinone-7 发酵大豆纳豆在华法林依赖患者中的首次临床试验
DOI：
10.1089/jmf.2021.0036
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发表时间：
2021
影响因子：
2.4
通讯作者：
Hiramatsu Yuji
中科院分区：
文献类型：
--
作者：
Nakajima Tomomi;Taya Yuki;Nishikawa Takanobu;Kitamura Yutaka;Kato Hideyuki;Mathis Bryan J.;Hiramatsu Yuji
枯草芽孢杆菌发酵大豆(纳豆)含有高水平的维生素K2，主要是孟喹酮-7(MK-7)，华法林依赖患者必须避免食用。这是第一份报告，证明了低MK-7纳豆的特征和临床相关性。我们创作了一部小说，变种B。枯草杆菌TTCC2051经短期发酵，MK-7产量降低，产量为正常MK-7含量的19-24%。经过功能评估和临床前试验，10名华法林依赖患者接受了临床试验，并进行了为期7天的低MK-7纳豆摄取试验。功能评估令人满意，临床前试验显示，服用7天后血浆MK-7水平没有增加。在临床试验中，每天服用20 g的低MK-7纳豆可显著提高血浆MK-7水平，而每天服用10 g纳豆则不显著。然而，两组小剂量MK-7纳豆均未改变凝血酶原时间国际标准化比值(PT-INR)。如果每天摄入20 g(46μg)的MK-7纳豆，低剂量的MK-7纳豆既不会改变PT-INR值，也不会引发不良反应。因此，这种新型食品有潜力供华法林依赖患者食用。
Bacillus subtilisfermented soybeans (natto) contain high vitamin K2 levels, mostly as menaquinone-7 (MK-7), and must be avoided by warfarin-dependent patients. This is the first report which demonstrates the characteristics and clinical relevance of a low MK-7 natto for such patients. We generated a novel, mutantB. subtilisstrain TTCC2051 with short-term fermentation and reduced MK-7 production, yielding 19–24% of the normal MK-7 content. After functional assessments and a preclinical trial, 10 warfarin-dependent patients underwent a clinical trial with a 7-day ingestion test of the low MK-7 natto. Functional assessments were satisfactory, and the preclinical trial showed no increases in plasma MK-7 levels after 7 days of ingestion. In the clinical trial, 20 g/day of the low MK-7 natto significantly increased plasma MK-7 levels while 10 g/day did not. However, neither dose of low MK-7 natto changed international normalized ratio of prothrombin time (PT-INR) values in either group. The low MK-7 natto neither changed PT-INR values nor precipitated adverse events if ingested with a once-daily maximum of 20 g (46μg of MK-7). Thus, this novel food product has potential for consumption by warfarin-dependent patients.