Conly J M, Stein K E
Department of Microbiology, University of Saskatchewan, Saskatoon.
Clin Invest Med. 1993 Feb;16(1):45-57.
After optimizing conditions for maximal production of menaquinones (MK), S. aureus and B. vulgatus were grown in batches, harvested and extracted for qualitative and quantitative MK content utilizing HPLC (high performance liquid chromatography) until a total of 6 mg was available. Five normal healthy male volunteers were placed on a vitamin K1 deficient diet (< or = 25 micrograms/day) and were subsequently warfarinized to maintain a prothrombin time (PT) 1.5-2 times control. Following stabilization of daily warfarin dosage 1 mg doses of the extracted MK were orally administered. As a control, the same volunteers were later warfarinized but no MK was given. Within 24 h of MK administration the prothrombin time (PT) decreased (mean +/- SEM) 3.6 +/- 1.0 s (p < 0.005) and the Factor VII level increased 0.36 +/- 0.3 u/ml (p < 0.005) vs a PT increase of 1.0 +/- 1.0 s (p > 0.1) and a Factor VII level increase of 0.03 +/- 0.1 u/ml (p > 0.1) in the control phase. Within 48 h of MK administration the PT was normal in all subjects but remained > or = 1.5 times control in the control phase. These data demonstrate for the first time the absorption and bioactivity of bacterially synthesized vitamin K in humans.
在优化甲萘醌(MK)最大产量的条件后,金黄色葡萄球菌和普通拟杆菌进行分批培养,收获并利用高效液相色谱法(HPLC)提取以测定MK的定性和定量含量,直至总共获得6毫克MK。五名正常健康男性志愿者采用维生素K1缺乏饮食(≤25微克/天),随后给予华法林以维持凝血酶原时间(PT)为对照值的1.5 - 2倍。在每日华法林剂量稳定后,口服给予1毫克提取的MK。作为对照,相同志愿者后来再次给予华法林,但未给予MK。在给予MK的24小时内,凝血酶原时间(PT)下降(均值±标准误)3.6±1.0秒(p<0.005),因子VII水平升高0.36±0.3单位/毫升(p<0.005),而在对照阶段PT升高1.0±1.0秒(p>0.1),因子VII水平升高0.03±0.1单位/毫升(p>0.1)。在给予MK的48小时内,所有受试者的PT均恢复正常,但在对照阶段仍≥对照值的1.5倍。这些数据首次证明了细菌合成的维生素K在人体中的吸收和生物活性。