Objective: To evaluate the efficacy of oral nattokinase (NK) in the reduction of common carotid artery intimal medial thickness (CCA-IMT) and carotid artery plaque size and in lowering blood lipids, and to explore the underlying mechanism of actions of NK and its potential clinical use. Methods: All enrolled patients were from the Out-Patient Clinic of the Department of TCM at the 3(rd) Affiliated Hospital of Sun Yat-sen University. Using randomised picking method, all patients were randomly assigned to one of two groups, NK and Statin (ST) group. NK Group-patients were given NK at a daily dose of 6 000 FU and ST Group-patients were treated with statin (simvastatin 20 mg) daily. The treatment course was 26 weeks. CCA-IMT, carotid plaque size and blood lipid profile of the patients were measured before and after treatment. Results: A total of 82 patients were enrolled in the study and 76 patients (NK 39, ST 37) completed the study. Following the treatments for 26 weeks, there was a significant reduction in CCA-IMT and carotid plaque size in both groups compared with the baseline before treatment. The carotid plaque size and CCA-IMT reduced from(0.25±0.12)cm(2) to (0.16±0.10)cm(2) and from (1.13±0.12)mm to (1.01±0.11)mm, repectively. The reduction in the NK group was significantly profound (P<0.01, 36.6% reduction in plaque size in NK group versus 11.5% change in ST group). Both treatments reduced total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG). While the reduction in both groups was shown to be statistically significant (P<0.01), the reduction of TC, LDL-C and TG in ST group was significantly greater (P<0.05). In addition, NK significantly increased the level of high-density lipoprotein cholesterol (HDL-C) (P<0.05), in contrast, HDL-C in the ST group did not change. The lipid lowering effect observed in the NK group was not correlated to the reduction of CCA-IMT and carotid artery plaque size (r=0.35, P=0.09). Conclusions: Our findings from this pioneer clinical study suggests that daily NK supplementation is an effective way to manage the progression of atherosclerosis and potentially may be a better alternative to statins which are commonly used to reduce atherosclerosis and further to prevent cardiovascular attack and stroke in patients. The mechanism underlying the reduction of carotid atherosclerosis by NK may be independent from its lipid-lowering effect, which is different from that of statins.
目的： 评估纳豆激酶(NK)在降低颈总动脉中膜厚度(CCA－IMT)、颈动脉斑块面积和血脂中的作用，探讨其作用机制和潜在临床应用。 方法： 入选病例来自于中山大学附属第三医院中医科门诊，按抽签法随机分为两组(每组41例)，NK组：患者每天口服纳豆激酶6 000 FU，ST组：患者每天口服辛伐他汀20 mg，疗程26周。在治疗前和治疗后，采集记录患者的CCA－IMT、颈动脉斑块面积和血脂谱[总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL－C)和高密度脂蛋白胆固醇(HDL－C)]，并进行统计学分析。 结果： 入选82例患者，其中76例(NK 39例，ST 37例)按要求完成疗程。经26周治疗后，NK组患者的斑块面积和CCA－IMT显著下降(P<0.01)，斑块面积从(0.25±0.12)cm(2)下降到(0.16±0.10)cm(2)，而CCA－IMT从(1.13±0.12)mm降到(1.01±0.11)mm, NK组的下降幅度显著大于ST组(P<0.01)，NK组和ST组的斑块面积变化率分别是－36.6%与－11.5%; NK能显著降低TG、TC和LDL－C水平(P<0.05)，但是与ST组比较，下降幅度相对较小(约为ST组的50%); NK同时有提升HDL－C的作用(P<0.05)，而ST对HDL－C水平没有影响。NK组患者降脂幅度与动脉粥样硬化的改善指标没有正相关关系(r＝0.35，P＝0.09)。 结论： 本研究为纳豆激酶有效改善颈动脉粥样硬化的先驱性临床研究。观察结果显示，每天服用NK是控制颈动脉粥样硬化发展的有效方法，效果比辛伐他汀更显著。在管理动脉粥样硬化上，NK可能是潜在的比他汀类更好的选择。NK改善动脉粥样硬化的机制可能与降低血脂没有直接关系，与他汀类药作用机制不同。.
Keywords: Atherosclerosis; Carotid artery diseases; Dyslipidaemias; Nattokinase; Simvastatin.