Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants

Hongjie Chen; Jiepeng Chen; Fuping Zhang; Yuanhui Li; Ronghua Wang; Qiang Zheng; Xu Zhang; Jun Zeng; Feng Xu; Yiguang Lin

doi:10.3389/fcvm.2022.964977

Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants

Front Cardiovasc Med. 2022 Aug 22:9:964977. doi: 10.3389/fcvm.2022.964977. eCollection 2022.

Authors

Hongjie Chen¹, Jiepeng Chen², Fuping Zhang³, Yuanhui Li⁴, Ronghua Wang², Qiang Zheng², Xu Zhang², Jun Zeng², Feng Xu⁵, Yiguang Lin^{1

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Affiliations

¹ Department of Traditional Chinese Medicine, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
² Sungen Bioscience Co. Ltd., Shantou, China.
³ Department of Pharmacy, Shenyang Red Cross Hospital, Shenyang, China.
⁴ Guangzhou Center, Sinopharm Group Pharmaceutical Co., Ltd., Guangzhou, China.
⁵ Antithrombotic & Thrombolytic Innovative Drug Research Center, Shenyang Pharmaceutical University, Shenyang, China.
⁶ The Central Laboratory, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.
⁷ School of Life Sciences, University of Technology Sydney, Sydney, NSW, Australia.

Abstract

Nattokinase (NK), known as a potent fibrinolytic and antithrombotic agent, has been shown to have antiatherosclerotic and lipid-lowering effects. However, data on human clinical studies are limited. In this clinical study involving 1,062 participants, our objective was to examine the efficacy of NK in atherosclerosis and hyperlipidemia and safety at the dose of 10,800 FU/day after 12 months of oral administration. Various factors, including lower doses that influence NK pharmacological actions, were also investigated. We found that NK at a dose of 10,800 FU/day effectively managed the progression of atherosclerosis and hyperlipidemia with a significant improvement in the lipid profile. A significant reduction in the thickness of the carotid artery intima-media and the size of the carotid plaque was observed. The improvement rates ranged from 66.5 to 95.4%. NK was found to be ineffective in lowering lipids and suppressing atherosclerosis progression at a dose of 3,600 FU/day. The lipid-lowering effect of NK was more prominent in subjects who smoked, drank alcohol, and subjects with higher BMI. Regular exercise further improved the effects of NK. Co-administration of vitamin K2 and aspirin with NK produced a synergetic effect. No noticeable adverse effects associated with the use of NK were recorded. In conclusion, our data demonstrate that atherosclerosis progression and hyperlipidemia can be effectively managed with NK at a dose of 10,800 FU/day. The lower dose of 3,600 FU per day is ineffective. The dose of 10,800 FU/day is safe and well tolerated. Some lifestyle factors and the coadministration of vitamin K2 and aspirin lead to improved outcomes in the use of NK. Our findings provide clinical evidence on the effective dose of NK in the management of cardiovascular disease and challenge the recommended dose of 2,000 FU per day.

Keywords: Nattokinase (NK); anti-atherogenic drug; atherosclerosis; hyperlipidaemia; lipid lowering agent; lipid lowering effect; nattokinase; retrospective study.