Nattokinase atherothrombotic prevention study: A randomized controlled trial

Article type: Research Article

Authors: Hodis, Howard N.^{a; b; c; *} | Mack, Wendy J.^{a; c} | Meiselman, Herbert J.^d | Kalra, Vijay^e | Liebman, Howard^b | Hwang-Levine, Juliana^{a; b} | Dustin, Laurie^c | Kono, Naoko^c | Mert, Melissa^c | Wenby, Rosalinda B.^d | Huesca, Emiliano^e | Rochanda, Leanne^b | Li, Yanjie^a | Yan, Mingzhu^a | St. John, Jan A.^{a; c} | Whitfield, Lora^a

Affiliations: [a] Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA | [b] Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA | [c] Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA | [d] Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA | [e] Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

Correspondence: [*] Corresponding author: Howard N. Hodis, M.D., Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, 2250 Alcazar Street, CSC 132, Los Angeles, CA 90033, USA. Tel.: +1 323 442 1478; Fax.: +1 323 442 2685; E-mail: athero@usc.edu.

Abstract: BACKGROUND:Described to be antithrombotic and antihypertensive, nattokinase is consumed for putative cardiovascular benefit. However, no large-scale, long-term cardiovascular study has been conducted with nattokinase supplementation. OBJECTIVE:To determine the effect of nattokinase on subclinical atherosclerosis progression and atherothrombotic biomarkers. METHODS:In this double-blinded trial, 265 individuals of median age 65.3 years, without clinical evidence of cardiovascular disease (CVD) were randomized to oral nattokinase 2,000 fibrinolytic units or matching placebo. Primary outcome was rate of change in subclinical atherosclerosis measured by serial carotid ultrasound every 6 months as carotid artery intima-media thickness (CIMT) and carotid arterial stiffness (CAS). Additional outcomes determined at least every 6 months were clinical parameters including blood pressure and laboratory measures including metabolic factors, blood rheology parameters, blood coagulation and fibrinolysis factors, inflammatory markers and monocyte/macrophage cellular activation markers. RESULTS:After median 3 years of randomized treatment, annualized rate of change in CIMT and CAS did not significantly differ between nattokinase supplementation and placebo. Additionally, there was no significant effect of nattokinase supplementation on blood pressure or any laboratory determination. CONCLUSIONS:Results of this trial show that nattokinase supplementation has a null effect on subclinical atherosclerosis progression in healthy individuals at low risk for CVD.

Keywords: Nattokinase, natto, fermented soy, soybeans, fibrinolysis, atherosclerosis, cardiovascular disease, carotid artery intima-media thickness, blood pressure, thrombosis, blood rheology

DOI: 10.3233/CH-211147

Journal: Clinical Hemorheology and Microcirculation, vol. 78, no. 4, pp. 339-353, 2021