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Related Experiment Video

Updated: Nov 9, 2025

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Nattokinase atherothrombotic prevention study: A randomized controlled trial.

Howard N Hodis1,2,3, Wendy J Mack1,3, Herbert J Meiselman4

  • 1Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Clinical Hemorheology and Microcirculation
|April 12, 2021
PubMed
Summary

Nattokinase supplementation did not significantly impact subclinical atherosclerosis progression or cardiovascular biomarkers in a 3-year trial. This study found no cardiovascular benefits of nattokinase in healthy individuals.

Keywords:
Nattokinaseatherosclerosisblood pressureblood rheologycardiovascular diseasecarotid artery intima-media thicknessfermented soyfibrinolysisnattosoybeansthrombosis

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Area of Science:

  • Cardiovascular research
  • Nutritional science
  • Biomedical research

Background:

  • Nattokinase is purported to offer cardiovascular benefits due to its antithrombotic and antihypertensive properties.
  • Previous research lacked large-scale, long-term studies on nattokinase's cardiovascular effects.
  • Subclinical atherosclerosis and atherothrombotic biomarkers are key indicators of cardiovascular risk.

Purpose of the Study:

  • To investigate the long-term effects of nattokinase supplementation on subclinical atherosclerosis progression.
  • To assess the impact of nattokinase on various atherothrombotic biomarkers.
  • To evaluate nattokinase's influence on blood pressure and other clinical parameters.

Main Methods:

  • A double-blinded, randomized trial involving 265 participants aged 65.3 years without diagnosed cardiovascular disease (CVD).
  • Participants received either 2,000 fibrinolytic units of oral nattokinase or a placebo daily for a median of 3 years.
  • Primary outcome measured was the change in carotid artery intima-media thickness (CIMT) and carotid arterial stiffness (CAS) via serial carotid ultrasound.

Main Results:

  • No significant difference in the annualized rate of change for CIMT and CAS between the nattokinase and placebo groups.
  • Nattokinase supplementation showed no significant effect on blood pressure.
  • No significant impact was observed on metabolic factors, blood rheology, coagulation/fibrinolysis markers, inflammatory markers, or monocyte/macrophage activation markers.

Conclusions:

  • Nattokinase supplementation demonstrated a null effect on the progression of subclinical atherosclerosis in healthy, low-risk individuals.
  • The study suggests nattokinase does not provide significant cardiovascular benefits in this population.
  • Further research may be needed to explore potential effects in different populations or at different dosages.