High-Dose Nattokinase and Its Potential Benefits for Blood Vessel and Lipid Health

Posted on by Jesse Santiano, M.D.

Update:
This article has been revised and updated on November 21, 2025, to meet current E-E-A-T standards. The information has been reviewed for accuracy, clarity, and medical safety to ensure readers receive high-quality, evidence-based guidance.

English audio below. Press play to listen

🎧 Audio Introduction — Spanish (Latinoamérica)

En este audio hablaremos sobre la nattokinasa en dosis altas y los posibles beneficios que mostró en estudios recientes para la salud de los vasos sanguíneos y los niveles de lípidos. Explicaremos qué encontraron los investigadores, cómo interpretarlo y qué consideraciones de seguridad deben tenerse en cuenta. Esta información es educativa y no reemplaza el consejo médico profesional.

🎧 Audio Introduction — Mandarin (中文普通话)

在这段音频中，我们将介绍高剂量纳豆激酶，以及研究中观察到的它对血管健康和血脂水平的潜在益处。我们会说明主要发现、如何理解这些结果，以及需要注意的安全事项。本内容仅供教育参考，不能替代专业医疗建议。

Contents hide
Introduction
Understanding Nattokinase
The 2022 Chen et al. Study
Key Findings
Important Considerations
Cautions and Responsible Use
Balanced Perspective
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Introduction

Recent research suggests that higher doses of nattokinase (NK)—an enzyme naturally derived from natto, the traditional Japanese fermented soybean food—may help support cardiovascular and metabolic health.
Natto has been consumed safely for centuries, and nattokinase is widely available as a dietary supplement.

Understanding Nattokinase

Nattokinase activity is measured in Fibrin Units (FU), which indicate the enzyme’s potency.
A typical 100 mg capsule provides around 2,000 FU. Many countries, including members of the European Union and Japan, recommend a daily intake near this level.

However, new research explored whether higher doses could produce additional cardiovascular benefits.

The 2022 Chen et al. Study

A large study by Chen et al., published in Frontiers in Cardiovascular Medicine in August 2022, followed 1,062 participants aged 63–85 years for one year. Participants consumed 10,800 FU per day (three 3,600 FU tablets daily). Tests were done before and after the treatment periodHigh-Dose Nattokinase to Shrink….

The dose selection was influenced by earlier studies:

  • A 2021 trial by Hodis et al. found that 2,000 FU/day did not significantly slow plaque progression.
  • A 2017 study by Ren et al. compared 6,000 FU of NK with 20 mg of simvastatin and observed favorable effects on arterial thickness and lipid markers.

Based on these findings and nattokinase’s long safety history, Chen et al. tested the higher 10,800 FU dosage.

Key Findings

1. Markers of Arterial Health

After 12 months, participants showed measurable reductions in carotid artery intima-media thickness (CCA-IMT) and plaque size, suggesting improved arterial elasticity and structure.
CCA-IMT is a non-invasive ultrasound measure reflecting early atherosclerotic changesHigh-Dose Nattokinase to Shrink….

2. Lipid Profile Improvements

Average levels of:

  • Triglycerides (TG) fell by about 15%.
  • Total cholesterol (TC) dropped by roughly 16%.
  • Low-density lipoprotein (LDL-C) decreased by about 18%.
  • High-density lipoprotein (HDL-C) rose by nearly 16%.

These favorable shifts suggest potential lipid-balancing properties, especially among participants who smoked, drank alcohol, or had higher body mass index (BMI).

3. Lifestyle Factors

Participants who regularly exercised (more than 5,000 steps per day) experienced greater improvements than sedentary individuals.
Researchers attributed this to better lifestyle discipline and compliance with supplementation.

4. Synergistic Combinations

Some participants also took vitamin K₂ (180 μg/day) or low-dose aspirin (100 mg/day).
The combination appeared to enhance cardiovascular markers, possibly through complementary effects on vascular function.
However, this interaction requires further controlled investigation.

5. Safety

No adverse effects were reported with the 10,800 FU/day dose. Prior studies examining toxicity, genotoxicity, and chromosome safety found no evidence of harm even at elevated doses.

Important Considerations

The study’s authors emphasized that:

  • The trial was retrospective rather than randomized.
  • Long-term benefits and mortality outcomes remain unknown.
  • Several co-authors were affiliated with the company that produced the nattokinase used in the study.

Further large-scale, independent randomized controlled trials are needed to confirm these findings and determine optimal dosing.

Cautions and Responsible Use

  • Individuals taking anticoagulants like warfarin should avoid nattokinase because it may alter blood clotting mechanisms.
  • Pregnant or breastfeeding women should not use nattokinase due to insufficient research.
  • Always consult a qualified healthcare provider before starting any new supplement.
  • Supplements should not replace medical therapy for heart disease or high cholesterol.

Balanced Perspective

Nattokinase continues to draw attention for its potential to support cardiovascular wellness, particularly through effects on blood flow and lipid metabolism.
While preliminary data are promising, supplementation should be viewed as an adjunct to lifestyle measures—including diet, physical activity, and smoking cessation—rather than a substitute for medical care.

Doctor’s Best Nattokinase

Source: By Blausen.com staff (2014). Medical gallery of Blausen Medical 2014

Doctor’s Best Nattokinase

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  14. Nattokinase is Nontoxic with a High Safety Margin. 

References:

  1. Chen H, Chen J, Zhang F, Li Y, Wang R, Zheng Q, Zhang X, Zeng J, Xu F, Lin Y. 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. Erratum in: Front Cardiovasc Med. 2022 Dec 05;9:1076420. PMID: 36072877; PMCID: PMC9441630.
  2. Hodis HN, Mack WJ, Meiselman HJ, Kalra V, Liebman H, Hwang-Levine J, Dustin L, Kono N, Mert M, Wenby RB, Huesca E, Rochanda L, Li Y, Yan M, St John JA, Whitfield L. Nattokinase atherothrombotic prevention study: A randomized controlled trial. Clin Hemorheol Microcirc. 2021;78(4):339-353. doi: 10.3233/CH-211147. PMID: 33843667.
  3. Union E. Commission Implementing Decision (EU) 2017/115 of 20 January 2017 Authorising the Placing on the Market of Fermented Soybean Extract as a NOVEL FOOD INGREDIENT UNDER REGULATION (EC) No 258/97 of the European Parliament and of the Council (notified under document C(2017) 165). In: Union TE, editor. Brussels. (2017).
  4. Ren NN, Chen HJ, Li Y, Mcgowan GW, Lin YG. [A clinical study on the effect of nattokinase on carotid artery atherosclerosis and hyperlipidaemia]. Zhonghua Yi Xue Za Zhi. 2017 Jul 11;97(26):2038-2042. Chinese. doi: 10.3760/cma.j.issn.0376-2491.2017.26.005. PMID: 28763875.
  5. Taniguchi-Fukatsu A, Yamanaka-Okumura H, Naniwa-Kuroki Y, Nishida Y, Yamamoto H, Taketani Y, Takeda E. Natto and viscous vegetables in a Japanese-style breakfast improved insulin sensitivity, lipid metabolism and oxidative stress in overweight subjects with impaired glucose tolerance. Br J Nutr. 2012 Apr;107(8):1184-91. doi: 10.1017/S0007114511004156. Epub 2011 Sep 7. Erratum in: Br J Nutr. 2013 Oct;110(7):1356. PMID: 21899797.
  6. Lampe BJ, English JC. Toxicological assessment of nattokinase derived from Bacillus subtilis var. natto. Food Chem Toxicol. (2016) 88:87–99. 10.1016/j.fct.2015.12.025 

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