Nattokinase
TL;DR
Fibrinolytic enzyme from Japanese fermented soybeans (natto) with blood-thinning properties
Meta-analysis of RCTs shows significant blood pressure reduction (−3.5/−2.3 mmHg)
One trial showed 36.6% carotid plaque reduction over 26 weeks, outperforming simvastatin
Dissolves fibrin directly — unlike aspirin, which prevents clots but cannot break them down
Significant interaction risk with warfarin and other anticoagulants — do not combine
Cost: ~$10-20/month
Best for: Blood pressure support, cardiovascular protection (in those NOT on blood thinners)
What it is
Nattokinase is a serine protease enzyme extracted from natto, a traditional Japanese food made by fermenting soybeans with Bacillus subtilis. First discovered by researcher Hiroyuki Sumi in 1987, who noticed natto could dissolve artificial blood clots (fibrin) in a petri dish. Unlike most oral enzymes, nattokinase survives digestion and enters the bloodstream intact, where it acts as a direct fibrinolytic — meaning it can break down fibrin, the protein mesh that forms blood clots. This makes it mechanistically unique among supplements: while aspirin and fish oil prevent new clots from forming, nattokinase can actually dissolve existing fibrin. It also appears to suppress renin activity, which may explain its blood-pressure-lowering effects. Measured in FU (fibrinolytic units), the standard supplemental dose is 2,000 FU per day.
What the research says
Nattokinase has the strongest evidence base of any fibrinolytic supplement. Blood Pressure. A 2023 meta-analysis of 6 RCTs with 546 participants found nattokinase significantly reduced systolic blood pressure by 3.45 mmHg and diastolic by 2.32 mmHg compared to placebo [1]. The landmark Kim 2008 RCT in 86 subjects with prehypertension showed a 5.55 mmHg systolic reduction at 2,000 FU/day for 8 weeks, with a corresponding drop in plasma renin activity [2]. Atherosclerosis. A striking 2017 Chinese trial by Ren et al. enrolled 82 patients with carotid atherosclerosis and compared nattokinase (6,000 FU/day) against simvastatin (20 mg/day) for 26 weeks. Nattokinase reduced carotid plaque size by 36.6% and intima-media thickness by 10.6% — outperforming simvastatin's 11.5% plaque reduction [3]. Fibrinolysis. Laboratory and animal studies consistently demonstrate nattokinase's ability to dissolve fibrin clots by inactivating plasminogen activator inhibitor (PAI-1), thereby boosting the body's natural clot-dissolving pathway [4].
Limited Direct Evidence The 2023 meta-analysis found that purified nattokinase supplementation at typical doses did not significantly improve total cholesterol, LDL-C, or HDL-C levels [1]. This contrasts with crude natto extract studies, which contain soy isoflavones and other compounds that may independently affect lipids. A large 1,062-participant open-label trial using high-dose nattokinase (10,800 FU/day for 12 months) showed some benefit for atherosclerosis progression and lipids, but this dose is far above standard supplementation and the study lacked placebo control. Nattokinase is not recommended primarily for metabolic support.
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Safety
Nattokinase is generally well-tolerated in healthy adults not taking anticoagulant medications. The most common side effects are mild GI symptoms. However, its inherent fibrinolytic (blood-thinning) activity means it carries a meaningful bleeding risk that distinguishes it from most supplements.
Critical Warning: Nattokinase must not be combined with warfarin, direct oral anticoagulants (apixaban, rivaroxaban, dabigatran), or antiplatelet drugs (aspirin, clopidogrel) without physician supervision. A published case report describes a patient who substituted nattokinase for warfarin after mechanical aortic valve replacement and developed valve thrombosis requiring repeat surgery.
Contraindicated in bleeding disorders, before surgery (discontinue 2 weeks prior), and during pregnancy/nursing.
Interactions
- Warfarin — serious interaction. Additive anticoagulant effect creates significant bleeding risk. Additionally, natto food (not purified nattokinase supplements) contains vitamin K which can destabilize INR.
- DOACs (apixaban, rivaroxaban, dabigatran) — serious interaction. Combined fibrinolytic and anticoagulant effects increase hemorrhage risk.
- Aspirin / Clopidogrel — moderate interaction. Combined antiplatelet and fibrinolytic activity may increase bleeding.
- Blood pressure medications — minor interaction. Additive hypotensive effect; monitor BP.
Dosing
Standard Cardiovascular Dose 2,000 FU (fibrinolytic units) per day, equivalent to roughly 100 mg of nattokinase. This is the dose used in the Kim 2008 blood pressure RCT [2].
Higher-Dose Research The Ren 2017 atherosclerosis trial used 6,000 FU/day [3]. Some studies have used up to 10,800 FU/day, though this is not a standard recommendation.
Form Look for supplements standardized to FU (fibrinolytic units), not just milligrams. Quality varies between manufacturers. NSP-2 (nattokinase from B. subtilis natto) is the most studied strain.
Timing Can be taken with or without food. Some practitioners suggest evening dosing based on circadian fibrinolysis patterns, but no RCT has compared timing.
Cost
Nattokinase supplements cost $10-20 per month at the standard 2,000 FU daily dose. Products standardized by FU provide more reliable potency than those listing only milligrams. Given the moderate evidence base and relatively niche indication (cardiovascular support in those not on anticoagulants), it represents reasonable value for the right patient profile.
The bottom line
Nattokinase occupies a unique niche in cardiovascular supplements — it's one of the few oral agents that can directly dissolve fibrin clots, and its blood pressure benefits are supported by a meta-analysis of RCTs. The Ren 2017[3] plaque reduction data, while from a single trial, is genuinely striking. However, its significant interaction risk with anticoagulants limits its audience considerably. If you're not on blood thinners, have mildly elevated blood pressure, or are interested in cardiovascular protection, nattokinase is a reasonable evidence-based choice. If you take warfarin, DOACs, or aspirin daily, this supplement is not for you — the bleeding risk is real and documented.
References
- Li X, Wang X, Liang L, et al. Nattokinase supplementation and cardiovascular risk factors: a systematic review and meta-analysis of randomized controlled trials. Rev Cardiovasc Med. 2023;24(8):234.
- Kim JY, Gum SN, Paik JK, et al. Effects of nattokinase on blood pressure: a randomized, controlled trial. Hypertens Res. 2008;31(8):1583-1588.
- Ren NN, Chen HJ, Li Y, et al. A clinical study on the effect of nattokinase on carotid artery atherosclerosis and hyperlipidaemia. Zhonghua Yi Xue Za Zhi. 2017;97(26):2038-2042.
- Weng Y, Yao J, Sparks S, et al. Nattokinase: an oral antithrombotic agent. Clin Pharmacol. 2017;57(10):1266-1275.
Sources for this page include published meta-analyses, systematic reviews, and NIH dietary supplement fact sheets. All claims reflect the evidence as of early 2026.
This is not medical advice. Consult your healthcare provider before starting any supplement, especially if you take medications.