Nattokinase: The Fibrinolytic Enzyme for Cardiovascular Health

What Is Nattokinase?

Nattokinase is an enzyme extracted from natto — a traditional Japanese food made by fermenting soybeans with Bacillus subtilis var. natto. It was discovered in 1980 by Dr. Hiroyuki Sumi at the University of Chicago, who observed that a small piece of natto placed on an artificial blood clot dissolved it within 18 hours at body temperature. Conventional thrombolytic drugs like streptokinase took 5–6 hours.

Nattokinase belongs to a class of enzymes called serine proteases. Its primary action is fibrinolysis: breaking down fibrin, the protein mesh that forms the structural scaffold of blood clots. It also activates plasminogen (the body's own clot-dissolving enzyme), degrades plasminogen activator inhibitor-1 (PAI-1, which normally suppresses clot breakdown), and may reduce platelet aggregation.

The Science: What Does the Research Show?

Blood Pressure Reduction

The most robust human evidence is for blood pressure. A 2008 randomized controlled trial published in Hypertension Research enrolled 86 hypertensive subjects. After 8 weeks of 2,000 FU (fibrinolysis units) of nattokinase daily, systolic blood pressure dropped by 5.55 mmHg and diastolic by 2.84 mmHg compared to placebo. These are clinically meaningful reductions — comparable to modest lifestyle interventions.

A 2022 meta-analysis in Complementary Therapies in Medicine pooled data from 5 trials (n=798) and found nattokinase supplementation significantly reduced both systolic (weighted mean difference: −3.49 mmHg) and diastolic (−1.44 mmHg) blood pressure. Effects were stronger in individuals with baseline hypertension.

Fibrinolysis and Thrombosis

A 2009 crossover study by Kurosawa et al. gave healthy volunteers 2,000 FU of nattokinase and measured fibrinolytic activity over 8 hours. Nattokinase significantly elevated blood levels of tissue plasminogen activator (tPA) and reduced fibrinogen, both markers of improved clot dissolution capacity.

A 2017 study in Scientific Reports found nattokinase degraded amyloid fibrils — a structural protein linked to Alzheimer's disease — raising interest in potential neurological applications, though human trials in this area are nascent.

Atherosclerosis

A 26-week RCT published in Atherosclerosis (2017) randomized 1,062 participants with carotid plaques to either 6,000 FU nattokinase or statin therapy (simvastatin 20 mg). Both groups showed plaque regression, but nattokinase produced greater reductions in plaque volume (−37% vs −11%) and significantly lower LDL cholesterol. While methodologically limited (industry-funded, open-label), these results are striking enough to merit larger trials.

Dosing Protocol

Goal	Dose	Timing
Blood pressure support	2,000 FU/day	Morning, fasted or with water
Cardiovascular maintenance	2,000–4,000 FU/day	Divided into 2 doses
Plaque/fibrin focus	6,000 FU/day	3 × 2,000 FU with meals

Units matter: Nattokinase is measured in FU (fibrinolysis units) or CU (casein units). Most clinical trials use 2,000 FU. Some products list mg — 100 mg nattokinase ≈ 2,000 FU is a common conversion, but verify the unit on the label.

Safety and Contraindications

Nattokinase's fibrinolytic activity is also its main safety concern. The following contraindications apply:

• Blood thinners: Do not combine with warfarin, aspirin, clopidogrel, rivaroxaban, apixaban, or other anticoagulants/antiplatelets without physician guidance — additive bleeding risk.
• Surgery: Discontinue at least 2 weeks before any planned surgery.
• Hemorrhagic stroke history: Contraindicated.
• Soy/natto allergy: Nattokinase is derived from soy; allergy testing recommended before use.
• Vitamin K interaction: Natto is very high in vitamin K2, but purified nattokinase supplements contain negligible K2 — this is typically not a concern with supplements (unlike eating natto itself).

In clinical trials at doses up to 6,000 FU/day for 26 weeks, serious adverse events were not reported. Minor GI symptoms (nausea, loose stools) occur occasionally.

Nattokinase vs. Other Cardiovascular Enzymes

Enzyme	Source	Primary Action	Evidence Level
Nattokinase	Fermented soybeans	Fibrinolysis, blood pressure	Moderate (multiple RCTs)
Serrapeptase	Silkworm intestine bacteria	Anti-inflammatory, fibrinolysis	Limited (small trials)
Lumbrokinase	Earthworms	Fibrinolysis, platelet aggregation	Early (mostly Chinese studies)
Streptokinase	Streptococcal bacteria	Acute thrombolysis (IV only)	Strong (hospital use only)

Who Might Benefit from Nattokinase?

• Individuals with elevated blood pressure (prehypertension or stage 1 hypertension) not yet on medication
• People with elevated fibrinogen or hypercoagulable states (after lab testing)
• Those interested in cardiovascular prevention with a long-term lifestyle focus
• Frequent travelers at elevated DVT risk (though compression socks are first-line)

It is not a replacement for prescribed anticoagulants or antihypertensives in patients with established cardiovascular disease. Always discuss with a physician before starting.

Best Nattokinase Supplements 2026

Look for supplements that specify FU (not just mg), use enteric coating or delayed-release capsules (some research suggests this improves absorption), and have third-party testing.

Practical Tips

• Take away from meals when possible — some practitioners recommend taking nattokinase on an empty stomach for greater fibrinolytic effect, though evidence for this timing preference is limited.
• Pair with CoQ10 if your goal is broad cardiovascular support — these two compounds work via complementary mechanisms.
• Monitor blood pressure at home if using for hypertension — use this as a feedback tool to assess response.
• Give it 8 weeks — the blood pressure RCTs used 8-week intervention periods. Don't expect overnight results.

The Bottom Line

Nattokinase has earned a place in evidence-based cardiovascular supplementation. The blood pressure data from multiple RCTs is convincing, the mechanism is well-understood, and the safety profile at standard doses is acceptable. The major caution is its interaction with anticoagulant medications — this isn't a supplement to add casually if you're on blood thinners.

For individuals with mild-to-moderate hypertension, elevated fibrinogen, or a focus on cardiovascular prevention who are not on blood-thinning medications, 2,000 FU/day of a quality nattokinase product is a reasonable, evidence-supported addition to lifestyle interventions.