Does nattokinase lower blood pressure and help prevent blood clots?

Nattokinase is a serine protease produced by the bacterium Bacillus subtilis var. natto during the fermentation of soybeans. Its primary mechanism is fibrinolytic: it directly cleaves fibrin, the insoluble protein mesh that forms the structural scaffold of blood clots. Unlike prescription thrombolytics (clot-dissolving drugs) that must be injected, nattokinase is stable enough to be absorbed through the intestinal wall and maintain activity in the circulation³.

Beyond direct fibrinolysis, nattokinase also activates the body's own plasmin system — the natural pathway for dissolving clots — and inhibits platelet aggregation. Together these effects reduce blood viscosity and the tendency toward pathological clotting without fully suppressing normal clot formation³.

Blood pressure effects appear to be mediated at least partly through renin inhibition. Renin is an enzyme that initiates a hormonal cascade (the renin-angiotensin system) that raises blood pressure. A controlled trial found that nattokinase reduced renin activity by 1.17 ng/mL/h in addition to lowering blood pressure values¹.

Dosing and Forms

Nattokinase is typically measured in fibrinolytic units (FU) rather than milligrams. Standard research doses have ranged from 2,000 FU to 10,800 FU per day:

• 2,000 FU/day was used in the landmark Korean blood pressure trial¹
• 100 mg/day (approximately 2,000 FU) was used in the North American multicenter trial²
• 10,800 FU/day was used in the large Chinese atherosclerosis study⁴

Supplements are widely available as capsules standardized to activity levels (commonly 2,000 FU per capsule). Look for products that have removed vitamin K2, which is naturally present in natto but may interact with anticoagulant medications like warfarin.

Important caution: Nattokinase has real blood-thinning effects. People taking warfarin, aspirin, clopidogrel, or other anticoagulants should consult their physician before use, as the combination can increase bleeding risk.

Who May Benefit Most

The strongest evidence is for people with elevated blood pressure (pre-hypertension or stage 1 hypertension) and those with cardiovascular risk factors including elevated cholesterol, early atherosclerosis, or a family history of blood clots. The enzyme naturally occurs in natto, and populations with high natto consumption historically have lower rates of cardiovascular mortality — though dietary pattern and genetics confound this observation.

See our fermented foods page for more on natto as a whole food and its broader nutritional profile.

Blood Pressure: Randomized Controlled Trials

The foundational clinical trial on nattokinase and blood pressure was conducted by Kim et al. (2008), a randomized, double-blind, placebo-controlled study of 86 Korean adults with untreated systolic blood pressure of 130–159 mmHg¹. Participants received either nattokinase (2,000 FU/capsule) or placebo for 8 weeks. Compared to the control group, the nattokinase group showed net reductions of -5.55 mmHg systolic and -2.84 mmHg diastolic (both p < 0.05). Renin activity also fell by -1.17 ng/mL/h in the treatment group, suggesting a renin-angiotensin system mechanism¹.

Jensen et al. (2016) extended these findings to a North American population in a multicenter, randomized, double-blind, placebo-controlled trial of 79 subjects with elevated blood pressure who consumed 100 mg nattokinase (NSK-SD, vitamin K2-free) or placebo daily for 8 weeks². This is important because prior evidence came largely from Asian populations. The study confirmed blood pressure reductions in a Western cohort, with reductions more robust in male participants. Nattokinase also significantly reduced von Willebrand factor — a protein involved in platelet adhesion and a marker of endothelial dysfunction — suggesting vascular wall benefits beyond simple pressure reduction².

Meta-Analysis Summary

A 2023 systematic review and meta-analysis by Li et al. synthesized data from six randomized controlled trials encompassing 546 participants⁵. Nattokinase supplementation significantly reduced:

• Systolic blood pressure: -3.45 mmHg (MD, 95% CI reported)
• Diastolic blood pressure: -2.32 mmHg (MD, 95% CI reported)

The meta-analysis found that nattokinase significantly reduced blood pressure but showed no lipid benefit: relatively low total doses had a negative effect on total, HDL and LDL cholesterol, relatively high total doses still gave a higher total cholesterol than control, triglycerides showed no significant association, and blood glucose rose slightly; the authors cautioned that relatively low-dose nattokinase may have no significant lipid-lowering effect. The authors concluded that nattokinase can serve as effective adjunctive therapy for hypertension management⁵.

Atherosclerosis and Lipids: Large-Scale Clinical Study

Chen et al. (2022) conducted a prospective clinical study of 1,062 participants taking 10,800 FU nattokinase per day for 12 months to assess effects on atherosclerosis progression and lipid profiles⁴. Significant findings included:

• Reduced carotid artery intima-media thickness (a surrogate marker for atherosclerosis)
• Decreased carotid plaque size
• Improvement in total cholesterol, LDL cholesterol, and triglyceride levels

The study's large sample size and 12-month duration give it meaningful statistical power, though the lack of blinding (it was an open-label observational study) limits causal inference. Nonetheless, the magnitude of the atherosclerosis findings is notable and consistent with the enzyme's known fibrinolytic and anti-inflammatory mechanisms⁴.

Fibrinolytic Mechanism: Review Evidence

Weng et al. (2017) published a comprehensive mechanistic review of nattokinase as an oral antithrombotic agent³. Key points from their analysis:

• Nattokinase demonstrates direct fibrinolytic activity comparable to plasmin in vitro, and retains activity after oral absorption in humans
• It activates endogenous tissue plasminogen activator (tPA) and urokinase, amplifying the body's own fibrinolytic system
• The enzyme inhibits platelet aggregation through multiple pathways, including reduction of thromboxane B2
• A pharmacokinetic study confirmed the enzyme survives gastrointestinal digestion and achieves detectable fibrinolytic activity in plasma following a single oral dose

Limitations and Evidence Gaps

The overall evidence base for nattokinase is promising but has important limitations:

• Most trials are short (8–12 weeks), and long-term cardiovascular outcome data (heart attacks, strokes) are not yet available from randomized trials
• The large Chinese atherosclerosis study used observational design, limiting causal conclusions
• Optimal dosing is still being established; effective doses across studies range from 2,000 to 10,800 FU/day
• Drug interaction studies with anticoagulants are limited; caution is warranted for anyone on blood-thinning medications

On balance, the evidence supports nattokinase as a well-tolerated, bioavailable supplement with genuine effects on blood pressure and fibrinolytic markers. The effect sizes are modest but clinically relevant, particularly for people in the borderline-hypertensive range looking for non-pharmacological support.