Evidence Review
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 mmHg [1]. 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 mechanism [1].
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 weeks [2]. 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 reduction [2].
Meta-Analysis Summary
A 2023 systematic review and meta-analysis by Zhou et al. synthesized data from six randomized controlled trials encompassing 546 participants [5]. 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 lower-dose supplementation had limited lipid-lowering effects, but hypertension benefits were consistent across trials. The authors concluded that nattokinase can serve as effective adjunctive therapy for hypertension management [5].
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 profiles [4]. 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 mechanisms [4].
Fibrinolytic Mechanism: Review Evidence
Weng et al. (2017) published a comprehensive mechanistic review of nattokinase as an oral antithrombotic agent [3]. 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.