Nattokinase, an enzyme extracted from the traditional Japanese fermented soybean dish natto, has gained attention as a natural supplement with potential cardiovascular benefits. Among the claims, one of the most intriguing is its ability to reduce arterial plaque—a central factor in atherosclerosis and cardiovascular disease. But does high-dose nattokinase truly shrink arterial plaque, or is this another overhyped supplement?
This deep dive examines the latest clinical studies, mechanisms of action, safety considerations, and what the science really says about nattokinase’s role in managing arterial plaque.
Understanding Arterial Plaque and Atherosclerosis
Atherosclerosis is a chronic condition characterized by the build-up of fatty plaques in arterial walls. These plaques narrow the arteries, reduce blood flow, and can lead to heart attacks and strokes. Reducing or stabilizing plaque is a key goal in cardiovascular health.
What Is Nattokinase?
Nattokinase is a fibrinolytic enzyme, meaning it can break down fibrin, a protein involved in blood clotting. Derived from natto, nattokinase has been studied for its blood-thinning, antithrombotic, and potential anti-atherosclerotic effects.
Clinical Evidence: Does High Dose Nattokinase Reduce Plaque?
Large-Scale Clinical Study with Over 1,000 Participants
A 2022 clinical study involving 1,062 participants investigated nattokinase’s effects on atherosclerosis progression and hyperlipidemia. Participants received a high dose of nattokinase—around 10,800 fibrinolytic units (FU) daily, which is notably higher than typical doses.
Findings:
- Significant reduction in carotid artery plaque size.
- Improvement in lipid profiles (lower LDL cholesterol and triglycerides).
- Decreased carotid intima-media thickness (a marker of arterial wall thickening).
- Comparable anti-atherosclerotic effects to aspirin, as nattokinase shares similar pathways in preventing platelet aggregation and inflammation.
This study suggests that high-dose nattokinase can effectively slow progression and even reduce arterial plaque burden in patients with existing atherosclerosis (Frontiers in Cardiovascular Medicine, 2022).
Meta-Analysis of Randomized Controlled Trials
A 2023 meta-analysis reviewing multiple randomized trials found that administration of high-dose nattokinase (around 6,500 FU daily for 26 weeks or longer) was effective in inhibiting the progression of atherosclerotic plaques and improving cardiovascular risk factors, including blood pressure and lipid levels (PMC, 2023).
Other Clinical Findings
- Reduction in common carotid artery intima-media thickness (CCA-IMT), a surrogate marker for atherosclerosis.
- Improvement in endothelial function, which helps arteries dilate and maintain healthy blood flow.
- Lipid-lowering effects contributing to plaque stabilization (Sage Journals, 2018).
How Does Nattokinase Work Against Arterial Plaque?
Fibrinolytic and Antithrombotic Effects
Nattokinase promotes the breakdown of fibrin, which not only helps dissolve blood clots but may also contribute to degrading fibrin-rich components of arterial plaques, potentially shrinking soft plaques and preventing new clot formation.
Anti-Inflammatory and Antioxidant Properties
Chronic inflammation drives plaque formation and instability. Nattokinase has been shown to reduce inflammatory markers and oxidative stress, which could slow plaque progression and stabilize existing plaques.
Gene Regulation and Cellular Effects
Recent research suggests nattokinase upregulates genes related to autophagy (cellular cleanup processes) and reduces necroptosis (a form of programmed cell death linked to inflammation), further protecting vascular health (ScienceDirect).
Safety and Dosage of High-Dose Nattokinase
Typical and High Doses
- Common doses range from 2,000 to 4,000 FU daily.
- High doses used in clinical studies are around 6,500 to 10,800 FU daily.
Safety Profile
- Generally considered safe when taken orally for up to 3 years.
- Potential bleeding risk exists, especially when combined with other anticoagulants or in patients with bleeding disorders.
- Monitoring is advised for those on blood thinners or with surgery planned (WebMD, Examine.com).
Practical Considerations
- Consult your healthcare provider before starting nattokinase, especially if you are on blood thinners or have bleeding risks.
- High doses have shown promising results but require careful monitoring.
- Nattokinase can be a complementary approach, but it should not replace conventional therapies for atherosclerosis.
Summary
- High-dose nattokinase (6,500 to 10,800 FU daily) has demonstrated potential to reduce arterial plaque size and improve cardiovascular risk markers in clinical studies.
- Its mechanisms include fibrinolytic activity, anti-inflammatory effects, and gene-level modulation protecting vascular cells.
- Safety is generally acceptable at studied doses, but bleeding risk should be considered.
- More large-scale, long-term studies are needed to fully establish nattokinase’s role in clinical practice.
References and Credits
- Chen H, Chen J, Zhang F, Li Y, Wang R. "Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants." Frontiers in Cardiovascular Medicine, 2022. Link
- Li X, Long J, Gao Q, Pan M, Wang J, et al. "Nattokinase supplementation and cardiovascular risk factors: a systematic review and meta-analysis of randomized controlled trials." PMC, 2023. Link
- Chen H, McGowan EM, Ren N, Lal S, et al. "Nattokinase: a promising alternative in prevention and treatment of cardiovascular diseases." Biomarker Insights, 2018. Link
- Liu M, Xu Z, Wang Z, Wang D, Yang M, Li H, et al. "Lipid-lowering, antihypertensive, and antithrombotic effects of nattokinase combined with red yeast rice in patients with stable coronary artery disease: a randomized, double-blind trial." Frontiers in Nutrition, 2024. Link
- WebMD, Nattokinase Safety and Use. Link
- Examine.com, Nattokinase Supplement Review. Link
In conclusion, high-dose nattokinase shows promising evidence for reducing arterial plaque and improving cardiovascular health markers, but it’s no magic bullet. It’s best seen as part of an integrative approach alongside lifestyle changes and conventional therapies, under medical supervision.
