Can Nattokinase Clean Arteries? The Scientific Evidence

Nattokinase, an enzyme extracted from the Japanese fermented soybean food natto, has generated real scientific interest for its effects on blood clots, cholesterol, and arterial plaque. One large clinical study did report measurable plaque shrinkage in participants taking nattokinase over 12 months. But calling it an artery cleaner overstates the current evidence, which is still limited in quality and complicated by contradictory findings on key markers like cholesterol. The reality is more nuanced than supplement marketing suggests and less dismissive than many mainstream physicians assume.

What Nattokinase Does in the Body

Nattokinase is a protein-digesting enzyme produced by the bacterium Bacillus subtilis during the fermentation of soybeans into natto, a sticky, pungent staple in parts of Japan. Its primary claim to fame is fibrinolysis, the breakdown of fibrin, the mesh-like protein that forms the structural backbone of blood clots.¹ Unlike most pharmaceutical clot-busters, which work through a single pathway by activating plasminogen, nattokinase appears to act on multiple fibrinolytic and anti-thrombotic pathways simultaneously.²

This is an important distinction because dissolving clots and shrinking arterial plaque are not the same thing. A blood clot is a relatively fresh structure made of fibrin, platelets, and trapped blood cells. Arterial plaque, by contrast, is a slow-building deposit of cholesterol, calcium, inflammatory cells, and fibrous tissue embedded in the artery wall. Plaque removal requires something far more complex than just breaking down fibrin. So when researchers investigate whether nattokinase can “clean arteries,” they are really asking whether its effects on clotting, inflammation, cholesterol, and blood flow add up to measurable changes in the artery wall over time.

The Largest Clinical Study on Plaque Shrinkage

The most cited piece of evidence for nattokinase’s effect on arterial plaque comes from a study of 1,062 participants published in Frontiers in Cardiovascular Medicine. After 12 months of nattokinase consumption, the average thickness of the carotid artery wall dropped from 1.33 mm to 1.04 mm, and plaque size decreased by up to 36%.³ About two-thirds of participants showed improvement in plaque size, and roughly 78% showed improvement in artery wall thickness.

Those numbers sound striking, but they come with significant caveats. The study was not a randomized controlled trial with a placebo group. Without a control arm, it is impossible to separate nattokinase’s effects from other changes participants may have made during the year, such as diet, exercise, or statin use. The study population was Chinese, and dietary and genetic differences may influence how broadly the results apply. Still, the sheer size of the study and the magnitude of change have made it a frequent reference point, and it has prompted calls for properly controlled trials.

What the Evidence Says About Cholesterol

A review published in Nutrients concluded that large-scale clinical trials have confirmed nattokinase significantly improves lipid profiles and reduces plaque area and artery wall thickness.⁴ That is a confident statement, but the picture looks less clear when you dig into the pooled trial data.

A systematic review and meta-analysis of randomized controlled trials found something unexpected. When researchers pooled the results of multiple trials, the nattokinase groups actually had higher total cholesterol and higher LDL cholesterol compared to control groups, not lower. At lower doses, the nattokinase group also showed lower HDL (the “good” cholesterol). No significant effect on triglycerides was found at any dose.⁵

This is a genuine conflict in the literature, and it matters. The 1,062-participant study reported lipid improvements, but it lacked a control group. The meta-analysis, which pooled randomized controlled trials (a stronger study design for isolating an effect), did not find what supplement proponents typically claim. It is possible that nattokinase affects lipids differently depending on the population, the dose, or the formulation, but as of now, the highest-quality pooled evidence does not support the claim that nattokinase reliably lowers cholesterol.

Blood Pressure and ACE Inhibition

One of the more intriguing lines of research involves nattokinase’s effect on blood pressure. High blood pressure is a major driver of arterial damage and plaque progression, so anything that lowers it has downstream implications for artery health. Nattokinase appears to inhibit angiotensin-converting enzyme (ACE), the same target that a widely prescribed class of blood pressure medications goes after. One study reported that nattokinase inhibited ACE activity by up to about 87%.⁶

More recently, researchers identified specific short peptides released when nattokinase is digested that directly inhibit ACE. One of these peptides showed potent competitive inhibition in lab tests.⁷ This is a different mechanism from the enzyme’s fibrinolytic activity. It suggests that nattokinase may exert cardiovascular benefits not just as an intact enzyme breaking down fibrin, but also through the smaller peptide fragments produced during digestion. Whether those peptide fragments reach the bloodstream in meaningful concentrations in living humans, rather than just in lab simulations, remains an open question.

Vascular Inflammation

Atherosclerosis is fundamentally an inflammatory disease. Cholesterol deposits trigger an immune response in the artery wall, recruiting white blood cells that eventually form the fatty, unstable plaques responsible for heart attacks and strokes. If nattokinase reduces vascular inflammation, that could slow plaque growth or even promote regression regardless of its effects on cholesterol numbers.

Animal research has found that nattokinase reduced vascular inflammation in mice by activating autophagy, a cellular cleanup process, and by inhibiting the NLRP3 inflammasome, a molecular complex involved in triggering the inflammatory cascade.⁸ These are meaningful biological pathways, not fringe science. The NLRP3 inflammasome in particular has become a major target of pharmaceutical cardiovascular research. But the jump from mouse models to proven human benefit is a long one, and no controlled human trial has yet confirmed these anti-inflammatory effects in arterial tissue.

Can Your Body Actually Absorb an Enzyme?

The skeptic’s objection to nattokinase has always been bioavailability. Enzymes are proteins, and the stomach is designed to break proteins apart. So how can swallowing nattokinase produce any systemic effect at all?

The answer is not fully settled, but the evidence suggests at least partial absorption. An older study in humans found that oral nattokinase (or natto itself) produced a mild but measurable increase in fibrinolytic activity in the blood, along with increased tissue plasminogen activator, a molecule your body uses to dissolve clots.⁹ A single-dose study in healthy volunteers confirmed measurable changes in clotting markers, including elevated D-dimer (a fibrin breakdown product) and prolonged clotting times, all within the normal range.² Something is clearly getting through.

Animal research using a rat intestinal model measured a small intestine absorption rate of about 37% for nattokinase-derived peptides, with the absorbed fragments being mostly small and hydrophobic.¹⁰ The picture that emerges is that nattokinase probably does not survive the gut intact as a fully functional enzyme in large quantities. Instead, it may work partly through active peptide fragments generated during digestion and partly through whatever fraction of intact enzyme makes it through. Formulation matters here too. Researchers have developed enteric-coated tablets specifically designed to protect nattokinase from stomach acid and release it in the intestine, where absorption conditions are more favorable.¹¹ Newer encapsulation approaches using gel bead systems aim to improve this further.¹²

The practical takeaway is that if you’re taking a cheap, uncoated nattokinase supplement, you may be getting much less active compound than the label implies. The dose range used across clinical trials varies wildly, from 1,200 to 8,000 fibrinolytic units per day.⁵ That kind of variability makes it hard to compare results across studies and even harder for consumers to know what dose might be effective.

Safety, Bleeding Risk, and Drug Interactions

Nattokinase is often marketed as having no side effects, and for most healthy people taking moderate doses, serious adverse events appear to be rare. But its very mechanism of action, enhancing fibrinolysis and affecting clotting pathways, is also its main safety concern. The single-dose human study showed that nattokinase raised D-dimer levels, prolonged clotting time, reduced factor VIII activity, and increased antithrombin levels. All of these changes stayed within the normal range in healthy volunteers.² But “within normal range in healthy volunteers” does not mean safe for everyone.

Nattokinase’s bleeding risk becomes a real concern when combined with blood thinners or antiplatelet drugs, or in people with bleeding disorders. A review of anti-atherosclerotic supplements, including nattokinase, specifically flagged this, noting that clinical usefulness depends on formulation, dosage, and patient characteristics and may be limited by bleeding risk or drug interactions.¹³

The starkest warning comes from a case report of a patient who replaced warfarin with nattokinase after mechanical aortic valve replacement. After nearly a year on nattokinase alone, the patient developed a blood clot on the prosthetic valve and required repeat surgery.¹⁴ This case is a single anecdote, but the lesson is unambiguous: nattokinase is not a substitute for prescription anticoagulants in high-risk situations. If you’re on blood thinners for atrial fibrillation, a mechanical heart valve, or a history of deep vein thrombosis, adding or substituting nattokinase without your cardiologist’s knowledge is genuinely dangerous.

Blood Viscosity and Microcirculation

Beyond clot-busting and cholesterol, nattokinase may affect cardiovascular health through a less-discussed route: blood viscosity. Thicker, more viscous blood flows less easily through small vessels and creates more shear stress on artery walls, which can worsen endothelial damage and promote plaque formation. In laboratory experiments, nattokinase reduced red blood cell clumping and lowered whole blood viscosity in a dose-dependent manner, with effects appearing at concentrations similar to those achieved in animal studies.¹⁵ This is a plausible mechanism by which nattokinase could improve circulation and reduce arterial stress over time, though it has not been confirmed in controlled human trials.

Natto in the Traditional Japanese Diet

Some of the most compelling evidence for a cardiovascular benefit comes not from nattokinase supplements but from population studies of people who eat natto regularly. The Takayama study, a large prospective study of Japanese adults, found that those in the highest quartile of natto intake had a roughly 25% lower risk of dying from cardiovascular disease compared to those who ate the least natto.¹⁶

This is epidemiological data, not a clinical trial, so it cannot prove that natto itself caused the lower mortality. People who eat natto regularly may differ in many ways from those who do not, including overall diet quality, exercise habits, and healthcare access. Still, the association is notable and consistent with the biological mechanisms researchers have identified. It is also worth noting that natto contains vitamin K2 in addition to nattokinase, and vitamin K2 has its own body of research related to vascular calcification and arterial stiffness. The 1,062-participant study examined co-administration of vitamin K2 with nattokinase and found a synergistic effect on blood lipids in people with high cholesterol, though no significant impact on other atherosclerosis markers.³ This raises the possibility that eating natto, which delivers both compounds together in a food matrix, may work differently from taking isolated nattokinase capsules.

Where the Evidence Actually Stands

Nattokinase has real biological activity. It dissolves fibrin, it affects clotting markers, it appears to produce peptides that inhibit ACE, and it reduces vascular inflammation in animal models. One large study reported meaningful plaque reduction over 12 months. Epidemiological data from Japan links regular natto consumption to lower cardiovascular mortality. These are not nothing.

But the gaps are substantial. The plaque regression study lacked a control group. The meta-analysis of randomized trials found nattokinase groups had worse, not better, cholesterol numbers. The anti-inflammatory and blood viscosity effects have not been confirmed in controlled human trials. Dosing is inconsistent across studies, absorption depends heavily on formulation, and the supplement market is unregulated, meaning what is on the label may not be in the bottle. The enzyme was undergoing a Phase II clinical trial in the United States for atherothrombotic prevention as of a 2017 review.¹ Results from well-designed trials like these are what the field needs before nattokinase can be recommended with any confidence for arterial plaque management.

Why Supplement Marketing Gets Ahead of the Science

The disconnect between what nattokinase supplement ads promise and what the science shows is a pattern common to the entire dietary supplement industry. A supplement that can dissolve fibrin in a test tube gets described as an “artery cleaner.” A single uncontrolled study becomes “clinically proven.” A traditional food’s epidemiological association with lower heart disease becomes “Japanese secret to clean arteries.” Each step in that chain drops a qualifier, and by the time the claim reaches a product label or a YouTube video, it bears little resemblance to what researchers actually found.

This does not mean nattokinase is worthless. The biological plausibility is there, the early clinical signals are interesting, and the safety profile in healthy people appears reasonable. But the honest answer to whether nattokinase can clean your arteries is that the science is promising, incomplete, and not yet strong enough to recommend it as a treatment for atherosclerosis. If you have arterial plaque, the interventions with the strongest evidence remain statins, blood pressure management, smoking cessation, exercise, and dietary changes. Nattokinase might eventually earn a supporting role in that lineup, but it has not done so yet.

1
PubMed Central. Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease
2
Scientific Reports. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles
3
PubMed Central. Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants
4
PubMed Central. Research Progress of Nattokinase in Reducing Blood Lipid
5
PubMed Central. Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
6
Food Science and Human Wellness. Nattokinase as a functional food ingredient: therapeutic applications and mechanisms in age-related diseases
7
PubMed. Identification and mechanistic characterization of novel ACE-inhibitory peptides derived from Nattokinase
8
PubMed. Nattokinase attenuates endothelial inflammation through the activation of SRF and THBS1
9
PubMed. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase
10
Food Bioscience. Decoding nattokinase efficacy: From digestion and absorption to lipid pathway modulation in high-fat diet-induced atherosclerosis
11
PubMed. Stabilization and target delivery of Nattokinase using compression coating
12
PubMed. Enhancing nattokinase stability through synergistic interactions:Construction and mechanism analysis of multi-level encapsulation structures in fig-like gel beads
13
PubMed Central. Navigating the Effects of Anti-Atherosclerotic Supplements and Acknowledging Associated Bleeding Risks
14
PubMed Central. Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis
15
PubMed. Effects of nattokinase, a pro-fibrinolytic enzyme, on red blood cell aggregation and whole blood viscosity
16
The American Journal of Clinical Nutrition. Dietary soy and natto intake and cardiovascular disease mortality in Japanese adults: the Takayama study