Nattokinase and Stroke Research: Understanding the Evidence

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This article discusses how nattokinase can protect the brain from the destructive effects of strokes. 

About Dr. Santiano

As a physician with extensive experience in internal medicine and emergency medicine, I frequently evaluate cardiovascular and neurological conditions, including ischemic strokes, atrial fibrillation, and clot-related disorders. This article summarizes peer-reviewed findings on nattokinase and stroke physiology to help readers understand the evidence and limitations behind its potential benefits.

Why Stroke Prevention Research Matters

Ischemic strokes remain a leading cause of death and disability worldwide. Because most strokes are caused by blood clots or advanced atherosclerosis, any intervention that safely reduces clot formation or improves vascular function is worth scientific attention.

The research discussed here provides biological plausibility for nattokinase’s effects, but should not be interpreted as medical treatment or a substitute for established stroke therapies.

Nattokinase (NK) is an enzyme derived from natto, a fermented Japanese food. It has been consumed for over a thousand years. 

Important Medical Disclaimer

Stroke is a medical emergency. Anyone with symptoms such as facial drooping, weakness, or difficulty speaking should call emergency services immediately.

Nattokinase is not a replacement for proven treatments such as anticoagulants, blood pressure management, or emergency thrombolysis. The findings summarized here are from animal studies, small human studies, and mechanistic research.

Supplements should never be started, stopped, or replaced for prescription medications without the guidance of a qualified healthcare professional.

Stroke

Strokes or ischemic cerebrovascular accidents (CVA) cause cerebral ischemia, a condition in which the blood and oxygen supply to the brain tissues are lost. If not reperfused, neurons die, and a body part’s function is lost. 

Typically, the offending clot can come from the heart if there is atrial fibrillation (AF).

In atrial fibrillation, the left atrium, one of the heart’s upper chambers, quivers instead of pumping. The shivering starts blood clotting. 

That is why people with AF are typically on blood thinners like warfarin or apixaban (Eliquis) and dabigatran (Pradaxa). 

Another common cause is a piece of atherosclerosis or clot that broke off from an atherosclerotic plaque from the carotid artery.

Brain tissue damage from stroke

Cerebral ischemia releases calcium in the brain’s arteries, causing them to constrict, further compromising blood flow.

Apoptosis or programmed cell death can also happen to neurons that don’t have enough oxygen (hypoxic).

Typically, the body uses its tissue plasminogen activator (TPA) to form plasmin, which dissolves the fibrin in blood clots with its fibrinolytic effect.

However, it is not predictable how fast that can happen. 

TPA

That’s why hospitals specializing in strokes (stroke centers) use recombinant TPA to dissolve blood clots.

Careful monitoring follows since intracranial bleeding may occur after.

If it does, it will be a disaster because the bleeding will be inoperable for several hours due to the presence of blood thinners.

Ischemia-reperfusion injury can also happen once the blockage is removed.

The resumption of blood flow can trigger inflammation and damage more tissues. It can occur in stroke, myocardial infarction, and limb ischemia.

How to Interpret Stroke Mechanisms

Stroke pathophysiology is complex—clot formation, inflammation, oxidative stress, endothelial dysfunction, and reperfusion injury all contribute to tissue loss.

Because these mechanisms involve fibrin, platelets, nitric oxide, and smooth muscle constriction, researchers have explored whether nattokinase’s biochemical properties could influence stroke risk or tissue damage.

However, these findings do not confirm that nattokinase prevents or treats strokes in real-world clinical settings.

With that brief background, here is how NK could be helpful in cerebral ischemia.  

Neuroprotective Effects of Nattokinase on Strokes

Understanding the Evidence

Current findings on nattokinase and stroke come from:

• Animal models
• Laboratory cell studies
• Small human observational studies

These studies offer promising insights—reduced clot formation, improved blood flow, and decreased infarct volume—but they are not large clinical trials.

Readers should view these results as early-stage scientific exploration, not established medical therapy.

Prevention

Anti-atherosclerosis

NK protects against strokes by preventing glucose spikes and insulin resistance, which are the root causes of atherosclerosis. 

Insulin Resistance and Atherosclerosis and the Nattokinase Solution

But if atherosclerosis is already present, NK can still help. Nattokinase has been shown to decrease atherosclerosis in two human studies. I discussed those at:

• The Outstanding Vascular Effects and Dose of Nattokinase
• Insulin Resistance and Atherosclerosis and the Nattokinase Solution

Anticoagulant

Nattokinase is an effective anticoagulant as it prevents blood clots from forming. One way is by blocking platelet clumping, which starts a clot.

Typically, aspirin is initiated in some patients to avoid clots. However, between 8 % and 45% of patients are aspirin resistant.[2]

Moreover, some patients cannot take aspirin for one reason or another. One study from Bulgaria shows how NK may be of help. 

Nattokinase vs. Aspirin and Clopidogrel

Why Comparative Studies Matter

The study comparing nattokinase with aspirin and clopidogrel is valuable because it evaluates real-world patients, including those who could not tolerate antiplatelet medication.

Still, the study size (n=191) and the six-month duration mean the findings should be interpreted cautiously. Larger trials are needed to verify whether nattokinase provides similar long-term protection as standard antiplatelet therapy.

A study by Maslarov and Drenska studied two groups. One took nattokinase (NK) (160 mg, 3,000 FU) n=96. Another took aspirin (325 mg) and clopidogrel (Plavix 75 mg daily) n=95.  All were followed for six months.

The NK group consisted of those who could not take aspirin. They are the following:

• Moderate and high risk of gastrointestinal bleeding (62.5%)
• A history of cerebral hemorrhage (6.3%)
• Rare episodes of atrial fibrillation/flutter (12.5%)
• Individual intolerance or unwillingness for treatment with antithrombotic drugs (18.7%).
• 17.7% of patients have cancer compared to 12.6% of the control group.

The results showed no statistical difference between the NK versus the aspirin and Plavix groups in the number of ministrokes or Transient ischemic Attacks (TIA), strokes, and heart attacks after six months of follow-up.[2]

The image below compares the number of cardiovascular diseases, TIA, and strokes.  Nattokinase is gray. And red is aspirin and Plavix groups. m=months.

More importantly, the number of adverse reactions in both groups was also statistically insignificant.[2]

Therapeutic

Dissolves Fibrin

Platelets and red blood cells adhere to a scaffold of fibrin bridges. NK has fibrinolytic properties that can dissolve the fibrin bridges and allow blood flow to resume.

It is interesting to note that TPA and NK are both serine proteases. Proteases are enzymes that can cleave peptide bonds in proteins. 

Ahn et al. showed that NK prevented the formation of a blood clot and hastened the dissolution of blood clots in an experimental stroke in animals, resulting in improved blood flow in all brain regions.[1]

Ultimately, the volume of the infarcted brain was smaller in those who received nattokinase compared to the control.[1]

Wang et al. also demonstrated a 54-68% reduction in infarct volumes in both low and high-dose NK doses in gerbils. A low dose (4mg/day) of NK was also shown to decrease inflammation following strokes. [4]

Biological Plausibility

Multiple studies—including Ahn et al., Wang et al., and Ji et al.—describe mechanisms through which nattokinase may affect the brain during ischemia:

• decreased platelet aggregation
• enhanced fibrinolysis
• nitric-oxide-driven vasodilation
• reduced apoptosis

These mechanisms support the theoretical neuroprotective potential of nattokinase. However, mechanisms alone do not prove clinical benefit. Only randomized controlled trials can determine actual stroke-prevention outcomes.

Mechanisms of Cerebral Protection

Ji et al. examined the intricate pathways on how NK can protect the brain. They found the following.[3]

1. NK has antiplatelet activity.  
2. NK has anti-apoptosis activity and could prevent brain cell death. 
3. NK can relax smooth muscles by releasing nitric oxide in blood vessels and increasing blood flow. 
4.  NK increases fibrinolytic activity and facilitates spontaneous thrombolysis. 

In summary, nattokinase prevents strokes by preventing and decreasing atherosclerosis.

It can inhibit and dissolve blood clots and protect brain cells from injuries due to low oxygen levels.  

Medical Disclaimer

This article is for educational purposes only. The studies cited include animal experiments, in vitro research, and limited human observations. Nattokinase should not replace prescribed cardiovascular or anticoagulant medications.

People taking warfarin, apixaban, rivaroxaban, aspirin, or other blood thinners should avoid nattokinase unless supervised by a physician, as combining them may increase bleeding risk.

Always consult your healthcare provider before adding supplements for stroke prevention.

Talk to your doctor before starting any supplements. The following contains affiliate links. 

• Doctor’s Best Nattokinase – 2,000 FU of Enzyme – this formulation is NSK-SD with no vitamin K2. Vitamin K2 counters the effect of warfarin. 
• Best Naturals Nattokinase, 2000 FU, 100 Mg, 90 Vegetarian Capsules – This has vitamin K2 that is good for cardiovascular and bone health.

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Related:

1. Insulin Resistance and Atherosclerosis and the Nattokinase Solution
2. Protective Effects of Nattokinase against Strokes
3. How to dose Nattokinase, Bromelain and NAC
4. High-Dose Nattokinase to Shrink Atherosclerosis and Lower Blood Lipids
5. Nattokinase is Nontoxic with a High Safety Margin
6. The Outstanding Vascular Effects and Dose of Nattokinase
7. Another Study shows Nattokinase can Destroy the S1 Spike Protein
8. Nattokinase Degrades the SARS-CoV-2 Spike Protein
9. Soy Foods Do Not Increase Breast Cancer Risk

References:

1. Ahn Y et al. Neuroprotective Effect of Nattokinase Mediated by Inhibition of Platelet Aggregation and Thrombosis in Photothrombotic Stroke. Stroke. 2015;46:AWP262. 9 Feb 2015. https://doi.org/10.1161/str.46.suppl_1.wp262
2. Maslarov D, Drenska D. Use of Nattokinase in patients with ischemic stroke and transient ischemic attacks. Neurol Neurosci. 2020; 1(2):1-5.
3. Ji H, Yu L, Liu K, Yu Z, Zhang Q, Zou F, Liu B. Mechanisms of Nattokinase in protection of cerebral ischemia. Eur J Pharmacol. 2014 Dec 15;745:144-51. doi: 10.1016/j.ejphar.2014.10.024. Epub 2014 Oct 27. PMID: 25446567.
4. Wang JM, Chen HY, Cheng SM, et al. Nattokinase reduces brain infarction, fibrinogen and activated partial thromboplastin time against cerebral ischemia-reperfusion injury. J Food Drug Anal. 2012; 3: 686-91.
5. Chen H, McGowan EM, Ren N, et al. Nattokinase: A Promising Alternative  in Prevention and Treatment of Cardiovascular Diseases. Biomark Insights 2018; 13: 1177271918785130.
6. Pham PT, Han B, Hoang BX. Nattospes as Effective and Safe Functional Supplements in Management of Stroke. J Med Food. 2020 Aug;23(8):879-885. doi: 10.1089/jmf.2019.0183. Epub 2020 Jan 14. PMID: 31934821; PMCID: PMC7415874.

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