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Ntk8.5
Nattokinase Research
Mixed evidenceModerate safety
25 peer-reviewed studies
What the evidence says
Mixed evidence
Studies are split: Nattokinase helped in 1 of 3 cases, with the rest inconclusive or showing no benefit.
Most evidence is from high-quality randomised trials published 2008–2026 with a typical study size of 73 participants.
Based on 25 studies · 11 RCTs · 1,029 total participants
Confidence
High
What the studies found
1helped2unclear· 22 more without graded effect data
By outcome
Heart & blood pressureImproved blood flow and cardiovascular markers within 4-8 weeks · 4-8 weeks
Mixed evidence25 studies
Fibrinolysis & blood clot
Mostly mechanism / observational13 studies
Safety profile
Mostly mechanism / observational5 studies
Cholesterol & lipidsImproved blood flow and cardiovascular markers within 4-8 weeks · 4-8 weeks
Mostly mechanism / observational4 studies
Therapeutic & clinical
Mostly mechanism / observational3 studies
Cognitive function
Mostly mechanism / observational3 studies
Neuroprotection & brain aging
Too few graded studies2 studies
Bone health
Too few graded studies1 study
Glucose & metabolic
Too few graded studies1 study
By the numbers
Pulled from 14 studies with measurable effects
Likely real effects
50%
across studies
People studied
1,029
typical study: 73 people
Strongest designs
11
0 pooled, 11 randomised
Showed benefit
33%
1/3 studies
How long studies ran
Under a week
1
1–3 months
2
3+ months
2
Populations Studied
Non-communicable diseases patients1
Cardiovascular disease patients1
CVD patients1
Cardiovascular patients1
Active research area
17 studies in the last 5 years
200820172026
1Systematic ReviewCited 3×2025
There are various types of nattokinase preparations on the market, and consumers should choose regular products with high activity and purity, and pay attention to their safety and applicable population.
Wei C et al. · Nutrients (2025)
Large-scale clinical trials have confirmed that nattokinase significantly improves the lipid profile and reduces the atherosclerotic plaque area and intima-media thickness with a favorable safety profile.
There are various types of nattokinase preparations on the market, and consumers should choose regular products with high activity and purity, and pay attention to their safety and applicable population.
Given the variability in evidence and product quality, their use should be individualized, with further large-scale clinical trials needed to establish safety and efficacy.
Dobre MZ et al. · International journal of molecular sciences (2025)
Omega-3 fatty acids, berberine, garlic, and nattokinase exert favorable metabolic and vascular effects, yet their clinical efficacy depends on formulation, dosage, and patient characteristics and may be limited by bleeding risk or drug interactions.
Antioxidant agents such as vitamin C, vitamin E, resveratrol, astaxanthin, and coenzyme Q provide additional vascular protection but can interfere with hemostasis, metabolism, or redox-sensitive pathways.
Similarly, ginkgo biloba, ginger, ginseng, and curcumin exhibit anti-inflammatory vascular activity but also increase the risk of bleeding when combined with antithrombotic therapy.
Potential future studies focused on developing functional fermented foods and easy-to-use supplements based on fermented plant products are suggested.
Bernacka K et al. · Nutrients (2025)
Fermented fruits and vegetables, including table olives, caper fruits, and kimchi, contain polyphenols and probiotic bacteria, which are beneficial in terms of obesity and impaired glucose and lipid metabolism.
Fermented legumes are a valuable source of bioactive peptides and isoflavone aglycones.
Among fermented soybean products, natto stands out due to the presence of γ-polyglutamic acid, which improves glucose tolerance and the lipid profile, and nattokinase, an enzyme that acts as an angiotensin-converting enzyme inhibitor.
Furthermore, the study of NK on the cardiovascular system leads to certain assumptions, which include the impact on vasculature function and the ability to manage blood flow, which is the key featu...
Mahakalakar N et al. · Brain research (2025)
Furthermore, the study of NK on the cardiovascular system leads to certain assumptions, which include the impact on vasculature function and the ability to manage blood flow, which is the key feature of BBB integrity.
Such assumed mechanisms are fibrinolytic action, anti-inflammatory and antioxidant action, and endothelium function modulation.
There are many positive research findings, and it seems that NK may serve as an effective opponent for BBB breakdown; however, a new research level should be taken to disclose the application and therapeutic use of NK in brain neurodegenerative disease.
6Fibrinolytic and antithrombotic activity reviewSystematic ReviewCited 10×2024
Due to the fibrinolytic and antithrombotic activity of nattokinase, and more recently added to the anti-inflammatory and antioxidant effects, this enzyme can be used as a new adjuvant therapeutic strategy to mitigate inflammation and oxidative stress in NCDs, including CVD.
Granito M et al. · Expert review of cardiovascular therapy (2024)
By combining evidence from basic research with clinical findings, we aim to elucidate the comparative cardioprotective efficacy of these interventions and highlight their respective roles in modern cardiovascular care.
Muric M et al. · Biomolecules (2024)
This enzyme showed not only fibrinolytic activity due to its ability to degrade fibrin, but also an affinity as a substrate for plasmin.
Recent studies have shown that NK has additional cardioprotective effects, such as antihypertensive and anti-atherosclerotic effects.
In this narrative review, we presented the cardioprotective properties of two different approaches that go beyond anticoagulation: NOACs and NK.
8Nattokinase synthesis and application potentialSystematic ReviewCited 15×2023
Finally, the possible future directions focused on NK studies were proposed and provided suggestions for subsequent researchers.
Sheng Y et al. · Food & function (2023)
If multiple simple and efficient precipitation methods and purification materials are combined to purify NK, it may be possible to solve the current challenges.
Additionally, the application potential of NK in biomedicine was reviewed, but functional foods with NK are challenging for acceptance in daily life due to their unpleasant odor.
Accordingly, multi-strain combination fermentation or food flavoring agents can improve the odor of fermented foods and increase people's acceptance of them.
Moreover, the paper reviews the enzyme nattokinase's role in thrombotic prevention due to its fibrinolytic activity.
Gasmi A et al. · Critical reviews in food science and nutrition (2022)
Research has linked vitamin D deficiency to the development of diabetes mellitus, hypertension, cancer, and osteoporosis.
Vitamin K has been associated with a reduced risk of osteoporosis, cancer, and cardiovascular diseases (due to improved vascular elasticity).
This review highlights the importance of vitamins D and K in the metabolism of calcium and phosphorus and explores various molecular mechanisms that help maintain the system's mineral homeostasis.
10Clinical applications of nattokinaseSystematic ReviewCited 40×2022
Finally, this review summarizes the clinical applications of nattokinase.
Yuan L et al. · Biomolecules (2022)
Bacillus nattokinase is a potential low-cost thrombolytic drug without side-effects and has been introduced into the consumer market as a functional food or dietary supplement.
This review firstly summarizes the biodiversity of sources and the fermentation process of nattokinase, and systematically elucidates the structure, catalytic mechanism and enzymatic properties of nattokinase.
In view of the problems of low fermentation yield, insufficient activity and stability of nattokinase, this review discusses the heterologous expression of nattokinase in different microbial hosts and summarizes the protein and genetic engineering progress of nattokinase-producing strains.
Opportunities for utilizing plant systems for the large-scale production of NK, or for the production of edible plants that can be used to provide oral delivery of NK without extraction and purification are also discussed.
Weng Y et al. · International journal of molecular sciences (2017)
Multiple NK genes have been cloned, characterized, and produced in various expression system studies.
Recombinant technology represents a promising approach for the production of NK with high purity for its use in antithrombotic applications.
This review covers the history, benefit, safety, and production of NK.
This review is the first to cover all the natural and recombinant thrombolytic agents used in enzyme therapy.
Kotb E · Biotechnology progress (2014)
According to data provided by the World Health Organization (WHO) in 2000, heart diseases are responsible for 29% of the total mortality rate in the world.
Furthermore, recombinant DNA technology has succeeded in improving and decreasing the undesirable effects of the first generation of enzymes.
This review is the first to cover all the natural and recombinant thrombolytic agents used in enzyme therapy.
15Lipid profile improvementRCTCited 6×n=113 · medium study2023
However, it did not significantly affect serum TG, HDL-C, and CIMT.
Liu X et al. · Nutrients (2023)
There were no significant differences in coagulation, liver function, renal function, or other indicators.
No intervention-related adverse events, such as mouth ulcers, drooling, and stomach pain, were reported.
The study results demonstrate that NMSs can ameliorate lipid levels (TC, LDL-C, non-HDL-C, and the LDL-C to HDL-C ratio) without the occurrence of adverse events.
16Global cognition (MoCA score)RCTn=120 · medium study2026
Six-month NK supplementation did not improve global cognition in asymptomatic intracranial/carotid stenosis patients.
Zhang K et al. · Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association (2026)
No clear effect
← WorseNo effectBetter →
Could be chance
A total of 120 subjects were ultimately included (60 in the NK group and 60 in the placebo group), with balanced baseline characteristics between the two groups (average age 58.3 years, female 40.9 %).
Per-protocol analysis results found no significant between-group differences in the Montreal Cognitive Assessment (MoCA) score changes (mean difference: 0.038; 95 % CI: -1.109, 1.163; P = 0.948).
Six-month NK supplementation did not improve global cognition in asymptomatic intracranial/carotid stenosis patients.
Therefore, we can conclude that the use of nattokinase represents an efficient and safe treatment able to both prevent and treat patients with vascular diseases.
Gallelli G et al. · Nutrients (2021)
During the study, we enrolled 153 patients (age 22-92 years), 92 females (60.1%) and 61 males (39.9%;), and documented that nattokinase was able to improve the clinical symptoms (p < 0.01) without the development of adverse drug reactions or drug interactions.
Among the enrolled patients, during follow-up, we did not record new cases of vascular diseases.
Attention to patients' clinical evolution, monitoring of the INR, and timely and frequent adjustment of dosages represent the cornerstones of the safety of care for patients administered fibrinolytic drugs as a single treatment or in pharmacological combination.
18Subclinical atherosclerosis progressionRCTCited 14×n=265 · medium study2021
Results of this trial show that nattokinase supplementation has a null effect on subclinical atherosclerosis progression in healthy individuals at low risk for CVD.
Hodis HN et al. · Clinical hemorheology and microcirculation (2021)
No clear effect
← WorseNo effectBetter →
Results of this trial show that nattokinase supplementation has a null effect on subclinical atherosclerosis progression in healthy individuals at low risk for CVD.
19Stroke symptom improvementRCTCited 11×n=61 · small study2020
The findings of the study may also encourage further extensive clinical trials to fully explore the prospect of Nattospes as a nutraceutical adjunct in the management of cardiovascular disease.
Pham PT et al. · Journal of medicinal food (2020)
After 60 days, results showed that both Trial and Control groups achieved significant improvements in physical activities, blood pressure control, serum lipid panels, and quality of life.
Nattospes as a food supplement has good supportive effects on treatment and rehabilitation after ischemic stroke by showing statistically significant improvement of stroke-related symptom in scores from modified Rankin, Orgogozo, and Barthel scales.
In addition, Nattospes showed a good safety profile, with no adverse effects reported in both clinical and paraclinical parameters.
20Collagen-epinephrine closure timeRCTCited 8×n=50 · small study2019
In conclusion, nattokinase supplementation was associated with prolonged C-EPI CT and aPTT in nondiabetic and borderline-to-moderate hypercholesterolemic subjects.
Yoo HJ et al. · Food & function (2019)
Likely real
After 8 weeks of treatment, the nattokinase group exhibited significant increases in C-EPI CT, PT, and aPTT.
The nattokinase group showed significantly greater increases in C-EPI CT (P = 0.001) and aPTT (P = 0.016) than the placebo group.
Moreover, at 8 weeks, the nattokinase group showed a significantly higher C-EPI CT than the placebo group (P = 0.001).