Ntk8.5

Nattokinase Research

29 peer-reviewed studies · Evidence score: 8.5/10

Research Progress of Nattokinase in Reducing Blood Lipid

Wei C et al. • Nutrients (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.

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.
Further research warranted to confirm findings

Systematic Review

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Navigating the Effects of Anti-Atherosclerotic Supplements and Acknowledging Associated Bleeding Risks

Dobre MZ et al. • International journal of molecular sciences (2025)

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.

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.

Systematic Review

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Fermented Fruits, Vegetables, and Legumes in Metabolic Syndrome: From Traditional Use to Functional Foods and Medical Applications

Bernacka K et al. • Nutrients (2025)

Potential future studies focused on developing functional fermented foods and easy-to-use supplements based on fermented plant products are suggested.

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.

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"Nattokinase as a potential therapeutic agent for preventing blood-brain barrier dysfunction in neurodegenerative disorders"

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 featu...

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.Copyright © 2024 Elsevier B.V.

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[Novel foods-What must be considered?]

Toussaint F et al. • Dermatologie (Heidelberg, Germany) (2025)

The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.

Consumption of natto, a Japanese dish containing fermented soy beans, can lead to delayed anaphylaxis.
Nattokinase as well as polyglutamic acid (PGA) are well-known triggering allergens.
It is postulated that sensitization to PGA may be acquired from skin contact to jellyfish and potentially by cosmetics containing PGA.

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Nattokinase as an adjuvant therapeutic strategy for non-communicable diseases: a review of fibrinolytic, antithrombotic, anti-inflammatory, and antioxidant effects

Granito M et al. • Expert review of cardiovascular therapy (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.

Systematic review examining Nattokinase efficacy
Further research warranted to confirm findings

Systematic Review

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Comparative Cardioprotective Effectiveness: NOACs vs. Nattokinase-Bridging Basic Research to Clinical Findings

Muric M et al. • Biomolecules (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.

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.

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Microbial nattokinase: from synthesis to potential application

Sheng Y et al. • Food & function (2023)

Finally, the possible future directions focused on NK studies were proposed and provided suggestions for subsequent researchers.

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.

Systematic Review

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Phosphocalcic metabolism and the role of vitamin D, vitamin K2, and nattokinase supplementation

Gasmi A et al. • Critical reviews in food science and nutrition (2022)

Moreover, the paper reviews the enzyme nattokinase's role in thrombotic prevention due to its fibrinolytic activity.

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.

Systematic Review

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Biotechnology, Bioengineering and Applications of Bacillus Nattokinase

Yuan L et al. • Biomolecules (2022)

Finally, this review summarizes the clinical applications of nattokinase.

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.

Systematic Review

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Fibrinolytic Enzyme - An Overview

Abdul Rahim P et al. • Current pharmaceutical biotechnology (2022)

This review deals with the fibrinolytic enzymes, their mechanisms, sources, and their therapeutic potential.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Fibrinolytic agents degrade fibrin through enzymatic and biochemical processes.
There are various enzymes that are currently used as a treatment for CVDs, like streptokinase, nattokinase, staphylokinase, urokinase, etc.
These enzymes are derived from various sources, like bacteria, fungi, algae, marine organisms, plants, snakes, and other organisms.

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Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease

Weng Y et al. • International journal of molecular sciences (2017)

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.

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.

Systematic Review

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Fibrinolytic Enzymes for Thrombolytic Therapy

Kumar SS et al. • Advances in experimental medicine and biology (2019)

Reported enzymes from various sources with potential to be used as cardiovascular therapeutic is also discussed here.

Inability of plasma fibrinolytic system demands better thrombolytic drugs.
Major thrombolytic enzymes belonging to plasminogen activators and plasmin like enzymes.
Currently used fibrinolytic enzymes and their limitations are revisited in the present chapter.

Systematic Review

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Pharmacotherapy of Vitreomacular Traction

Wan R et al. • Current pharmaceutical design (2018)

Traditionally, vitreomacular traction was treated with vitrectomy surgery.
In the past few years, there is a paradigm shift towards pharmacologic vitreolysis, which involves the intravitreal injection of enzymatic and non-enzymatic agents that facilitate posterior vitreous detachment.
Many agents have been investigated and trialled including plasmin, microplasmin (Ocriplasmin), hyaluronidase, nattokinase, chondroitinase and dispase.

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Microbial production of nattokinase: current progress, challenge and prospect

Cai D et al. • World journal of microbiology & biotechnology (2017)

Finally, the prospect of microbial nattokinase production was also discussed regarding the recent progress, challenge, and trends in this field.

The selection of optimal nattokinase producing strain was the crucial starting element for improvement of nattokinase production.
Genetic engineering, protein engineering, fermentation optimization and process control have been proved to be the effective strategies for enhancement of nattokinase production.
Also, extraction and purification of nattokinase are critical for the quality evaluation of nattokinase.

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The biotechnological potential of fibrinolytic enzymes in the dissolution of endogenous blood thrombi

Kotb E • Biotechnology progress (2014)

This review is the first to cover all the natural and recombinant thrombolytic agents used in enzyme therapy.

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.

Systematic Review

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The Effect of Nattokinase-Monascus Supplements on Dyslipidemia: A Four-Month Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Liu X et al. • Nutrients (2023)

However, it did not significantly affect serum TG, HDL-C, and CIMT.

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.

RCTn=113

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Nattokinase supplementation for cognitive enhancement in asymptomatic intracranial/carotid stenosis: A randomized controlled trial

Zhang K et al. • Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association (2026)

Six-month NK supplementation did not improve global cognition in asymptomatic intracranial/carotid stenosis patients.

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.

RCTn=120

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Data Recorded in Real Life Support the Safety of Nattokinase in Patients with Vascular Diseases

Gallelli G et al. • Nutrients (2021)

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.

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.

RCTn=153

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Nattokinase atherothrombotic prevention study: A randomized controlled trial

Hodis HN et al. • Clinical hemorheology and microcirculation (2021)

Results of this trial show that nattokinase supplementation has a null effect on subclinical atherosclerosis progression in healthy individuals at low risk for CVD.

Results of this trial show that nattokinase supplementation has a null effect on subclinical atherosclerosis progression in healthy individuals at low risk for CVD.
Further research warranted to confirm findings

RCTn=265

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