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Effects of nattokinase: What you should know about this enzyme

Discover the function of nattokinase, potential applications, and results of current research.

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Introduction

Effects of nattokinase: What you should know about this enzyme

Nattokinase - what's that? Many people do not know this enzyme at all. Yet it has a long history of being used, especially in Japan. So today we're going to talk about the enzyme nattokinase, its role in the body, and potential conclusions for helping with therapy.

As always, however, this article is not a substitute for medical advice, but rather provides general information. A therapy concept must be established in consultation with a physician or therapist.

Well then, let's dive deeper into the exciting topic of enzymes in relation to the cardiovascular system.

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Content
• What is nattokinase?
• What is the effect of nattokinase in the body?
• Nattokinase: effects on blood clotting
• Nattokinase & inflammation
• Nattokinase, Vascular Health & Cardiovascular Diseases
• Nattokinase: dosage
• Are there any risks or side effects of taking nattokinase?
•Conclusion: Nattokinase has a promising future
• Bibliography

What is nattokinase?

Before going deeper into the subject, it is best to answer this general question: What is nattokinase?

Nattokinase is an enzyme that owes its name to Natto. So what is Natto? It is a Japanese soybean dish for which the beans are cooked and fermented. They are then rich in nattokinase. In Japan, eating natto, which contains more than just this one enzyme, is considered very healthy.

A little side info for all chemistry fans: Contrary to what the name suggests, this enzyme is not a kinase, which is a class of enzymes, but a protease. Proteases divide proteins; nattokinase, for example, splits fibrin, or more precisely, the fibrin polymers that form during blood clotting. This is why nattokinase and other enzymes like it are often called natural blood thinners. To what extent this is true, we will look at in detail today.

What is the effect of nattokinase in the body?

Nattokinase, acting as a protease, is quite specific for the splitting of fibrin, but also activates tPA (tissue plasminogen activator), which in turn cleaves plasminogen to the active clot-dissolving plasmin1.

All in all, nattokinase has potential fibrinolytic and thrombolytic effects and thus a wide range of potential applications. And it is precisely these that we now want to take a closer look at.

Nattokinase: effects on blood clotting

That nattokinase has an effect on blood clotting is obvious based on its function. Therefore, let's take a look at studies on blood clotting and nattokinase:

A double-blind, randomized, placebo-controlled intervention study from 2015 that was published in Scientific Reports, a journal of the renowned nature publishing group, showed how strong the fibrinolytic effect was after a single administration of 2,000 fibrinolytic units (FU)2.

The result was that even with the single dose, there was a significant increase in fibrin degradation products after about 6 hours, indicating that enzymatic cleavage occurred. In addition, the parameter D-dimer was elevated at 4 and 8 hours. The D-dimer also indicates that dissolution of fibrin polymers occurred. Antithrombin concentrations were also significantly elevated.

All in all, this result suggests that there was a significant change after taking nattokinase, but they were still within the normal range. This is important because an abnormal change would presumably be associated with a strong side effect profile. Thus, it can be suggested that nattokinase causes some blood thinning, but within a healthy range.

Nattokinase & inflammation

Chronic inflammation plays a role in the development of many diseases. Cardiovascular diseases such as atherosclerosis are in fact also due to chronic inflammatory processes in the vascular wall.

For this reason, a 2020 in vitro and in vivo study addressed whether and how nattokinase can influence these inflammatory processes and the increased oxidative stress3. It revealed that the enzyme can inhibit LPS-induced inflammatory processes and thus regulate macrophage overactivation. Overall, it was shown that nattokinase could reduce oxidative stress and showed anti-inflammatory effects at least in vitro as well as in vivo in mice.

How this effect can be transferred to humans remains to be seen - after all, the enzyme was only discovered in 1987, so science is still partly in its early stages.

Nattokinase, Vascular Health & Cardiovascular Diseases

When we talk about blood clotting and chronic inflammation, the road leads to the cardiovascular system. Did you know that cardiovascular disease was responsible for about 27% of deaths worldwide in 20194? In Germany, it even accounted for just over 33% of deaths in 20215.

Therefore, there is a constant need to also preventively support the body in the fight against these diseases with as few side effects as possible. So what is the evidence regarding nattokinase and vascular health?
Let's first take a look at the topic of blood pressure. This is something that some research groups are also looking at, trying to show whether the fibrinolytic enzyme has an impact here.

For example, a randomized controlled trial with double-blinding and placebo control from 2008 showed that in patients with untreated hypertension or borderline elevated blood pressure, both systolic and diastolic blood pressure decreased6. The reason for this is probably, at least partially, its action as an ACE inhibitor7. ACE, the angiotensin-converting enzyme, is a popular target of many antihypertensive drugs.

Other research groups focused on the effects on blood lipid levels and atherosclerosis. For example, a large clinical trial involving 1,062 participants8 showed that 12 months of 10,800 FU nattokinase significantly decreased both LDL cholesterol and triglycerides, while increasing "good" HDL cholesterol.
In addition, 683 patients were evaluated for improvement in artherosclerotic changes of the carotid arteries by ultrasound examination. The size of existing plaques and vessel thickness decreased significantly, with an average improvement of 66.5% in size compared to before the study.

So, again, nattokinase seems to have positive effects and thus is a promising addition to the treatment plan. Of course, we must continue to wait for results until safe recommendations can be made.
Until then, however, we can at least address two other questions: At what dosage does one take nattokinase and what are the side effects?

Nattokinase: dosage

As already described, the enzyme is found in the fermented dish natto and can also be consumed as a dietary supplement in the form of capsules. The nattokinase capsules usually contain an enzyme quantity with an enzyme activity of 2,000 FU. This information is important because the amount of enzyme does not directly correspond to the activity. Therefore, 2 mg of nattokinase do not necessarily have the same enzyme activity.

The specified maximum activity that a product may currently contain per daily dose corresponds to these 2,000 FU mentioned. As described above, in studies an effective dose is sometimes only suspected at a higher activity of, for example, 10,000 FU. However, this dose is currently not recommended - especially not without medical consultation. For safety reasons, upper limits are usually kept quite low, especially in the EU - to avoid risks and side effects as far as possible. Speaking of which, what side effects does nattokinase have?

Are there any risks or side effects of taking nattokinase?

In general, nattokinase is considered to have very few side effects, but caution is advised, especially when taking blood thinners at the same time, as the effect could be potentiated. The following therefore applies: Nattokinase and blood thinners should only be taken together with prior consultation and monitoring by a physician.
Nattokinase alone, on the other hand, is shown to be safe, as demonstrated by a toxicology study in 20169. In healthy individuals, the tolerated dose was significantly higher than the currently recommended dose.

Conclusion: Nattokinase has a promising future

If we summarize all the results to date, it is clear that nattokinase has a promising future and may be useful to accompany therapy. Since this enzyme is still quite new, the science is still in its infancy in some areas and it will probably take some time until nattokinase has arrived in everyday practice.

However, supplementation is definitely worth considering - isn't it?
Bibliography
1 Peng, Y., Yang, X. & Zhang, Y. (2005). Microbial fibrinolytic enzymes: an overview of source, production, properties, and thrombolytic activity in vivo. Appl Microbiol Biotechnol, 69, 126–132. https://doi.org/10.1007/s00253-005-0159-7

2 Kurosawa, Y., Nirengi, S., Homma, T. et al. (2015). A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep, 5, 11601. https://doi.org/10.1038/srep11601

3 Wu, H., Wang, Y., Zhang, Y., Xu, F., Chen, J., Duan, L., Zhang, T., Wang, J., & Zhang, F. (2020). Breaking the vicious loop between inflammation, oxidative stress and coagulation, a novel anti-thrombus insight of nattokinase by inhibiting LPS-induced inflammation and oxidative stress. Redox biology, 32, 101500. https://doi.org/10.1016/j.redox.2020.101500

4 The top 10 causes of death. (2020). Who.int. Abgerufen 25. August 2023, von https://www.who.int/news-room/fact- sheets/detail/the-top-10-causes-of-death

5 Todesursachen (2023). Statistisches Bundesamt. Abgerufen 5. September 2023, von https://www.destatis.de/DE/Themen/Gesellschaft-Umwelt/Gesundheit/Todesursachen/_inhalt.html

6 Kim, J., Gum, S., Paik, J. et al. (2008). Effects of Nattokinase on Blood Pressure: A Randomized, Controlled Trial. Hypertens Res, 31, 1583–1588. https://doi.org/10.1291/hypres.31.1583

7 Okamoto, A., Hanagata, H., Kawamura, Y. et al. (1995). Anti-hypertensive substances in fermented soybean, natto. Plant Food Hum Nutr, 47, 39–47. https://doi.org/10.1007/BF01088165

8 Chen, H., Chen, J., Zhang, F., Li, Y., Wang, R., Zheng, Q., Zhang, X., Zeng, J., Xu, F., & Lin, Y. (2022). Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants. Frontiers in cardiovascular medicine, 9, 964977. https://doi.org/10.3389/fcvm.2022.964977

9 Lampe, B. J., English, J. C. (2016). Toxicological assessment of nattokinase derived from Bacillus subtilis var. natto. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 88, 87–99. https://doi.org/10.1016/j.fct.2015.12.025