benefits of nattokinase

Benefits Of Nattokinase: Side Effects & Usage

Nattokinase is a natural enzyme extracted from natto, a traditional Japanese food made from fermented soybeans. It has been used in traditional medicine for centuries due to its various health benefits. Nattokinase supplements have gained popularity in recent years as a natural alternative to synthetic blood-thinning medications such as warfarin. In this article, we will discover the benefits of nattokinase enzyme as well as how to take Nattokinase supplement for overall health.


What Is Nattokinase Enzyme?

Nattokinase is an enzyme that is extracted from natto, a fermented soybean dish. It has been used in traditional Japanese medicine for centuries and recently gained popularity as a dietary supplement due to its potential health benefits. Nattokinase is known for its powerful clot-busting properties, making it a popular supplement for heart health.

nattokinase enzyme is extracted from natto

How Does Nattokinase Work?

Nattokinase primarily operates by breaking down fibrin, a fibrous protein crucial for blood clot formation. While fibrin plays a vital role in wound healing and halting bleeding, excessive levels can result in thicker blood and a heightened risk of cardiovascular conditions such as heart attacks and strokes.

Nattokinase functions by converting plasminogen, an inactive precursor, into plasmin, an enzyme responsible for fibrin degradation. This action aids in preventing blood clot formation and enhancing overall blood circulation throughout the body.

Apart from its thrombolytic properties, nattokinase also has anti-inflammatory effects. It can inhibit the release of inflammatory compounds and reduce swelling in damaged tissues. This makes it useful for conditions such as arthritis and other inflammatory disorders.

Moreover, nattokinase has demonstrated its antioxidant attributes, enabling it to counteract detrimental free radicals and safeguard cells from oxidative harm. This aspect is crucial for upholding general well-being and mitigating chronic ailments.

Additionally, there are indications from research that nattokinase could offer other potential advantages, including the reduction of blood pressure and the enhancement of cholesterol profiles. Nonetheless, further investigations are required to comprehensively grasp the extent of these impacts.

Benefits Of Nattokinase

Prevent Blood Clots and Stroke

Benefits of Nattokinase on blood clots

The benefits of Nattokinase on blood clots, stroke, and cardiovascular diseases have been the subject of extensive research. Several studies have examined its impact on blood flow, particularly in preventing conditions such as blood clots and red blood cell aggregation.

Pais and colleagues conducted a study suggesting that nattokinase is an effective fibrinolytic enzyme. Their research observed a significant reduction in red blood cell aggregation, which was dose-dependent with lower shear viscosity [1].

Another study noted an improvement in blood flow through the inhibition of platelet aggregation and the formation of blood clots. Specifically, Nattokinase reduced the production of Thromboxane B2 (a prostaglandin that promotes vasoconstriction and platelet aggregation) and slowed arterial thrombosis induced by FeCl3 [2].

Furthermore, research indicated that at high doses (500 mg/kg), Nattokinase could entirely prevent the mentioned conditions, equivalent to aspirin (an antiplatelet drug) at a dose of 30 mg/kg, without significant side effects [2].

Due to its impact on clot formation, Nattokinase also contributes to the effectiveness of cardiovascular disease prevention. Studies, such as the one by Yungqi Weng and colleagues, have synthesized various research findings that overwhelmingly support this hypothesis [3].

Another study suggests that Nattokinase, produced by certain bacteria, particularly Bacillus, is highly effective in preventing cardiovascular disorders and related complications. Its mechanism of action is through the degradation of fibrin, a substance involved in clot formation [4].

Potential Alzheimer's Disease Benefits

Potential Alzheimer's Disease Benefits of Nattokinase

Numerous studies have examined the benefits of Nattokinase on symptoms associated with Alzheimer's disease. Often studied alongside serrapeptase, another serine protease enzyme, these investigations have yielded interesting results. For instance, a study titled "Serrapeptase and nattokinase intervention for relieving Alzheimer's disease pathophysiology in a rat model" was conducted on rats afflicted with AD.

The study observed that the AD group treated with low or high doses of serrapeptase (10,800 or 21,600 U/kg body weight) or Nattokinase (360 or 720 FU/kg body weight) experienced a significant reduction in brain cholinesterase activity compared to the untreated AD group [5].

The potential anti-amyloid, fibrinolytic, and anti-blood clot properties of Nattokinase highlight its promising role in the treatment of Alzheimer's disease. Prakash Chandra Bhatt and colleagues conducted research exploring the encapsulation of Nattokinase in PLGA as a potential therapeutic agent against AD [6].

Improving Chronic Rhinosinusitis With Nasal Polyps

Nattokinase is being evaluated for its potential to reduce nasal polyp tissue and decrease mucus viscosity in chronic rhinosinusitis with nasal polyps (CRSwNP). This effect is linked to its ability to minimize fibrin and facilitate the fibrinolytic process mentioned earlier.

A 2017 study titled "Nattokinase, a proficient enzyme in promoting fibrinolysis effectively reduces nasal polyp tissue and lowers mucus viscosity" suggests that Nattokinase holds promise as a treatment for both CRSwNP and asthma.

Specifically, Nattokinase has demonstrated the ability to shrink nasal polyp tissue by breaking down fibrin. When patients with CRSwNP and asthma were treated with an NK solution, there was a significant decrease in the viscosity of nasal secretions and mucus [7]. A subsequent study in 2018 reached similar conclusions regarding the impact of Nattokinase's fibrinolytic mechanism on mucus viscosity [8].

Additionally, research has been conducted on the expression of L-plastin in nasal polyps of patients with non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NERD). The findings suggest that Nattokinase is effective in fibrinolysis, further reinforcing the notion that reducing fibrin through Nattokinase significantly affects these conditions [9].

Manage Cancer

Numerous studies have investigated the effects of Nattokinase on various types of cancer. In one study, Nattokinase derived from the fermentation process of natto with Bacillus subtilis showed promising results in inhibiting the growth of breast cancer in mice.

The researchers observed that the supernatant and spore-forming bacteria had an impact on the distribution of blood vessels within the tumor, leading to a reduction in the expression of FOXM1 and MMP2 in the tumor tissue [10].

Another study examined the effects of Nattokinase on hepatocellular carcinoma in mice and found that Nattokinase from Bacillus subtilis natto improved survival rates and inhibited tumor growth [11].

In addition to reducing the risk of cardiovascular disease in Japanese women, Nattokinase has also shown effectiveness against overall cancer incidence, as noted by research from The Japan Public Health Center-based Prospective [12].
Furthermore, a study exploring the effectiveness of anti-tumor activity highlighted the enhanced anti-tumor activity achieved by combining NK-PSA and DOX-SAL [13].

Benefits of Nattokinase for Diabetics

Benefits of Nattokinase for Diabetics

Nattokinase has gained recognition for its notable impact on diabetes and obesity. A study investigating its protective effects against microvascular disease and neuropathy in diabetic retinopathy suggests that Nattokinase regulates the inflammatory state associated with diabetes by modulating HMGB1 signaling in activated microglia. This contributes to Nattokinase benefits in treating diabetic retinopathy [14].

Furthermore, another study examining the combined effects of Aronia, Ginseng, Shiitake Mushroom, and Nattokinase observed improvements in glucose metabolism. These improvements were achieved by enhancing insulin secretion and reducing insulin resistance in type 2 diabetic mice with insulin deficiency [16].

Additionally, Nattokinase has been evaluated for its potential in weight reduction among obese women with diabetes. The research was conducted on obese female subjects with diabetes over a three-month period [16].

Benefits of Nattokinase for Hypercholesterolemia

Nattokinase has become increasingly popular as a natural remedy for various health conditions, especially hypercholesterolemia, which refers to high cholesterol levels in the blood.

Hypercholesterolemia is a medical condition characterized by an elevated cholesterol level, and it stands as a major risk factor for cardiovascular diseases like heart attack and stroke. Elevated cholesterol levels can lead to the buildup of plaque in the arteries, causing them to narrow and increasing the risk of blockage.

A study titled "Lipid-Lowering Effect of Nattokinase in Patients with Primary Hypercholesterolemia" observed a trend toward a greater reduction in total serum cholesterol levels in the group that used an enteric capsule containing 400 mg (4000 FU) of Nattokinase over an 8-week period compared to the placebo group [17].

Dosage & Side Effects Of Nattokinase

An evaluation titled "Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease" mentions that while Nattokinase is widely reported to be safe and associated with minimal significant side effects, further research is needed regarding acute toxicity and genotoxicity [3].

Several studies mentioned found no significant adverse effects of Nattokinase at a dosage of 2000 mg/kg with a single daily dose for 14 days. Another study repeated a daily dose of 1000 mg/kg over 90 days and did not observe any abnormalities.

In a clinical study, a daily oral dose (10 mg/kg) for 28 days also did not report significant side effects of Nattokinase in humans[3].

According to this assessment, the recommended dosage for Nattokinase is two capsules (100 mg per capsule) per day. This Nattokinase dosage is associated with limited concerns about toxicity based on previously published safety studies [3].

Another study titled "Data Recorded in Real Life Support the Safety of Nattokinase in Patients with Vascular Diseases" tested Nattokinase on patients of both genders at a dose of 100 mg per day and also did not report side effects of Nattokinase [18].

A study on Nattokinase toxicity concluded that the maximum daily dose in mice could be as high as 480,000 FU/kg, which is 1000 times higher than the recommended daily dose for humans. Additionally, the study found that Nattokinase did not exhibit mutagenic activity, as tested through both Ames testing and in vivo micronucleus testing [19].

How To Take Nattokinase Supplement?

Nattokinase is typically taken orally as a dietary supplement. It is commonly found in capsule form, with recommended dosage varying from 50 mg to 200 mg per day. The capsules are usually enteric-coated to protect the enzyme from stomach acid and ensure it reaches the small intestine, where it can be absorbed into the bloodstream.

It is recommended to take Nattokinase supplement with water on an empty stomach for maximum absorption. For those taking blood-thinning medication, it is advised to consult a healthcare professional before starting Nattokinase supplementation.

Who Should Not Take Nattokinase?

Pregnant and nursing women should avoid Nattokinase

Although Nattokinase has exhibited encouraging outcomes in addressing diverse health concerns, it may not be appropriate for everyone. Individuals with bleeding disorders or those using blood-thinning medications like warfarin should refrain from Nattokinase without seeking advice from a healthcare expert.

Furthermore, it is recommended that pregnant and nursing women avoid Nattokinase supplementation because there is insufficient research on its implications during pregnancy and breastfeeding.

Individuals who have had recent surgery or are scheduled for surgery should also avoid Nattokinase, as it may increase the risk of bleeding complications.


Nattokinase, a natural enzyme derived from fermented soybeans, offers promising potential in managing hypercholesterolemia, providing relief from pain and inflammation, and regulating blood pressure. It is generally considered safe, with minimal side effects at recommended dosages. However, further research is needed to comprehensively understand its long-term effects as well as benefits of Nattokinase and potential interactions with other medications.


How Long Does Nattokinase Stay In Your System?

Nattokinase is usually metabolized and removed from the body within several hours. While the specific duration can vary based on individual factors, most studies suggest that its effects can last up to 8 to 12 hours after ingestion.

Does Nattokinase Increase Estrogen?

Nattokinase does not increase estrogen levels. It is an enzyme derived from fermented soybeans, known for its blood-thinning properties and its efficacy in managing cardiovascular health. There is currently no scientific evidence suggesting any impact of Nattokinase on estrogen levels.

How Does Nattokinase Affect The Brain?

Nattokinase may have a positive impact on brain health by improving cerebral blood flow thanks to its blood-thinning properties. It has the potential to help prevent stroke and other cerebrovascular diseases. However, more research is required to understand its effects on the brain entirely.

Does Nattokinase Cause Insomnia?

There is no scientific evidence to suggest that Nattokinase directly causes insomnia. However, as with any dietary supplement, individuals may have different reactions. If you experience sleep disturbances after starting Nattokinase, it's recommended to consult with a healthcare professional.

Are There Any Nattokinase Side Effects On Liver?

No specific evidence currently suggests adverse effects of Nattokinase on the liver. In fact, there is evidence indicating its potential in preventing hepatocellular carcinoma (HCC) [21]. Additionally, Nattokinase provides valuable zinc supplementation for individuals with zinc deficiency, which can worsen liver conditions by impairing ammonia detoxification [20].


1. Pais, E., Alexy, T., Ralph, & Meiselman, H. J. (2006). Effects of nattokinase, a pro-fibrinolytic enzyme, on red blood cell aggregation and whole blood viscosity. Clinical Hemorheology and Microcirculation, 35(1-2), 139–142.
2. Jang, J., Kim, T., Cai, J., Kim, J., Kim, Y., Shin, K., Kwang Sei Kim, Sung Kyeong Park, Lee, S.-P., Choi, E., Man Hee Rhee, & Kim, Y.-B. (2013). Nattokinase improves blood flow by inhibiting platelet aggregation and thrombus formation. Laboratory Animal Research, 29(4), 221–221.
3. Weng, Y., Yao, J., Sparks, S., & Kevin Yueju Wang. (2017). Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease. International Journal of Molecular Sciences, 18(3), 523–523.
4. Reddy, P. Praveen. (2014). Homology modeling of microbial Nattokinase enzyme, An Anti-blood clotting (Fibrinolytic) agent using computational tools. Research Journal of Pharmacy and Technology, 13(9), 4135–4138.
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6. Development of surface-engineered PLGA nanoparticulate-delivery system of Tet1-conjugated nattokinase enzyme for inhibition of Aβ40 plaques in Alzheimer’s disease. (2017). International Journal of Nanomedicine.
7. Takabayashi, T., Imoto, Y., Masafumi Sakashita, Kato, Y., Tokunaga, T., Yoshida, K., Narita, N., Ishizuka, T., & Shigeharu Fujieda. (2017). Nattokinase, profibrinolytic enzyme, effectively shrinks the nasal polyp tissue and decreases viscosity of mucus. Allergology International, 66(4), 594–602.
8. Takabayashi, T., Imoto, Y., Masafumi Sakashita, Kato, Y., Tokunaga, T., Yoshida, K., Narita, N., Ishizuka, T., & Shigeharu Fujieda. (2018). Effects of nattokinase, profibrinolytic enzyme, on the patients with chronic rhinosinusitis with nasal polyp. The Journal of Allergy and Clinical Immunology.
9. Takabayashi, T., Tanaka, Y., Dai Susuki, Yoshida, K., Tomita, K., Masafumi Sakashita, Imoto, Y., Kato, Y., Narita, N., Nakayama, T., Shinichi Haruna, Schleimer, R. P., & Shigeharu Fujieda. (2018). Increased expression of L‐plastin in nasal polyp of patients with nonsteroidal anti‐inflammatory drug‐exacerbated respiratory disease. Allergy, 74(7), 1307–1316.
10. Zhang, B., Chai, J., He, L., Dusanbieke, M., & Gong, A. (2019). Original Article Nattokinase produced by natto fermentation with Bacillus subtilis inhibits breast cancer growth. Int J Clin Exp Med, 12(12), 13380–13387.
11. Yan, Y., Wang, Y., Qian, J., Wu, S., Ji, Y., Liu, Y., Zeng, J., & Gong, A. (2019). Nattokinase Crude Extract Inhibits Hepatocellular Carcinoma Growth in Mice. Journal of Microbiology and Biotechnology, 29(8), 1281–1287.
12. Miho Nozue, Shimazu, T., Charvat, H., Mori, N., Michihiro Mutoh, Sawada, N., Iwasaki, M., Taiki Yamaji, Yoshihiro Kokubo, Yamagishi, K., Hiroyasu Iso, & Shoichiro Tsugane. (2020). Fermented soy products intake and risk of cardiovascular disease and total cancer incidence: The Japan Public Health Center-based Prospective study. European Journal of Clinical Nutrition, 75(6), 954–968.
13. Kou, Y., Feng, R., Chen, J., Duan, L., Wang, S., Hu, Y., Zhang, N., Wang, T., Deng, Y., & Song, Y. (2020). Development of a nattokinase–polysialic acid complex for advanced tumor treatment. European Journal of Pharmaceutical Sciences, 145, 105241–105241.
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15. Hye Jeong Yang, Min Jung Kim, Dae Young Kwon, Da Sol Kim, Zhang, T., Ha, C., & Park, S. (2018). Combination of Aronia, Red Ginseng, Shiitake Mushroom and Nattokinase Potentiated Insulin Secretion and Reduced Insulin Resistance with Improving Gut Microbiome Dysbiosis in Insulin Deficient Type 2 Diabetic Rats. Nutrients, 10(7), 948–948.
16. Cobos, L., Sanchez-De, Y., Herbst, K. L., & Karen Guzmán Béltran. (2020). SAT-618 Nattokinase to Improve Insulin Sensitivity and Weight Loss in Women with Obesity +/- Diabetes. Journal of the Endocrine Society.
17. Wu, D.-J., Lin, C.-S., & Lee, M.-Y. (n.d.). Lipid-Lowering Effect of Nattokinase in Patients with Primary Hypercholesterolemia. Retrieved November 6, 2023, from
18. Gallelli, G., Giulio Di Mizio, Palleria, C., Siniscalchi, A., Rubino, P., Gallelli, L., Cione, E., Salerno, M., Giovambattista De Sarro, & Gallelli, L. (2021). Data Recorded in Real Life Support the Safety of Nattokinase in Patients with Vascular Diseases. Nutrients, 13(6), 2031–2031.
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20. Yan, Y., Wang, Y., Qian, J., Wu, S., Ji, Y., Liu, Y., Zeng, J., & Gong, A. (2019). Nattokinase Crude Extract Inhibits Hepatocellular Carcinoma Growth in Mice. Journal of Microbiology and Biotechnology, 29(8), 1281–1287.
21. Kodama, H., Tanaka, M., Naito, Y., Katayama, K., & Moriyama, M. (2020). Japan’s Practical Guidelines for Zinc Deficiency with a Particular Focus on Taste Disorders, Inflammatory Bowel Disease, and Liver Cirrhosis. International Journal of Molecular Sciences, 21(8), 2941–2941.
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Ralph S. Albert, with over 10 years of expertise in nutrition and research, now heads the Research division at Vinatura Supplements. His dedication and extensive knowledge ensure top-quality articles on nutrition and health, collaborating with a skilled team. He has successfully completed The VINATURA Expertise Research Training Program, underscoring his commitment to Vinatura's mission. Ralph has also published numerous articles and conducted valuable research in the field, making him a trusted resource for individuals on their wellness journey.

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