What is Nattokinase?

Nattokinase (pronounced nat-oh-KY-nase) is a powerful enzyme extracted and purified from a traditional Japanese functional food called natto. Natto is a cheese-like product made from boiled or steamed soybeans fermented with beneficial bacteria known as Bacillus subtilis or Bacillus natto.1,2 Natto has a characteristically slippery consistency and strong aroma, but it is generally tasteless. Although a variety of soy-based products contain active enzymes, only natto preparations are known to produce nattokinase.3


Natto has been an important part of the Japanese diet for over a century, and is known for its therapeutic effects on vascular and heart disease.4 Nattokinase is widely recognized for its potent fibrinolytic properties, and can dissolve dangerous blood clots through a variety of mechanisms.5 In this respect, nattokinase acts much like our body’s own naturally-produced fibrin-degrading enzyme known as plasmin. Human plasmin is found in the blood and serves as a defense system against hazardous blood clots associated with cardiovascular disease and stroke.6 Nattokinase also shares a similar clot-dissolving mechanism with other commonly-used thrombolytic drugs. However, nattokinase is much cheaper and carries a lower risk of side effects.7


While natto may not be readily available in all regions, its active ingredient nattokinase can be found in the form of a dietary supplement. Since traditional natto is an acquired taste, some people prefer the supplemental form of nattokinase, especially since it offers similar benefits.3


How is Nattokinase produced?

In ancient times, natto was made by wrapping cooked or boiled soybeans in rice straw and burying the entire bundle underground for a week. Over that time, the natural bacillus in the straw would infuse the soybeans and enhance fermentation.1 This fermentation process enriched the nutrient content of the soybeans, and also increased the health-promoting effects.8


While this crude method of fermenting soybeans was an effective technique for ancient cultures, more recent studies suggest that fermentation under these natural conditions can increase product variability.9 Therefore, the modern production of natto often occurs in a controlled laboratory environment, with pure Bacillus natto added or injected into the soybeans. The fermentation process is controlled and sometimes enhanced by adding other ingredients such as glucose and peptone in precise amounts at very specific times.7 This has resulted in the ability to produce large quantities of high quality natto, containing a high concentration of the active enzyme nattokinase.7





Processed vs. Raw (Living) Nattokinase


An estimated 90% of the Nattokinase supplements on the market today contain the Nattokinase brand NSK-SD™. Nattokinase NSK-SD™ is a standardized form of nattokinase created by the Japan Bio Science Laboratory Company (JBSL). In 1998 NSK-SD™ was the first nattokinase to be isolated and marketed. JBSL’s patented NSK-SD™ product is processed in such a way that it is stripped of its naturally-occurring components such as vitamin K. This is because large amounts of vitamin K2 can interact with blood thinning drugs like Coumadin. Therefore, native vitamin K was removed from the nattokinase, so that it could be safely administered with Coumadin. Fortunately, vitamin K2 inhibitors such as Coumadin are being replaced by a newer, safer class of blood thinners called direct thrombin inhibitors (DTIs). Consequently, more and more patients requiring blood thinners are now able to safely take raw (un-processed) nattokinase supplements to help dissolve blood clots.


Based on the philosophy that most enzymes and other nutrients perform and absorb better in their raw form, Arthur Andrew Medical developed the product Nattobiotic™ in 2011, as the world’s first commercially packaged and sold raw nattokinase supplement. In contrast to NSK-SD™, Nattobiotic™ still contains all of its naturally-occurring vitamin K as well as all of the essential amino acids, antioxidants and raw vitamins that are otherwise stripped out of 99% of the nattokinase supplements on the market today. The importance of vitamin K cannot be understated, as it regulates the removal of hardened calcium in arteries and ensures that calcium is properly bonded to bones instead. Vitamin K2 is also considered to have extraordinary cardiovascular-protective qualities.11 Furthermore, abnormally low vitamin K levels can cause hardening of the arteries.12,13,14,15


While processed nattokinase products contain no probiotics, raw nattokinase products such as Nattobiotic™ are known to contain Bacillus natto in its probiotic spore form. This means that raw nattokinase can support the healthy growth of B. natto bacteria in the gut, while processed nattokinase cannot. As a result, the beneficial effects of raw nattokinase continue long after the original dose has been metabolized and excreted.


In the past, processed nattokinase was known to be more concentrated than contemporary raw preparations. This is largely because processed nattokinase has had all of its other natural components (i.e., vitamin K2) isolated and removed. However, recent advancements in nattokinase-processing techniques have made it possible to now produce a raw nattokinase product that has better potency.For example, the consumption of just 2,500 fu’s of raw nattokinase (over time) may lead to the production of millions of units of nattokinase in your digestive system.


The intrinsic activity or potency of nattokinase is often measured by the enzyme’s ability to degrade fibrin over a given amount of time, and is represented by “Fibrinolytic Units”.16 Nattobiotic™ is rated at 2,500 Fibrinolytic Units (FU’s) per capsule, while Nattokinase NSK-SD™ has a maximum per capsule rating of only 2,000 FU’s. This represents a 25% increase in potency over the processed version of nattokinase.


Compared to processed nattokinase products like NSK-SD™, raw nattokinase products such as Nattobiotic™ have higher potency, more nutrients, and probiotic activity. Therefore, natural nattokinase products like Nattobiotic™ represent a greater value at a cheaper price.


Health Benefits of Nattokinase


Nattokinase’s ability to break down fibrin as well as increase blood flow and tissue oxygen levels are the main mechanisms which allow it to reduce the risk of cardiac disease.16


Fibrinolytic and Anti-Thrombotic Activity of Nattokinase


Although the human body produces a number of enzymes that promote the growth of a thrombus (blood clot), the only natural enzyme that works to breaks down the thrombus is called plasmin.6 Since nattokinase is similar in molecular structure to plasmin, it makes sense that it would also have a similar mechanism of action.17 However, in addition to having direct fibrinolytic actions (like plasmin),18 nattokinase can also increase the body’s own production of plasmin, as well as several other agents that assist in dissolving blood clots (e.g., urokinase).


Nattokinase has been shown to be effective for preventing the unwanted formation of blood clots in the legs (DVT) after a 7-8 hour airplane flight. In light of the data supporting nattokinase, Dr. Martin Milner from the Center for Natural Medicine in Portland has stated that nattokinase is not only highly effective in breaking down a thrombus, but seems to be even more potent than the traditional “clot-busting” drugs (i.e., Tissue plasminogen activatortPA).6 In fact, nattokinase is considered to be the most potent fibrinolytic enzyme ever discovered.1


According to Dr. Milner, drugs like tPA can sometimes fail to dissolve the clot, even though they are generally effective for this condition. This is because clots that reach a certain stage tend to become more resistant to traditional drugs. Fortunately, nattokinase can dissolve these resistant clots when taken orally at 100 mg/day.49,48


Since it takes 4-6 hours for half of the nattokinase taken to be broken down,19 its therapeutic effects can last even after the patient stops taking nattokinase. This means that the actions of nattokinase last longer than most clot-dissolving drugs available on the market.4 As a result, nattokinase not only dissolves existing clots, but can also help prevent future clots from developing.20


Since circulating amounts of both FDP (fibrin degradation products) and EFA (euglobulin fibrinolytic activity) are known to rise when clots are being dissolved, these compounds can be used to monitor nattokinase’s lingering effects. After measuring the EFA and FDP levels, researchers found that the activity of nattokinase can last for 8 to 12 hours.50,48


Cardiovascular Health Benefits


In addition to its ability to fight stroke, nattokinase has a number of other actions that benefit the cardiovascular system.21 For example, nattokinase has been shown to reduce blood pressure by inhibiting the angiotensin II converting enzyme (ACE).22,23 Reductions in blood pressure are well known to decrease your risk of cardiovascular disease.


Nattokinase has also shown promise for the treatment of hyperlipidemia.24 Nattokinase has also been suggested for preventing atherosclerosis and it’s more general form, arteriosclerosis.16, 25, Atherosclerosis is a disorder in which the arterial walls harden and narrow.


Immunomodulatory Effects


A 2012 study conducted among mice has demonstrated that nattokinase is able to enhance the immune function of macrophages.26 Macrophages are a type of white blood cell responsible for engulfing foreign substances that may be threatening to the body. As such, macrophages act as a security system, alerting the immune system to foreign invaders.


There is also some evidence that suggests that the active bacteria found in natto may indirectly induce the production of cytokines in the intestinal mucosa.27 This is important because cytokines (e.g., interleukins, interferons, and growth factors) act as protein messengers, allowing immune cells to communicate with each other in order to mount an appropriate immune response.28


Given the promising results of this animal study, it is expected that further human studies will be designed to demonstrate nattokinase’s beneficial effects on the immune system.


Additional Health Benefits


Most people who research nattokinase are amazed by the sheer number of potential health benefits it is associated with. For instance, it has been suggested that nattokinase may benefit conditions like diabetes, which often leads to excess platelet aggregation. Nattokinase may also be beneficial for senile dementia, which is characterized by cerebral thrombi formation as well as poor circulation/blood supply.19 Further potential health benefits of nattokinase include reducing chronic migraine, fibromyalgia, chronic fatigue syndrome, Lyme disease, and menstrual cramps.16Some studies even suggest that natto may display activity against tumor growth.29


A 2006 study demonstrated that nattokinase has helpful effects on a common eye condition called Posterior Vitreous Detachment (PVD).30 This condition occurs frequently with old age and involves a decrease in the volume of ocular gel that makes up nearly 70% of the liquid in the eye. This causes a decreased blood supply to the retina and interferes with normal vision.31


Nattokinase has also shown potential for use in preventing and alleviating Alzheimer’s disease.22 This illness involves the development of amyloid ﬁbrils, which are clumps of fibrous protein that form in the brain and other areas of the body, causing various deleterious effects.32 Research conducted on nattokinase shows that it possesses amyloid-degrading properties, thus warranting further study for this indication.33


Nattokinase also shows promise as a treatment for sciatic nerve injury, since it suppresses injury-induced fibrin production and reduces inflammatory cytokines.34 Nattokinase also enhances nerve myelination and contributes to nerve regeneration, which means that it may be beneficial for a variety of disorders of the nervous system.35


Probiotic Effects of Bacillus Subtillus Natto


Unprocessed (raw) natto-based products like Nattobiotic™ are known for their ability to improve the intestinal microflora, thus producing a probiotic effect.23 This means that raw nattokinase can support the healthy growth of B. natto bacteria in the gut, while processed nattokinase cannot. As a result, the beneficial effects of raw nattokinase can live on long after the original dose has been metabolized and excreted. For example, the consumption of just 2,500 units of raw nattokinase (over time) may produce millions of units of nattokinase in the digestive system.


Although the mechanism by which natto is able to achieve its probiotic effects are still being studied, experts believe that it may partially be due to B. natto’s ability to enhance the growth and/or viability of lactobacilli in the gut.23 As you may already know, Lactobacillus bacteria are considered to be one of the most prominent and influential types of probiotics.


Nattokinase Research Organization


The Nattokinase Research Organization (NRO) is part of a larger group of research websites, all of which are operated by the Enzyme Research Organization (ERO). The ERO maintains and operates several enzyme-related research and review websites including, but not limited to: Serrapeptase.org, Bromelain.org, Papain.org and Enzymes.org. Some of these sites are still being developed, but check back frequently to stay up to date on the latest news and research in the world of oral systemic enzymes. ERO is a nonprofit collaboration of scientist, doctors, enzymologists and technical experts from around the world. Members of the ERO volunteer their time performing research and gathering consumer information. ERO does not have a central headquarters or base of operation, rather the consortium exists online only. Funding and proceeds are derived from donations, advertising dollars, and contributors like you.


NRO is continuously gathering the latest information and breakthroughs in manufacturing for the miracle enzyme nattokinase. If you would like to submit information regarding your company’s nattokinase or if you have information that you feel may be beneficial to the organization please feel free to contact us. If you have specific questions regarding any of the products reviewed on our website please feel free to contact us as well. In many cases if we cannot answer your questions we can put you in contact with the manufacturer who will be happy to assist you. For general questions please visit our message board, where you can share information with peers and address questions to our experts.


ERO Disclaimer


The ERO is limited to answering questions that are not specifically medical or disease related. By law we cannot assist you with any medical advice including dosages, drug interactions or advice regarding specific diseases and medical issues. Please understand that our staff will try to assist you with any questions as they pertain to your health and enzymes in general. The content of our website is published for educational purposes only and is not intended to diagnose, treat or prevent disease. Please use this site and its contents with caution, and always consult your physician before taking any supplements.