Nattokinase caution
Discuss with your health care professional before nattokinase use, especially if you are taking anti-coagulants, aspirin, coumadin or other medicines or herbs that thin the blood.

Nattokinase 1000 units fibrinolytic activity - Club Natural
Nattokinase is a systemic enzyme isolated from the traditional Japanese soy food, natto. It has been shown to support healthy blood flow by assisting the circulatory clearing system of the body.

Amount per serving
Nattokinase 50 mg, providing 1,000 fibrin units ( FU ) of activity
Nattokinase daily value not established.

Click here to purchase Nattokinase, Serrapeptase, to see a list of hundreds of high quality supplements, or to subscribe to a FREE newsletter

Subscribe to a FREE Supplement Research Update newsletter. Twice a month you will receive an email with a review of several studies on various supplements and natural medicine topics and their practical interpretation by Ray Sahelian, M.D. We will discuss new nattokinase enzyme research as it becomes available.



Suggested Use: As a dietary supplement, take 1 nattokinase capsule as directed by a healthcare practitioner. Nattokinase may be taken with or without food. Take with a few ounces of water. Use under medical supervision. Nattokinase is contraindicated in any condition associated with bleeding.

Nattokinase side effects or risks
No significant nattokinase side effects have yet been reported in the medical literature when used without other anticoagulants. However, this does not mean that nattokinase is side effect free, it just means that we don't have enough human trials to know all the benefits and risks with nattokinase enzyme treatment. One action of nattokinase is as a blood thinner, hence those on Coumadin, aspirin, or other anticoagulants need to be careful and discuss with their doctor the use of a nattokinase supplement. Using nattokinase with warfarin or aspirin could enhance bleeding risk.

Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds.
Intern Med. March 3, 2008.. Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
We report a patient, having used aspirin for secondary stroke prevention, who had an acute cerebellar hemorrhage after taking nattokinase 400 mg daily for 7 consecutive days. In addition to the hemorrhagic lesion, multiple microbleeds were demonstrated on brain MR images. We suggest that nattokinase may increase risk of intracerebral hemorrhage in patients who have bleeding-prone cerebral microangiopathy and are receiving other antithrombotic agents at the same time.

Possible mechanisms of action
Nattokinase inactivates plasminogen activator inhibitor type 1 and potentiates fibrinolytic activity. In other words, it could dissolve fibrin. Fibrin is a protein involved in the clotting of blood that is polymerised to form a "mesh" that forms a hemostatic plug or clot (in conjunction with platelets). Fibrin is made from fibrinogen, a soluble plasma glycoprotein synthesized by the liver. Nattokinase prevents aggregation of red blood cells.

Nattokinase and Coumadin ( warfarin )
We have been asked many times regarding the interaction of nattokinase supplement use and warfarin. Can they be taken together? Can nattokinase substitute for warfarin? Here is a typical question we received in Sept 2007.

Q. I am a stroke survivor and since i had my stroke I have been extremely wary about taking ant kind of vitamin supplement. Recently my doctor has given me the green light to take some CO-Q10 as well as a multiple vitamin. i was looking at your information about the supplement nattokinase, and its benefits and side effects. I have been thinking about taking this product after first having my dr. review the info. i have been on Coumadin since my stroke in 2005. Currently I have been getting some blood clots in my legs. My dr. advised me that he wants to keep my INR level thinner then normal to help keep from having another one. He wants the INR level to be at least 3.0 to 3.5. I am wondering if I started to take nattokinase and other herbal supplements like hawthorn will it keep my blood thin enough to accomplish this task and my dependency on Coumadin could be eliminated.
   A. Each person is different on how they respond to nattokinase and other supplements. It is impossible to predict your response. Your doctor may wish to read this page on nattokinase and then decide if he or she wants to add this supplement to your existing regimen while perhaps decreasing the dose of the Coumadin. Unfortunately, we have not seen any clinical studies regarding the combination of low dose nattokinase and low dose Coumadin to determine how they interact and whet the appropriate combination dosages would be. Therefore, close monitoring is required if the Coumadin dose is being reduced while the nattokinase dose started. The best option is to do the transition is tiny dose changes, even if it involves initially taking part of a nattokinase capsule.

Nattokinase and blood clotting
Effects of nattokinase, a pro-fibrinolytic enzyme, on red blood cell aggregation and whole blood viscosity.
Clin Hemorheol Microcirc. 2006;35(1-2):139-42. Pais E, Alexy T, Holsworth RE Jr, Meiselman HJ. Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
A fibrinolytic enzyme, termed nattokinase, can be extracted from natto; the enzyme is a subtilisin-like serine protease composed of 275 amino acid residues and has a molecular weight of 27.7 kDa. In vitro and in vivo studies have consistently demonstrated the potent pro-fibrinolytic effect of the enzyme. Blood samples were incubated with nattokinase for 30 minutes at 37 degrees C. Our in vitro results showed a significant, dose-dependent decrease of RBC aggregation and low-shear viscosity, with these beneficial effects evident at concentrations similar to those achieved in previous in vivo animal trials. Our preliminary data thus indicate positive in vitro hemorheological effects of nattokinase, and suggest its potential value as a therapeutic agent and the need for additional studies and clinical trials.

Dietary supplementation of fermented soybean, natto, suppresses intimal thickening and modulates the lysis of mural thrombi after endothelial injury in rat femoral artery.
Life Sci. 2003 Jul 25;73(10):1289-98. Department of Pharmacology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu City, Shizuoka 431-3192, Japan.
We have previously demonstrated that natto extracts containing nattokinase inactivate plasminogen activator inhibitor type 1 and then potentiates fibrinolytic activity. In the present study, we investigated the effects of dietary supplementation with natto extracts on neointima formation and on thrombolysis at the site of endothelial injury. Endothelial damage in the rat femoral artery was induced by intravenous injection of rose bengal followed by focal irradiation by transluminal green light. Dietary natto extracts supplementation containing nattokinase of 50 or 100 CU/body was started 3 weeks before endothelial injury and then continued for another 3 weeks. Intimal thickening in animals given supplementation was significantly suppressed compared with controls, In conclusion, dietary natto-extracts supplementation suppressed intimal thickening produced by endothelial injury in rat femoral artery. These effects may partially be attributable to nattokinase, which showed enhanced thrombolysis near the vessel wall.

Nattokinase Research Update
Dietary supplementation with fermented soybeans suppresses intimal thickening.
Nutrition. 2003 Mar;19(3):261-4.
Although soy foods have been consumed for more than 1000 years, it is only in the past 20 y that they have made inroads into Western diets. We investigated the effect of dietary supplementation with natto extracts produced from fermented soybeans on intimal thickening of arteries after vessel endothelial denudation. Natto extracts include nattokinase, a potent fibrinolytic enzyme having four times greater fibrinolytic activity than plasmin. Intimal thickening was induced in the femoral arteries by intravenous infusion of rose bengal followed by focal irradiation with a transluminal green light. Nattokinase extract supplementation was started 3 wk before endothelial injury and continued for another 3 wk after. Nattokinase supplementation suppressed intimal thickening compared with the control group. Nattokinase shortened euglobulin clot lysis time, suggesting that their thrombolytic activities were enhanced. These findings suggest that nattokinase, because of its thrombolytic activity, suppress intimal thickening after vascular injury as a result of the inhibition of mural thrombi formation.

Thrombolytic effect of nattokinase on a chemically induced thrombosis model in rat.
Biol Pharm Bull. 1995 Oct;18(10):1387-91.
Nattokinase is a new fibrinolytic enzyme which cleaves directly cross-linked fibrin in vitro. In this study, we investigated the thrombolytic effect of nattokinase on a thrombus in the common carotid artery of rat in which the endothelial cells of the vessel wall were injured by acetic acid. When a section of occluded vessel was stained for CD61 antigen by immunofluorescence utilizing a monoclonal antibody, the antigen was localized around the surface of the occluded blood vessels. This result suggests that the occlusive thrombosis was caused by platelet aggregation. In addition, thrombolysis with urokinase (UK; 50000 IU/kg, i.v.) or tissue plasminogen activator (tPA; 13300 IU/kg, i.v.) in our model was observed to restore the blood flow over a 60 min monitoring period. The results indicate that our chemically induced model is useful for screening and evaluating a thrombolytic agent. We evaluated the thrombolytic activity of nattokinase using this model and compared it with fibrino(geno)lytic enzyme, plasmin or elastase. On a molar basis, the recovery of the arterial blood flow with nattokinase, plasmin and elastase were 62%, 15% and 0%, respectively. The results indicate that the thrombolytic activity of nattokinase is stronger than that of plasmin or elastase in vivo.

Transport of nattokinase across the rat intestinal tract.
Biol Pharm Bull. 1995 Sep;18(9):1194-6.
Intraduodenal administration of nattokinase at a dose of 80 mg/kg, resulted in the degradation of fibrinogen in plasma suggesting transport of nattokinase across the intestinal tract in normal rats. The action of nattokinase on the cleavage of fibrinogen in the plasma from blood samples drawn at intervals after intraduodenal administration of the enzyme was investigated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting analysis with an anti-fibrinogen gamma chain antibody. The 270 kDa fragment carrying antigenic sites for the binding of the anti-fibrinogen gamma chain antibody appeared within 0.5 h and was then degraded gradually to a 105 kDa fragment via a 200 kDa fragment. This suggests that fibrinogen was degraded to a 105 kDa fragment via several intermediates (270 and 200 kDa). In parallel with the degradation process, plasma recalcification times were remarkably prolonged NK was also detected in the plasma from blood samples drawn 3 and 5 h after administration of the enzyme by SDS-PAGE and Western blotting analysis with an anti-nattokinase antibody. The results indicate that nattokinase is absorbed from the rat intestinal tract and that nattokinase cleaves fibrinogen in plasma after intraduodenal administration of the enzyme.

Purification and characterization of a strong fibrinolytic enzyme nattokinase in the vegetable cheese natto, a popular soybean fermented food in Japan.
Biochem Biophys Res Commun. 1993 Dec 30;197(3):1340-7.
A strong fibrinolytic enzyme nattokinase was purified from the vegetable cheese natto. Nattokinase was extracted from natto with saline and isolated by sequential use of hydrophobic chromatography. The isolated protein gave a single sharp band on SDS-PAGE either before or after reduction. The sequence consisted of a total 275 amino acid residues (M.W = 27,728) and exhibited a high homology with the subtilisins. The purified nattokinase digested not only fibrin but also several synthetic substrates. The results indicate that nattokinase is a subtilisin-like serine protease.

Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase.
Acta Haematol. 1990;84(3):139-43.
The existence of a potent fibrinolytic enzyme nattokinase in the traditional fermented food called 'natto', was reported by us previously. It was confirmed that oral administration of nattokinase (or natto) produced a mild and frequent enhancement of the fibrinolytic activity in the plasma, as indicated by the fibrinolytic parameters, and the production of tissue plasminogen activator. Nattokinase capsules were also administered orally to dogs with experimentally induced thrombosis, and lysis of the thrombi was observed by angiography. The results obtained suggest that nattokinase represents a possible substance for use not only in the treatment of embolism but also in the prevention of the disease, since nattokinase has a proven safety and can be mass produced.

Secretory expression of a heterologous nattokinase in Lactococcus lactis.
Appl Microbiol Biotechnol. 2007 May;75(1):95-101. Center for Metabolic Engineering of Microorganisms, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100080, People’s Republic of China.
Nattokinase has been reported as an oral health product for the prevention of atherosclerosis. We developed a novel strategy to express a nattokinase from Bacillus subtilis in a live delivery vehicle, Lactococcus lactis. Promoter P( nisZ) and signal peptide SP(Usp) were used for inducible and secretory expression of nattokinase in L. lactis. Western blotting analysis demonstrated that nattokinase was successfully expressed, and about 94% of the enzyme was secreted to the culture. The recombinant nattokinase showed potent fibrinolytic activity, equivalent to 41.7 urokinase units per milliliter culture. Expression and delivery of such a fibrinolytic enzyme in the food-grade vehicle L. lactis would facilitate the widespread application of nattokinase in the control and prevention of thrombosis diseases.

Nattokinase emails
Q. If I could beg your indulgence for a question on nattokinase and an allergy to soy. If a person is allergic to soy, would nattokinase pose a problem? Some say that it is only proteins that cause allergies and since nattokinase is an enzyme, it would not. Yet, many of the nattokinase preparations marketed are in a base of soy oil and soy lecithin…. which would be a whole other issue besides the nattokinase enzyme, itself.
   A. It's a good question, I really don't know the answer but I would think that nattokinase itself would not cause an allergy, but perhaps if it is in soy base, the product could.

Q.  Is it safe to use nattokinase while breastfeeding? The dose of nattokinase that I have on hand is 100mg per capsule.
   A. There's very little human research with nattokinase, and we don't really know how well it goes through breast milk. To be on the safe side, it would be best not to use it during pregnancy.

Q. Is nattokinase enzyme helpful in fibroids?
   A. I don't know, I have not seen any studies relating to fibroids and nattokinase.

Q.  I know you stated that nattokinase is a blood clot remover. Could nattokinase break up or remove blocked arteries and veins?
   A. There is not enough human research on nattokinase and blood clots or blocked arteries for us to know this answer at this time, but the initial nattokinase research regarding blood clot dissolving potential looks promising.

Q.  I am a health food store owner, ordered mattokinase for a gentleman that was supposed to have by bypass surgery, He is also on a vegan diet, He has been taking the nattokinase medicine for a few months and when he went to the doctor last week, they told him he did not have to have bypass surgery. He is still on the plan but he wants to know how long does he have to take the nattokinase medicine.
   A. This is interesting. We really are not in a position to say how long a person should or should not take a nattokinase supplement. That is the decision of their doctor.

Q. Why is nattokinase enzyme sold separately from fermented soy? If I consume fermented soy supplements ( natto ), wouldn't I also be consuming the nattokinase enzyme found in it?
   A. Hi, sure you could get nattokinase from fermented soy, but it may not be found nearly enough. This is the same as vitamin C. Let's say you wish to have 1000 mg of vitamin C, that means you would have to ingest a dozen or more oranges. We are not sure how much nattokinase is in an ounce of fermented soy, a lot depends on how it is prepared.

Q. 2 years ago I had a central retinal vein occlusion, thank God my vision has been restored almost completely, except for a tiny area in my right eye. Would it be advisable to take nattokinase enzyme to dissolve the clot?
   A. We have not seen any studies regarding nattokinase enzyme use and central retinal vein occlusion, hence we can't advise.

Q. is it true that nattokinase is not safe for people with high blood pressure and/or who are taking medication for it? if so, why?
   A. We have not seen any research that indicate nattokinase should or should not be used by those on blood pressure medication or those who have hypertension.

Q. My mom had a recent TIA as a result of her pulmonary valve stenosis. She was released from the hospital yesterday. I would like to have my Mom use nattokinase instead of Coumadin for obvious reasons. However I am concerned about your warnings and my doctor says nattokinase research is inconclusive, so he can’t advise. Mom has atrial fibrillation due to a mitral valve stenosis (one doctor calls it atrial valve stenosis). The result is that blood pools in the lung and there is danger of throwing clots from the pooled blood. Of course, the other problem with the pooled blood is that it goes out into the lung cavity in the form of fluid, which must be drawn off using a diuretic, Lasix. Mom is also on Lopressor to control the heart rate, and in the process it lowers blood pressure. Ma was on a drug similar to Coumadin while in the hospital, but when she was discharged, the doctor put her on aspirin, while waiting for a decision from the family as to whether to switch to Coumadin or nattokinaise. Obviously, it would be one or the other, NOT both! The doctor warns that on aspirin alone, the danger of having another stroke is 80% over the next 2 months, so we need to find a suitable substitute. The reason that aspirin is ineffective is that it is a blood thinner, in the sense that it prevents platelets from sticking together. However, the source of her clots is not sticky platelets, but because the blood is pooling in the lungs, forming clots. She requires a substance that will prevent such clots from forming and will dissolve clots already formed. Please provide whatever information you can on nattokinaise and its viability in this sort of case.
   A. There has not been enough human research with nattokinase and heart valve stenosis and subsequent clot formation to determine whether nattokinase is effective in these conditions or whether it is a substitute for Coumadin or other drugs. This is a complicated situation and we cannot get involved in diagnosis or treatment suggestions. Her doctor may wish to read this nattokinase page and make a decision.

Q. I read that nattokinase can reverse or reduce plaque buildup and fatty deposits in the arteries. Do you know if that is that true? If so, can you tell me now much nattokinase needs to be taken daily for this to be effective? Is nattokinase NSK-SD better? And how long does it normally take before there is significant reduction of plaque buildup and fatty deposits?
   A. These are good questions but we still have not seen enough human studies with nattokinase to have a clear idea of the effectiveness of this enzyme in terms of atherosclerosis or blood thinning. There is no research comparing different brands of nattokinase, hence we can't say Nattokinase NSH-SD is better or worse than other brands. There's too little human research available with nattokinase to know the ideal dosage and length of use or its overall effectiveness.

Q. I have been taking nattokinase for years to lower fibrinogen, and I think it works. Today I had my blood drawn for a fibrinogen test, and the technician asked me if I was taking a blood thinner and mentioned two drugs. I said no, but asked why she was asking. She said be cause if I was she would have to prepare the sample differently for sending to the lab. I asked her if nattokinase would make a difference. She had never heard of it. I asked her to call the lab the check it out. She did and was told that they never heard of it. Later, I was picking up a prescription and asked the pharmacist, and she had never heard of it and had nothing in her database about it either. Seems to me that if you are not supposed to take blood thinners with it, and it must have blood thinning properties and might need to be handled at the lab the same as a blood thinner. What do you think? Could my results be off because it was not handled a certain way? Would it be higher or lower?
   A. There's a lot we still need to learn about nattokinase and how it influences various blood coagulation proteins and factors when taken as a supplement. But research is being done and within a few years we should have a more complete understanding. In the meantime, it does appear that nattokinase breaks down firbrinogen and prevent red blood cells from aggregating, and it does have blood thinning properties. How potent nattokinase is when compared to Coumadin? I don't know.

Q. What do you think of taking a nattokinase supplement before a long flight to prevent blood clotting?
   A. This is an interesting idea. However, whether nattokinase offers any advantages over aspirin is not clear to me.

Q. Could you please tell me if this product has been found to be safe for pregnant women and their developing baby?
   A. We are not aware of any research with nattokinase in women who are pregnant. It is preferable to be on the safe side and not take nattokinase during pregnancy. 

Q. Could you tell me if there has been any new research or studies on nattokinase? It seems that all your posted questions are pretty much answered with the same answer; There’s not enough nattokinase research. I’m very interested in this product but am not convinced there is enough evidence that would sway my decision to use it. I have had 2 stents put in and have factor 5 liden blood protein abnormality. I would like to find a proven product that would prevent clots.
   A. We will update our site as more nattokinase studies are published. Until then we can't say too much. Sorry. We don't want to make false promises if studies do not support them.

Q. Are there any reliable studies regarding any possible adverse reaction when taking nattokinase in a person with a known or possible penicillin allergy.
   A. We have not seen such studies. A search on Medline with the keywords nattokinase and penicillin reveals no articles published on this topic.

Q. Must products with nattokinase be enteric-coated capsules?
   A. We have not seen any studies comparing nattokinase supplement that are enteric coated to those that are not.

Q. Since there are people taking mattokinase in an effort to reduce blood clotting, why isn't the standard Prothrombin Time test used to measure it's affect? This would seem to resolve any doubts, at no risk to the patients, and little expense. It works, or it doesn't, and with what variables.

Q. How is natto made?
   A. Natto is made by steaming or boiling soybeans and then fermenting this with a bacterium called Bacillus subtilis natto. Natto contains a high amount of vitamin K2.

Q. Does the use of nattokinase supplement lower blood pressure?
   A. I have not seen studies focusing on the use of nattokinase as a treatment for hypertension, but I have read articles by a few doctors who claim that the use of nattokinase had a mild effect in lowering blood pressure. However, caution is advised since nattokinase is also a blood thinner and problems may arise when used in combination with aspirin or other blood thinners.
 

This nattokinase web page was last updated in March 2008.