The Super Enzyme Nattokinase

NattoThere probably is more than one way to skin a cat, but why would you do that in the first place? What do you do with the pelt, make a coat? or the flesh? Stew? Nah. Still there is more than one way to approach a job and to get it done. This philosophy applies to healthcare as well as to mechanical tasks. Long before there was what we now call conventional medicine, there was folk medicine, which today falls into the category of integrative, or complementary, or alternative medicine. To the surprise, and even chagrin, of the orthodox model, some of these folk remedies actually work—and they do so without side effects or contraindications. Take honey, for example. It’s been around since prehistory and has been used to ease sore throats and upper respiratory troubles since then. And…it’s making a comeback (Cohen, 2012) (Paul, 2007) (Fashner, 2012).

One of the Creator’s gifts to mankind is derived from a cultural food called natto, a traditional Japanese comestible made by fermenting boiled soybeans with Bacillus subtilis, a type of soil bacterium commensal to the human gut. This bacterial strain is noted for contributing to a healthy microflora and for enhancing the status of vitamin K2. The product extracted from natto is called nattokinase, an enzyme that is able to break the peptide bonds in proteins (Fujita, 1993) using a biochemical activity resembling trypsin, which is a proteolytic enzyme made by the pancreas to separate proteins into amino acids. Despite its name, nattokinase is not a kinase enzyme. That is a catalyst in phosphorus-related functions. Instead, it’s a subtilisin enzyme, as its name suggests. Because it can break apart proteins, it exhibits potent fibrinolytic characteristics (Fujita, 1993) (Sumi, 1987), hence its use in complementary and alternative medicine as a clot-buster. The term “fibrinolytic” means that a substance is able to liquefy coagulated blood by dissolving fibrin, the elastic, stringy protein that forms a kind of mesh to attract and hold platelets to make a clot. This is an activity we want when cut, but not inside a blood vessel.

People have used nattokinase to attend to cardiovascular matters, including stroke, angina, deep vein thrombosis, atherosclerosis, intermittent claudication, and even hemorrhoids and varicose veins. (Cesarone, 2003) (Fujita, 1993). Because of its fibrinolytic activity at the blood vessel wall, where a thrombus is likely to form, nattokinase is thought to be helpful in treating atherosclerosis (Suzuki, March 2003; July 2003).

Although nattokinase is not to be taken with aspirin or other blood thinners, including fish oil (separate by a two-hour window), it works differently. Aspirin inhibits an enzyme known as cyclo-oxygenase (COX). COX activates a chemical called thromboxane A2, which makes platelets stick together to form a plug over a damaged area of a blood vessel, as in a shaving nick. The work of aspirin cannot be undone because it lasts as long as a platelet is alive and working, about a week (Roth, 1975). This makes us wonder why aspirin is recommended every day instead of only once—or maybe twice—a week.  Clots are aggregates of platelets, red blood cells and fibrin. If a clot stays still, it’s a thrombus; if it moves, it’s an embolus. Nattokinase works by removing fibrin from the equation; aspirin prevents stickiness of platelets.

As promising as nattokinase can be, it is not without its critics—a common element with alternatives to allopathic medicine. There have been no definitive outcomes regarding this agent as an alternative to conventional treatments using aspirin, clopidogrel (Plavix) or warfarin (Coumadin). One factor is the dissolution and bioavailability of nattokinase. The effects of gastric acid on nattokinase are unknown, but the enteric coated form, at 1.3 grams three times a day, seems to increase measures of fibrinolytic activity for up to eight hours after ingestion (Sumi, 1990).

When fibrin accumulates in blood vessels, it almost always causes thrombosis, possibly leading to a cardiac event. You see, this is a property of wound healing. Insults to an arterial wall, as from chronic inflammation, reactive oxygen species or illness, may hasten the inflammatory cascade that demonstrates the activation of platelets and the eventual formation of plaque-producing macrophages, all in the name of damage repair. This is where anti-inflammatory agents and anti-oxidants get their celebratory publicity…and it isn’t mere hype. This also is where nattokinase gains attention as a potential functional food additive (Peng, 2005).

If arteries are clear, and if blood has the proper viscosity, elevated blood pressure will likely be a non-issue, but this appears to be more rare than common. At Yonsei University’s Institute of Science for Ageing, in Seoul, Korea, researchers wondered about the relevance of nattokinase to blood pressure homeostasis. Studying untreated hypertensive subjects, they found that 2000 fibrinolytic units (FU)—about 100 mg—of nattokinase for eight weeks effected a drop of almost 6 points in both diastolic and systolic readings (Kim, 2008). A similar finding was reported by the pharmacology department of Hiroshima University, in Japan, a few years later (Fujita, 2011). To add feathers to the cap, nattokinase activity may parallel that of the ACE inhibitors  commonly prescribed to treat hypertension (Murakami, 2012).

More study on this fermented soybean product is needed, but its future is promising. Nattokinase does not interact with any foods and does not interfere with blood tests. It should be avoided by pregnant women for lack of safety studies. Those scheduled for surgery are admonished to discontinue using nattokinase, or any other blood-thinning agent, a couple of weeks beforehand. But we’ll leave on an encouraging note:  nattokinase may have a place in Alzheimer’s treatment as a degradation agent for amyloid fibrils (Hsu, 2009).


Cesarone MR, Belcaro G, Nicolaides AN, Ricci A, Geroulakos G, Ippolito E, Brandolini R, et al
Prevention of venous thrombosis in long-haul flights with Flite Tabs: the LONFLIT-FLITE randomized, controlled trial.
Angiology. 2003 Sep-Oct;54(5):531-9.

Cohen HA, Rozen J, Kristal H, Laks Y, Berkovitch M, Uziel Y, Kozer E, Pomeranz A, Efrat H.
Effect of honey on nocturnal cough and sleep quality: a double-blind, randomized, placebo-controlled study.
Pediatrics. 2012 Sep;130(3):465-71. doi: 10.1542/peds.2011-3075. Epub 2012 Aug 6.

Fashner J, Ericson K, Werner S.
Treatment of the common cold in children and adults.
Am Fam Physician. 2012 Jul 15;86(2):153-9.

Fujita M, Nomura K, Hong K, Ito Y, Asada A, Nishimuro S.
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.

Fujita M, Hong K, Ito Y, Fujii R, Kariya K, Nishimuro S.
Thrombolytic effect of nattokinase on a chemically induced thrombosis model in rat.
Biol Pharm Bull. 1995 Oct;18(10):1387-91.

Fujita M, Ohnishi K, Takaoka S, Ogasawara K, Fukuyama R, Nakamuta H.
Antihypertensive effects of continuous oral administration of nattokinase and its fragments in spontaneously hypertensive rats.
Biol Pharm Bull. 2011;34(11):1696-701.

GUO Ting, YAO Wen-bing, GAO Xiang-dong
Study on the fibrinolytic activity and the mechanism of nattokinase
Chinese Journal of Biochemical Pharmaceutics 2004-04

Ruei- Amyloid-degrading ability if nattokinase from Bacillus subtilis Natto
Lin Hsu, Kung-Ta Lee, Jung_Hao Wang, Lily Y.L. Lee and rRta P.Y. Chen
J of Agr and Food Chem. 2009; 57: 503-508

Keiko Murakami, Naoki Yamanaka, Katsunori Ohnishi, Minoru Fukayama and Masataka Yoshino
Inhibition of angiotensin I converting enzyme by subtilisin NAT (nattokinase) in natto, a Japanese traditional fermented food
Food Funct., 2012,3, 674-678

Kim JY, Gum SN, Paik JK, Lim HH, Kim KC, Ogasawara K, Inoue K, Park S, Jang Y, Lee JH.
Effects of nattokinase on blood pressure: a randomized, controlled trial.
Hypertens Res. 2008 Aug;31(8):1583-8. doi: 10.1291/hypres.31.1583.

Paul IM, Beiler J, McMonagle A, Shaffer ML, Duda L, Berlin CM Jr.
Effect of honey, dextromethorphan, and no treatment on nocturnal cough and sleep quality for coughing children and their parents.
Arch Pediatr Adolesc Med. 2007 Dec;161(12):1140-6.

Peng Y, Yang X, Zhang Y.
Microbial fibrinolytic enzymes: an overview of source, production, properties, and thrombolytic activity in vivo.
Appl Microbiol Biotechnol. 2005 Nov;69(2):126-32. Epub 2005 Nov 12.

G J Roth and P W Majerus
The mechanism of the effect of aspirin on human platelets. I. Acetylation of a particulate fraction protein.
J Clin Invest. 1975 September; 56(3): 624–632.

Sumi H, Hamada H, Tsushima H, Mihara H, Muraki H.
A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet.
Experientia. 1987 Oct 15;43(10):1110-1.

Sumi H, Hamada H, Nakanishi K, Hiratani H.
Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase.
Acta Haematol. 1990;84(3):139-43.

Suzuki Y, Kondo K, Ichise H, Tsukamoto Y, Urano T, Umemura K.
Dietary supplementation with fermented soybeans suppresses intimal thickening.
Nutrition. 2003 Mar;19(3):261-4.

Suzuki Y, Kondo K, Matsumoto Y, Zhao BQ, Otsuguro K, Maeda T, Tsukamoto Y, Urano T, Umemura K.
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.

Urano T, Ihara H, Umemura K, Suzuki Y, Oike M, Akita S, Tsukamoto Y, Suzuki I, Takada A.
The profibrinolytic enzyme subtilisin NAT purified from Bacillus subtilis Cleaves and inactivates plasminogen activator inhibitor type 1.
J Biol Chem. 2001 Jul 6;276(27):24690-6. Epub 2001 Apr 26.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Print Friendly, PDF & Email