Enzymes: Nature’s Clot Busters
Blood clotting is not something most people worry about. You get a cut, clot forms, the bleeding stops, end of story. Yet excessive clotting can be deadly. As J. Heinrich and colleagues note: “Coronary thrombosis is regarded as the final occlusive event in the progress of coronary heart disease (CHD). Disturbances of the hemostatic system may favor this process and thus may indicate an increased risk of myocardial infarction [or cerebrovascular event].” 
Translation: inappropriate, unnecessary blood clots may form in your blood vessels and trigger a heart attack or stroke. This happens to millions of Americans every year, often leading to permanent disability or death. The question is: Why? And what can be done about it?
A clot (technically known as a “thrombus”) forms when platelets and red blood cells clump together. It is the blood protein fibrin that “glues” them together. Fibrin is formed at the site of a clot from the soluble circulating protein fibrinogen. If the clot forms at the site of a broken or cut blood vessel, it is appropriate, even lifesaving. If the clot forms inside a blood vessel in the absence of a wound or trauma, it is unnecessary, even life-threatening, since it may plug up a crucial heart or brain artery. There are more than 20 enzymes involved in the coagulation cascade that creates clots, but only one enzyme-plasmin that can dissolve fibrin and thus break up small clots.
Plasmin, a thrombolytic (clot-dissolving) enzyme, is made from plasminogen through the action of an enzyme, tissue plasminogen activator (TPA). Thromobolytic enzymes are produced in blood vessel linings, and their production drops with age. To make matters worse, even in healthy people fibrinogen levels rise by 25 mg/dl per decade.  “There are several pathways by which acute or chronic increase in fibrinogen levels can lead to a cardiovascular [or cerebrovascular] event…, including…increased platelet aggregation and thrombus formation, and increased fibrin formation.”  In other words, high fibrinogen levels tend to promote the spontaneous formation of unnecessary fibrin-clots. High fibrinogen (and thus implicitly, high fibrin) levels are such a serious risk factor for heart attacks and strokes that one major study of 2,116 men found that those who had high LDL (“bad”) cholesterol-but low fibrinogen levels-had only one-sixth the heart attack risk of men with high LDL and high fibrinogen levels. 
Fortunately, nature has provided us with a way to augment our gradually diminishing clot-busting activity. In 1980, while studying physiological chemistry at the University of Chicago Medical School, Japanese researcher Hiroyuki Sumi accidentally discovered that a traditional Japanese food-natto-had the ability to dissolve thrombi.  He and his research group published a brief paper on the discovery in 1987, describing the “strong fibrinolytic [clot-dissolving] activity” of the fermented soy cheese, natto.  The Sumi research group was able to purify and identify a specific enzyme from the soy cheese that he called “nattokinase.”  Because natto has been widely consumed in Japan for over a thousand years, Dr. Sumi felt safe in performing human and animal experiments with nattokinase. In 1990 the Sumi research group published the results of a series of experiments demonstrating nattokinase’s potent fibrinolytic activity. 
In the first study, 12 volunteers (six men and six women) were fed 200 grams (seven ounces) of natto, and two methods of measuring their blood’s fibrinolytic activity were used. In the euglobulin clot lysis test, a blood sample was taken and the formation of a thrombus (clot) was then artificially stimulated. The time required for the blood to completely dissolve the clot was then measured. The time needed to completely dissolve the clot was cut in half compared to those in the control group. The fibrin plate method was then used on other blood samples. In this test, blood was added to a plate with a special polymerized fibrinogen to see how much it would dissolve in four hours. The control group’s blood had no effect in this test, but the natto group’s blood dissolved 15 mm of fibrinogen in this test.
Next, the research team had volunteers take crude nattokinase tablets for eight days, using the same two tests plus the fibrin degradation product test. They also measured tissue plasminogen activator (TPA) blood levels. These tests further confirmed nattokinase’s clot-busting power, with the men showing an increase in TPA activity as well. While Dr. Sumi had previously shown that nattokinase had direct fibrinolytic activity,  the finding of increased TPA activity (which increases plasmin) showed nattokinase to augment the body’s own fibrinolytic activity. Finally, the Sumi team gave one group of dogs nattokinase tablets and another group a placebo. The team then created a thrombus in a major leg vein in each dog which completely blocked the vein, as shown in angiograms. Within five hours the nattokinase-fed dogs had a complete reopening of their leg vein circulation, while the dogs fed the placebo still had complete vein occlusion (blockage) 18 hours later. 
More Nattokinase Research
In 1995 M. Fujita and colleagues reported their results with rats and nattokinase.  The carotid artery (which feeds the brain) was injured to induce thrombus formation, which completely blocked the artery. Three enzymes-elastase, plasmin, and nattokinase-were then tested on different rats. After one hour, elastase (a close “chemical cousin” of plasmin and nattokinase) had produced no reopening of the blocked carotid artery whatsoever. Plasmin restored about 16 percent of normal circulation in one hour. But the nattokinase succeeded in restoring carotid brain circulation 62 percent. As the researchers modestly concluded: “The results indicate that the thrombolytic [clot-dissolving] activity of nattokinase is stronger than that of plasmin or elastase in vivo.” 
In 1994, an amazing case was reported demonstrating nattokinase’s ability to restore blood circulation. A 58-year-old man suffering from central retinal vein occlusion in his right eye came to a university hospital. The clot had caused fluid accumulation and bleeding in the eye, leading to loss of vision. The researchers prescribed a 100-gram (three-ounce) dose of natto, to be eaten before bed every night as a way to get nattokinase to his eye. He was also prescribed a drug to reduce the blockage-induced bleeding. By the tenth day eye bleeding was halted. By the twentieth day his eye circulation was so improved his vision returned and he was released from the hospital. He continued to eat natto two days weekly, and two months later a retinal angiogram showed a complete clearing of the retinal blockage. 
Serrapeptase, also called serratia peptidase, is an enzyme derived from the Serratia bacteria, which lives in the intestinal tract of silkworms. It has been used for over 30 years in Europe and Asia (where it is called Danzen) to reduce pain, inflammation and excessive mucous secretion. [9,10,11] Serrapeptase has been shown to be well-absorbed from the intestinal tract, although it must be enterically coated to protect it from degradation in the stomach. [12,13]
Hans Nieper, a pioneering medical doctor in Germany, has recommended serrapeptase for decades to gradually reduce atherosclerotic plaque buildup. Mazzone and coworkers note that “serritia peptidase (Danzen)…, which is available in tablet form to enable it to be absorbed from the intestinal lumen, has been shown to induce intense fibrinolytic, anti-inflammatory, and anti-edemic activity…”  Since inflammation increases fibrinogen levels,2 and increased fibrinogen increases pathological clotting risk, [1,2,3] the powerful anti-inflammatory activity of serrapeptase [10,14] complements its fibrinolytic activity. An ideal natural clot-busting supplement should, therefore, combine nattokinase and enterically coated serrapeptase granules.
Nattokinase, naturally present in and absorbed from natto, has been consumed safely in Japan for a thousand years. Serrapeptase has been safely and widely used in Europe and Asia for more than 30 years. They are helpful in preventing or reversing the pathological hypercoagulation tendencies common among modern Americans. Yet not everyone should take nattokinase/serrapeptase (NKSP). People with bleeding disorders, such as hemophilia or a group of diseases called “hemorrhagic diathesias,” should not take NKSP. People with ongoing bleeding problems, including ulcers, recent surgery, recent major trauma, or hemorrhoids, should not take NKSP. Anyone who has ever suffered intracranial bleeding, or who have had neurosurgery or ischemic stroke in the previous six months, should also avoid NKSP. Severe uncontrolled high blood pressure is also a contraindication for NKSP. Last, those taking blood-thinning drugs such as heparin, Coumadin or aspirin should use NKSP only if advised and carefully monitored by their prescribing physician.
In Dr. Sumi’s original nattokinase paper, it was reported that natto had an average of 40 fibrinolytic units (FUs) per gram.  In human research, 50 to 200 grams is the typical daily food dose used to supply nattokinase. This would be equivalent to a dose of 2,000 to 8,000 FUs. The nattokinase currently available for supplements supplies 20,000 FU/gram, while serrapeptase supplies 60,000 FU/gram. A combination of 36 mg nattokinase and 5 mg serrapeptase would yield 1,020 FUs. Taking one such capsule two or three times daily on an empty stomach with water would be a reasonable preventive or maintenance dose. Anyone suffering any medical condition that might involve bleeding or coagulation issues should check with a health care professional before using nattokinase and serrapeptase.
- Heinrich, J. et al. “Fibrinogen and factor VII in the prediction of coronary risk.” Arterioscler Thromb 1994, 14:54-59.
- Hager, K. et al. “Fibrinogen and Aging.” Aging (Milano) 1994, 6:133-38.
- Montalescot, G. et al. “Fibrinogen as a risk factor for coronary heart disease.” Eur Heart J 1998, 19 Suppl H:H11-17.
- Interview with Doctor of Medicine Hiroyuki Sumi, Japan Bio Science Laboratory Co., Ltd., 1998.
- Sumi, H. et al. “A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese natto….” Experientia 1987, 43:1110-11.
- Sumi, H. et al. “Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase.” Acta Haematol 1990, 84: 139-43.
- Fujita, M. et al. “Thrombolytic effect of nattokinase on a chemically induced thrombosis model in rat.” Bio Pharm Bull 1995, 18:1387-91.
- Nishimura, K. et al. “Natto diet was apparently effective in a case of incipient central retinal vein occlusion.” Jpn Rev Clin Ophthalmol 1994, 88:1381-85.
- Kee, W. et al. “The treatment of breast engorgement with serrapeptase (Danzen&Mac226;): a randomized double-blind controlled trial.” Singapore Med J 1989, 30:48-54.
- Tomoda, K. and Miyatam, K. “Some information on the composition of tracheal secretions before and after the administration of Danzen&Mac226;” Exper Ther 1972, 477:9-16.
- Mazzone, A. et al. “Evaluation of serratia peptidase in acute or chronic inflammation of otorhinolaryngology pathology: a multicentre, double-blind, randomized trial versus placebo.” J Int Med Res 1990, 18:379-88.
- Miyata, K. “Intestinal absorption of serratia peptidase.” J Appl Biochem 1980, 2:111-16.
- Moriya, N. et al. “Intestinal absorption of serrapeptase (TSP) in rats.” Biotechnol Appl Biochem 1994, 20 (pt.1):101-08.
- Esch, P. et al. “A reduction of postoperative swelling. Objective measurement of swelling of the upper ankle joint in treatment with serrapeptase-a prospective study” (in German). Fortschr Med 1989,107:67-68,71-72.