Nattokinase enzymes taken orally directly support the metabolic enzymes of the body and show effectiveness in many health concerns

Recently, a new metabolic, biological enzyme with potent fibrinolytic activity that rivals pharmaceutical agents has been discovered by Hiroyuki Sumi, MD.1 It shows potential in providing support for hypercoagulative states and supporting the activation of the 3,000 endogenous enzyme bodies.

Until now, the nutritional use of enzyme supplements has been almost exclusively in the digestive form. This new metabolic enzyme has been isolated from a traditional fermented Japanese food natto (although it is consumed by other cultures in the same or similar forms), which appears to have metabolic effects and work directly in concert with the metabolic enzymes.

Natto has been used in Japan for more than 1,000 years for its popular taste and as a folk remedy for heart and vascular diseases. Natto is produced by a fermentation process by adding Bacillus natto, a beneficial bacterium, to boiled soybeans resulting in the nattokinase (NK) enzyme. Its most intriguing role promises to be its involvement in coagulation homeostasis. While other soy foods contain beneficial enzymes, it is only the natto preparation that contains the specific NK enzyme.

This all-natural enzyme shows promise in supporting areas, such as cardiovascular disease, stroke, angina, venous stasis, thrombosis, emboli, atherosclerosis, fibromyalgia/chronic fatigue, claudication, retinal pathology, hemorrhoid, varicose veins, soft tissue rheumatisms, muscle spasm, chronic inflammation and pain, peripheral vascular disease, hypertension, tissue oxygen deprivation, infertility, and other gynecology conditions—endometriosis and uterine fibroids.

An enzyme deficiency state has been linked to chronic disease, accelerated aging, and premature death. Enzymes function by activating vitamins and minerals to forms usable by the body, assisting in the liberation of nutrients from food, helping to destroy harmful microbial agents, signaling and regulating chemical processes (such as detoxification), and activating other enzymes and hormones.

There are three major groups of biological enzymes: 1) food, 2) digestive, and 3) metabolic. In the past, therapeutic use has largely focused on the use of digestive enzymes, which can be directly beneficial because they assist in digestion, help regulate immune responses in the intestinal tract, and relieve the body of its relative requirement of digestive enzyme production, allowing for biological energy and resources to be further allocated to the production of metabolic enzymes.

Coagulation Homeostasis
To understand the impact of NK on coagulation, a review of coagulation homeostasis and therapy is warranted. Some of the endogenous and exogenous agents involved in coagulation homeostasis are plasmin, heparin, coumarin/warfarin, tissue plasminogen activator (t-PA), and streptokinase. However, most of these agents have limitations and/or serious side effects.

• Plasmin is an endogenous protease that resembles trypsin (a digestive protease), and is the activated form of plasminogen. It is able to digest fibrin fibers; however, its limitation is that it is slowly activated, slow-acting, and works better to dissolve small clots, rather than larger ones.

• Heparin is a drug-given intravenous (IV) that acts as an anticoagulant by inhibiting thrombin. Heparin is often associated with side effects, such as increased bleeding and hemorrhage.

• Coumarin/warfarin is a drug that works by competing with vitamin K for reactive sites in the enzymatic process for the formation of prothrombin and clotting factors, thereby blocking the clotting action of vitamin K.

• t-PA is a clot buster that is effective in activating plasminogen to plasmin. Although given as an IV drug, this is also a naturally occurring substance produced endogenously, albeit in much smaller amounts used as a pharmaceutical agent.

• Streptokinase is another enzyme derived from beta-hemolytic streptococci that is used as a clot buster. Its limitation is that its effect is short-lived and eventually its therapeutic efficiency declines.

In addition to serious side effects and limitations, the clot busters lack true broad utility, in that to be therapeutic, it must be injected. Therefore, there has been a renewed interest in discovering and using oral anticlotting enzymes.

Fibrinolytic therapy by oral administration of enzymes was investigated by Sumi more than 10 years ago2,3 in an animal model where enteric-coated urokinase (UK) capsules were given to normal and experimental dogs with saphenous vein thrombosis. Previous findings indicated that IV administration did not show any clear thrombolytic effect, but that oral administration enhanced the fibrinolytic activity, serving as a treatment to lyse the thrombi in a mild, but maintained way. The dogs treated with NK regained 62% of blood flow, whereas, those treated with plasmin regained only 15.8% of blood flow.

The underlying mechanism of such fibrinolytic therapy by oral administration was then confirmed by basic research to involve absorption of the administered UK across the intestinal tract and release into the blood of endogenous plasminogen activator, which originated from the liver and/or endothelial cells. The enteric-coated UK capsules (60,000 U per day for 7 days) also exhibited a clinical efficacy against cerebral thrombi. Moreover, more effective results were obtained in double-blind tests at multicenter trials employing a dose of 120,000 U per day for 7 days. This supported the idea that oral enzyme agents can and do have systemic fibrinolytic properties. However, an oral fibrinolytic agent that had sustained activity and minimal side-effects was further pursued.

NK was found to be an ideal oral fibrinolytic agent—not only reversing clots, but in preventing and modulating the clotting process in ways that help re-establish coagulation homeostasis.

Effect on Fibrin/Blood Clots
Fibrin is a protein that when activated forms fibrinogen, which is responsible for blood clotting. This important and protective mechanism protects the body from excessive bleeding. However, in many instances, this process becomes overactivated or becomes stuck in high gear. This dysregulation of clotting has been implicated in a variety of serious health conditions, namely, cardiovascular disease. NK has many, if not most, of the benefits of pharmaceutical agents designed to regulate blood clotting (ie, warafin, heparin, t-PA, and urokinase) without any of the side effects of these medications. Furthermore, while these medications must be injected and is beneficial for a very brief time (a few hours), NK is effective when taken orally, and its benefits linger much longer. Standard doses of NK vary from 250 mg to 1,000 mg, and positive effects can be seen with as little as 50 mg.

Fibrinolytic enzymes, which break down fibrin and thrombi, are normally generated in the endothelial cells. As the body ages, production of these enzymes begin to decline, making blood more prone to coagulation. Since these cells exist throughout the body, such as in the arteries, veins, and lymphatic system, poor production of thrombolytic enzymes can lead to the development of clotting-prone conditions virtually anywhere in the body. This hypercoagulability has been linked to a variety of conditions.4

Underlying connective tissue weakness due to nutritional deficiencies and dysfunction of the endothelium gives rise to inflammatory and repair mechanism. Once initiated, this pro-inflammatory/pro-oxidative process is not only the underlying process of atherosclerosis and vascular dysfunction, but also causes a propensity to thrombi and thrombo-emboli. More than 50 important substances that affect blood coagulation are found in the blood and tissues.

The final clot is composed of a meshwork of fibrin fibers, running in all direction and entrapping blood cells, platelets, and plasma. Normally, the body has its own anticoagulants that are able to keep balance between the procoagulants, allowing for repair and healing, but not overshooting to cause pathological mechanisms. However, chronic nutritional deficiencies, infection, cell senility, and/or trauma can overwhelm the bodies endogenous coagulation homeostasis, resulting in thrombus and emboli.

Although it is extremely important to treat the underlying cause, such as replenishing the necessary nutritional factors to allow for the formation and repair of healthy connective tissue and to support proper endothelial function, often immediate and acute modulation of a decompensated clotting system is needed.

While the human body contains several enzymes that promote the creation of blood clots, plasmin is the only one that it produces. It is interesting to note that oral NK is more effective than plasmin in dissolving thrombi. Studies5 indicate that the mechanisms of NK stems from its close resemblance to endogenous plasmin, the ability to dissolve fibrin directly, and the enhancement of the body’s own production of plasmin. Furthermore, NK has angiotensin converting enzyme (ACE) inhibitor activity, and in studies6 has been able to lower systolic blood pressure up to 11% and diastolic pressure up to 9.7%.

NK also produces a prolonged action (unlike antithrombin drugs that wear off shortly after IV treatment is discontinued) in two ways: it prevents coagulation of blood and dissolves existing thrombus. Both the efficacy and the prolonged action of NK can be determined by measuring levels of euglobulin fibrinolytic activity (EFA) and fibrin degradation products (FDP), both of which become elevated as fibrin is being dissolved. By measuring EFA and FDP levels, activity of NK has been determined to last from 8 to 12 hours. An additional parameter for confirming the action of NK following oral administration is a rise in blood levels of t-PA antigen that indicates its release from the endothelial cells and/or the liver.

Another research team from JCR Pharmaceuticals, Oklahoma State University, and Miyazaki Medical College7 tested NK on 12 healthy Japanese volunteers (6 men and 6 women, between the ages of 21 and 55). They gave the volunteers 200 grams of natto (the food) before breakfast, then tracked fibrinolytic activity through a series of blood plasma tests.The tests indicated that the natto generated a heightened ability to dissolve blood clots. On average, the volunteers’ ELT (a measure of how long it takes to dissolve a blood clot) dropped by 48% within 2 hours of treatment, and they retained an enhanced ability to dissolve blood clots for 2 to 8 hours. As a control, researchers later fed the same amount of boiled soybeans to the same volunteers and tracked their fibrinolytic activity. The tests showed no significant change. CP

Nicholas Calvino, DC, is a nutritional consultant, master herbalist candidate, and author and lecturer on the subject of health and nutrition. He currently works with a multidisciplinary, integrative clinic, Alternative Medicine Solutions™ and Allergy Research Group®. Calvino can be reached at 810-385-6737, or via email: drcalvino@nhpartner.com.

References
1. Sumi H, Hamada H, Mihara H. A novel strong fibrinolytic enzyme (nattokinase) in the vegetable cheese “natto.” International 5. Abstracts of the ninth international congress on fibrinolysis, Amsterdam. Journal of Fibronolysis and Thrombolysis. 1988;2(1):67.
2. Sasaki K, Moriyama S, Sumi H, Toki N, Robbins K. The transport of 125 I-labeled human high molecular weight urokinase across the intestinal tract in a dog model with stimulation of synthesis and/or release of plasminogen activators. Blood. 1985;66:67–75.
3. Robbins K, Sumi H, Sasaki K, Toki N. The transport of high molecular weight human urinary urokinase across the intestinal tract of dogs and human subjects. In: Mannucci A. Urokinase: Basic and Aspects. Academic Press: New York; 1982:673–71.
4. Astrup T, Egeblad K. Thromboelastographic patterns produced by fibrinolytic agents incorporated in fibrin. Am J Physiol. 1965;209:84–94.
5. 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.
6. Maruyama M, Sumi H. Effect of Natto Diet on Blood Pressure. JTTAS. 1995.
7. 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;43(10):1110–1.