Mechanisms Of Action

Enzymes, like their application in medicine, exert their effects in a multitude of ways. One primary focus of enzymatic action is on the protein fibrin. Fibrin is an insoluble protein involved in blood clotting. In the many steps of the clotting cascade, fibrin is the final product. It is derived from its soluble protein precursor, fibrinogen. Fibrin is laid down inside blood vessels that have been compromised by disease or injury. Fibrin forms minuscule strands that eventually dry and harden, which captures the blood vessel components effectively. Certainly, fibrin occupies a vital role in health and healing; however, fibrin may also be responsible for an overzealous propensity to form inappropriate clots in the body. Inappropriate clotting, of course, is a major risk factor for myocardial infarctions and strokes.1 When correctly balanced, deposition and removal of fibrin maintains an avoidance of blood loss and adverse viscosity in the vascular system. A balance tipped in favor of fibrin overproduction leads to dangerous clotting.


In the interest of preventive medicine, proteolytic enzymes can be used as interventional medicines that serve to inhibit overactivity of fibrin. One particular enzyme, known as nattokinase, has demonstrable fibrinolytic activity.2 Nattokinase is derived from a Japanese food known as natto, a preparation of soybeans that has undergone fermentation with a bacterium known as Bacillus subtilis natto.3 Hiroyuki Sumi, M.D., University of Chicago, is credited with the discovery of nattokinase. Thought to be produced specifically from this process of fermentation, nattokinase is not derived directly from other soy-based foods. Nattokinase causes mild enhancement of fibrinolysis in plasma, as evidenced by its effect on fibrinolytic parameters and production of tissue plasminogen activator, a potent thrombolytic agent that causes fibrinolysis at the site of a blood clot.4 Nattokinase is thought to work by inhibiting plasminogen activator inhibitor-1 (PAI-1).5 That is, nattokinase works by preventing the inhibition of plasminogen activator by PAI-1, thus potentiating clot dissolution. The fibrinolytic activity of nattokinase is fourfold that of plasmin, a main fibrinolytic enzyme found in the body.6

In animal studies, nattokinase can reduce markedly the thickening of blood vessel walls that normally occurs following an injury to the endothelium. In addition, nattokinase leads to dissolution of clots that build inside vessel walls as responses to injuries.7 These actions suggest that nattokinase can be used to treat and prevent atherosclerosis because of its fibrinolytic activity at the blood-vessel wall. When taken orally in humans, nattokinase retains its activity (thereby escaping degradation during the digestive process) and has been shown to raise the level of fibrinolytic activity significantly for several hours after dosing.4 Other applications of nattokinase include treating cardiovascular diseases, such as stroke, angina, deep-vein thrombosis, atherosclerosis, venous stasis, peripheral vascular disease, and claudication. Arteriosclerosis, excessive clotting, and inflammation are routine in developing arterial plaques. Enzyme therapy digests the fibrin and reverses the inflammation, which decreases the size of the artery-obstructing plaques. We have noted that symptoms of angina, impaired blood flow to the brain, and poor circulation to the legs often disappear with enzymatic treatment for cardiovascular conditions. The gentle, yet effective use of nattokinase for preventing cardiovascular diseases makes this an optimal choice from preventive and treatment perspectives. Combination with other anticoagulative therapies or drugs should be approached with great caution, however. Nattokinase is widely available today; one particular version of this enzyme is marketed as a preventive treatment for deep-vein thrombosis on long flights.8

Your Heart and Nutrition

Your Heart and Nutrition

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