Nattokinase, a large enzyme of the serine protease family, is isolated from the fermented food product known as nattō (boiled soybeans fermented with the bacterium Bacillus subtilis). Interest in using nattokinase as a supplement has grown because of its cardiovascular benefits of reducing blood clotting and blood pressure.^[1][2][3] Although there’s some concern of an increased bleeding risk, reports of bleeding have been very rare and limited to people with chronic conditions or who are already taking blood thinning medications.^[8][9]

There is interest in using nattokinase for its cardiovascular benefits such as reducing blood clotting and lowering blood pressure.^[1][2][3] However, nattokinase does not seem to lower cholesterol nor reduce atherosclerosis. In a randomized trial in 265 adults with an average age of 65 years, taking 100 mg (2,000 fibrinolytic units (FU)) of nattokinase daily for about 3 years did not slow the progression of atherosclerosis compared to a placebo.^[10] The same dose taken for 6 months also did not lower cholesterol levels compared to a placebo,^[11] except when it was used in combination with red yeast rice, which is a natural source for the cholesterol-lowering drug lovastatin.^[12] Some researchers insist that higher doses of nattokinase may have a benefit for cholesterol. In fact, one large observational study in Chinese patients found that taking 10,800 FU of nattokinase daily for a year was associated with a reduction in cholesterol, while a lower dose of 3,600 FU daily was not associated with a reduction in cholesterol.^[6] This observational study cannot show cause and effect, so further interventional research is needed. It’s unclear if these effects are generalizable to other geographic locations.

Generally, nattokinase seems to be safe in adults when taken by mouth in doses of 100 mg (2,000 fibrinolytic units) daily.^[5] Although this dose may reduce blood coagulability biomarkers (e.g., prolonged activated partial thromboplastin time (aPTT), a measure of how long it takes blood to clot),^[3] there have been no reports of bleeding in adults without apparent health conditions even at doses up to 552 mg daily for four weeks.^[2] However, in older adults with chronic conditions, there have been rare reports of bleeding.^[8][9]

There have been reports of severe allergic reactions to nattokinase, including FAQ:What is anaphylaxis?, an itchy rash, and difficulty breathing. This can occur in people allergic to either polygamma glutamic acid (PGA, a sticky substance also found in jellyfish) or to nattokinase itself.^[13] However, the European Commission concluded that the risk of allergic reactions with nattokinase is no higher than the risk with soy products.^[5]

Nattokinase seems to have some anti-inflammatory and antioxidant effects that can contribute to cardioprotection,^[4] but its claim to fame is its ability to reduce blood clotting. Nattokinase seems to reduce blood clotting by breaking down fibrin (a molecule that entangles platelets and creates blood clots) by degrading plasminogen activator inhibitor-1 (PAI-1, a protein that makes clotting more efficient). PAI-1 disables plasminogen activators (PAs), including tissue-type plasminogen activator (tPA), a serine protease which is administered therapeutically to break up blood clots in conditions such as ischemic stroke and heart attack.^[4][14] Studies in humans have shown that ingesting a single dose of nattokinase increases blood levels of tPA for about 3 hours,^[15] while regular administration (taking 1,300 mg of nattokinase 3 times daily for 8 days) seems to gradually increase tPA in the blood over time.^[7] Small studies conducted in generally healthy people, as well as people on dialysis and with cardiovascular disease, showed that taking 800 mg (4,000 fibrinolytic units) of enteric-coated nattokinase 30 minutes after dinner every day for 2 months reduced serum fibrinogen by 7%–10%, factor VII by 7%–14%, and factor VIII by 17%–19% compared to baseline. The reduction in fibrinogen in people with cardiovascular disease and the reduction in factor VII in people on dialysis did not reach statistical significance, possibly due to insufficient power in the study.^[16]