Nattokinase
Also known as: Natto extract, subtilisin NAT, Orokinase, NSK-SD, NKCP
Overview
Nattokinase is an enzyme derived from the fermented soy food product nattō which appears to have some direct fibrinolytic (blood-clot-busting) activity. It is thought to have cardioprotective effects.
Benefits
Nattokinase seems to have some anti-inflammatory and antioxidant effects that can contribute to cardioprotection, 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. Studies in humans have shown that ingesting a single dose of nattokinase increases blood levels of tPA for about 3 hours, 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. 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.
How it works
There is interest in using nattokinase for its cardiovascular benefits such as reducing blood clotting and lowering blood pressure. 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. The same dose taken for 6 months also did not lower cholesterol levels compared to a placebo, except when it was used in combination with red yeast rice, which is a natural source for the cholesterol-lowering drug lovastatin. 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. 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.
Side effects
Most commonly, 100 mg (2,000 fibrinolytic units (FU)) of nattokinase are taken by mouth daily. This dose is reported to not cause adverse effects by the European Food Safety Authority (EFSA). Limited research using higher doses of nattokinase also reported no adverse effects. People living in China have taken 540 mg (10,800 FU) of nattokinase daily for a year and adults living in the United States have taken 552 mg of nattokinase daily for four weeks without any reported adverse effects. Nattō itself can be used, and some anti-clotting effects have been noted with 12 grams of nattō daily over 2 weeks.
Dosage
Generally, nattokinase seems to be safe in adults when taken by mouth in doses of 100 mg (2,000 fibrinolytic units) daily. 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), there have been no reports of bleeding in adults without apparent health conditions even at doses up to 552 mg daily for four weeks. However, in older adults with chronic conditions, there have been rare reports of bleeding. There have been reports of severe allergic reactions to nattokinase, including 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. However, the European Commission concluded that the risk of allergic reactions with nattokinase is no higher than the risk with soy products.
FAQs
What is nattokinase?
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. 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.
How is nattokinase produced?
Nattokinase is extracted from nattō, a food made of boiled soybeans fermented with the bacterial strain Bacillus subtilis. To extract nattokinase from the fermentation broth, processes such as protein salting-out, organic solvent distillation, microfiltration, and ultrafiltration are used. Because of increasing interest in nattokinase, methods of production that increase yield and stability have been explored. For example, irradiation of the bacterial strain B. subtilis natto with gamma or ultraviolet rays seems to improve its heat stability and to increase the yield of nattokinase. Furthermore, using glucose (instead of sucrose or maltose), adding soy milk, and adding certain ions such as calcium and magnesium sulfate to the fermentation medium has been shown to increase the yield of nattokinase.
What are nattokinase’s main drawbacks?
Generally, nattokinase seems to be safe in adults when taken by mouth in doses of 100 mg (2,000 fibrinolytic units) daily. 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), there have been no reports of bleeding in adults without apparent health conditions even at doses up to 552 mg daily for four weeks. However, in older adults with chronic conditions, there have been rare reports of bleeding. There have been reports of severe allergic reactions to nattokinase, including 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. However, the European Commission concluded that the risk of allergic reactions with nattokinase is no higher than the risk with soy products.
How likely is nattokinase to cause bleeding?
Nattokinase seems to alter blood coagulation chemistry, and there’s a concern it may increase the risk of bleeding. In people with mildly elevated cholesterol levels, taking 2,000 fibrinolytic units (FU) of nattokinase daily for 8 weeks prolonged the aPTT (activated partial thromboplastin time — a measure of how long it takes blood to clot). However, there have been only 2 reported cases of bleeding with nattokinase in older adults with cardiovascular conditions. In one case, 400 mg of nattokinase was taken daily for 7 days with aspirin (a blood thinner). In the other case, an unknown, likely large dose of nattokinase (sometimes a “handful” of capsules) was taken daily.
Does nattokinase lower blood pressure?
Small studies suggest that nattokinase can mildly lower blood pressure in some people; however, it's not clear if this effect persists in the long term. A clinical study in 86 patients with high blood pressure showed that taking 100 mg (2,000 fibrinolytic units (FU)) of nattokinase daily for 8 weeks reduced systolic blood pressure by about 6 mmHg and diastolic blood pressure by about 3 mmHg compared to a placebo. Another small study in adults without known health conditions showed that taking 552 mg (11,040 FU) of nattokinase (NSK-SD) daily for four weeks resulted in small and variable decreases in blood pressure. However, the reduction in diastolic blood pressure was only statistically significant in female participants.
