Nattokinase

Nattokinase is a potent blood-clot dissolving protein used for the treatment of cardiovascular diseases, produced by the bacterium Bacillus subtilis during the fermentation of soybeans to make natto. ^[1] It is an alkaline serine protease with strong thrombolytic activity, valued as a potential therapeutic agent for thrombotic diseases because of its safety and economy. ^[2] Natto has been consumed as a traditional fermented food in Japan for thousands of years, and nattokinase is regarded as a valuable dietary supplement or nutraceutical. ^{[1] [3]}

Nattokinase's main interest is its direct fibrinolytic activity, and it is stable enough in the gastrointestinal tract to serve as an agent for oral thrombolytic therapy. ^[3] Beyond fibrinolysis it has demonstrated antihypertensive, anti-atherosclerotic, lipid-lowering, antiplatelet, and neuroprotective effects. ^[4] More recent work indicates nattokinase can also mitigate molecular pathways related to inflammation and oxidative stress, supporting its use as an adjuvant strategy in non-communicable diseases. ^[5]

In a systematic review and meta-analysis of six randomized controlled trials with 546 participants, nattokinase significantly reduced systolic and diastolic blood pressure compared with placebo. ^[6] That analysis reported a mean reduction in systolic blood pressure and a mean reduction in diastolic blood pressure with no notable adverse events reported due to intake of nattokinase. ^[6] The lipid-lowering effect was inconsistent, as relatively low-dose supplementation showed no significant lipid-lowering effect and more work is needed to determine whether efficacy is dose-dependent. ^[6] Nattokinase has been undergoing a Phase II clinical trial in the USA for atherothrombotic prevention. ^[1]

Cardiovascular disease is the leading cause of death in the world, and consumption of natto has been linked to a reduction in cardiovascular disease mortality. ^[4] As a nutraceutical, nattokinase is proposed as an effective adjunctive therapy for hypertension rather than a standalone replacement for established drugs. ^[6] Because it acts on hemostasis, its use should be individualized given the potential for bleeding risk or drug interactions when combined with antithrombotic therapy. ^[7]