Nattokinase for Elevated Blood Pressure

The short answer: nattokinase may lower high blood pressure slightly, but the evidence is thin and inconsistent. In 86 Korean adults with untreated pre-hypertension or stage 1 hypertension, 2,000 FU a day for 8 weeks lowered systolic pressure by 5.55 mmHg and diastolic by 2.84 mmHg more than placebo (Kim 2008). A 2023 meta-analysis pooled that trial with two other 8-week trials, 223 people in all, and found average falls of 3.45 mmHg systolic and 2.32 mmHg diastolic (Li 2023).

Against that, a 3-year trial in 265 adults with a median age of 65.3 found no significant effect on blood pressure (Hodis 2021). Nattokinase also lengthens clotting times, which matters because many people with high blood pressure take aspirin or anticoagulants. We rate it mixed: a possible small add-on for mild hypertension in someone not taking blood thinners, and no substitute for treatment.

Nattokinase (subtilisin NAT) is a protein-digesting enzyme made by the bacterium that ferments soybeans into natto. After a single 2,000 FU capsule it was detectable in the blood of 11 healthy volunteers, peaking at about 13.3 hours (Ero 2013). In 12 healthy young men, one 2,000 FU dose raised markers of clot breakdown (D-dimer and fibrin degradation products) and lengthened clotting time, though all values stayed within the normal range (Kurosawa 2015).

Taken daily, it lowers clotting factors. In an open-label study without a control group, 4,000 FU a day for 2 months lowered fibrinogen by 7-10% and factor VIII by 17-19% (Hsia 2009). In spontaneously hypertensive rats, high-dose nattokinase lowered blood pressure together with plasma fibrinogen, without changing renin or ACE activity (Fujita 2011). Thinner, less sticky blood is one proposed route to lower pressure.

There is a second lead. In the test tube, nattokinase and its breakdown peptides inhibit angiotensin-converting enzyme (ACE), the target of ACE-inhibitor medicines, and heat-treated enzyme inhibited it more (Murakami 2012). In rats, nattokinase fragments with no enzyme activity lowered blood pressure and angiotensin II (Fujita 2011). The two human trials disagree on renin, the hormone upstream of ACE: it fell in the Korean trial (Kim 2008) and rose in some low-renin participants in the North American one (Jensen 2016).

So the mechanisms are plausible but unconnected to a reliable effect in people. They come from laboratory and animal work at doses that don't translate directly to a capsule, and the same clot-dissolving action that might help blood flow is what creates the bleeding risk.

Both main blood pressure trials used 2,000 FU (fibrinolytic units, a measure of clot-dissolving activity) once a day for 8 weeks (Kim 2008; Jensen 2016). In the North American trial that was a 100 mg capsule standardised to at least 2,000 FU, but milligrams don't translate across products, so the FU figure on the label is what to compare.

Higher doses have been used for other purposes. A Chinese study of 1,062 people reported benefits for atherosclerosis and cholesterol at 10,800 FU a day for 12 months, and none at 3,600 FU (Chen 2022). One of the three trials pooled for blood pressure used 6,000 FU a day, according to the meta-analysis's study table (Li 2023), but nobody has shown that more nattokinase lowers blood pressure more, and higher doses mean more effect on clotting.

Kim 2008 randomised 86 Korean adults aged 20-80 with untreated systolic pressure of 130-159 mmHg to nattokinase 2,000 FU or placebo for 8 weeks; 73 completed. Systolic pressure fell 5.55 mmHg more than with placebo (95% CI -10.5 to -0.57) and diastolic 2.84 mmHg more (95% CI -5.33 to -0.33), both p < 0.05.

Jensen 2016 enrolled 79 North American adults with systolic pressure of at least 130 or diastolic of at least 90 mmHg, and 74 completed 8 weeks. Diastolic pressure fell from 87 to 84 mmHg with nattokinase and stayed at 87 mmHg with placebo (P < 0.05), with a larger drop in men (86 to 81 mmHg). Systolic pressure fell from 144 to 140 mmHg, only a statistical trend (P < 0.1). The study was sponsored by the US distributor of the product it tested.

A 2023 meta-analysis of six randomised trials (546 people) pooled blood pressure from three of them, Kim 2008, Jensen 2016 and an 8-week Korean trial in people with high cholesterol (Yoo 2019): 223 participants. Nattokinase lowered systolic pressure by 3.45 mmHg and diastolic by 2.32 mmHg versus placebo, and no notable adverse events were reported (Li 2023). That is a small effect from small, short trials.

The largest and longest trial found nothing. In the Nattokinase Atherothrombotic Prevention Study, 265 adults with a median age of 65.3 and no cardiovascular disease took 2,000 FU or placebo for a median of 3 years. Nattokinase had no significant effect on blood pressure, any laboratory measure, or the main outcome, thickening of the carotid artery walls (Hodis 2021). Its participants weren't selected for high blood pressure, which may explain part of the gap, but it means the short-term falls haven't been shown to last.

In a 90-day trial in 178 Chinese patients with stable coronary artery disease, systolic pressure fell in every group, including placebo (-3.78 mmHg) and nattokinase alone at about 3,600 FU a day (-6.33 mmHg). Only nattokinase combined with red yeast rice lowered diastolic pressure (-7.39 mmHg) (Liu 2024). The trial was funded by a supplement company's research foundation.

No trial has measured strokes, heart attacks or deaths, none has tested nattokinase on top of blood pressure medicines in people with uncontrolled hypertension, and the trials designed around blood pressure lasted only 8 weeks.

In the blood pressure trials nattokinase was well tolerated, and the meta-analysis found no notable adverse events (Li 2023). The real concern is bleeding. In 100 adults with high cholesterol, 8 weeks of nattokinase lengthened platelet closure time (P = 0.001) and activated partial thromboplastin time, a clotting test (P = 0.016), more than placebo (Yoo 2019). Even one 2,000 FU dose lengthened clotting time in healthy men, though within the normal range (Kurosawa 2015).

Case reports show what can go wrong. A patient taking aspirin after a stroke had a bleed in the cerebellum after 7 days of nattokinase 400 mg a day, and MRI showed multiple small old bleeds in the brain (Chang 2008). Another patient with a mechanical heart valve swapped warfarin for nattokinase and, nearly a year later, needed the valve replaced because of a clot on it (Elahi 2015). Nattokinase is not an anticoagulant you can substitute for a prescribed one.

The measures with the best evidence are the ones in standard care. NHLBI recommends a heart-healthy eating plan such as DASH, noting that DASH combined with a low-salt diet can be as effective as medicines; limiting alcohol; regular physical activity, even 10 minutes of walking a day; losing 3-5% of body weight if you're overweight; quitting smoking; managing stress; and 7-9 hours of sleep (NHLBI). When lifestyle changes aren't enough, ACE inhibitors, angiotensin receptor blockers, calcium channel blockers and thiazide diuretics are the next step, and many people need two or more.

Among supplements, potassium for high blood pressure and garlic extract are better studied than nattokinase.

The interactions that matter all involve clotting. Nattokinase lengthens clotting times on its own (Yoo 2019), so it adds to the effect of anticoagulants and antiplatelet drugs; a review of anti-atherosclerotic supplements notes that bleeding risk and drug interactions may limit its use (Dobre 2025). Natto the food interacts with warfarin in the opposite direction, by raising vitamin K levels (Kudo 1990).

Products are made from fermented soy, so people with a soy allergy should check the source with their clinician. Combinations with red yeast rice have been tested in trials, but red yeast rice carries its own interactions.