Nattokinase for Atherosclerosis

The short answer: nattokinase has not been shown to slow or reverse atherosclerosis. In the Nattokinase Atherothrombotic Prevention Study, 265 adults with a median age of 65.3 and no cardiovascular disease took 2,000 FU (fibrinolytic units) or a matching placebo. After a median of 3 years, the yearly change in carotid intima-media thickness (CIMT, the thickness of the artery wall on ultrasound) and in carotid stiffness did not differ between the groups (Hodis 2021).

The encouraging numbers come from weaker designs. A 26-week trial in 82 patients compared 6,000 FU a day with simvastatin 20 mg rather than placebo, and reported plaque shrinking more with nattokinase (Ren 2017). A review of the records of 1,062 people, most of whom took 10,800 FU a day, reported plaques 36% smaller after 12 months, but it had no placebo or untreated control group, the same research group ran it, and five authors worked for the tablet's manufacturer (Chen 2022). Without a placebo group, neither can show the change came from nattokinase.

Nattokinase is a protein-digesting enzyme from Bacillus subtilis, the bacterium in natto, a traditional Japanese soy food (Hsia 2009; Nagata 2017). It is described as a clot-dissolving (fibrinolytic) and antithrombotic agent (Chen 2022). In 12 healthy young men, a single 2,000 FU dose raised markers of clot breakdown and lengthened a clotting test, though all values stayed in the normal range (Kurosawa 2015).

Taken daily, it may lower clotting factors. In an open-label study without a control group, 45 adults took 4,000 FU a day for 2 months; fibrinogen fell 7-10%, factor VII 7-14% and factor VIII 17-19%, depending on the group, while blood lipids did not change (Hsia 2009).

Over 3 years against placebo, nattokinase had no significant effect on any laboratory measure, including blood flow properties, coagulation and fibrinolysis factors, inflammatory markers and monocyte and macrophage (immune cell) activation markers (Hodis 2021). So the clotting-factor falls in the short uncontrolled study did not show up long term, although short placebo-controlled studies did find clotting tests lengthened (Kurosawa 2015; Yoo 2019).

Cholesterol is no clearer. A meta-analysis of six randomised trials (546 people) found that lower total doses of nattokinase were linked to higher total and LDL cholesterol and lower HDL cholesterol than placebo, and higher doses to higher total cholesterol than control treatments (Li 2023). The large lipid falls reported at 10,800 FU a day come from the uncontrolled records review (Chen 2022).

No dose of nattokinase has been shown to help atherosclerosis. The placebo-controlled trial used 2,000 FU a day for a median of 3 years and found no effect (Hodis 2021). The statin-comparison trial used 6,000 FU a day for 26 weeks (Ren 2017), and the records review 10,800 FU a day for 12 months, reporting no change at 3,600 FU a day (Chen 2022). The combination trial used a product stated to contain 2,500 FU of nattokinase and 7 mg of lovastatin from red yeast rice (Liu 2023).

The trials dosed nattokinase by activity in FU, so the FU figure on a label is the one to compare. The placebo-controlled trials that measured artery thickness used about 2,000-2,500 FU. A 90-day placebo-controlled trial in coronary artery disease used about 3,600 FU a day but measured blood markers only (Liu 2024), so no dose has been shown to benefit plaque.

Hodis 2021 randomised 265 adults with a median age of 65.3 and no clinical cardiovascular disease to nattokinase 2,000 FU or a matching placebo, double-blind. The primary outcome was the rate of change in carotid intima-media thickness and carotid arterial stiffness, measured by ultrasound every 6 months. After a median of 3 years, neither rate differed between the groups, and nattokinase had no significant effect on blood pressure or any laboratory measure. The authors call it a null effect on subclinical atherosclerosis in healthy people at low cardiovascular risk.

That last point is the main limit: the trial tells us about prevention in low-risk people, not about people who already have plaque. No placebo-controlled trial has measured plaque or artery thickness with nattokinase alone in people with established atherosclerosis.

Ren 2017 randomly assigned 82 patients from a Chinese hospital clinic to nattokinase 6,000 FU a day or simvastatin 20 mg for 26 weeks; 76 completed. Carotid intima-media thickness and plaque size fell from baseline in both groups, and plaque size fell 36.6% with nattokinase versus 11.5% with the statin (P < 0.01). The statin lowered total cholesterol, LDL cholesterol and triglycerides more (P < 0.05), while nattokinase raised HDL cholesterol. There was no placebo group.

Chen 2022 looked back at the records of 1,062 adults with high cholesterol (average age 67.5); 1,001 took 10,800 FU a day for 12 months and 61 took 3,600 FU for comparison. In the 683 with atherosclerosis, average common carotid intima-media thickness fell from 1.33 to 1.04 mm and plaque size by 36%. The authors state it was retrospective, not a randomised controlled trial; some participants also took vitamin K2 (181) or aspirin (96); and five authors were employed by the tablet's manufacturer. It comes from the same research group as Ren 2017, so the positive findings lack independent replication.

Liu 2023 randomised 113 adults aged 30-70 with abnormal blood lipids to a nattokinase and red yeast rice product or placebo for 120 days, double-blind. It lowered total cholesterol by 0.52 mmol/L and LDL cholesterol by 0.43 mmol/L more than placebo, but carotid intima-media thickness did not differ. The cholesterol fall can't be credited to nattokinase, because the product also supplied lovastatin, a statin. A 90-day placebo-controlled trial in 178 patients with stable coronary artery disease tested about 3,600 FU of nattokinase a day, alone and with red yeast rice. It measured blood markers, not plaque: lactate dehydrogenase improved more with nattokinase alone or combined than in the other groups, and no adverse effects were reported (Liu 2024).

No trial has measured heart attacks, strokes or deaths. The closest evidence is about the food: in a Japanese study of 29,079 adults followed for 16 years, those who ate the most natto had a lower risk of dying from cardiovascular disease than those who ate the least (hazard ratio 0.75) (Nagata 2017). That is an observational link with a food, not a test of nattokinase capsules.

In trials nattokinase was generally well tolerated: a meta-analysis found no notable adverse events (Li 2023), and the red yeast rice combination trial found no intervention-related adverse events or changes in coagulation tests (Liu 2023). The 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).

Case reports show the risks. 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 microbleeds, tiny traces of past bleeding in the brain (Chang 2008). Another patient replaced warfarin with nattokinase after a mechanical aortic valve replacement, and after nearly a year developed a clot on the valve that needed repeat surgery (Elahi 2015).

NHLBI's treatment advice for atherosclerosis starts with a heart-healthy lifestyle: an eating plan such as DASH, at least 150 minutes a week of moderate activity, quitting smoking, 7-9 hours of sleep, and losing 3-5% of body weight if needed. Medicines include statins and other cholesterol drugs, blood pressure medicines and, for some people, antiplatelet drugs. NHLBI notes that atherosclerosis can sometimes be reversed over time with lifestyle changes and medicines (NHLBI).

If you are weighing supplements, the evidence is thin across the board. The site's page on vitamin K2 for atherosclerosis covers another option with mixed trial results, and the high cholesterol page covers the cholesterol evidence.

The interactions that matter involve clotting. Nattokinase lengthens clotting times on its own (Yoo 2019), so it can add to anticoagulants and antiplatelet drugs; a 2025 review of anti-atherosclerotic supplements notes that bleeding risk or drug interactions may limit its use, and flags bleeding concerns with omega-3, garlic and ginkgo too (Dobre 2025).

Combination products need a second look. The nattokinase and red yeast rice product in the combination trial supplied lovastatin, a statin (Liu 2023), and NHLBI notes an FDA warning about some red yeast rice products (NHLBI). Check with your prescriber before combining such a product with a prescribed statin.

Natto the food is a separate issue: it is high in vitamin K (about 850 mcg as MK-7 in 3 ounces), and people taking warfarin need a consistent vitamin K intake because sudden changes can strengthen or weaken its effect (NIH ODS).