Can This Fermented Dish Prevent Heart Attacks and Strokes?

Edited and approved by Stephen C. Rose, Phd, MS

Nattokinase sounds like a lab-made drug, but it starts in a very ordinary place: natto, the sticky fermented soybean food popular in Japan. During fermentation, Bacillus subtilis var. natto produces an enzyme that can break down fibrin, one of the protein threads that helps blood clots hold together. That basic fact explains why nattokinase has attracted so much attention for heart and blood-vessel health. It also explains why the claims around it need careful handling. An enzyme that nudges clotting biology is not the same thing as a proven replacement for aspirin, statins, blood-pressure medicine, or anticoagulants [1].

The easiest way to picture fibrin is as a mesh. When the body needs to stop bleeding, fibrin helps form a net over the injury. Later, the body uses a cleanup system called fibrinolysis to dissolve that net. Early human and animal work suggested that oral nattokinase, or natto itself, could mildly increase fibrinolytic activity in blood, including signs related to tissue plasminogen activator, one of the body's clot-dissolving tools [2]. That is biologically interesting, but it is not proof that a supplement prevents heart attacks or strokes.

So where is the evidence strongest? At the moment, the most consistent human signal is blood pressure, not cholesterol or plaque. A 2023 systematic review and meta-analysis of randomized controlled trials found that nattokinase was associated with modest reductions in systolic and diastolic blood pressure, while lipid findings were mixed and did not support a clear triglyceride benefit [3]. In plain English, the randomized evidence suggests a small blood-pressure effect may be real, but the cholesterol story is still unsettled.

That distinction is important because cardiovascular marketing often mashes very different outcomes together. Lowering a marker, such as fibrinogen or systolic blood pressure, is not the same as proving fewer heart attacks. Improving an ultrasound measurement is not the same as proving longer life. Researchers often start with markers because they are easier and cheaper to measure, but the most meaningful cardiovascular questions require large trials that track real events over time. For nattokinase, that event-level evidence is not yet available.

Chen and colleagues reviewed records from 1,062 adults in China who took nattokinase for 12 months, mostly at 10,800 fibrinolytic units, or FU, per day. The study reported lower triglycerides, total cholesterol, and LDL cholesterol, higher HDL cholesterol, thinner carotid artery intima-media measurements, and smaller carotid plaques after supplementation [4]. Those are impressive numbers, especially because carotid measurements are closer to artery health than a simple cholesterol panel.

But study design matters. This was a retrospective study, meaning the researchers looked back at existing records instead of randomly assigning people to nattokinase or placebo. Without randomization, it is harder to know whether nattokinase caused the improvements. Diet changes, exercise, medication use, better follow-up, and the fact that people with worse starting numbers have more room to improve can all bend the results. The authors themselves called for randomized trials using higher doses [4]. The fair label for this evidence is promising but not established.

That caution becomes even more important when you compare the 2022 study with a randomized trial published in 2021. In that double-blind trial, 265 adults without clinical cardiovascular disease were assigned to 2,000 FU of nattokinase or placebo. The investigators did not find that nattokinase slowed progression of subclinical atherosclerosis or improved a broad set of atherothrombotic biomarkers in that lower-risk group [5]. This does not prove nattokinase never works. It does show that dose, population, baseline risk, and study design may change the answer.

Dose is one of the unresolved issues. Many commercial products provide about 2,000 FU per day, which is the dose used in several trials. The retrospective 2022 study reported its strongest findings at 10,800 FU per day and found little effect in a smaller group taking 3,600 FU [4]. That does not automatically mean more is better. It means the field has not nailed down a dependable effective dose, an upper safe dose for different patient groups, or whether any benefit plateaus. Higher doses also make drug interactions more important, not less.

Blood pressure studies are more encouraging, although still modest. In a randomized, controlled trial of 86 adults with prehypertension or stage 1 hypertension, 2,000 FU daily for eight weeks lowered systolic blood pressure more than placebo, with a smaller effect on diastolic pressure [6]. A single-dose study also found short-term changes in fibrinolysis and coagulation markers after 2,000 FU, including changes in D-dimer and clotting-related measures [7]. These marker changes help explain why researchers remain interested in nattokinase, but markers are not the same as fewer strokes or heart attacks.

Safety deserves its own paragraph because nattokinase is often marketed as natural and therefore gentle. Natural does not mean risk-free. The 2022 retrospective study reported no noticeable adverse effects at 10,800 FU per day, and several smaller studies have not flagged major short-term problems [4]. Still, nattokinase affects clot-related pathways, so people taking anticoagulants, antiplatelet drugs, aspirin, or preparing for surgery should treat it as a conversation for a clinician, not a casual add-on. A published case report described a patient with a mechanical aortic valve who substituted nattokinase for warfarin and developed valve thrombosis requiring repeat valve surgery [8]. The lesson is straightforward: nattokinase is not a substitute for prescribed blood thinners.

There is also a soy angle. Natto is a food made from soybeans, so people with soy allergy should avoid natto-derived products unless a clinician says otherwise. Vitamin K is another source of confusion. Natto food is rich in a type of vitamin K called K2 M-7, while purified nattokinase supplements may contain little or none depending on manufacturing. That matters because vitamin K can interfere with warfarin management, while nattokinase raises different clotting questions. Consumers should not assume that natto, vitamin K2, and purified nattokinase have identical effects.

Another practical issue is product quality. In the United States, dietary supplements are regulated differently from drugs. The FDA does not approve dietary supplements for safety and effectiveness before they are sold, and products marketed to treat, prevent, cure, or diagnose disease can cross into drug-claim territory [9]. For consumers, that means labels, doses, and enzyme activity can be harder to interpret than prescription medications. FU is a measure of enzyme activity, not simply milligrams of powder, so two bottles with similar capsule weights may not be equivalent.

What should a careful consumer take from all this? Nattokinase is a plausible cardiovascular supplement with a real biochemical basis. The strongest current human evidence points to modest blood-pressure effects. Evidence for lowering cholesterol or reducing carotid plaque is intriguing but not settled, especially because the most dramatic results come from retrospective or non-placebo-controlled settings. The evidence for preventing heart attacks, strokes, or dangerous clots is uncertain because those outcomes require large, long-term trials.

A useful way to rank the claims is like a traffic light. Green, or reasonably supported, is the idea that nattokinase can affect fibrin-related biology. Yellow, or possible but still uncertain, is a modest benefit for blood pressure and perhaps selected lipid or artery markers in some groups. Red, or not proven, is the claim that nattokinase prevents cardiovascular events or can replace prescription therapy. That traffic-light view keeps the science useful without turning preliminary findings into promises.

If someone is healthy, curious, and not taking blood-thinning medication, nattokinase may be worth discussing with a health professional, especially if blood pressure is borderline. If someone has cardiovascular disease, a stent, atrial fibrillation, a clotting disorder, a mechanical valve, upcoming surgery, pregnancy, or a prescription for aspirin, clopidogrel, apixaban, rivaroxaban, warfarin, or similar drugs, the risk-benefit calculation changes. In those cases, using nattokinase without medical guidance is not evidence-based self-care; it is experimenting with clotting biology.

The bottom line is balanced, not dramatic. Nattokinase is not snake oil, but it is also not a proven cardiovascular treatment. It sits in the middle: biologically active, supported by some human trials, contradicted or limited by others, and still waiting for better dose-finding and outcome studies. Until that evidence arrives, the most accurate claim is that nattokinase may modestly improve some cardiovascular risk markers, particularly blood pressure, but it should not replace established medical treatment or the basics that consistently move risk: not smoking, regular activity, blood-pressure control, lipid management, diabetes care, sleep, and a high-quality diet.

References

1. Chen H, McGowan EM, Ren N, Lal S, Nassif N, Shad-Kaneez F, et al. Nattokinase: a promising alternative in prevention and treatment of cardiovascular diseases. Biomark Insights. 2018;13:1177271918785130.
2. Sumi H, Hamada H, Nakanishi K, Hiratani H. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematol. 1990;84(3):139-143.
3. Li X, Long J, Gao Q, Pan M, Wang J, Yang F, et al. Nattokinase supplementation and cardiovascular risk factors: a systematic review and meta-analysis of randomized controlled trials. Rev Cardiovasc Med. 2023;24(8):234.
4. Chen H, Chen J, Zhang F, Li Y, Wang R, Zheng Q, et al. Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: a clinical study with 1,062 participants. Front Cardiovasc Med. 2022;9:964977.
5. Hodis HN, Mack WJ, Meiselman HJ, Kalra V, Liebman H, Hwang-Levine J, et al. Nattokinase atherothrombotic prevention study: a randomized controlled trial. Clin Hemorheol Microcirc. 2021;78(4):339-353.
6. Kim JY, Gum SN, Paik JK, Lim HH, Kim KC, Ogasawara K, et al. Effects of nattokinase on blood pressure: a randomized, controlled trial. Hypertens Res. 2008;31(8):1583-1588.
7. Kurosawa Y, Nirengi S, Homma T, Esaki K, Ohta M, Clark JF, et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep. 2015;5:11601.
8. Elahi MM, Choi CH, Konda S, Shake JG. Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis. Proc (Bayl Univ Med Cent). 2015;28(1):81-82.
9. U.S. Food and Drug Administration. FDA 101: Dietary Supplements.