Nattokinase: What the Research Actually Shows

Human evidence for nattokinase is limited and mostly drawn from small, short trials, so its claimed benefits should be read with caution rather than treated as settled.

The short answer

Nattokinase is an enzyme extracted from natto, a traditional Japanese food made by fermenting soybeans with the bacterium Bacillus subtilis var. natto. In a test tube it breaks down fibrin, the protein that forms the structural mesh of a blood clot, which is why it is marketed for "circulation", "clot support" and cardiovascular health [Sumi 1987].

What the human evidence actually shows is more modest. The clearest finding is a small reduction in blood pressure in short trials, summarised in one meta-analysis of six randomised trials [Li 2023]. A handful of small studies also report changes in clotting markers such as fibrinogen [Hsia 2009]. Beyond that, much of the supporting work is in cells, animals or short studies with surrogate measures rather than long-term health outcomes. No trial has shown that nattokinase prevents heart attacks, strokes or deaths, and it should not be treated as a substitute for any prescribed medicine.

The most important practical point is safety: because nattokinase can affect clotting, it carries a plausible bleeding risk and may interact with anticoagulant and antiplatelet drugs. That risk deserves more attention than most of the marketing gives it.

What nattokinase is

Natto has been eaten in Japan for centuries. In 1987 the researcher Hiroyuki Sumi isolated a fibrinolytic (clot-dissolving) enzyme from it and named it nattokinase [Sumi 1987]. Chemically it is a serine protease, closely related to subtilisin, produced as the bacteria ferment the beans [Wu 2009].

A few defining features:

• It is an enzyme, not a vitamin or mineral. The supplement is typically the purified protein rather than whole natto.
• Doses are usually expressed in fibrinolytic units (FU), a measure of clot-dissolving activity, not in milligrams alone. Common supplement doses sit around 2,000 FU per capsule, with study doses ranging up into the 10,000 FU range per day.
• Quality and potency vary between products, because FU labelling is not tightly standardised across manufacturers. This is a recurring problem with enzyme supplements and one reason published doses are hard to translate to a shop shelf. For background on why this matters, see our note on how supplements are regulated.

One detail worth flagging: whole natto is also very high in vitamin K2, which can interfere with warfarin. Purified nattokinase supplements are supposed to have the vitamin K removed, but this is not guaranteed across all products.

The claims made for it

Marketing for nattokinase tends to cluster around three areas:

• Fibrinolytic / "clot dissolving" — the idea that it thins the blood or breaks down existing clots.
• Cardiovascular — broad claims about heart health, circulation and arterial plaque.
• Blood pressure — claims that it lowers blood pressure.

These claims are not equally supported. The honest position is that the blood-pressure signal is the best evidenced, the clotting-marker effects are biologically plausible and partly measured, and the bigger cardiovascular outcome claims are not established in humans. Separating a measured surrogate from a real-world benefit is exactly the kind of step where supplement marketing tends to overreach, something we cover in how "evidence-based" gets misused.

What the human evidence shows

The honest summary is that human trials are few, small and short, and most measure surrogate markers rather than clinical events.

Blood pressure. The strongest signal. A 2023 systematic review and meta-analysis pooled six randomised controlled trials with 546 participants in total [Li 2023]. It reported a statistically significant reduction in systolic blood pressure (about 3 to 4 mmHg) and diastolic blood pressure (about 2 mmHg) versus placebo. The authors rated the included studies as reasonably high quality, but six small trials is a thin base, and a 3 mmHg average reduction is real but modest. The review framed nattokinase as a possible adjunct, not a replacement, for hypertension management.

Clotting markers. An open-label, self-controlled study of 45 people across healthy, cardiovascular-risk and dialysis groups gave 4,000 FU daily for two months and reported falls in fibrinogen, factor VII and factor VIII of roughly 7 to 19 per cent [Hsia 2009]. The lack of a randomised placebo group is an important limitation, and these are blood markers, not patient outcomes. A separate single-dose study in healthy adults found short-term changes in fibrinolysis and anticoagulation markers, including D-dimer, after one oral dose [Kurosawa 2015]. Again, these are mechanistic markers measured over hours, not evidence of clinical benefit.

Lipids and combination products. Nattokinase alone has not shown a reliable cholesterol-lowering effect; the 2023 meta-analysis found low-dose nattokinase had no significant lipid effect [Li 2023]. A 2024 randomised, double-blind, placebo-controlled trial in 178 people with stable coronary artery disease tested nattokinase, red yeast rice, both together, or placebo over 90 days [Liu 2024]. The clearest lipid and blood-pressure improvements came from the combination, and red yeast rice contains monacolin K, which is chemically equivalent to the statin lovastatin. So that trial does not cleanly isolate a nattokinase effect on lipids.

It is worth being clear about what is missing. There are no large, long-term trials showing nattokinase reduces heart attacks, strokes or death. The trials that exist are short (weeks to months), modest in size, and rely on surrogate endpoints. For why this pattern is so common in nutrition, see why nutrition research is hard and how to read a clinical trial.

What is preclinical only

A good deal of the enthusiasm rests on laboratory and animal work, which is useful for understanding mechanism but does not establish that something works or is safe in people.

• In test tubes, nattokinase degrades fibrin directly and inhibits platelet aggregation, reducing thromboxane formation [Jang 2013, Ren 2018].
• In rats, oral nattokinase delayed chemically induced arterial clotting in a dose-dependent way, with high doses comparable to aspirin in that specific model [Jang 2013].
• Broader cardiovascular claims, including effects on arterial plaque, draw heavily on this animal and cell evidence plus observational data [Ren 2018].

These findings are genuinely interesting, but the leap from a rat carotid-artery model to "good for your heart" in humans is exactly the leap that the human trials have not yet made.

Safety and interactions

This is the section that matters most, and the one most often glossed over.

The mechanism that makes nattokinase interesting, its effect on clotting, is also the source of its main risk. If a substance plausibly reduces clotting, it plausibly increases bleeding.

• Bleeding risk. A published case report describes a patient on aspirin (for stroke prevention) who developed a cerebellar haemorrhage after taking nattokinase 400 mg daily for a week; the patient had pre-existing cerebral microbleeds [Chang 2008]. This is a single case, not proof of a population-level hazard, but it is a clear warning signal for the combination of nattokinase with antiplatelet or anticoagulant therapy.
• Anticoagulant and antiplatelet drugs. Nattokinase should be used with great caution, if at all, alongside warfarin, direct oral anticoagulants (such as apixaban or rivaroxaban), aspirin, clopidogrel or other agents that affect clotting. The combined effect on bleeding is not well quantified, and any use in this situation should be supervised by a clinician.
• Warfarin and vitamin K. Whole natto is very high in vitamin K2 and can interfere with warfarin. Purified supplements are meant to have vitamin K removed, but this is not guaranteed across products, adding another reason for caution if you take warfarin.
• Surgery and procedures. Because of the theoretical bleeding risk, it is sensible to stop nattokinase well before any planned surgery or dental procedure and to tell your medical team you have been taking it.
• General tolerability. In the short trials conducted, no serious adverse events were attributed to nattokinase, and a toxicological assessment of nattokinase derived from Bacillus subtilis var. natto did not identify major toxicity concerns in the doses studied [Lampe 2016, Li 2023]. That is reassuring as far as it goes, but these were short studies in selected participants and do not capture rare events or long-term use.
• Who should avoid it. People with bleeding disorders, those on the medicines above, anyone scheduled for surgery, and people who are pregnant or breastfeeding (where evidence is absent) should not take nattokinase without specific medical advice.

The bottom line

Nattokinase is a real enzyme with a plausible biological mechanism and a small, mostly short body of human research. The best-supported finding is a modest reduction in blood pressure in small randomised trials, where it has been framed as a possible adjunct rather than a treatment [Li 2023]. There are also preliminary changes in clotting markers [Hsia 2009, Kurosawa 2015], but these are surrogate measures, not demonstrated health outcomes.

What the evidence does not support is the bigger framing it is often sold under: that it meaningfully dissolves clots in people, clears arterial plaque, or prevents cardiovascular events. None of that has been shown in robust human trials.

The risk side deserves equal weight. A supplement that influences clotting can increase bleeding, and the documented case of haemorrhage in combination with aspirin is a reminder that the interaction with blood-thinning medicines is not theoretical [Chang 2008].

If you are considering nattokinase, treat it as a low-evidence supplement rather than a proven therapy, and do not start it, or stop any prescribed medicine for it, without speaking to a clinician first, particularly if you take anticoagulants or antiplatelet drugs or have surgery coming up.

Related Proco pages

• How supplements are regulated
• Why nutrition research is hard
• How to read a clinical trial
• How "evidence-based" gets misused

Sources

Talk to a clinician before taking nattokinase, especially if you take blood thinners, antiplatelet drugs or have surgery planned.