Nattokinase: Evidence, Risks and How It Differs From K2

Disclaimer: This article is for information only and is not medical advice. Nattokinase may affect blood clotting, and vitamin K2 can interfere with warfarin. Ask your clinician before taking nattokinase if you take blood thinners or antiplatelet drugs, have a bleeding disorder, are pregnant, or have surgery coming up. BiohackList may earn commissions from qualifying purchases in the future (disclosure).

Safety first. If you take a blood thinner or antiplatelet drug, have a bleeding disorder, or have surgery coming up, don't take nattokinase without your clinician's advice. Never use it to replace a prescribed anticoagulant.

Nattokinase is an enzyme made by the bacteria that ferment natto, and it is not vitamin K2, a vitamin found in the same food. Its human studies are small and short, and we found none showing that it prevents heart attacks or strokes.

In the US, nattokinase is sold as a dietary supplement. The FDA says it doesn't have the authority to approve dietary supplements for safety and effectiveness before they are sold, Nattokinase isn't approved to treat or prevent any condition.

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What nattokinase is

Nattokinase is a protein-digesting enzyme produced by Bacillus subtilis var. natto, the bacterium used to ferment soybeans into natto, a traditional Japanese food. In lab tests it breaks down fibrin, the protein mesh that holds blood clots together. Brands market it for circulation: Doctor's Best, for example, says on its product page that it "helps support the circulatory system".

Supplements list nattokinase activity in fibrinolytic units (FU), a measure of how much fibrin the enzyme breaks down in a lab assay. Milligrams alone don't tell you the activity, because enzyme preparations vary.

One branded ingredient, NSK-SD, is the form used in several trials below: a fermented soybean extract with vitamin K2 removed.

Nattokinase vs vitamin K2 (MK-7): same food, different molecules

Why the warfarin interaction runs both ways

Warfarin works by blocking the recycling of vitamin K. The NIH Office of Dietary Supplements says people on warfarin need a consistent vitamin K intake, because changes in intake shift the drug's effect.

A 2013 study in Journal of Thrombosis and Haemostasis tested MK-7 in healthy volunteers taking acenocoumarol, a drug in the same class as warfarin (vitamin K antagonists). Of 18 enrolled, 15 reached the target INR and went on to MK-7. At 45 mcg a day, the group's average INR, the standard blood test of anticoagulation, fell by about 40%, and uncarboxylated factor II, an inactive form of the clotting protein prothrombin, also fell by about 40%. At lower doses, two hematologists judged each person's INR and found a clinically relevant drop in at least 40% of participants at 10 mcg a day and at least 60% at 20 mcg a day. The authors concluded that MK-7 supplements "need to be avoided in patients receiving VKA therapy."

Nattokinase may push the other way: a small study found clotting markers shifted after a single dose, and case reports describe bleeding when it was combined with other drugs.

Combined products and vitamin K supplements

Some products combine nattokinase and vitamin K2, so read labels closely and ask a clinician before using one. A vitamin K supplement, including one sold as "full-spectrum", provides the vitamin (K1, MK-4 or MK-7, per NIH) and contains no nattokinase unless the label lists it.

Nattokinase benefits: what the studies show

Blood pressure (8 weeks). A 2016 trial in Integrated Blood Pressure Control gave 100 mg a day of NSK-SD (K2 removed) or placebo to North American adults screened for elevated blood pressure (systolic 130 or higher, or diastolic 90 or higher). Of 79 enrolled, 74 finished. These are average before and after values within each group. Diastolic pressure fell from 87 to 84 mmHg in the nattokinase group and stayed at 87 mmHg in the placebo group, a difference the authors reported as statistically significant. Among men in the nattokinase group, it fell from 86 to 81 mmHg. A drop in von Willebrand factor, a clotting protein, in women didn't reach standard statistical significance. The authors worked at a contract research organization.

Clotting markers (one dose). A 2015 study in Scientific Reports gave 12 healthy young men a single 2,000 FU dose of NSK-SD. Markers of clot breakdown (D-dimer and fibrin degradation products) rose over the next several hours, factor VIII fell, and a clotting time test (aPTT) lengthened. All values stayed within normal ranges.

Atherosclerosis (3 years). The largest and longest trial, published in 2021, randomized 265 adults (median age 65) without heart disease to 2,000 FU a day or placebo for a median of 3 years. It found no difference in carotid artery wall thickening or arterial stiffness, and no effect on blood pressure or the lab markers measured.

Pooled evidence. A 2023 meta-analysis in Reviews in Cardiovascular Medicine combined 6 studies with 546 participants, using 1,200 to 8,000 FU a day. Compared with placebo, systolic pressure was about 3.5 mmHg lower and diastolic about 2.3 mmHg lower. It also found a slight rise in blood glucose and higher total cholesterol in some analyses. Trials reported no notable adverse events, but the authors flagged published case reports of bleeding and allergy.

What's missing: we found no trial showing that nattokinase prevents heart attacks, strokes or dangerous clots. Treat it as an experimental supplement, not a substitute for proven therapy.

Nattokinase side effects and who should avoid it

The main safety concern is bleeding, and case reports show what can go wrong.

• Brain bleed with aspirin. A 2008 case report in Internal Medicine described a cerebellar hemorrhage in a patient who took 400 mg of nattokinase a day for a week while also taking aspirin. The patient had small preexisting bleeds in the brain.
• Valve clot after stopping warfarin. A 2015 case report described a patient with a mechanical aortic valve who replaced warfarin with nattokinase. About a year later, a clot formed on the valve and the patient needed a second valve replacement.
• Allergy. The 2023 meta-analysis cites reports of allergic reactions, including anaphylaxis in a person allergic to natto.

The EU's position. The European Food Safety Authority (EFSA) reviewed NSK-SD in 2016 and concluded it was safe for adults at up to 100 mg a day under the proposed conditions of use. When the EU authorized it in 2017, it excluded pregnant and breastfeeding women and required labels to state that people taking medication should use it only under medical supervision.

Who should avoid nattokinase unless a clinician advises otherwise:

• People taking anticoagulants (warfarin, apixaban, rivaroxaban, dabigatran) or antiplatelet drugs (aspirin, clopidogrel).
• People with a bleeding disorder or a history of bleeding in the brain.
• Anyone with surgery or dental work coming up. ConsumerLab notes nattokinase may increase bleeding from trauma or surgery.
• Pregnant or breastfeeding women.
• People with a soy allergy, if the product contains soy. Doctor's Best, for example, lists "Contains Soy".
• People on blood pressure medicines, where ConsumerLab advises caution.

Fish oil and other supplements. The NIH Office of Dietary Supplements says fish oil can have antiplatelet effects at high doses and might prolong clotting times when taken with warfarin, though most research found 3 to 6 g a day didn't significantly affect anticoagulation. If you already take fish oil, ask your clinician before adding nattokinase.

How to read a nattokinase label

• FU, not just mg. ConsumerLab recommends a product that lists enzyme activity in FU, and suggests at least 1,000 to 2,000 FU per unit.
• K2 status. Look for "vitamin K2 removed" or "K2-free" if you want nattokinase alone.
• Ingredient name. NSK-SD is the branded form used in several trials.
• Allergens. Check for soy.
• Independent testing. Of 8 products ConsumerLab tested in 2025 (review updated March 16, 2026), 5 provided their listed enzyme activity within a reasonable margin, while 2 provided much less and 1 much more.
• Warnings. Look for a label that warns against use with anticoagulants and in pregnancy.

The best nattokinase supplements (how we'd choose)

We haven't tested these products, and we don't rank a #1.

ConsumerLab's tested brands included Doctor's Best, NOW and Pure Encapsulations NSK-SD, but its pass and fail results are paywalled, so we can't say which passed.

Whatever you choose, tell your clinician and pharmacist you take it, especially before any procedure.

FAQ

Is nattokinase the same as vitamin K2? No. Nattokinase is an enzyme that breaks down fibrin in lab tests. Vitamin K2 is a vitamin your body uses to activate clotting and bone proteins. Both come from natto, but they relate to clotting in different ways. Some nattokinase capsules, such as Doctor's Best, state that vitamin K2 has been removed.

Can I take nattokinase and vitamin K2 together? Ask your clinician first. On warfarin or another vitamin K antagonist, K2 can weaken the drug and nattokinase may add to bleeding risk. If you take no blood thinners, we found no trials testing the two together.

What should you avoid when taking nattokinase? Blood thinners and antiplatelet drugs unless a clinician advises it, and stop before surgery as your surgical team directs. ConsumerLab advises caution with blood pressure medicines, and the NIH says high-dose fish oil can have antiplatelet effects. Avoid products with soy if you're allergic.

Is there a downside to taking nattokinase? Bleeding, especially with other drugs that affect clotting. Case reports describe a brain bleed in a patient also taking aspirin and a heart valve clot after a patient swapped warfarin for nattokinase. Allergic reactions have been reported. And of 8 products ConsumerLab tested in 2025, 3 did not match their stated enzyme activity.

How much nattokinase is in a typical dose? Doctor's Best, for example, lists 2,000 fibrinolytic units (FU) per capsule, the daily dose used in the 3-year trial. Trials in a 2023 meta-analysis used 1,200 to 8,000 FU a day. The EU caps the NSK-SD ingredient at 100 mg a day for adults.

Does nattokinase lower blood pressure? A 2023 meta-analysis of small trials pooled modest drops of about 3.5 mmHg systolic and 2.3 mmHg diastolic compared with placebo. A 3-year trial found no effect on blood pressure. Nattokinase isn't a treatment for high blood pressure and shouldn't replace prescribed medicine.

Disclaimer: This article is for information only and is not medical advice. Nattokinase may affect blood clotting, and vitamin K2 can interfere with warfarin. Ask your clinician before taking nattokinase if you take blood thinners or antiplatelet drugs, have a bleeding disorder, are pregnant, or have surgery coming up. BiohackList may earn commissions from qualifying purchases in the future (disclosure).

Sources

• Jensen GS, Lenninger M, Ero MP, Benson KF. Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial. Integr Blood Press Control. 2016;9:95-104. PMID 27785095
• Kurosawa Y, et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep. 2015;5:11601. PMID 26109079
• Hodis HN, et al. Nattokinase atherothrombotic prevention study: a randomized controlled trial. Clin Hemorheol Microcirc. 2021;78(4):339-353. PMID 33843667
• Li X, 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. PMID 39076715
• Chang YY, et al. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med. 2008;47(5):467-469. PMID 18310985
• Elahi MM, et al. 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. PMID 25552810
• Theuwissen E, et al. Effect of low-dose supplements of menaquinone-7 (vitamin K2) on the stability of oral anticoagulant treatment: dose-response relationship in healthy volunteers. J Thromb Haemost. 2013;11(6):1085-1092. doi:10.1111/jth.12203
• NIH Office of Dietary Supplements. Vitamin K: Fact Sheet for Health Professionals
• NIH Office of Dietary Supplements. Omega-3 Fatty Acids: Fact Sheet for Health Professionals
• EFSA NDA Panel. Safety of fermented soybean extract NSK-SD as a novel food pursuant to Regulation (EC) No 258/97. EFSA Journal. 2016;14(7):4541. doi:10.2903/j.efsa.2016.4541
• U.S. FDA. FDA 101: Dietary Supplements
• Commission Implementing Decision (EU) 2017/115 authorising the placing on the market of fermented soybean extract as a novel food ingredient
• ConsumerLab. Nattokinase Supplements Review (products tested in 2025; updated March 16, 2026; public summary)
• Doctor's Best Nattokinase 2,000 FUs product page (checked Oct 7, 2026)