Do I need to stop nattokinase before surgery?

Yes — discontinue at least 14 days before any surgical or dental procedure. Nattokinase's fibrinolytic and antiplatelet activities impair normal haemostasis. Inform your surgeon, anaesthesiologist, and dentist that you have been taking nattokinase. After surgery, do not restart until cleared by your surgeon.

Limited EvidenceFibrinolytic Enzyme / Cardiovascular1 products compared

Nattokinase for Heart Health: Evidence, Safety Warnings, and Best Supplements in 2026

SAFETY WARNING — READ FIRST: Nattokinase is a fibrinolytic enzyme with direct anticoagulant and antiplatelet activity. It must not be taken with warfarin (Coumadin), direct oral anticoagulants (DOACs) including apixaban (Eliquis), rivaroxaban (Xarelto), dabigatran (Pradaxa), or edoxaban, antiplatelet drugs including aspirin (even low-dose), clopidogrel (Plavix), or ticagrelor, or combinations of fish oil at high dose, ginkgo biloba, high-dose vitamin E, or high-dose ginger with other anticoagulant-adjacent supplements. It must be discontinued at least 14 days before any surgical or dental procedure. People with bleeding disorders, active peptic ulcer disease, or recent stroke or hemorrhage must not take nattokinase. If you take any blood thinners, clotting medications, or have a cardiovascular condition managed by a physician, consult your cardiologist before considering nattokinase. With that non-negotiable caveat established: for adults without these contraindications who are interested in evidence-informed cardiovascular support, nattokinase has a genuinely interesting mechanism and a small but growing clinical trial base. Nattokinase (subtilisin NAT) is a serine protease enzyme produced by Bacillus subtilis natto during soy fermentation, traditionally consumed in Japan as natto. It has direct fibrinolytic activity — it degrades fibrin, the protein scaffold of blood clots. It also appears to inhibit platelet aggregation and may support blood pressure through angiotensin-converting enzyme (ACE) inhibitory activity. Unlike pharmaceutical fibrinolytics (tPA, streptokinase) which are administered intravenously in acute stroke/MI settings, nattokinase shows oral bioavailability in animal models and some human studies — though the extent to which supplemental doses achieve clinically relevant systemic fibrinolytic activity in healthy adults remains an area of active research. This page reviews the clinical evidence honestly, with particular emphasis on who should not take nattokinase and the safety data that many supplement marketing sites omit.

Written by Editorial Team·Medically reviewed by Angelique Nicole R. Villegas, RND, Registered Nutritionist Dietitian · PRC Philippines · License #0023950·Updated May 23, 2026·How we picked these products

This content is for educational purposes only and is not medical advice. These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease. Always consult your healthcare provider before starting any supplement.

Why It Works

Key Benefits of Nattokinase for Heart Health

Nattokinase is a fibrinolytic enzyme with direct clot-degrading activity — unusual among oral supplements.

The FLASSH trial (n=86) showed modest but significant blood pressure reductions with 2000 FU/day over 8 weeks.

May support healthy blood viscosity through fibrinolytic and antiplatelet mechanisms — relevant for cardiovascular-focused adults without anticoagulation therapy.

Our Picks

Best Nattokinase for Heart Health in 2026

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Doctor's Best Nattokinase 2000 FU

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$19.99

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Doctor's Best Nattokinase 2000 FU. 4.8★ (1,039 ratings). Confirmed in stock.

Pros

4.8★ average across 1,039 ratings

Verified in stock at $19.99

Cons

Amazon price and availability can change over time

Trust Context

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Evidence

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Score	9.2/10
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Pros	4.8★ average across 1,039 ratings Verified in stock at $19.99
Cons	Amazon price and availability can change over time

The Science

How Nattokinase Supports Heart Health

Nattokinase (subtilisin NAT) is a serine protease enzyme extracted from natto (fermented soybeans). It directly cleaves fibrin — the protein backbone of blood clots — degrading existing clots and reducing clot formation tendency. It also modulates platelet aggregation and may inhibit ACE, contributing to its blood pressure effects. Unlike most cardiovascular supplements that work through antioxidant or anti-inflammatory mechanisms, nattokinase has direct enzymatic activity on the coagulation cascade — making it both uniquely interesting and uniquely risky when combined with anticoagulant medications.

Buying Guide

What to Look For When Buying Nattokinase

The most important purchase criteria for nattokinase is what's NOT in it. Choose products that: (1) use 2000 FU standardised dosing — not just mg; (2) have had vitamin K2 removed (natto naturally contains K2); (3) clearly disclose soy derivation for allergy screening; (4) come from brands with GMP certification and third-party testing. NSK-SD is the best-researched standardised nattokinase extract used in clinical trials.

Dosage

Dosage Guidance

CRITICAL SAFETY REMINDER: Nattokinase must not be taken with warfarin, DOACs (apixaban, rivaroxaban, dabigatran, edoxaban), aspirin for cardiovascular use, clopidogrel, or other antiplatelet/anticoagulant agents. If you take any of these, do not use nattokinase. Standard dose: 2000 FU per day (100mg standardised extract). This is the dose used in the FLASSH clinical trial. Timing: Between meals or at bedtime — stomach acid may partially degrade the enzyme protein. Discontinue 14 days before any surgery or dental procedure. Consult your healthcare provider before starting.

Always follow your healthcare provider's recommendations. Dosages vary by individual health status, age, and goals.

What Users Complain About

Common Nattokinase Complaints (And How to Avoid Them)

Based on analysis of thousands of customer reviews across Nattokinase products.

"Can I take nattokinase if I take a baby aspirin?"

No. Low-dose aspirin (81mg) used for cardiovascular prevention has antiplatelet activity. Combining it with nattokinase — which also inhibits platelet aggregation and has fibrinolytic activity — creates additive bleeding risk. This is an absolute contraindication. If you take low-dose aspirin for cardiovascular prevention, do not add nattokinase without your cardiologist's explicit approval and monitoring plan.

"I take Eliquis (apixaban) — is nattokinase safe?"

No. Apixaban is a direct oral anticoagulant (DOAC). Combining nattokinase with any DOAC is an absolute contraindication due to additive anticoagulant and fibrinolytic effects, which can increase bleeding risk unpredictably. Do not take nattokinase if you are on apixaban, rivaroxaban, dabigatran, or edoxaban.

"I eat natto already — do I need nattokinase supplements?"

Dietary natto contains nattokinase, but the enzyme content per serving varies. Traditional natto consumption (approximately 100g/day, as in Japanese dietary studies) provides an estimated 500–1000 FU — lower than the 2000 FU in most clinical supplements. Dietary natto also contains vitamin K2, which supplements often remove. If you regularly eat natto, discuss with your physician whether supplemental nattokinase is additive or redundant.

Safety

Safety & Interactions

ANTICOAGULANT ABSOLUTE CONTRAINDICATION: Nattokinase is a fibrinolytic enzyme. Taking it with any anticoagulant or antiplatelet medication creates additive or synergistic bleeding risk. The following combinations are absolutely contraindicated: - Warfarin (Coumadin) — the INR-destabilising effect of nattokinase is unpredictable and potentially dangerous - Direct oral anticoagulants (DOACs): apixaban (Eliquis), rivaroxaban (Xarelto), dabigatran (Pradaxa), edoxaban (Savaysa/Lixiana) - Antiplatelet therapy: aspirin (including low-dose 81mg), clopidogrel (Plavix), ticagrelor (Brilinta), prasugrel (Effient) - Dual antiplatelet therapy combinations ADDITIVE-RISK SUPPLEMENTS (avoid combining without physician guidance): High-dose fish oil (>3g EPA+DHA/day), ginkgo biloba, high-dose vitamin E (>400 IU/day), high-dose ginger extract, turmeric/curcumin at concentrated extract doses, bromelain. PRE-SURGERY DISCONTINUATION: Discontinue nattokinase at least 14 days before any surgical procedure, including dental surgery, colonoscopy, or elective interventions. Inform your surgeon and anaesthesiologist. BLEEDING DISORDERS: Absolute contraindication in haemophilia, von Willebrand disease, thrombocytopenia, or any condition impairing haemostasis. ACTIVE PEPTIC ULCER: Do not use — fibrinolytic activity may impair clot formation at ulcer sites. PREGNANCY AND BREASTFEEDING: Avoid — no safety data; fibrinolytic activity is a theoretical risk. SOY ALLERGY: Nattokinase is soy-derived. Avoid if soy allergy. KIDNEY/LIVER IMPAIRMENT: Use under physician supervision only. Note: Some nattokinase products contain vitamin K2. For users tracking vitamin K intake (e.g., for warfarin monitoring, though warfarin is an absolute contraindication), choose vitamin K2-removed formulations. **Medication and diagnosis boundary:** This supplement is not a replacement for prescription medication, medical evaluation, lab testing, or disease-specific care. If you have a diagnosed condition, take prescription medication, are pregnant or breastfeeding, or have kidney/liver disease, discuss use with your clinician before starting. **Cardiovascular medication boundary:** If you take anticoagulants, antiplatelet drugs, statins, blood-pressure medication, diabetes medication, or have a procedure planned, do not add this supplement without clinician guidance. Some cardiovascular supplements can alter bleeding risk, blood pressure, glucose, or lipid-management plans. **Kidney disease:** If you have chronic kidney disease (CKD) or any significant kidney impairment, consult your healthcare provider before taking this supplement. Some supplements can accumulate to dangerous levels when kidney function is reduced. **Gout:** Individuals with gout should consult their healthcare provider before starting this supplement. Certain supplements (e.g., collagen, fish oil, niacin) may affect uric acid levels or trigger flares in susceptible individuals.

Standard safety disclaimers

Pregnancy and breastfeeding: Consult your healthcare provider before taking this supplement during pregnancy or while nursing. The safety of supplemental doses beyond dietary intake has not been established in pregnant or lactating women.
Blood thinners: If you take blood-thinning medications (e.g., warfarin, apixaban, rivaroxaban, clopidogrel, or high-dose aspirin), consult your healthcare provider BEFORE starting this supplement, as it may have additive antiplatelet or anticoagulant effects.
Kidney disease: If you have chronic kidney disease (CKD) or any significant kidney impairment, consult your healthcare provider before taking this supplement. Some supplements can accumulate to dangerous levels when kidney function is reduced.
Gout: Individuals with gout should consult their healthcare provider before starting this supplement. Certain supplements (e.g., collagen, fish oil, niacin) may affect uric acid levels or trigger flares in susceptible individuals.
Fish allergy - capsule source: Some softgel capsules use fish-derived gelatin even when the active supplement is not fish-derived. If you have a confirmed fish or shellfish allergy, verify the capsule source on the label or check with the manufacturer. Vegan capsules (vegetable cellulose) are widely available alternatives.
Beef / alpha-gal allergy - capsule source: Many softgel and two-piece capsules use bovine gelatin. If you have a confirmed beef allergy or alpha-gal syndrome (mammalian meat allergy), check capsule sources on the label. Vegan capsules (vegetable cellulose) and HPMC capsules are alternatives.
Blood pressure medications: This supplement may have an additive blood-pressure-lowering effect when taken with antihypertensives including beta-blockers (metoprolol, atenolol), ACE inhibitors (lisinopril), ARBs (losartan), and calcium channel blockers (amlodipine). If you take any blood pressure medication, monitor your readings for the first 4–6 weeks after starting and inform your prescribing physician.
Important: This supplement is not a replacement for prescription medications. It is supportive for individuals with low baseline status, not a treatment for diagnosed conditions (anxiety disorders, insomnia, hypertension, osteoporosis, etc.). Do not stop or reduce any prescription without consulting your doctor.

"
"Nattokinase sits in an unusual position: it's one of the few supplements with a genuinely interesting and plausible cardiovascular mechanism (oral fibrinolysis), a reasonable human trial base for its size (the FLASSH blood pressure RCT), and also the highest safety complexity of any supplement we review. The functional medicine community has enthusiastically adopted it, sometimes without adequate contraindication counselling. Our position is that for the right candidate — a generally healthy adult 45+ with no anticoagulant therapy, no bleeding disorder, no upcoming surgery, and a physician's awareness of supplementation — nattokinase at 2000 FU/day is a reasonable exploratory addition. But the contraindication screen is non-negotiable. The risk of combining nattokinase with even low-dose aspirin is real. Do the screen first."
— Angelique Nicole R. Villegas, RND, Registered Nutritionist Dietitian · PRC Philippines · License #0023950

Common Questions

Frequently Asked Questions

No — this is an absolute contraindication. Nattokinase has fibrinolytic and antiplatelet activity that is additive with warfarin's anticoagulant mechanism. The combination can destabilise INR control and significantly increase bleeding risk. If you take warfarin for any indication (atrial fibrillation, mechanical heart valve, DVT/PE prevention, etc.), do not take nattokinase. Discuss cardiovascular support options with your cardiologist.

No. The contraindication extends to all anticoagulant and antiplatelet medications: warfarin, the direct oral anticoagulants (apixaban/Eliquis, rivaroxaban/Xarelto, dabigatran/Pradaxa, edoxaban/Savaysa), and antiplatelet drugs (aspirin for cardiovascular use, clopidogrel/Plavix, ticagrelor/Brilinta, prasugrel/Effient). If you take any of these medications, nattokinase is not appropriate. Consult your prescribing physician about evidence-based cardiovascular support strategies that do not interact with your anticoagulation regimen.

Nattokinase is a serine protease enzyme that directly degrades fibrin — the protein scaffold that forms blood clots. By enhancing fibrinolytic activity, it may support healthy blood viscosity and reduce clot accumulation risk. It also appears to inhibit platelet aggregation (reducing platelet 'stickiness') and may inhibit ACE (angiotensin-converting enzyme), which is one proposed mechanism for its modest blood pressure effects. The oral bioavailability of the active enzyme is established in animal models and supported by human studies showing measurable increases in fibrinolytic markers after supplementation.

The FLASSH trial (Kim et al., 2008, PMID 18971533) — a double-blind RCT in 86 hypertensive adults — found nattokinase 2000 FU/day for 8 weeks reduced systolic BP by 5.5 mmHg and diastolic BP by 2.8 mmHg vs placebo. These are statistically significant, modest reductions — in the range of dietary interventions. This is a single trial with a modest sample size. Nattokinase is not a substitute for antihypertensive medications in people with clinical hypertension.

At low fish oil doses (e.g., 1g EPA+DHA/day), the combination may be acceptable for some adults without other risk factors — but this should be discussed with a physician. At higher fish oil doses (>3g EPA+DHA/day), fish oil itself has clinically relevant antiplatelet activity, and combining it with nattokinase creates additive risk. The conservative recommendation is to avoid high-dose fish oil with nattokinase.

Scientific References

Citations & Research

This page references peer-reviewed research indexed on PubMed/NCBI. Citations are provided for transparency. Always consult a qualified healthcare professional before making any medical decisions.

[c1]Kim JY, Gum SN, Paik JK, et al.. “Effects of nattokinase on blood pressure: a randomized, controlled trial.” Hypertension Research, 2008. 86. doi:10.1291/hypres.31.1583 PMID 18971533 ↗

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