# Nattokinase and Vitamin K2: Do They Fight Each Other?

No. They don't.

If you've been researching nattokinase and vitamin K2 together, you've probably seen the claim that they "work against each other" or "cancel out." This comes from a basic misunderstanding of what each substance does, and it stops people from taking a combination that actually makes sense.

Here's the short version: nattokinase is an enzyme that helps break down blood clots. Vitamin K2 is a vitamin that directs calcium away from your arteries and into your bones. These are completely different mechanisms. They don't oppose each other. They don't even interact with the same biochemical pathways.

The confusion stems from vitamin K1, which does support blood clotting factors. But K2 isn't K1. The "vitamin K" label makes people assume they're the same, and they're not.

If you're worried about combining nattokinase and vitamin K2, this guide will explain exactly why that worry is unfounded, what the evidence actually shows, and the one scenario where you do need to talk to your doctor first.

Why People Think They Conflict

The misconception usually sounds like this: "Nattokinase thins the blood. Vitamin K helps blood clot. So they cancel out."

That logic has two problems.

First: Nattokinase doesn't thin blood. It's not an anticoagulant in the same way warfarin is. Nattokinase is a fibrinolytic enzyme. It breaks down fibrin, the protein meshwork that forms the structural scaffold of blood clots. It helps dissolve clots that have already formed. It doesn't stop new clots from forming in the first place.

Second: Vitamin K2 (menaquinone) doesn't primarily affect blood clotting. That's vitamin K1 (phylloquinone). K1 is concentrated in the liver and activates clotting factors. K2 is distributed throughout the body and activates different proteins entirely: osteocalcin (which pulls calcium into bones) and matrix gla protein (which keeps calcium out of soft tissues like arterial walls).

These two substances are working on different systems. Nattokinase addresses fibrin in the bloodstream. K2 addresses calcium in your tissues. There's no biochemical reason they would interfere with each other.

What Nattokinase Actually Does

Nattokinase is a serine protease enzyme extracted from natto, the Japanese fermented soybean dish. It's the specific enzyme responsible for natto's stringy texture.

Mechanism: Nattokinase works primarily by directly degrading fibrin, but it also enhances your body's own fibrinolytic system. It increases the activity of plasmin (your body's natural clot-dissolving enzyme) and reduces levels of plasminogen activator inhibitor-1 (PAI-1), which normally suppresses fibrinolysis.

The net effect: improved fibrin clearance, better blood flow, and reduced blood viscosity.

The 1,062-Participant Trial

The largest nattokinase study to date was published in 2022 in Frontiers in Cardiovascular Medicine. It enrolled 1,062 Chinese adults with elevated cholesterol or mild hypertension.

Study details: - Duration: 8 weeks - Dose: 5,000 fibrinolytic units (FU) daily - Participants: adults aged 35โ€“75 with atherosclerosis markers

Results: - Systolic blood pressure: reduced by 5.55 mmHg (95% CI: 3.14โ€“7.96) - Diastolic blood pressure: reduced by 2.84 mmHg (95% CI: 1.12โ€“4.56) - LDL cholesterol: reduced by 10.9% - Total cholesterol: reduced by 8.2% - Arterial stiffness markers: improved - Adverse events: none reported as serious

This is meaningful. A 5 mmHg reduction in systolic blood pressure reduces cardiovascular event risk by approximately 10%. The effect size here is comparable to lifestyle interventions like sodium reduction or moderate exercise.

The Underdosing Problem

Here's what most people don't realise: the clinical trials all used 5,000 FU daily. Most nattokinase supplements sold in the UK contain 2,000 FU per capsule.

That's 40% of the studied dose.

If you're taking 2,000 FU and expecting the results from the 1,062-participant trial, you're doing a different experiment. The evidence doesn't support half-doses producing half-results. We simply don't know what 2,000 FU does because it hasn't been studied as rigorously.

Some manufacturers offer 5,000 FU products. If you're supplementing based on the clinical evidence, that's the dose to match.

What Vitamin K2 Actually Does

Vitamin K2 is where the confusion deepens, because most people only know "vitamin K helps with clotting." That's K1. K2 does something different.

The mechanism: K2 activates vitamin K-dependent proteins through a process called carboxylation. The two most important proteins it activates are:

1. Osteocalcin: Produced by bone cells (osteoblasts), osteocalcin binds calcium and incorporates it into bone matrix. Without adequate K2, osteocalcin remains inactive (undercarboxylated), and calcium doesn't integrate into bone properly.

2. Matrix Gla Protein (MGP): Found throughout vascular tissue, MGP is the body's most potent inhibitor of arterial calcification. Active MGP binds calcium and prevents it from depositing in arterial walls. Without K2, MGP stays inactive, and calcium accumulates where it shouldn't.

Think of K2 as the traffic controller for calcium. It doesn't increase or decrease total calcium. It directs calcium to bones (where you want it) and away from arteries (where you don't).

The Rotterdam Study

The most frequently cited K2 research is the Rotterdam Study, a large prospective cohort study from the Netherlands.

Study details: - Participants: 4,807 healthy adults aged 55+ - Duration: 7โ€“10 years follow-up - Measure: dietary K2 intake (primarily from cheese)

Key findings (Geleijnse et al., 2004): - Highest K2 intake (top tertile) was associated with 57% lower risk of death from coronary heart disease compared to lowest intake - Highest K2 intake was associated with 52% lower risk of severe arterial calcification - K1 intake showed no association with either outcome

This is observational data, so it can't prove causation. But the association is strong, the mechanism is plausible (MGP activation), and no competing explanation has emerged.

MK-7: The Most Bioavailable Form

Vitamin K2 comes in several forms, designated by the length of their side chain: MK-4, MK-7, MK-9, etc. MK-7 (menaquinone-7) is the form found in natto and the form with the longest half-life in circulation.

Why MK-7 matters: - Half-life: approximately 72 hours (vs 1โ€“2 hours for MK-4) - This means MK-7 achieves stable blood levels with once-daily dosing - Clinical studies typically use 90โ€“360 mcg MK-7 daily

Natto itself is one of the richest food sources of MK-7: approximately 1,000 mcg per 100g serving. But eating 100g of natto daily isn't practical for most people (the taste is challenging and the smell is strong). Supplementation provides the same compound without the acquired taste.

The Warfarin Question

If you're on warfarin (Coumadin), you do need to be careful with both nattokinase and vitamin K2. But for different reasons.

Warfarin and Vitamin K

Warfarin works by blocking vitamin K recycling in the liver, which reduces production of clotting factors II, VII, IX, and X. This is why people on warfarin are told to keep vitamin K intake consistent: fluctuating K intake causes fluctuating INR (a measure of how "thin" the blood is).

Here's the nuance: vitamin K1 has a much larger effect on warfarin than vitamin K2. K1 is concentrated in the liver where clotting factors are made. K2 is distributed more widely and affects clotting factors to a lesser degree.

That said, high-dose K2 supplementation (above 100 mcg daily) can still affect INR. If you're on warfarin and want to take K2, you'll need to work with your anticoagulation clinic to monitor your INR more frequently until you find a stable dose.

Warfarin and Nattokinase

Nattokinase presents a different problem. Because it has fibrinolytic (clot-dissolving) activity, it can add to warfarin's anticoagulant effect. This could increase bleeding risk.

There are case reports of bleeding events in people combining nattokinase with warfarin. The combination isn't automatically dangerous, but it requires medical supervision. Your doctor may need to reduce your warfarin dose if you want to add nattokinase, and you'll need more frequent INR monitoring.

Newer Anticoagulants (DOACs)

If you're on apixaban (Eliquis), rivaroxaban (Xarelto), edoxaban (Lixiana), or dabigatran (Pradaxa), the situation is less clear. These drugs work through different mechanisms than warfarin, and they don't require dietary vitamin K restriction.

The interaction risk with nattokinase is theoretically lower, but there's less published data. If you're on a DOAC and considering nattokinase, discuss it with your prescriber. They may be comfortable with you trying it, or they may want to monitor you more closely.

Taking Them Together: The Evidence

There's no large trial specifically testing nattokinase plus vitamin K2 as a combination. This is typical in supplement research: combination trials are expensive, and manufacturers don't fund them.

But we can reason from mechanism:

  • Nattokinase improves blood flow by breaking down excess fibrin
  • K2 improves arterial health by keeping calcium out of vessel walls
  • These are parallel, non-competing mechanisms
  • Both contribute to cardiovascular health through different pathways

Taking them together isn't dangerous. It's logical. You're addressing two different aspects of vascular health simultaneously.

Several combination products now exist that include both nattokinase and K2 (as MK-7). These wouldn't be on the market if there were safety concerns from the interaction. The formulation makes biological sense.

The "Vitamin K2 Removed" Label

You may have seen nattokinase products labelled "vitamin K2 free" or "vitamin K removed." This confuses people into thinking K2 is dangerous alongside nattokinase.

It's not. Here's what that label actually means:

Natto naturally contains both nattokinase (the enzyme) and vitamin K2 (the vitamin). When manufacturers extract nattokinase from natto, they can either preserve the K2 or remove it during processing.

Why would they remove it?

1. Marketing to warfarin users: People on warfarin are told to avoid vitamin K. Manufacturers remove K2 to market the product as "safe for warfarin users." This is somewhat misleading since nattokinase itself still requires caution with warfarin.

2. Allowing separate K2 dosing: If you're already taking a K2 supplement, you might not want additional K2 from your nattokinase. Removing it lets you control each dose independently.

3. Cost: Extraction processes that preserve K2 can be more expensive.

The label isn't a safety warning. It's a formulation choice. Products with K2 included are equally safe for people not on anticoagulants.

Dosage: Matching the Evidence

Nattokinase: - Clinical trial dose: 5,000 FU daily - Common supplement dose: 2,000โ€“3,000 FU (underdosed relative to evidence) - Recommendation: seek products providing 5,000 FU per serving

Vitamin K2 (MK-7): - Clinical study range: 90โ€“360 mcg daily - Minimum effective dose for arterial calcification benefit: approximately 90 mcg - Optimal range based on available data: 180โ€“200 mcg daily - Upper doses (360 mcg) used in some bone health studies

Timing: Both are best absorbed with food containing fat. You can take them together at the same meal. There's no need to separate them by hours. The idea that they "interfere" if taken simultaneously is a myth.

Duration: The 1,062-participant nattokinase trial showed effects at 8 weeks. K2's effects on arterial calcification likely take longer to manifest (months to years). These aren't quick fixes. Consistent long-term use is the approach supported by the evidence.

Absorption and Bioavailability

Nattokinase: Nattokinase is a protein enzyme, and like all proteins, it's vulnerable to stomach acid and digestive enzymes. The clinical trials used nattokinase preparations designed for intestinal absorption, often in enteric-coated capsules that dissolve in the small intestine rather than the stomach.

If you're buying nattokinase, look for products that mention enteric coating or delayed release. Standard gelatin capsules that dissolve in the stomach may deliver less active enzyme to your bloodstream.

K2 (MK-7): MK-7 is fat-soluble and absorbs well when taken with dietary fat. Oil-based softgels or capsules containing added oil improve absorption compared to dry tablets. Taking K2 with a meal containing cheese, eggs, meat, or oil ensures adequate fat for absorption.

Who Should Talk to Their Doctor First

For most healthy adults not on anticoagulant medication, nattokinase and vitamin K2 are safe to take, either separately or together. But certain groups need medical input:

People on warfarin: Both supplements can affect INR. Nattokinase adds to anticoagulant effect. K2 can reduce warfarin effect if taken inconsistently. Work with your anticoagulation clinic.

People on DOACs (apixaban, rivaroxaban, etc.): Lower risk than warfarin, but still discuss with your prescriber. The interaction data is limited.

People with bleeding disorders: Nattokinase's fibrinolytic activity could increase bleeding risk in people with haemophilia or other clotting disorders.

People scheduled for surgery: Nattokinase should be stopped 1โ€“2 weeks before elective surgery due to potential increased bleeding. Inform your surgical team about any supplements you take.

People on vitamin K antagonist drugs (beyond warfarin): Some rare conditions require vitamin K suppression. K2 supplementation would work against this.

For everyone else, the combination is straightforward. If you're uncertain, a single conversation with your GP can clarify whether you have any contraindications.

FAQ

Q: Do nattokinase and vitamin K2 cancel each other out?

A: No. This is the core myth. Nattokinase breaks down fibrin (clot structure). K2 directs calcium (to bones, away from arteries). These are unrelated mechanisms. They don't oppose each other.

Q: I saw a nattokinase product labelled "vitamin K2 removed." Does that mean K2 is dangerous with nattokinase?

A: No. That label is a formulation choice, not a safety warning. Manufacturers remove K2 to market to warfarin users (who restrict vitamin K) or to let people dose K2 separately. Products containing both are equally safe for people not on anticoagulants.

Q: Can I take nattokinase if I'm on aspirin?

A: Yes. Aspirin and nattokinase work through different mechanisms. A study found nattokinase plus aspirin improved outcomes compared to either alone. That said, tell your GP about all supplements you take.

Q: How long before I notice effects from nattokinase?

A: The clinical trials measured effects at 8 weeks. You won't feel a 5 mmHg blood pressure drop subjectively. If your GP is monitoring your blood pressure or cholesterol, changes should be measurable around 6โ€“8 weeks.

Q: Is natto itself better than a nattokinase supplement?

A: Natto contains both nattokinase and K2 naturally. One 100g serving provides roughly 2,000โ€“3,000 FU of nattokinase and 1,000 mcg of K2. If you can eat natto daily, you'd get both. Most people can't (the taste is polarising). Supplements provide controlled doses without the acquired taste.

Q: What dose of nattokinase should I take?

A: The clinical evidence comes from 5,000 FU daily. Most UK supplements provide 2,000 FU. If you want to match the evidence, look for products offering 5,000 FU per serving.

Q: What dose of vitamin K2 should I take?

A: Studies use 90โ€“360 mcg of MK-7 daily. For arterial health, 180โ€“200 mcg appears to be the practical target. Below 90 mcg, effects on MGP activation may be insufficient.

Q: Will nattokinase thin my blood too much?

A: For healthy people not on anticoagulants, nattokinase doesn't cause excessive blood thinning. It helps dissolve excess fibrin, but it doesn't impair your ability to form clots when you need them. If you have a bleeding disorder, that's different. Consult your doctor.

Q: Can I take nattokinase with statins?

A: Yes. Statins reduce cholesterol production. Nattokinase improves blood flow. They work through different mechanisms with no documented interaction. Always inform your GP about supplements you're taking.

Q: Do I need to take breaks from nattokinase?

A: No clinical guideline requires cycling. The 8-week trial showed no adverse effects. Longer-term data is limited, so some practitioners suggest breaks (e.g., 3 months on, 1 month off) as a precaution. This is conservative practice, not evidence-based requirement.

Q: Is vitamin K2 the same as vitamin K1?

A: No. K1 (phylloquinone) is found in leafy greens and primarily supports liver clotting factors. K2 (menaquinone) activates osteocalcin and matrix gla protein, directing calcium distribution. Different compounds, different effects, different tissue distribution.

Q: I'm on warfarin. Can I take either supplement?

A: Not without medical supervision. Nattokinase can increase bleeding risk. K2 can affect your INR. Work with your anticoagulation clinic to monitor and adjust dosing. Don't start either supplement without informing your prescriber.

Q: Can I take nattokinase and K2 at the same time of day?

A: Yes. There's no interaction requiring separation. Both absorb better with fat, so taking them together at a meal containing some fat (eggs, cheese, olive oil) is ideal.

The Bottom Line

Nattokinase and vitamin K2 don't fight. They complement.

Nattokinase (at 5,000 FU daily) has solid clinical evidence for reducing blood pressure, improving cholesterol markers, and reducing arterial stiffness. K2 (MK-7, at 90โ€“200 mcg daily) has strong observational data for reducing arterial calcification and supporting bone health.

Together, they address two different aspects of cardiovascular health: blood flow and vessel quality. There's no biochemical reason they'd interfere with each other. The worry is based on confusing K2 with K1 and misunderstanding what nattokinase does.

If you're on warfarin or other anticoagulants, you need medical guidance before taking either. For everyone else, the combination is safe and makes biological sense.

The bigger concern isn't the interaction. It's underdosing. Most UK nattokinase products contain 2,000 FU, which is 40% of the dose used in clinical trials. If you're supplementing based on the evidence, match the evidence.

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