Drug & supplement interaction

Nattokinase + Metformin

Metformin brand names: Glucophage, Metformin.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 13, 2026
The bottom line No known interaction

We found no known interaction between Nattokinase and Metformin in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first. Additionally, although there is no interaction, the two are separately associated with some of the same side effects, which would make a new symptom harder to attribute to one or the other.

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Interaction report

Nattokinase and Metformin

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Metformin and Nattokinase in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

Nattokinase safety at a glance

Nattokinase overall Use caution Generally tolerated short-term, but its blood-thinning effect means caution for people with bleeding risk.
Pregnancy Avoid Not enough safety data, so it is best avoided during pregnancy.
Breastfeeding Avoid Safety is unknown while breastfeeding, so avoid it to be safe.

Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Metformin and Nattokinase? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Metformin

Interactions in our licensed database are recorded against drug classes, not just single drug names. Metformin is filed under 5 classifications — including organic cation transporter 2 (oct2) substrates, antidiabetes drugs, oral drugs. Nattokinase has documented interactions with 2 drug classes — the most serious being anticoagulant/antiplatelet drugs (moderate) and antihypertensive drugs (moderate) — and none of Metformin’s classifications are among them.

Classification data comes from our licensed Natural Medicines dataset. A medication can belong to classes beyond those recorded there, so this describes how the check was run — it is not a safety guarantee.

Keep it in perspective

Nattokinase Does Interact With Other Medications

Nattokinase has 289 moderate known drug interactions in our database — Metformin isn’t one of them. If you take anything else, check it against the full list below.

Moderate 289 No known interaction 2,541 (incl. Metformin)
Taking anything else?

Check Another of Your Medications Against Nattokinase

Covers the 2,830 medications we’ve checked against Nattokinase. Pick one to open its full report.

What to actually watch for

No Interaction Found — But Data Suggests Nattokinase and Metformin May Share Several of the Same Side Effects

This is not an interaction. Neither one changes how your body handles the other, and nothing here says they react together. What our sources do show is that each has separately been linked to the effects below — so taking both can make those effects more likely to turn up, and harder to pin on one or the other if they do. One of them is worth acting on rather than waiting out — marked below.

  • Shortness of breath Worth acting on Additional detail

    Nattokinase

    “Orally, nattokinase can cause hypersensitivity reactions, including anaphylaxis, in individuals sensitive to natto. A case series examining hypersensitivity reactions to natto shows that the causative allergen can be either nattokinase or polygamma glutamic acid (PGA), both of which are found in the sticky substance surrounding natto soybeans.”

    Nattokinase · Natural Medicines adverse-effect record, reported in dermatitis.

    2 sources cited
    1. 109552. Awatani-Yoshidome K, Hashimoto T, Satoh T. Anaphylaxis from nattokinase in a patient with fermented soybean (natto) allergy. Allergol Int 2022;71(1):153-4. PubMed
    2. 111253. Suzuki K, Nakamura M, Sato N, Futamura K, Matsunaga K, Yagami A. Nattokinase, a subtilisin family serine protease, is a novel allergen contained in the traditional Japanese fermented food natto. Allergol Int 2022.

    Metformin

    Listed in the ADVERSE REACTIONS section of the FDA label for Metformin. Read the label on DailyMed ›

  • Dizziness Additional detail

    Nattokinase

    “Orally, nattokinase has been associated with rare reports of hemorrhage. A case of intracranial hemorrhage (ICH) has been reported in a 52-year-old female who took nattokinase while taking low-dose aspirin for secondary prevention of ischemic stroke. Seven days after initiating nattokinase 400 mg daily, the patient reported vertigo and unsteady gait and was diagnosed with an acute cerebellar hemorrhage.”

    Nattokinase · Natural Medicines adverse-effect record, reported in atrial fibrillation.

    2 sources cited
    1. 64834. Chang, Y. Y., Liu, J. S., Lai, S. L., Wu, H. S., and Lan, M. Y. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med 2008;47(5):467-469. PubMed
    2. 109551. Ramachandran L, Aqeel A, Jafri A, Sidhu Y, Mohamed Djirdeh T. Nattokinase-associated hemoperitoneum in an elderly woman. Cureus 2021;13(12):e20074. PubMed

    Metformin

    Listed in the ADVERSE REACTIONS section of the FDA label for Metformin. Read the label on DailyMed ›

  • A skin rash Additional detail

    Nattokinase

    Recorded for Nattokinase in the same Natural Medicines adverse-effect record shown under Shortness of breath above.

    Metformin

    Listed in the ADVERSE REACTIONS section of the FDA label for Metformin. Read the label on DailyMed ›

Reported for Nattokinase but not commonly for Metformin: bleeding or bruising, an irregular heartbeat, an allergic reaction and a stroke or mini-stroke.

Effects for Metformin come from the ADVERSE REACTIONS section of its FDA label; effects for Nattokinase come from the Natural Medicines adverse-effect record, quoted above. Wording is matched across sources by our own clinical vocabulary, so treat this as a prompt to pay attention, not a diagnosis.

Overlapping uses

What Metformin Is Prescribed For, and What Nattokinase Has Been Studied For

These two come up together because they touch the same health topic — not because they do the same job. Metformin is a prescription medicine with approved uses on its FDA label. Nattokinase is a supplement: what follows is what researchers have looked at it for, and how strong that evidence is.

Metformin is prescribed for: Metformin is used to improve blood sugar (glucose) control in people with type 2 diabetes mellitus. It is always used together with diet and exercise, not instead of them. Metformin hydrochloride tablets and oral solution are approved for adults and children 10 years and older. Metformin hydrochloride extended-release tablets — including brands such as Fortamet, Glumetza, and Metformin Hydrochloride Extended Release — are approved for adults only.

Nattokinase has been studied for:

  • Stroke studied, not established Nattokinase has been studied for this. Natural Medicines rates the evidence: Insufficient Reliable Evidence To Rate Read what the research shows

    Nattokinase for stroke

    Although there has been interest in using oral nattokinase for stroke, there is insufficient reliable information about the clinical effects of nattokinase for this condition.

Effectiveness ratings and the research summaries above are the verbatim record from the Natural Medicines database, which grades evidence from “Effective” down to “Insufficient Reliable Evidence To Rate”. A rating below the top of that scale means researchers have looked at it — not that it works, and never that it can stand in for a prescribed medicine. Do not stop or replace Metformin on your own; if you are taking Nattokinase for the same health topic, tell your prescriber, especially if the medicine is being adjusted to a target.

From our Q&A

Questions About Nattokinase or Metformin

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Nattokinase or Metformin, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Metformin

This page covers Nattokinase only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Metformin page lists 258 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Siberian Cocklebur (major), Acai (moderate), African Wild Potato (moderate) and Agaricus Mushroom (moderate).

By severity: 2 major · 217 moderate · 39 minor.

From our pharmacist’s overview on the Metformin page

“Siberian cocklebur is the ingredient I most want anyone taking metformin (Glucophage) to know about. It has caused severe low blood sugar in people, documented in humans, and it should not be combined with any glucose-lowering medication.”

Reviewed by 2 · Jul 18, 2026

Open the Metformin interaction page

One more smart check

Taking Nattokinase as Part of a Dietary Supplement Product? Check It for Interactions

We hold 509 real supplement products containing Nattokinase, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Nattokinase. Even though Nattokinase itself has no known interaction with Metformin, another ingredient on your label might. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Nattokinase and Metformin Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Nattokinase
Top 25%

#247 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Metformin
Top 1%

#29 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Where does our data come from?
  • Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
  • Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Nattokinase reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Nattokinase and Metformin records this page draws on were last updated July 10, 2026.
  • What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.
Data structure & sourcing designed and verified by .
Supplement

About Nattokinase

What is Nattokinase?

Nattokinase
  • Heart and circulatory health
  • Blood clot prevention
  • High blood pressure
  • Improving blood flow
  • Cholesterol support

Nattokinase is an enzyme from the fermented soybean food natto that may have mild blood-thinning and blood-flow effects. Some small studies hint at benefits for blood pressure and circulation, but the evidence is limited and more research is needed. Because it can affect clotting, talk to your pharmacist or doctor before trying it, especially if you take medicines or have a bleeding risk.

Enzyme extracted from natto (fermented soybeans) · Capsules, tablets, softgels

An interaction check asks whether these two react with each other — it does not ask whether Nattokinase is a good idea for someone in your situation. Here is what our Nattokinase record says about it on its own.

Nattokinase: dosing

There is no official or standardized dose of nattokinase. Products are often measured in "fibrinolytic units" (FU), and the amount varies a lot from brand to brand.Because of this, the best approach is to follow the directions on the product label and not take more than recommended.

From our Nattokinase monograph — the full record covers uses, side effects and every documented interaction.

Read the full Nattokinase monograph & all interactions
Medication

About Metformin

What Is Metformin Used For?

Brand names: Glucophage, Metformin

Metformin is used to improve blood sugar (glucose) control in people with type 2 diabetes mellitus. It is always used together with diet and exercise, not instead of them.

Metformin hydrochloride tablets and oral solution are approved for adults and children 10 years and older. Metformin hydrochloride extended-release tablets — including brands such as Fortamet, Glumetza, and Metformin Hydrochloride Extended Release — are approved for adults only.

See full Metformin drug information
Keep checking

Other Drugs & Nattokinase

Browse every other medication we’ve checked against Nattokinase — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
289Moderate
0Minor
2,540No known interaction
289 Moderate 2,540 No interaction
Moderate

289 interactions

Showing 60 of 289 moderate interactions — see all 289 on the Nattokinase page.

No interaction 2,540 drugs checked — show the list

We also checked Nattokinase against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,540 medications checked with no known interaction — see the full Nattokinase list.

See the full Nattokinase interactions page
See every supplement checked against Metformin, ranked by severity
Evidence & sources

Nattokinase References

The 9 references that drive our Nattokinase monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. Suzuki Y, Kondo K, Matsumoto Y, et al. Dietary supplementation of fermented soybean, natto, suppresses intimal thickening and modulates the lysis of mural thrombi after endothelial injury in rat femoral artery. Life Sci 2003;73:1289-98.. PubMed
  2. Sumi H, Hamada H, Nakanishi K, Hiratani H. Enchancement of fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematol 1990;84:139-43.
  3. Chang, Y. Y., Liu, J. S., Lai, S. L., Wu, H. S., and Lan, M. Y. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med 2008;47(5):467-469. PubMed
  4. Kim, J. Y., Gum, S. N., Paik, J. K., Lim, H. H., Kim, K. C., Ogasawara, K., Inoue, K., Park, S., Jang, Y., and Lee, J. H. Effects of nattokinase on blood pressure: a randomized, controlled trial. Hypertens.Res 2008;31(8):1583-1588. PubMed
  5. <p>Maruyama M, Sumi H (eds): Effect of natto diet on blood pressure, in Basic and Clinical Aspects of Japanese Traditional Food Natto II. Japan Technology Transfer Association (JTTAS), 1998, pp 1–3.</p>
  6. Kurosawa Y, Nirengi S, Homma T, et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep 2015;5:11601. PubMed
  7. Ramachandran L, Aqeel A, Jafri A, Sidhu Y, Mohamed Djirdeh T. Nattokinase-associated hemoperitoneum in an elderly woman. Cureus 2021;13(12):e20074. PubMed
  8. Awatani-Yoshidome K, Hashimoto T, Satoh T. Anaphylaxis from nattokinase in a patient with fermented soybean (natto) allergy. Allergol Int 2022;71(1):153-4. PubMed
  9. Suzuki K, Nakamura M, Sato N, Futamura K, Matsunaga K, Yagami A. Nattokinase, a subtilisin family serine protease, is a novel allergen contained in the traditional Japanese fermented food natto. Allergol Int 2022.

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Pharmacist Counseling Corner

Taking Nattokinase and Metformin Together: Common Questions

Is it safe to take Nattokinase with Metformin?
We do not list a known interaction between Nattokinase and Metformin. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.
Do Nattokinase and Metformin have any of the same side effects?
Yes — our sources link each of them separately to 3 of the same effects. That is not an interaction: neither changes how your body handles the other. It does mean that if one of those effects turns up, it can be harder to tell which one is behind it. They are listed on this page with the source behind each.
Are Nattokinase and Metformin used for the same thing?
They overlap in purpose, which usually means the real question is whether you need both rather than whether they are safe together. This page lists the shared uses and how strong the evidence is for Nattokinase in each. That is a conversation for your prescriber, especially if Metformin is being adjusted to a target.
How was the Nattokinase and Metformin combination checked?
Interactions in our licensed database are recorded against drug classes. Metformin is filed under 5 classifications, and Nattokinase has documented interactions with 2 drug classes — none of Metformin's classifications are among them. A medication can belong to classes beyond those recorded in our dataset, so this describes how the check was run rather than guaranteeing safety.
Does Nattokinase interact with any other medications?
Yes. Nattokinase has 289 documented drug interactions in our database — Metformin is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.
Does Metformin interact with any supplements?
Yes. Metformin has documented interactions with 258 supplements in our database — Nattokinase is not one of them. The Metformin interaction page linked on this page lists every one, ranked by severity.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Where next

Keep Exploring

Nattokinase monograph Uses, safety profile, and every drug interaction in one place Metformin drug information The full plain-English guide to this medication Metformin supplement interactions Every supplement checked against Metformin, ranked by severity Supplement interaction checker Check any supplement or product against your medications Browse medications A–Z Every drug we’ve checked against herbs & supplements References The 9 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Metformin and Nattokinase?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.