Can You Take Nattokinase With Coumadin (Warfarin)?

In our latest question and answer, the pharmacist discusses the use of nattokinase with Coumadin (warfarin).

Question

Can I take nattokinase along with Coumadin? I have been taking Coumadin for 14 months since developing a blood clot in my leg. Nattokinase dissolves blood clots. I tried it before with remarkable results and it did dissolve my blood clot and completely cleared up the venous stasis w/ dermatitis I have had for about 15 years. I got another blood clot 10 months after treatment with the Nattokinase. Do you know how I can take Nattokinase again and still continue taking Coumadin as well? Could I alternate Coumadin dose or days?

Asked by prissc On Feb 17, 2019

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Feb 20, 2019
Nattokinase And Warfarin Pills

Nattokinase should not be taken with Coumadin (warfarin) as it can have unpredictable effects on blood clotting and will likely reduce the overall effectiveness of Coumadin.

Although there haven't been many studies regarding the potential interaction between Coumadin and nattokinase, the ones that have been published show conflicting results.

Nattokinase itself acts as an anticoagulant and thrombolytic (i.e. blot clot dissolver) and could potentially enhance the blood-thinning effects of Coumadin. Conversely, some studies show that long-term use of nattokinase may have a paradoxical effect, increasing the risk of clots over time.

Complicating matters is the fact that nattokinase is derived from natto, a traditional Japanese food. Natto is extremely high in vitamin K, which will antagonize (i.e. reverse) the effects of Coumadin. It is important to keep your vitamin K intake consistent while taking Coumadin to avoid dangerous fluctuations in efficacy.

Since Coumadin is a drug that requires fairly stringent laboratory monitoring to maintain safe and effective INR levels, taking drugs or supplements that can interfere with it is dangerous and risky.

In the next sections, I discuss nattokinase in greater detail and concerns over its use in those already on anticoagulant therapy.

What Is Nattokinase?

Natto Soy And Nattokinase Structure

Nattokinase is a proteinase enzyme that is extracted from natto, a traditional Japanese food made from soybean fermentation. Nattokinase is not a component of other soybean-based foods as it is made specifically via fermentation with the bacteria 'Bacillus subtilis'.

A 1987 study was one of the first to describe the enzyme nattokinase and discuss its similarities to human plasmin, an enzyme present in the blood of humans that degrades blood clots. Nattokinase was shown to be a potent thrombolytic enzyme itself and animal studies show it may be even more potent than plasmin.

It is important to differentiate natto from nattokinase. Nattokinase is the enzyme derived from natto, the food. Natto is very high in vitamin K, which will reverse the blood-thinning effects of Coumadin. In fact, natto contains higher concentrations of vitamin K than most other types of food according to the National Institute of Health.

Nattokinase itself does not contain vitamin K.

What Is It Used For?

Nattokinase has historically been used as an over the counter supplement for the treatment of:

  • Hypertension (high blood pressure)
  • Blood clots (e.g. DVT)

Although more high-quality studies are needed, preliminary data shows that nattokinase may reduce both systolic blood pressure (SBP) and diastolic blood pressure (DBP). One study published in Nature specifically noted that nattokinase decreased systolic blood pressure by 10.9% and diastolic blood pressure by 9.9% from baseline numbers.

Studies evaluating thrombolytic effects of the drug are few and far between, but one found that nattokinase may prevent DVTs (deep vein thrombosis) in those taking long flights.

Another suggested that it may be a viable alternative to Coumadin in certain situations, but this study only evaluated the effects of a single dose of nattokinase.

How Does It Work?

Evidence suggests that nattokinase has both antithrombotic and anticoagulant effects, or, in other words, can dissolve blood clots as well as thin the blood.

There are numerous theorized mechanisms of action but nattokinase appears to primarily work by inactivating plasminogen activator inhibitor 1.

Is It Safe?

Most studies show that nattokinase is safe when consumed in amounts found in foods. Additionally, single doses and extended dosing periods of up to a few months have reported few adverse effects.

There is one case report of cerebellar hemorrhage in an individual who combined it with aspirin, but adverse effects of that severity appear unlikely. Nevertheless, studies have not used nattokinase in conjunction with other anticoagulants (see drug interactions).

There have been studies that suggest long-term use of nattokinase could have paradoxical effects, and increase blood clotting.

One case study reported on a patient who substituted nattokinase for Coumadin for over a year after aortic valve replacement. The patient developed thrombus on the mechanical valve and nattokinase was suspected to be partly responsible:

"Thrombin activity has been found to be increased following thrombolysis, which in turn may have paradoxically increased our patient's risk of valve thrombosis."

Whether or not nattokinase directly contributed to the development of a blood clot, or whether the absence of Coumadin was the primary cause, isn't known.

All told, nattokinase does appear safe on its own, for short periods of time, but should not be considered a substitute or complement for your anticoagulant therapy unless directed by your doctor.

Drug Interactions

Nattokinase has documented thrombolytic and anticoagulant effects and needs to be used cautiously with other drugs that have antiplatelet or anticoagulant effects, like:

  • NSAIDs
  • Aspirin
  • Plavix
  • Brilinta
  • Fragmin
  • Coumadin
  • Lovenox
  • Heparin
  • Effient
  • Aggrenox

Taking nattokinase with any of the above could increase the risk of bleeding events.

How Does Nattokinase Interact With Coumadin (Warfarin)?

Pink Warfarin pills

Natto, and nattokinase, almost assuredly interact with Coumadin (warfarin).

Nattokinase has been shown to be both an anticoagulant (blood thinner) and thrombolytic (an agent that dissolves blood clots). Taking Nattokinase with Coumadin could potentially increase the risk of bruising and bleeding, including dangerous bleeding events.

Additionally, if nattokinase is introduced into the body by consuming natto (the food), the effects on Coumadin will be unpredictable. Natto contains very high concentrations of vitamin K and studies in both humans and animals show intake of natto increases blood vitamin K levels.

Increased vitamin K intake will have a serious and potentially dangerous interaction with Coumadin as Coumadin works by depleting vitamin K-dependent clotting factors. Increasing vitamin K intake will negate the effects of Coumadin, increasing the risk of blood clots.

Final Words

While nattokinase may have utility in some individuals and appears to be relatively safe when used for short periods of time, more studies are needed to learn more about its overall safety and efficacy.

Based on our current understanding of it, it should certainly not be taken with Coumadin or other anticoagulants as it could significantly increase the risk of side effects. There isn't enough data to safely use it on a 'rotating' basis with anticoagulants either.

If you are considering taking nattokinase, regardless of whether or not you take Coumadin, be sure to speak with your doctor. Perhaps they could assist with a regimen where you could be appropriately monitored for safety and effectiveness.


References
  • Thrombolytic effect of nattokinase on a chemically induced thrombosis model in rat. PubMed
  • A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet.Oral Dosage Forms That Should Not Be Crushed. PubMed
  • Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. PubMed
  • Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis. PubMed
  • Prevention of venous thrombosis in long-haul flights with Flite Tabs: the LONFLIT-FLITE randomized, controlled trial. PubMed
  • National Institute of Health: Vitamin K Fact Sheet for Health Professionals. NIH
  • Effects of Nattokinase on Blood Pressure: A Randomized, Controlled Trial. Nature
  • A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. PubMed

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Dr. Brian Staiger Pharm.D

Dr. Brian Staiger is a licensed pharmacist in New York State and the founder of PharmacistAnswers.com. He graduated from the University At Buffalo with a Doctor of Pharmacy degree in 2010. He has been featured in numerous publications including the Huffington Post as well as a variety of health and pharmacy-related blogs. Please feel free to reach out to him directly if you have any inquiries or want to connect! He's answered thousands of medication and pharmacy-related questions and he's ready to answer yours! Brian.Staiger@PharmacistAnswers.com Office: 716-389-3076

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