Systemic enzymes are a marketing term used to describe a category of supplemental health products.  The peer-reviewed, scientific literature make very little reference to “systemic enzymes” (most likely because the name is misleading).  Advertisers tell us that systemic means “body-wide” and “operate not just for digestion but throughout your body in every system and organ.”[1]

There are enzymes in the human body that meet this description, but the products sold as systemic enzymes do not.  However, these supplements still have value, but the mechanism of action and many of the claims made about them are unfounded.


One of the most popular systemic enzymes is serrapeptase, which is an enzyme that was found in the intestines of silkworms.  Later, it was discovered that it was not silkworms that produced serrapeptase, but bacteria called Serratia sp. E-15.[2]  Serrapeptase is a proteolytic enzyme, which means that it can break down proteins, and it is used to dissolve the cocoon during the final stage of the metamorphic process.[3]

Supplement companies will tell you to take serrapeptase on an empty stomach so that it can cross into the bloodstream without being digested and work its magic.  In the human model, there is not a transport system for this foreign enzyme.  Even in the silkworm model, it is used externally to dissolve the cocoon.  Even in the case of leaky gut, the majority of serrapeptase enzymes will not cross into the bloodstream.  This error in physiology provides for a different outlook on the supplemental use of serrapeptase.  After discovering this, can a supplement company really claim that their product will help with the degradation of fibrin, say, in your elbow?

There are some studies surrounding serrapeptase that show a decrease in inflammation.  There has been an interest in this enzyme for a while now following post-surgical care, because non-steroidal anti-inflammatory drugs do well to reduce inflammation, but they also promote bleeding.  There have been companies that have tried to make a pharmaceutical product using the serrapeptase enzyme, but they have been abandoned.  The clinical trials of serrapeptase and the reduction of inflammation have been mixed.[4][5][6]

The known application of supplemental serrapeptase that we can observe, measure, and duplicate, is its ability to degrade biofilm in the gut.  Listeria, for instance, can form biofilms that allow the colony to adhere to the intestines and acts as a shell to protect them from antibiotics.  When serrapeptase is used, it breaks down the biofilm and prevents them from adhering making treatment more effective.[7]  This implies that people who are dealing with issues like SIBO could potentially benefit from serrapeptase along with their antimicrobial treatments.

If you fall into this category, talk to your healthcare professional about taking serrapeptase to support your treatment plan.  We recommend Doctor’s Best Serrapeptase for its cost-effectiveness and potency.


Nattokinase is another systemic enzyme that is somewhat of a misnomer because it is not a kinase enzyme at all, but like serrapeptase, it is another proteolytic (protein-degrading) enzyme.  It was first discovered from the bacteria Bacillus subtilis (formally known as Bacillus natto).  This enzyme has a culinary use in making the famous Japanese dish, natto, a fermented food high in vitamin K2.

Unlike serrapeptase, there is an interesting article that describes the transport of the nattokinase enzyme from the small intestine into the plasma.[8]  Given what we know from other systemic enzymes, this seems unlikely, but when we look at the parameters of the experiment, we can sort out some of the cognitive dissonances.  The rats were given 80mg/kg, which is about sixty times the normal dose an adult would take in a supplement.  The nattokinase was also not delivered orally, but directly into the duodenum to bypass some of the digestive process.  This could indicate that through this form of delivery, the gut/blood barrier was compromised, and the enzyme was allowed access to the bloodstream.  So, there are problems with the study, but it is the only study out there that shows any sort of discussion on the transport of nattokinase.

The supplemental value of nattokinase comes from its ability to break down fibrin.  The positive rat study implies that humans could potentially use nattokinase to treat ganglion cysts, blood clots, and hypertension.  This is a bit of a leap from the current state of the research because none of this has been clinically tested through the typical research channels.  If you are going to take a leap of faith and try this supplement to treat any of the aforementioned conditions, please talk to your licensed medical professional first, because there are some interactions (warfarin for instance) that could be dangerous.

Like serrapeptase, nattokinase can break down biofilm in the gut.  Many people use these supplements in combination and claim that it has an increased effect.  Again, we recommend Doctor’s Best Nattokinase because it’s a good bang for the buck.

Some people have concerns about taking supplemental nattokinase because they question its purity, and given that it could be derived from Bacillus subtillis, they avoid taking these products.  Fortunately, this enzyme can be produced through recombination.[9]  So, if this is a worry for you, and you feel that you could benefit from this supplement, look for a company that uses E. Coli instead (although, this could pose a different set of problems).

Anecdotal Reports

This article holds systemic enzymes to a critical standard, but what about the anecdotal reports that we see about people using them and having success?  My theory is that they are reducing inflammation, which is a side effect of breaking down biofilms in the gut which controls the bacteria population, therefore reducing leaky gut.  If you have had positive results using these supplements, that’s great, but that doesn’t prove the mechanism, nor does it imply that other people will have a similar result.

The Best Product for Removing Biofilm

Klaire Labs makes a product called Interface Plus that really does a wonderful job of removing biofilm in the gut—much better than the systemic enzymes.  It contains a set of enzymes and the chelation agent, EDTA.  Biofilms require iron to complete the matrix, and EDTA binds the iron and the enzymes take care of the rest.  If you have SIBO, or another kind of GI infection, talk to your healthcare provider about Interface Plus to potentially enhance your treatment.

What has been your experience with systemic enzymes?  We would love to hear your story in the Fix Your Gut Forum!