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What Is Serrapeptase? The Silkworm Enzyme

Writer: Megan Elliott
Megan Elliott
Oct 13
11 min read

What is serrapeptase? It is a protein-cutting enzyme made by a bacterium that was first found in the gut of silkworms, sold in Japan as a prescription anti-inflammatory from 1968, pulled from that market in 2011 when placebo-controlled trials could not show a difference, and now sold worldwide as a supplement ingredient measured in SPU. The silkworm story is true. Most of what else is written about it online is not supported by the trials. This article covers where the enzyme comes from, what kind of enzyme it is and how it differs from nattokinase, what SPU measures, how a protein gets past your stomach, what the research found and did not find, and why 240,000 SPU sits beside nattokinase in a nattokinase serrapeptase supplement like ours.



Serrapeptase at a glance infographic: where the silkworm enzyme comes from, how it differs from nattokinase, and what the trials show
Serrapeptase at a glance: where the enzyme comes from, how it differs from nattokinase, and what the trials did and did not show.

Where serrapeptase comes from


The origin story sounds invented, but it is in the pharmacology monographs. In the 1960s, Japanese researchers isolated a bacterium, Serratia marcescens, from the intestines of the silkworm Bombyx mori. The enzyme it secretes breaks down the proteins of the silkworm's cocoon so the moth can emerge. The strain was first called E-15 and is now catalogued as ATCC 27117, according to the professional monograph on Drugs.com, reviewed in January 2026. The enzyme has collected names along the way: serratiopeptidase, serralysin, Serratia peptidase, and serrapeptase, which is its international nonproprietary name.


In 1968 it reached the Japanese pharmaceutical market "for a broad range of indications," the monograph notes. For four decades it was a prescription medicine there and in several other countries, which is why the product page for our formula calls it an enzyme "used in systemic enzyme therapy for decades." That history is why it has a research record at all, and why the record looks the way it does: most of the trials were drug trials for swelling and pain, not studies of healthy adults.


Today the enzyme is produced by fermenting Serratia marcescens in nutrient-rich media, as a 2020 review in Biotechnology Reports describes; no silkworms are involved.


What kind of enzyme it is, and how it differs from nattokinase


"Proteolytic" means protein-cutting. Serrapeptase is, in the 2020 review's words, "a zinc containing metalloprotease of molecular weight 45–60 kDa," classified as EC 3.4.24.40 in the serralysin family. It is most active at pH 9.0 and 40 °C, loses activity within 15 minutes at 55 °C, and keeps its folded structure across a pH range of 3 to 10. Researchers know it, the review says, "for its caseinolytic (proteolytic) and fibrinolytic properties" — it cuts casein, the milk protein used in standard enzyme assays, and fibrin, the protein mesh our explainer on what fibrin is covers.


Nattokinase is a different enzyme from a different family. It is a serine protease of 275 amino acids weighing about 27.7 kilodaltons, 99.3 percent identical in sequence to the bacterial enzyme subtilisin E, and distinguished by "a very specific affinity for fibrin," according to a 2017 review in the International Journal of Molecular Sciences. One enzyme uses a zinc ion at its active site; the other uses a serine residue. Both cut proteins, which is the whole reason a formula might carry both: they are two separate tools rather than two doses of one.


That is also the plain meaning of the phrase on our product page, "a second enzyme-based mechanism." It is a description of chemistry, not a promise about outcomes.


What SPU measures


A nattokinase and serrapeptase label carries two activity units, and neither is a weight. Our guide to what 10,800 FU means explains the first. SPU, usually read as serrapeptase units, works the same way for the second enzyme: it measures how much protein-cutting work the enzyme does under the assay's conditions. By the definition the Drugs.com monograph gives, one unit "produces 5 mcg of tyrosine per minute" from a protein substrate, and the monograph reports roughly 2,000 to 2,600 units per milligram of enzyme.


The pharmaceutical literature doses serrapeptase in milligrams — the monograph's usual adult dose is 10 mg three times a day — while supplement labels state units, and unit definitions and assay conditions differ between laboratories and manufacturers. Converting a label's SPU to the milligrams in a 1990 trial is unreliable, and this article does not do it. Compare SPU with SPU, and check whether the figure is per capsule or per serving. Our label states 240,000 SPU per two-capsule serving.


How an enzyme gets past the stomach


Enzymes are proteins, and the stomach is built to digest proteins. Serrapeptase's folded structure survives pH 3 to 10, the 2020 review notes, but the review also attributes the high doses needed in animal studies to "the low bioavailability of serratiopeptidase," and reports that enteric dispersion of the enzyme "has shown promising results for controlled release." Health Canada, which lists serrapeptase as a natural health product ingredient, permits the enteric-coated version, according to the same review's regulatory table.


The clearest absorption evidence is old and in animals. In a 1994 study in Biotechnology and Applied Biochemistry, researchers gave rats serrapeptase by mouth at 100 mg per kilogram and measured it in the blood with an antibody assay. Plasma levels peaked between 30 minutes and two hours, and the enzyme that arrived was still active: the authors concluded it "was absorbed from the intestinal tract and transferred into the circulation in an enzymically active form." Human absorption data are thinner, and a rat dose of 100 mg per kilogram is not a human serving.


This is the same problem the capsule has to solve for nattokinase, which the Japan NattoKinase Association calls "easily affected by stomach acid" — our article on natto vs nattokinase covers that half. Great Billiom's capsules are delayed-release vegetarian HPMC, designed to open past the stomach, and the label directs an empty stomach for the same reason.


What the trials found, and what they did not


Serrapeptase was prescribed, in the words of a 2013 systematic review in the International Journal of Surgery, "in various specialities like surgery, orthopaedics, otorhinolaryngology, gynaecology and dentistry for its anti-inflammatory, anti-edemic and analgesic effects." The most cited of the older trials is a 1990 multicentre study in the Journal of International Medical Research: 193 patients with acute or chronic ear, nose or throat complaints took the enzyme or a placebo, two tablets three times a day, for seven to eight days. The enzyme group showed "significant symptom regression" by day three or four, and tolerance "was found to be very good and similar for both groups."


Then the evidence was re-examined. In February 2011, Takeda voluntarily recalled Dasen, its serrapeptase tablets and granules, from the Japanese market. The Pharma Letter reported that in double-blind studies against placebo "no statistical significant differences were found," that the regulator's re-evaluation committee asked for further trials, and that Takeda concluded "it would be difficult to conduct additional studies as requested." Nine months later, Singapore's Health Sciences Authority announced it was phasing out the ten serrapeptase medicines registered there, because "there is no substantive scientific evidence to support the classification of serratiopeptidase as a medicinal product" and it "does not provide significant clinical benefit over the use of placebo for the approved indications." The same notice recorded a "long history of use" in Singapore "with minimal safety concerns."


The 2013 systematic review reached the matching verdict. Its authors found 24 clinical studies and graded them with the Scottish Intercollegiate Guidelines Network checklist. The evidence, they wrote, "is based on clinical studies which are of poor methodology"; the few randomized trials were usually placebo-controlled and limited in size, dose and duration went unspecified in some, and outcomes were unclear in others. Noting that the enzyme was by then also being promoted as a heart-health supplement, they concluded: "The existing scientific evidence for Serratiopeptidase is insufficient to support its use as an analgesic and health supplement. The data on long-term safety of this enzyme is lacking." The 2020 review is warmer, reporting "some strong evidences regarding the efficacy of serratiopeptidase," but adds that "data on safety, tolerability, and its mechanism of action need detailing."


Question

What the record shows

Source

Where does it come from?

Serratia marcescens (strain E-15, now ATCC 27117), isolated from the silkworm gut in the 1960s; on the Japanese drug market from 1968

Drugs.com monograph, 2026

What kind of enzyme is it?

A zinc metalloprotease, 45–60 kDa, EC 3.4.24.40; nattokinase is a 27.7 kDa serine protease

Jadhav 2020; Weng 2017

Is it absorbed when swallowed?

In rats, yes, in active form, peaking at 30 minutes to 2 hours; human data are thinner; low bioavailability is why enteric forms exist

Moriya 1994; Jadhav 2020

Did the drug trials show benefit?

Older placebo-controlled trials reported symptom relief in ENT and post-surgical swelling; a 2011 re-evaluation found no significant difference from placebo

Mazzone 1990; Pharma Letter 2011; HSA 2011

What did the systematic review conclude?

24 studies of poor methodology; evidence "insufficient to support its use as an analgesic and health supplement"; long-term safety data lacking

Bhagat 2013

Is it well tolerated?

Well tolerated in short-term trials of more than 1,400 patients; rare serious single-case reports; may raise bleeding risk with anticoagulants or antiplatelets

Drugs.com monograph, 2026


Read across the rows, the honest summary is this: serrapeptase is a real enzyme with a real pharmacological history, its older trials were limited in size and the 2011 re-evaluation did not confirm them, and no trial has tested it for circulation outcomes in healthy adults. Anything on a label or a blog that says more than that is ahead of the evidence.


Safety, and who should ask first


The safety record is more reassuring than the efficacy record, with a stated gap. Drugs.com reports that serrapeptase "was well tolerated in short-term clinical trials enrolling more than 1,400 patients," lists contraindications as "None known," and notes that those trials "do not provide long-term safety data." It records a handful of serious single-case reports, including severe skin reactions. The line that matters most for a circulation formula is this one: serrapeptase "may increase the risk of bleeding if coadministered with anticoagulants or antiplatelet drugs." That is the same caution nattokinase carries, and it is on our label. Anyone taking warfarin, aspirin, Eliquis, Plavix or any other medication that affects the blood, anyone pregnant or nursing, and anyone with surgery scheduled should talk to their doctor before taking either enzyme.


Where Great Billiom Nattokinase 10,800 FU fits


Great Billiom Nattokinase 10,800 FU with K2 MK-7 and 240,000 SPU serrapeptase beside a dish of silk cocoons — supports healthy blood flow and circulation
Great Billiom Nattokinase 10,800 FU with K2 MK-7 and 240,000 SPU serrapeptase — three ingredients, two enzymes, one two-capsule serving. Supports healthy blood flow and circulation.*

Serrapeptase is the third ingredient in our formula, and the product page describes its role in one sentence: it "adds proteolytic enzyme support … complementing nattokinase." That is the claim, and it is the whole claim. Everything above explains what "proteolytic enzyme support" means in chemistry — a second protein-cutting enzyme, from a different family, alongside the first. No trial has tested this three-ingredient formula, and the serrapeptase trials above were drug trials in patients, not studies of circulation in healthy adults, so this article makes no claim on serrapeptase's behalf beyond the one on the label. The uses serrapeptase is promoted for elsewhere online are not claims Great Billiom makes.


What the formula is built around is nattokinase. Each two-capsule serving delivers 10,800 FU, matching the higher dose arm of the largest nattokinase study to date, 1,062 adults followed for 12 months in Frontiers in Cardiovascular Medicine, whose authors state plainly that it "represents a retrospective study and not a randomized control trial." Alongside it sit 180 mcg of vitamin K2 as MK-7, which supports calcium delivery to bones and teeth, and 240,000 SPU of serrapeptase, in delayed-release vegetarian capsules — 90 per bottle, 45 servings, $19.99, or $17.99 on Subscribe & Save. The formula supports healthy blood flow and circulation and healthy fibrin metabolism for adults 40 and over.* The label directs two capsules daily on an empty stomach, at least an hour before or two hours after a meal. It contains soy, and the medication, pregnancy and surgery cautions above apply.



Key takeaways


  • Serrapeptase is a protein-cutting enzyme from the bacterium Serratia marcescens, first isolated from the silkworm's gut in the 1960s; the enzyme is what lets the moth out of its cocoon (Drugs.com monograph, 2026).

  • It is a zinc metalloprotease of 45–60 kDa; nattokinase is a 27.7 kDa serine protease. They are two different enzymes from two different families, which is what "a second enzyme-based mechanism" means (Jadhav 2020; Weng 2017).

  • SPU is an activity unit, not a weight. Compare SPU with SPU, check per capsule versus per serving, and do not convert to the milligram doses used in drug trials — unit definitions and assay conditions differ.

  • The enzyme was a prescription anti-inflammatory in Japan from 1968 until Takeda withdrew it in 2011 after placebo-controlled re-evaluation found no significant difference; a 2013 systematic review called the 24 trials "of poor methodology" and the evidence "insufficient to support its use as an analgesic and health supplement."

  • Short-term trials in more than 1,400 patients found it well tolerated, but long-term safety data are lacking and it may raise bleeding risk with anticoagulants or antiplatelets — ask your doctor first if you take any medication that affects the blood.


Now you know what the third line on the label is: a second protein-cutting enzyme, with a long history and a modest evidence base, riding alongside the ingredient the formula is built around. If what you want is daily support for healthy blood flow and circulation at the research-matched nattokinase dose, with K2 MK-7 and 240,000 SPU of serrapeptase in one two-capsule serving, Great Billiom Nattokinase 10,800 FU is $19.99.



Frequently asked questions


What is serrapeptase made from?


Serrapeptase is produced by fermenting the bacterium Serratia marcescens, originally isolated in the 1960s from the intestines of the silkworm Bombyx mori, where the enzyme breaks down the cocoon so the moth can emerge. Supplement-grade enzyme comes from controlled fermentation of the bacterium, not from silkworms. It is also called serratiopeptidase or serralysin.


Is serrapeptase the same as nattokinase?


No. Serrapeptase is a zinc-containing metalloprotease of 45–60 kilodaltons from Serratia marcescens; nattokinase is a 27.7-kilodalton serine protease from the Bacillus subtilis fermentation that makes natto. Both cut proteins, including fibrin, but they belong to different enzyme families and use different chemistry at the active site. A formula carrying both carries two separate enzymes.


What does SPU mean on a serrapeptase label?


SPU, usually read as serrapeptase units, measures enzyme activity — how much protein the enzyme cuts per minute under set assay conditions — not weight. By one published definition, one unit frees 5 micrograms of tyrosine per minute. Compare SPU with SPU, confirm whether the figure is per capsule or per serving, and approach milligram conversions with caution.


Does serrapeptase actually work?


The honest answer is that the evidence is limited. Older placebo-controlled trials in ear, nose and throat and post-surgical swelling reported symptom relief, but a 2011 Japanese re-evaluation found no significant difference from placebo, and a 2013 systematic review judged the 24 clinical studies to be of poor methodology. No trial has tested it for circulation in healthy adults.


Why is serrapeptase in a nattokinase supplement?


In Great Billiom Nattokinase 10,800 FU, serrapeptase adds proteolytic enzyme support alongside nattokinase — a second protein-cutting enzyme from a different family, 240,000 SPU per two-capsule serving. The formula is built around the 10,800 FU nattokinase dose used in the largest nattokinase study; serrapeptase's role is the one on the product page, and this article claims nothing beyond it.


Megan Elliott, Content Editor at Great Billiom. Every claim in this article is sourced from the primary research linked above. Read our editorial standards → thegreatbilliom.com/editorial-standards


Sources



*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. Individual results may vary.


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