Serrapeptase and nattokinase are both proteolytic enzymes sold as supplements, but they do fundamentally different things in the body. Serrapeptase is primarily an anti-inflammatory enzyme that breaks down proteins involved in swelling and fluid buildup, while nattokinase is primarily a fibrinolytic enzyme that dissolves the fibrin meshwork holding blood clots together. People often lump them together because both are marketed as “systemic enzymes,” but their origins, mechanisms, clinical evidence, and practical uses diverge in ways that matter if you’re trying to decide between them.
Where They Come From
Serrapeptase (also called serratiopeptidase) is produced by the bacterium Serratia marcescens. The enzyme was originally discovered in the intestines of silkworms, where it helps dissolve the cocoon so the moth can emerge. Today it is produced through bacterial fermentation rather than harvested from insects. Research strains of Serratia marcescens have been shown to produce substantial proteolytic activity in laboratory culture conditions.1Frontiers in Microbiology / Europe PMC. Bioprospecting of serratiopeptidase-producing bacteria from different sources
Nattokinase comes from an entirely different microbial world. It is produced by Bacillus subtilis var. natto during the fermentation of soybeans into natto, a traditional Japanese food with a distinctive sticky, stringy texture.2PubMed. Toxicological assessment of nattokinase derived from Bacillus subtilis var. natto Purified nattokinase is a relatively small protein, around 29,000 daltons, that works best at mildly alkaline pH and moderate temperatures.3PubMed. Purification and characterization of nattokinase from Bacillus subtilis natto B-12 The “kinase” in the name is actually a misnomer that stuck; nattokinase is a serine protease, not a true kinase, but the name is now universal in both supplement marketing and the research literature.
How They Work Differently
The distinction that matters most is what each enzyme targets once it reaches your bloodstream.
Serrapeptase acts on the inflammatory cascade. It reduces capillary permeability triggered by histamine, bradykinin, and serotonin, which are the chemical signals that cause tissues to swell after injury or surgery. It also breaks down abnormal exudates and proteins at sites of inflammation, helping the body reabsorb decomposed products through the blood and lymphatic systems.4Asian Journal of Pharmaceutical Sciences. The role of serratiopeptidase in the resolution of inflammation – Section: Molecular mechanism Think of it as a cleanup enzyme: it chews through the protein debris that accumulates when tissues are inflamed.
Nattokinase works on blood clots. It directly degrades fibrin, the structural protein that forms the scaffolding of a clot. But its effects go beyond simply dissolving fibrin. Research has found that even heat-deactivated nattokinase culture solutions can stimulate vascular endothelial cells to release tissue plasminogen activator (tPA), which is your body’s own clot-dissolving molecule.5Pathophysiology of Haemostasis and Thrombosis. Nattokinase-Promoted Tissue Plasminogen Activator Release from Human Cells This means nattokinase appears to work through both direct and indirect pathways to keep fibrin from building up in blood vessels. A review of the cardiovascular research described nattokinase as having fibrinolytic, antihypertensive, anti-atherosclerotic, lipid-lowering, and antiplatelet effects.6PubMed Central. Nattokinase: A Promising Alternative in Prevention and Treatment of Cardiovascular Diseases
The shorthand version: serrapeptase is an anti-inflammatory protease, nattokinase is a blood-thinning protease. They are not interchangeable, despite being sold side by side in the supplement aisle.
What the Clinical Trials Actually Show for Serrapeptase
Most of the solid clinical data on serrapeptase comes from oral and dental surgery, where post-operative swelling, pain, and restricted jaw opening (trismus) are easy to measure. In a randomized controlled trial after impacted wisdom tooth removal, serrapeptase significantly improved both swelling and trismus by the fourth day compared to control, though it did not make a meaningful difference in pain scores.7PubMed Central. Efficacy of serratiopeptidase after impacted third molar surgery: a randomized controlled clinical trial Another trial comparing serrapeptase head-to-head with the corticosteroid methylprednisolone found serrapeptase was actually better at resolving post-operative swelling and trismus after lower third molar surgery.8PubMed Central. Comparison of clinical efficacy of methylprednisolone and serratiopeptidase for reduction of postoperative sequelae after lower third molar surgery
That said, when compared with the corticosteroid dexamethasone in a separate trial, the picture was more nuanced. Serrapeptase reduced swelling from the second through the fifth postoperative day, but dexamethasone was more effective overall at controlling swelling.9PubMed Central. Role of Serratiopeptidase and Dexamethasone in the Control of Postoperative Swelling The evidence paints serrapeptase as a legitimate anti-swelling agent that performs respectably alongside pharmaceutical anti-inflammatories, though not as a universal replacement for them.
Where the evidence gets thinner is outside of surgical recovery. You will find serrapeptase promoted for sinusitis, joint pain, carpal tunnel, and even arterial plaque, but well-designed trials for these uses are sparse. The dental surgery trials are the foundation of serrapeptase’s clinical credibility, and the rest of the marketing runs well ahead of the data.
What the Clinical Trials Show for Nattokinase
Nattokinase’s clinical story centers on cardiovascular health, particularly blood pressure. A systematic review and meta-analysis of randomized controlled trials found that nattokinase supplementation lowered systolic blood pressure by about 3.5 mmHg and diastolic blood pressure by about 2.3 mmHg compared to placebo.10PubMed Central. Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Those numbers are modest, but they’re in line with what you’d expect from dietary interventions like reducing sodium or increasing potassium, and they come from pooled trial data rather than a single study.
An earlier randomized controlled trial focused specifically on blood pressure found that eight weeks of nattokinase supplementation reduced systolic blood pressure by about 5.5 mmHg compared to placebo, along with a reduction in renin activity, one of the hormonal drivers of blood pressure.11Hypertension Research. Effects of Nattokinase on Blood Pressure: A Randomized, Controlled Trial The same meta-analysis, however, found that relatively low-dose nattokinase supplementation did not produce a significant lipid-lowering effect, which tempers some of the broader cardiovascular claims you’ll see in marketing materials.12PubMed Central. Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
The fibrinolytic effects are well established in lab and animal models, and human pharmacokinetic data confirms that oral nattokinase does increase markers of fibrinolysis and anticoagulation in the blood. But the leap from “dissolves clots in a test tube” to “prevents strokes and heart attacks in humans” has not been definitively made in large-scale clinical outcomes trials. The cardiovascular research is promising enough to justify ongoing investigation, but researchers tend to describe nattokinase as a candidate for prevention and adjunctive therapy rather than a proven treatment.
Getting Them Into Your Bloodstream
Both enzymes face the same challenge every oral protein supplement does: surviving the acid bath of your stomach. The two handle it differently, and this has real implications for how they’re formulated.
Serrapeptase is particularly vulnerable to breakdown in the gastrointestinal tract because of its protein structure.13PubMed. Advances and challenges in serratiopeptidase topical formulation This is why virtually all serrapeptase supplements use enteric coating, a protective shell that resists stomach acid and dissolves only in the more alkaline environment of the small intestine. Research on formulation has shown that enteric-coated serrapeptase tablets can successfully restrict enzyme release in acidic conditions matching stomach pH.14PubMed Central. Formulation and development of Serratiopeptidase enteric coated tablets and analytical method validation by UV Spectroscopy If you buy a serrapeptase supplement without enteric coating or a delayed-release capsule, there’s a real question about how much active enzyme reaches your bloodstream.
Nattokinase appears to have a somewhat easier time. Animal models and cell studies show it is moderately absorbed across the intestinal lining through energy-dependent endocytosis pathways.15PubMed. Study on the transport and internalisation mechanism of dietary supplement nattokinase in the small intestine using animal and Caco-2 cell monolayer models A human pharmacokinetic study confirmed that after a single oral dose of 2,000 fibrinolytic units, nattokinase was detectable in serum, with peak levels at roughly 13 hours and measurable activity from about 2 hours through 24 hours.16PubMed. A pilot study on the serum pharmacokinetics of nattokinase in humans following a single, oral, daily dose A separate study looking at fibrinolysis and anticoagulation markers after a single dose of nattokinase confirmed increased activity between 2 and 8 hours after intake, consistent with genuine oral absorption.17Scientific Reports. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles
The practical takeaway: nattokinase has more robust pharmacokinetic data in humans showing it survives digestion and reaches the bloodstream in active form. Serrapeptase probably does too, but it’s more dependent on proper enteric coating, and the human bioavailability data is less developed.
Safety and Risk Profiles
Neither enzyme has a reputation for being dangerous at typical supplement doses, but the risk profiles differ in character because the enzymes do different things.
Serrapeptase’s reported side effects are rare but occasionally severe. Case reports in the literature include bullous pemphigoid (a blistering skin condition), pneumonitis, acute eosinophilic pneumonia, and Stevens-Johnson syndrome when combined with diclofenac.18MAMC Journal of Medical Sciences. An Assessment of Availability, Cost and Rationality of Serratiopeptidase Preparations in India These are isolated case reports, not common events, but they’re worth knowing about, especially because serrapeptase is often combined with NSAIDs in some markets. Gastrointestinal discomfort and nausea are the more typical complaints. The enzyme should be taken on an empty stomach for absorption, which can itself contribute to stomach upset in some people.
Nattokinase’s risks are tied directly to its blood-thinning mechanism. Anything that promotes fibrinolysis and has antiplatelet effects can, in theory, increase bleeding risk. This becomes especially dangerous when people use nattokinase as a substitute for prescribed anticoagulants without medical supervision. A well-documented case report describes a patient who replaced warfarin with nattokinase after mechanical aortic valve replacement. After nearly a year on nattokinase alone, the patient developed a clot on the mechanical valve and required emergency repeat surgery.19PubMed Central. Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis Nattokinase has real biological activity, but its potency and consistency are nowhere near sufficient to replace pharmaceutical anticoagulation in high-risk situations.
If you’re on blood thinners, antiplatelet drugs, or any medication affecting coagulation, nattokinase is not something to add casually. The interaction potential is real. Serrapeptase, while it may theoretically increase the absorption of certain co-administered drugs due to its protein-digesting activity, poses less direct risk to clotting, though combining it with anticoagulants still warrants caution.
When You Might Choose One Over the Other
The decision between serrapeptase and nattokinase comes down to what problem you’re trying to address, because their evidence bases barely overlap.
If your concern is post-surgical or post-injury swelling, serrapeptase has the more relevant clinical evidence. The dental surgery trials consistently show it reduces edema and improves jaw mobility, and there’s a reasonable biological basis for expecting similar effects on soft tissue swelling elsewhere. People recovering from minor surgeries, dealing with sinus congestion, or managing localized inflammation are the typical supplement buyers, and serrapeptase is the one with mechanistic and clinical data in that space.
If your concern is cardiovascular, nattokinase is the more studied and more logical choice. It has meta-analytic evidence for modest blood pressure reduction, well-characterized fibrinolytic activity in human blood, and a broader body of cardiovascular research. People interested in circulatory health, blood pressure support, or fibrin management would look to nattokinase.
Some supplement companies sell combination products containing both enzymes, marketing them as a comprehensive systemic enzyme formula. There isn’t published clinical trial data specifically testing the two together in a single study. The rationale is that their mechanisms don’t compete and could complement each other, but until someone actually runs the trial, that’s speculation rather than evidence.
Dosing Units Are Not Comparable
One source of confusion when comparing these supplements is that they use completely different measurement systems. Serrapeptase is typically dosed in SPU (serratiopeptidase units), with common retail doses ranging from 60,000 to 120,000 SPU. Nattokinase is dosed in FU (fibrinolytic units), with a common dose of 2,000 FU, which is the amount used in the pharmacokinetic study that first demonstrated human absorption.20PubMed. A pilot study on the serum pharmacokinetics of nattokinase in humans following a single, oral, daily dose You cannot convert between SPU and FU because they measure different enzymatic activities on different substrates. A higher number of SPU does not mean “stronger” than a lower number of FU. They’re measuring fundamentally different things.
Supplement labels sometimes list milligrams of enzyme instead of, or in addition to, activity units. Milligrams tell you how much protein powder is in the capsule but say nothing about how active the enzyme is. A poorly produced batch could have more milligrams but fewer activity units than a well-made one. Activity units are the more meaningful number if you want to know what you’re actually getting.
The Biofilm Question
A newer area of interest for both enzymes is their potential role against bacterial biofilms, the protective slime layers that bacteria build around themselves on surfaces like medical implants, chronic wound tissue, and sinus passages. Proteolytic enzymes can degrade the protein components of these biofilms, potentially making the bacteria inside more vulnerable to antibiotics. Research has suggested that using enzymes like serrapeptase in combination with antibiotics could be effective against microbes hiding within biofilm structures.21ADMET and DMPK. Natural serine proteases and their applications in combating amyloid formation – Section: Serratiopeptidase
Nattokinase, as a serine protease, has also shown some biofilm-disrupting potential in lab settings, though the research is less developed than for serrapeptase in this specific application. The idea of using proteolytic enzymes as biofilm disruptors is legitimate science, but it’s still largely in the preclinical stage. Nobody should be taking either supplement as a biofilm treatment based on current evidence. It is, however, one of the more interesting research directions for both enzymes, and it illustrates that their utility may eventually extend well beyond the anti-swelling and blood-thinning applications they’re currently known for.
Why the Regulatory Landscape Matters
In most Western countries, both serrapeptase and nattokinase are sold as dietary supplements, not pharmaceuticals. This has practical consequences. Supplement manufacturers are not required to demonstrate clinical efficacy before selling a product, only that the ingredients are generally recognized as safe. Purity, potency, and actual enzyme activity can vary between brands without any regulatory consequence unless a product causes documented harm.
In India and parts of Southeast Asia, serrapeptase occupies a different regulatory niche. It is prescribed by physicians and often combined with analgesics or antibiotics in fixed-dose formulations. This means some of the published clinical research on serrapeptase comes from contexts where it is treated as a drug rather than a supplement, with stricter manufacturing standards than what you might find in the over-the-counter supplement market elsewhere. In Japan, natto itself is a common food, and nattokinase extracted from it has a long history of dietary use, though supplement-grade nattokinase concentrates are a different product from eating natto at breakfast.
The unregulated nature of these supplements also means that the dosages used in published clinical trials may not match what’s in the bottle you buy. Enteric coating quality for serrapeptase, enzyme activity standardization for both products, and the presence or absence of other ingredients all vary. If the research was done using a pharmaceutical-grade preparation and you’re taking a budget supplement brand, you may not be comparing like with like.