Nattokinase vs. Serrapeptase

Two proteolytic enzymes dominate the systemic enzyme conversation in 2025 — nattokinase, derived from fermented soybeans, and serrapeptase, originally isolated from silkworm bacteria — and choosing between them starts with understanding what each one is actually built to do.

Both belong to the serine protease family and both are marketed for circulatory and inflammatory support. But they come from different biological sources, act through different pathways, and have meaningfully different bodies of clinical evidence behind them. A 2023 meta-analysis of six randomized controlled trials confirmed nattokinase's cardiovascular effects; the serrapeptase literature, by contrast, is strongest for localized post-surgical inflammation.

Table of Contents

1. What Are Systemic Enzymes?
2. How Nattokinase Works
3. How Serrapeptase Works
4. Research Evidence: A Realistic Comparison
5. Use Cases: Who Should Consider Which Enzyme?
6. Safety and Drug Interactions
7. BioAbsorb Nattokinase — What to Look for in a Quality Supplement
8. Frequently Asked Questions
9. Conclusion

What Are Systemic Enzymes?

Most people think of enzymes as digestive tools — substances that break down food in the gut. Systemic enzymes are different. When taken on an empty stomach, they are absorbed intact through the intestinal wall and enter the bloodstream, where they can exert effects throughout the body rather than just in the digestive tract. Both nattokinase and serrapeptase belong to this category, and both are classified as serine proteases — enzymes that use the amino acid serine at their active site to cleave peptide bonds in protein substrates.

The core concept behind systemic enzyme therapy is that the body accumulates excess proteins over time — fibrin deposits, inflammatory byproducts, scar tissue components — and that targeted enzymatic activity can help clear these substrates, supporting vascular health and reducing chronic inflammatory burden. Both nattokinase and serrapeptase contribute to systemic protein metabolism — nattokinase acting primarily on fibrin and the clotting cascade, serrapeptase acting more broadly on inflammatory proteins and dead tissue — but through different mechanisms and with different primary targets.

One practical distinction: neither enzyme survives unprotected transit through the stomach's acidic environment. This makes capsule technology a meaningful quality factor — look for delayed-release or enteric-coated formulations for either enzyme to have any systemic effect at all.

How Nattokinase Works

Nattokinase was first identified in 1987 by Japanese researcher Dr. Hiroyuki Sumi, who placed a sample of natto on an artificial blood clot in a petri dish and observed complete dissolution within 18 hours. The enzyme is produced by the bacterium Bacillus subtilis during the fermentation of soybeans into natto, and its fibrinolytic activity has since been characterized in considerable mechanistic detail.

Nattokinase operates through two complementary pathways. First, it directly cleaves and degrades fibrin — the cross-linked protein mesh that forms the structural scaffold of blood clots. Second, and more significantly for its cardiovascular relevance, it inactivates plasminogen activator inhibitor-1 (PAI-1). Research published in Biomarker Insights (2018) confirmed that nattokinase cleaves PAI-1 into low-molecular-weight fragments, which allows tissue plasminogen activator (tPA) to generate more plasmin — effectively amplifying the body's own fibrinolytic system rather than simply substituting for it. A third mechanism involves converting prourokinase to urokinase, adding a further upstream push to the clot-clearing cascade.

This multi-pathway action distinguishes nattokinase from simpler fibrinolytic agents. A double-blind, placebo-controlled crossover study in Scientific Reports (2015) found that a single oral 2,000 FU dose in 12 healthy males produced measurable increases in D-dimer and fibrin degradation products within 4–8 hours, alongside reductions in Factor VIII activity and increases in antithrombin — a coordinated shift across multiple clotting and fibrinolytic markers. Early characterization research estimated nattokinase's fibrinolytic activity to be approximately four times that of plasmin itself. For a deeper look at these pathways, see our article on how nattokinase works.

How Serrapeptase Works

Serrapeptase — also called serratiopeptidase — was originally discovered in the digestive tract of silkworms, where it dissolves the protein-rich cocoon to allow the emerging moth to escape. The enzyme is derived from Serratia marcescens bacteria (originally classified as Serratia E15) and has been used clinically in Japan and parts of Europe for decades, though it remains available only as a supplement in North America.

Unlike nattokinase's specificity for fibrin and the fibrinolytic cascade, serrapeptase is a broader proteolytic agent. A systematic review in the International Journal of Surgery (2013) describes its activity as anti-inflammatory, anti-edematous, and analgesic — primarily through its ability to break down non-living proteins including dead tissue, excess mucus, and inflammatory byproducts. Its analgesic effect is attributed in part to inhibition of bradykinin and other pain-mediating amines. Research in rats found that after oral administration, serrapeptase is absorbed from the intestine into the bloodstream and distributes preferentially to inflamed tissues, reaching concentrations at inflammation sites higher than those in plasma.

A critical formulation note: Examine.com's research breakdown confirms that serrapeptase is destroyed in the acidic environment of the stomach and requires enteric encapsulation to retain any bioactivity. Even with enteric coating, serrapeptase's hydrophilic nature means intestinal membrane permeability is low, and researchers have noted that relatively high doses may be needed to achieve significant anti-inflammatory effects systemically. This is a meaningful practical limitation that the enzyme's proponents do not always disclose.

Research Evidence: A Realistic Comparison

Nattokinase's clinical evidence base is broader, more consistent, and more replicable than serrapeptase's when it comes to systemic cardiovascular and fibrinolytic endpoints.

For nattokinase, a 2023 systematic review and meta-analysis published in Reviews in Cardiovascular Medicine pooled six randomized controlled trials (546 participants) and found statistically significant reductions in systolic blood pressure (mean difference: −3.45 mmHg) and diastolic blood pressure (mean difference: −2.32 mmHg) compared to placebo. A landmark 2008 RCT by Kim et al., published in Hypertension Research, had already found net reductions of 5.55 mmHg systolic and 2.84 mmHg diastolic over 8 weeks of 2,000 FU daily. A separate human trial confirmed that nattokinase significantly reduced circulating fibrinogen and clotting factors relative to placebo. These are consistent, replicated findings in human subjects using clinically relevant endpoints.

Serrapeptase's strongest human evidence sits in a different domain: localized post-surgical inflammation. A double-blind, placebo-controlled trial in 174 patients undergoing Caldwell-Luc antrotomy found significantly less buccal swelling in the serrapeptase group at every post-operative observation point through day five. A 2023 meta-analysis of serratiopeptidase in third molar surgery found it effective at reducing trismus (restricted jaw opening). However, the International Journal of Surgery systematic review explicitly noted that the overall evidence base for serrapeptase "is based on clinical studies which are of poor methodology" and called for better-designed trials across a wider range of conditions. Systemic anti-inflammatory effects beyond surgical contexts remain far less established.

In short: nattokinase is the more research-supported choice for cardiovascular-focused outcomes. Serrapeptase has legitimate evidence for post-surgical and localized inflammatory applications, but its systemic evidence is thinner and methodologically weaker. This is not a dismissal of serrapeptase — it is an honest account of where the literature currently stands.

Use Cases: Who Should Consider Which Enzyme?

The clearest way to think about this decision is by primary health goal.

Nattokinase is the stronger choice for cardiovascular and circulatory goals. If you are interested in supporting healthy blood flow, managing blood pressure, reducing excess fibrin in the bloodstream, or supporting your body's natural clot-clearing capacity, nattokinase has the more relevant and consistent research backing. This applies to people proactively managing cardiovascular risk factors, those with elevated blood pressure looking for an adjunctive approach under physician guidance, and health-conscious adults in the 45+ age group where fibrinolytic capacity naturally declines. The standard clinically studied dose — 100 mg (2,000 FU) once daily on an empty stomach — is the same dose used in the key human trials. For a full overview of dosing evidence, see the Nattokinase Dosage Guide.

Serrapeptase may be more relevant for inflammatory and recovery-focused goals. If your primary interest is supporting recovery from surgery, reducing chronic sinus congestion, or managing localized inflammatory conditions, serrapeptase has a more direct evidence base for those applications. Its broader proteolytic activity — targeting dead tissue, mucus, and inflammatory proteins rather than fibrin specifically — makes it mechanistically suited to these use cases even if the clinical evidence is thinner than its proponents sometimes suggest.

What about taking both? Some practitioners recommend combining nattokinase and serrapeptase for people seeking both cardiovascular and inflammatory support. There is some theoretical rationale for this — their mechanisms are complementary rather than redundant — but human evidence for the combination specifically is limited. Anyone on anticoagulant or antiplatelet medication should not add either enzyme, let alone both, without physician oversight.

For broader cardiovascular context, see our overview of nattokinase for heart health.

Safety and Drug Interactions

Both nattokinase and serrapeptase carry anticoagulant-like activity and can affect the body's clotting balance. This is precisely why they are of interest for cardiovascular health — but it also creates real risk in certain populations.

The most important safety consideration for both enzymes is concurrent use with anticoagulant or antiplatelet medications. Warfarin, heparin, aspirin, and clopidogrel all affect clotting through different mechanisms, and adding either enzyme to these regimens can amplify bleeding risk unpredictably. Memorial Sloan Kettering Cancer Center notes that nattokinase may increase bleeding risk when used with blood-thinning drugs. Anyone on these medications must consult their physician before starting either supplement.

For nattokinase specifically, additional considerations include: BioAbsorb's nattokinase is intentionally free of Vitamin K2, which is a meaningful distinction — some competing nattokinase products include K2, which can complicate things for people already supplementing or managing K2 intake. Most reported side effects for nattokinase are minor and dose-dependent; the 2023 meta-analysis noted no significant adverse events across any of the six included trials. Anyone scheduled for surgery should discontinue nattokinase in advance — consult your surgeon for specific guidance on timing.

For serrapeptase, rare adverse events have included serrapeptase-induced lung injury manifesting as acute eosinophilic pneumonia, identified in case reports in the literature. The International Journal of Surgery systematic review flagged this and other safety signals as reasons for the call for better-designed long-term trials. Pregnant or breastfeeding women are advised to avoid serrapeptase due to insufficient safety data. Standard gastrointestinal side effects (nausea, diarrhea, stomach discomfort) are among the more commonly reported effects for both enzymes at higher doses.

BioAbsorb Nattokinase — What to Look for in a Quality Supplement

Not all nattokinase supplements are equal, and the difference often comes down to three factors: potency verification, capsule technology, and formulation integrity.

Potency verification. Nattokinase is measured in fibrinolytic units (FU), not milligrams alone — two products may both say "100 mg" on the label and have completely different enzymatic activity levels. The clinically studied dose used in the key human trials is 2,000 FU per capsule. BioAbsorb Nattokinase delivers 100 mg / 2,000 FU per capsule — consistent with the dose range used across the literature — and each batch is third-party tested for nattokinase activity, heavy metals, gluten, and microbial contaminants.

Capsule technology. BioAbsorb uses DRcaps — a delayed-release veggie capsule technology that protects the enzyme from stomach acid and delivers it intact to the small intestine. This matters because nattokinase, like serrapeptase, must survive stomach transit to have any systemic effect. DRcaps achieve this without the phthalates and plasticizers found in conventional enteric-coated capsules — a meaningful distinction for a health-conscious consumer.

Formulation integrity. BioAbsorb Nattokinase is non-GMO, manufactured in a Canadian GMP-certified facility, and free of gluten, nuts, eggs, dairy, fish, shellfish, and all animal products — 100% vegetarian. It is also intentionally free of Vitamin K2, which allows for higher or longer-term use without the cardiovascular caveats associated with excess K2 accumulation, and makes it compatible for people already supplementing K2 separately. At $49.87 for a 180-day supply, the cost per day is approximately $0.28 — strong value compared to competing 60-capsule products at similar price points.

If you are comparing nattokinase to serrapeptase and cardiovascular support is your primary goal, the evidence consistently points to nattokinase as the better-studied choice. BioAbsorb does not currently offer a serrapeptase product, but does offer a nattokinase formulation engineered to the clinical standard the research used.

Frequently Asked Questions

Can you take nattokinase and serrapeptase together?

Some practitioners combine them on the basis that nattokinase targets fibrin and the clotting cascade while serrapeptase addresses broader inflammatory proteins and dead tissue. There is theoretical logic to this complementarity, but human clinical evidence for the combination specifically is limited. The more important caution applies to anyone on blood-thinning medications: both enzymes have anticoagulant-like activity, and combining them — let alone combining either with warfarin or antiplatelet drugs — requires physician oversight.

Which enzyme has more clinical evidence behind it?

Nattokinase has a substantially stronger and more consistent human evidence base for cardiovascular endpoints. A 2023 meta-analysis pooling 546 participants across six RCTs found statistically significant reductions in blood pressure, with no notable adverse events. Serrapeptase has legitimate evidence for post-surgical and localized inflammatory applications, but the International Journal of Surgery systematic review acknowledged that many of the serrapeptase trials are methodologically weak and called for better-designed research across a broader range of conditions.

Do both enzymes need to be taken on an empty stomach?

Yes, for systemic effect. Both nattokinase and serrapeptase are absorbed from the small intestine and act systemically — but if taken with food, they will act as digestive enzymes on the meal rather than being absorbed intact into the bloodstream. Taking either enzyme at least 30 minutes before eating or two hours after a meal maximizes the likelihood of systemic absorption. BioAbsorb's DRcaps delayed-release capsule provides additional protection from stomach acid regardless of timing, but empty-stomach dosing remains recommended.

Is serrapeptase better than nattokinase for inflammation?

For localized post-surgical or acute inflammatory conditions — particularly those involving swelling, pain, or excess mucus — serrapeptase has more direct evidence than nattokinase. For systemic or cardiovascular inflammation, nattokinase has stronger and more consistent human data. Neither enzyme should be considered a replacement for anti-inflammatory medications prescribed by a physician. If chronic systemic inflammation is your concern, discussing the evidence and your specific situation with a healthcare provider will give you better guidance than either supplement alone.

What is the difference in how these enzymes are measured?

Nattokinase potency is expressed in fibrinolytic units (FU), which measure the enzyme's ability to break down fibrin specifically. The clinically studied standard is 2,000 FU per dose. Serrapeptase potency is expressed in SPU (serratiopeptidase units) or sometimes IU, reflecting its general proteolytic activity against a broader range of protein substrates. These units are not interchangeable and comparing the two by milligrams alone is not meaningful — what matters is the enzymatic activity level confirmed by third-party testing, not the weight of the raw powder.

Which enzyme is right for long-term cardiovascular support?

For sustained cardiovascular support — including blood pressure, fibrinolysis, and circulation — nattokinase is the better-evidenced option. Its multi-pathway mechanism (direct fibrin degradation, PAI-1 inactivation, tPA amplification) is well characterized in human studies, and the 2,000 FU daily dose has been used safely in trials ranging from 8 to 26 weeks. Serrapeptase's systemic cardiovascular evidence is comparatively thin. That said, "long-term" should always mean under periodic physician review, particularly for anyone with a diagnosed cardiovascular condition or who takes any medication affecting clotting.

Conclusion

Nattokinase and serrapeptase are genuinely different tools — not interchangeable alternatives — and the evidence supports that distinction. If cardiovascular health, blood pressure, and fibrinolytic support are your goals, nattokinase has the deeper, more consistent human clinical record. If post-surgical recovery or localized inflammation is your primary concern, serrapeptase may be worth exploring, with realistic expectations about the quality of the evidence. A 2023 meta-analysis confirmed nattokinase's meaningful blood pressure reductions across six replicated trials — a standard the serrapeptase literature has not yet met for comparable systemic endpoints. If you are ready to start, BioAbsorb Nattokinase delivers the 2,000 FU clinical dose in DRcaps delayed-release veggie capsules, third-party tested, non-GMO, and manufactured in a Canadian GMP-certified facility.

Research References

1. Kim JY, Gum SN, Paik JK, et al. Effects of nattokinase on blood pressure: a randomized, controlled trial. Hypertension Research. 2008;31(8):1583–1588. doi:10.1291/hypres.31.1583
2. Kurosawa Y, Nirengi S, Homma T, et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Scientific Reports. 2015;5:11601. doi:10.1038/srep11601
3. Chen H, McGowan EM, Ren N, et al. Nattokinase: a promising alternative in prevention and treatment of cardiovascular diseases. Biomarker Insights. 2018;13:1177271918785130. doi:10.1177/1177271918785130
4. Yang T, Ge M, Zhan J, et al. Nattokinase supplementation and cardiovascular risk factors: a systematic review and meta-analysis of randomized controlled trials. Reviews in Cardiovascular Medicine. 2023;24(8):234. doi:10.31083/j.rcm2408234
5. Lin SY, Wu TH, Kuo CH, et al. Lipid-lowering, antihypertensive, and antithrombotic effects of nattokinase combined with red yeast rice in patients with stable coronary artery disease: a randomized, double-blinded, placebo-controlled trial. Frontiers in Cardiovascular Medicine. 2024. doi:10.3389/fcvm.2024.1385783
6. Tachibana M, Mizukoshi O, Harada Y, et al. A multi-centre, double-blind study of serrapeptase versus placebo in post-antrotomy buccal swelling. Pharmatherapeutica. 1984;3(8):526–530. PMID: 6366808
7. Bhagat S, Agarwal M, Roy V. Serratiopeptidase: a systematic review of the existing evidence. International Journal of Surgery. 2013;11(3):209–217. doi:10.1016/j.ijsu.2013.01.010
8. Arbildo-Vega H, Rendón-Alvarado A, Castillo-Cornock T, et al. Efficacy of serratiopeptidase in third molar surgery: a systematic review and meta-analysis. Journal of Oral Research. 2023;12(1):348–361. doi:10.17126/joralres.2023.030
9. Panthi VK, Bhattarai G, Acharya S, et al. Formulation and development of Serratiopeptidase enteric coated tablets. International Journal of Analytical Chemistry. 2021;2021:9749474. doi:10.1155/2021/9749474
10. Moriya N, Nakata M, Nakamura M, et al. Intestinal absorption of serrapeptase and its distribution to the inflammation sites. Biological and Pharmaceutical Bulletin. 1994;17(10):1427–1430.
11. Memorial Sloan Kettering Cancer Center. Nattokinase — Integrative Medicine. https://www.mskcc.org/cancer-care/integrative-medicine/herbs/nattokinase
12. Examine.com. Serrapeptase Research Breakdown. https://examine.com/supplements/serrapeptase/research/
13. BioAbsorb Nutraceuticals. Nattokinase Enzyme — Official Product Page. https://www.bioabsorbnutraceuticals.com/products/nattokinase-supplement-non-gmo-natto-extract-enzyme-100-mg-2000-fus-60-veggie-caps-60-day-supply

About the Author

David Kimbell is a health writer, digital entrepreneur and former aerospace engineer, based in Ottawa, Canada. He loves translating complex science into clear, actionable guidance for consumers seeking evidence-based solutions.

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Important Disclaimers

Medical Disclaimer: This article provides educational information only and is not intended as medical advice. Always consult with a qualified healthcare provider before starting any new supplement, especially if you have existing health conditions, take medications, or are pregnant or nursing.

FDA/Health Canada Statement: These statements have not been evaluated by the Food and Drug Administration or Health Canada. This product is not intended to diagnose, treat, cure, or prevent any disease.