Nattokinase and serrapeptase are two enzymes that have accumulated a significant following in the cardiovascular health and longevity supplement space. Marketed for everything from blood viscosity and circulation to fibrin breakdown and arterial health, they're often positioned together as "systemic enzyme" protocols.
The enthusiasm is understandable. The enzymes have plausible mechanisms and some legitimate research behind them. But the gap between what the evidence shows and what the marketing claims requires closer examination — particularly because these supplements have real biological effects that also mean real interaction risks.
Nattokinase
What It Is
Nattokinase is a serine protease enzyme extracted from natto — fermented soybeans, a traditional Japanese food. It degrades fibrin, the protein network that forms blood clots. This fibrinolytic activity is what drives most of the cardiovascular interest.
Blood clotting requires a balance: too little fibrinolytic activity, and clots may persist longer than they should. Too much, and bleeding risk increases. Nattokinase shifts this balance toward more efficient clot dissolution.
What the Evidence Shows
The nattokinase research base is growing but still limited compared to well-studied supplements. Key findings:
Blood pressure: The most consistent finding across multiple trials. A randomized controlled trial published in Hypertension Research found that nattokinase supplementation (2,000 FU daily) reduced systolic blood pressure by approximately 5.5 mmHg and diastolic by 2.8 mmHg over 8 weeks in people with pre-hypertension. This is a meaningful effect comparable to some lifestyle interventions.
Blood viscosity and fibrin: Nattokinase does degrade fibrin in laboratory and animal studies. The clinical translation is less clear — the enzyme is largely broken down by digestive proteases in the stomach, and how much intact enzyme reaches systemic circulation after oral dosing is debated. Some researchers argue the peptide breakdown products retain biological activity; others remain skeptical.
Atherosclerosis: Some animal studies and limited human data suggest nattokinase may help degrade fibrin deposits around existing plaques. This is mechanistically interesting but not established in humans.
Nattokinase is measured in FU (fibrinolytic units) or IU rather than milligrams. Most research has used 2,000 FU per day. Supplement labels sometimes list only mg, making dose comparison difficult. Products standardized and labeled in FU are preferable.
The Vitamin K2 Connection
Natto (the whole food) is one of the richest sources of vitamin K2 (MK-7 form). Vitamin K2 has its own independent cardiovascular evidence — it activates matrix Gla protein, which inhibits arterial calcification. Nattokinase extract is typically processed to remove vitamin K2, so if you're taking nattokinase specifically, you are not getting vitamin K2 alongside it. These are two separate supplements with separate mechanisms worth considering together.
Related: Our Supplement Comparison Tool can help you apply these ideas. For the complete picture, see our Heart & Cardiovascular Health guide and The Complete Guide to Supplement Tracking.
Serrapeptase
What It Is
Serrapeptase is a proteolytic enzyme originally isolated from the gut of the silkworm Bombyx mori. The silkworm produces it to dissolve its cocoon. Commercially, it is derived from bacteria (Serratia marcescens) via fermentation.
Serrapeptase degrades non-living tissue proteins — fibrin, mucus, dead cell debris. This activity underlies its use for post-surgical swelling and as a "plaque cleaner" in cardiovascular marketing.
What the Evidence Actually Shows
The honest assessment of serrapeptase for cardiovascular health: the human evidence is thin.
Inflammation and swelling: This is where serrapeptase has the most legitimate evidence, primarily in post-surgical and ENT contexts (swelling after oral surgery, sinusitis). These are not directly applicable to cardiovascular health, but they confirm biological activity.
Atherosclerotic plaque: The marketing claim that serrapeptase "dissolves plaques" is not supported by human clinical evidence. Animal studies have been cited, but none have been replicated with reliable human data. This is one of the more aggressively oversold claims in the supplement industry.
Fibrinolysis: Like nattokinase, serrapeptase has fibrinolytic activity. The bioavailability question is the same: a proteolytic enzyme faces significant degradation in the digestive tract. Enteric-coated formulations attempt to preserve the enzyme through the stomach, but clinical evidence for systemic fibrinolytic effects in humans remains limited.
Both nattokinase and serrapeptase have real anticoagulant-like effects. Anyone on blood thinners (warfarin, aspirin therapy, novel oral anticoagulants), scheduled for surgery, or with a known bleeding disorder should not add these supplements without medical guidance. This is not theoretical — the fibrinolytic activity is real even if the cardiovascular benefit is uncertain.
Pros
- +Nattokinase has legitimate RCT evidence for modest blood pressure reduction
- +Plausible fibrinolytic mechanisms supported by laboratory research
- +Nattokinase from whole natto food has centuries of Japanese dietary history
- +Some evidence for blood viscosity effects that could support circulation
- +Complementary to vitamin K2 in a broader cardiovascular stack
Cons
- -Serrapeptase's cardiovascular benefit in humans is largely undemonstrated
- -Oral bioavailability of intact enzyme is genuinely uncertain for both compounds
- -Both carry meaningful anticoagulant-like risk, particularly with medications
- -Marketing claims for 'plaque removal' are far ahead of the human evidence
- -Dosing standardization is inconsistent across products — FU vs mg confusion
- -Research quality is generally weak compared to more established cardiovascular supplements
Comparing the Two
| Factor | Nattokinase | Serrapeptase |
|---|---|---|
| Human RCT evidence | Moderate (BP, some fibrin data) | Weak for cardiovascular claims |
| Mechanism | Well-defined fibrinolysis | Proteolytic, anti-inflammatory |
| Bioavailability | Debated but some evidence | Enteric coating needed |
| Safety concern | Blood thinning interaction | Same |
| Food source | Traditional (natto) | Fermented commercial only |
How to Track Effects
If you're going to experiment with nattokinase specifically, blood pressure is the most trackable outcome with the most evidence behind it. Track morning blood pressure daily for 4 weeks before starting, then for 8 weeks on the protocol.
Other markers that may shift with improved fibrinolytic status include:
- D-dimer levels (a fibrin breakdown product, testable through labs)
- Plasma viscosity (specialty measurement)
- Subjective circulation symptoms (cold hands/feet, energy in lower extremities)
These are harder to measure at home but can be part of a bloodwork panel with a cooperative physician.
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The Bottom Line
Nattokinase has genuine, if moderate, evidence for blood pressure support and plausible fibrinolytic effects — it belongs in the "worth considering" category for cardiovascular health. Serrapeptase is the weaker of the two for cardiovascular purposes specifically; its real evidence base is in anti-inflammatory and post-surgical contexts, and the "plaque dissolution" claims are not supported by human research. Both supplements carry real anticoagulant-like risks that make them inappropriate for anyone on blood thinners without medical supervision. If you're going to use one of these, nattokinase at a standardized FU dose is the more rational choice, with blood pressure as your primary tracking metric.