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What Is Nattokinase?

2026-10-08
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Nattokinase
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Nattokinase


What Is Nattokinase?

Nattokinase is a potent fibrinolytic enzyme extracted from natto, a traditional Japanese food made from fermented soybeans. It was first discovered in 1987 by Dr. Hiroyuki Sumi at Kurashiki University in Japan, who identified a powerful clot-dissolving enzyme produced by Bacillus subtilis natto during the soybean fermentation process.

The name "nattokinase" combines "natto" (the food source) and "kinase" (an enzyme that acts on a specific substrate). It is a serine protease with a molecular weight of approximately 27,700 daltons and consists of 275 amino acids.

The global nattokinase market is valued at approximately USD 80-120 million (2024) and is growing at 10-13% CAGR, driven by increasing awareness of cardiovascular health, aging populations, and consumer preference for natural alternatives to pharmaceutical blood thinners.

Nattokinase vs. Natto: Understanding the Difference

AspectNatto (Food)Nattokinase (Extract)
FormFermented soybeansPurified enzyme powder/capsule
Nattokinase contentVariable (2,000-4,000 FU per serving)Standardized (e.g., 2,000-4,000 FU per capsule)
Taste/OdorStrong ammonia-like odorOdorless, tasteless
Vitamin K2High (menaquinone-7)Removed or minimal in purified extract
Soy allergensPresentReduced in purified extract
ConvenienceRequires preparationReady-to-consume supplement
Dosing precisionVariablePrecise (FU units per serving)

Production Method: Submerged Fermentation

Industrial Fermentation Process

Unlike plant extracts, nattokinase is produced through microbial fermentation:

Process Flow:

  1. Strain selection — Bacillus subtilis natto (strain CK SUMI 3077 or equivalent) is selected and cultured

  2. Seed culture preparation — Bacterial strain is grown in a nutrient-rich seed medium at 37°C for 12-24 hours

  3. Fermentation — Seed culture is transferred to a larger fermentation tank containing:

    • Soybean meal or soy peptone as the primary nitrogen source

    • Glucose or starch as the carbon source

    • Minerals and trace elements

    • Temperature: 35-40°C, pH: 6.5-7.5

  4. Fermentation duration — Typically 24-48 hours under controlled aeration and agitation

  5. Harvesting — Fermentation broth containing nattokinase is collected

  6. Ultrafiltration — Concentrates the enzyme while removing bacterial cells and debris

  7. Purification — Ion exchange chromatography or membrane filtration for higher purity

  8. Lyophilization (freeze-drying) — Preserves enzymatic activity; spray drying is an alternative

  9. Standardization — Adjusted to target FU (Fibrinolytic Units) per gram

  10. Quality testing — Fibrinolytic activity assay, microbial testing, purity analysis

Yield: Typical nattokinase activity in fermentation broth is 50,000-200,000 FU/mL before concentration

Key Production Parameters

ParameterOptimal RangeImpact
Fermentation temperature35-40°CAffects enzyme yield and activity
Fermentation pH6.5-7.5Optimal for B. subtilis natto growth
Aeration rate0.5-1.5 vvmOxygen supply critical for aerobic fermentation
Soy peptone concentration2-4%Primary nitrogen source for enzyme production
Fermentation time24-48 hoursLonger time may increase yield but risk contamination
Drying methodFreeze-drying preferredPreserves enzyme activity better than spray drying

Standardization: Understanding FU Units

What Is an FU (Fibrinolytic Unit)?

The FU (Fibrinolytic Unit) is the standardized measure of nattokinase enzymatic activity, defined by the Japanese Nattokinase Standardization Committee:

Definition: 1 FU is defined as the amount of enzyme that produces a clear zone of 1 mm diameter on a fibrin plate assay under standardized conditions (37°C, 24 hours).

This is the internationally recognized standard for nattokinase potency measurement.

Common Nattokinase Grades

GradeActivity (FU/g)Typical ServingPrimary Use
Standard powder20,000-30,000 FU/g100-200 mg (2,000-6,000 FU)General cardiovascular support
High-potency powder40,000-50,000 FU/g50-100 mg (2,000-5,000 FU)Premium supplements
Ultra-potency powder80,000-100,000 FU/g25-50 mg (2,000-5,000 FU)Clinical-grade formulations
Nattokinase + Vitamin K2 blend20,000-40,000 FU/g100-200 mgComprehensive cardiovascular support
Enteric-coated capsulesVaries by formulation2,000-4,000 FU per capsuleEnhanced GI survival

Quality Specification Sheet (Nattokinase Powder, 40,000 FU/g)

ParameterSpecificationTest Method
Nattokinase activity≥40,000 FU/gFibrin plate method (JNKA standard)
Protein content≥70%Kjeldahl method
Moisture≤8.0%USP <731>
Ash≤5.0%USP <281>
Heavy metalsPb ≤2.0 ppm, As ≤1.0 ppm, Cd ≤0.5 ppm, Hg ≤0.1 ppmICP-MS
Microbial limitsTPC <1,000 CFU/g, Yeast/Mold <100 CFU/gUSP <61>, <62>
Bacillus subtilisNegative (non-viable in final product)Microbiological assay
AflatoxinB1 <5 ppb, Total <10 ppbHPLC
Residual solventsEthanol <5,000 ppm (if used)GC (USP <467>)
AllergensSoy (declare if present)ELISA

Mechanism of Action

Direct Fibrinolysis

Nattokinase directly degrades fibrin, the protein that forms blood clots:

Fibrin (blood clot)
   │
   ├── Nattokinase directly cleaves fibrin
   │   (fibrinolytic protease activity)
   │
   ├── Nattokinase activates plasminogen → Plasmin
   │   (endogenous fibrinolytic system activation)
   │
   ├── Nattokinase increases t-PA (tissue plasminogen activator)
   │   (enhances body's natural clot-dissolving capacity)
   │
   └── Nattokinase reduces PAI-1 (plasminogen activator inhibitor)
       (removes the brake on natural fibrinolysis)

Result: Enhanced fibrinolytic activity → improved blood flow → reduced clot risk

Blood Pressure Modulation

Nattokinase has demonstrated blood pressure-lowering effects:

  • ACE inhibition — Mild angiotensin-converting enzyme (ACE) inhibitory activity

  • Improved endothelial function — Enhanced nitric oxide production

  • Reduced blood viscosity — Improved blood flow characteristics

Additional Cardiovascular Mechanisms

MechanismEvidence LevelImplication
Fibrin degradationStrong (in vitro, animal, clinical)Primary mechanism for cardiovascular support
Plasminogen activationStrong (in vitro)Endogenous fibrinolytic enhancement
Anti-platelet aggregationModerate (animal)Complementary anti-clot effect
Blood pressure reductionModerate (clinical)Mild antihypertensive effect
Anti-atheroscleroticGrowing (animal)Plaque formation prevention
Anti-thromboticModerate (animal/clinical)Clot prevention

Clinical Evidence Summary

Health AreaKey FindingsRepresentative Studies
Fibrinolytic activitySingle dose of 10 mg nattokinase significantly increased fibrinolytic activity and reduced fibrinogen levels in healthy adultsSumi et al. (1990), J Physiol Sci
Blood pressureNattokinase (2,000 FU/day) significantly reduced systolic (-5.4 mmHg) and diastolic (-2.8 mmHg) blood pressure in hypertensive subjects (8 weeks)Kim et al. (2008), Hypertens Res
Deep vein thrombosis preventionNattokinase (2,000 FU/capsule, 1-2 capsules) reduced DVT incidence in high-risk travelers during long-haul flightsJang et al. (2023), Front Nutr
Carotid artery plaqueNattokinase supplementation reduced carotid intima-media thickness and plaque size in atherosclerosis patients (26 weeks)Wu et al. (2023), Front Cardiovasc Med
Blood viscositySignificant improvement in whole blood viscosity and plasma viscosity after nattokinase supplementationChen et al. (2022), Evid Based Complement Alternat Med
Alzheimer's disease potentialNattokinase degraded amyloid-beta fibrils in vitro; potential neuroprotective applicationsSumi et al. (2022), J Agric Food Chem

Applications in Product Formulation

Cardiovascular Health Supplements

Formulation TypeRecommended GradeTypical DosageNotes
Capsules40,000-50,000 FU/g powder50-100 mg (2,000-5,000 FU)Standard cardiovascular dose
Enteric-coated capsulesEncapsulated powder2,000-4,000 FU per capsuleProtects enzyme from stomach acid
SoftgelsOil-dispersed nattokinase2,000-4,000 FUAlternative delivery format
Combination formulasNattokinase + Red Yeast Rice2,000 FU + Monacolin KComprehensive cardiovascular support
Powder sachetsStandard powder100-200 mgConvenience format

Combination Synergies

CombinationRationale
Nattokinase + Red Yeast Rice (Monacolin K)Fibrinolysis + cholesterol management = comprehensive cardiovascular support
Nattokinase + Vitamin K2 (MK-7)Cardiovascular protection + calcium metabolism + bone health
Nattokinase + Coenzyme Q10Blood flow + cellular energy; synergistic cardiovascular support
Nattokinase + Omega-3Anti-clot + anti-inflammatory; comprehensive heart health
Nattokinase + Garlic extractFibrinolysis + mild blood pressure support

Formulation Considerations

  • Enteric coating — Nattokinase is a protein enzyme that may be partially degraded by stomach acid; enteric coating ensures delivery to the small intestine

  • Temperature sensitivity — Nattokinase is heat-sensitive; avoid high-temperature processing during manufacturing

  • Storage — Store in cool, dry conditions; enzymatic activity degrades over time with heat and humidity

  • Shelf life — Typically 24 months when stored properly at room temperature

Sourcing Considerations for B2B Buyers

Key Questions for Suppliers

  1. What is the FU activity per gram? — Verify with independent fibrin plate assay

  2. Is the fermentation process GMP-certified? — Ensures consistent quality and safety

  3. Can you provide batch-to-batch consistency data? — Enzyme activity can vary between batches

  4. Is soy allergen content declared? — Important for allergen-free formulations

  5. What drying method is used? — Freeze-drying preserves more enzymatic activity than spray drying

  6. Is Vitamin K2 present or removed? — Important for customers on blood thinners

Quality Red Flags

  • Inconsistent FU values between batches — Indicates poor fermentation control or testing accuracy

  • Missing fibrin plate assay data — FU measurement is the only reliable potency indicator

  • Unusually high pricing for low FU product — Poor value proposition

  • No microbial testing — Fermentation products require thorough microbial screening

  • B. subtilis viable count in final product — Should be non-viable in purified nattokinase

Why Choose Greensky Bio as Your Nattokinase Supplier

  • GMP-certified production — ISO22000, BRCGS, Ecocert Organic Standard, SGS-GMP certified facilities

  • Advanced testing capabilities — Independent laboratory with HPLC, GC, UV, ICP-MS for comprehensive quality control

  • 20+ years experience — Established in 2004, with deep expertise in functional ingredient R&D and production

  • Global market presence — Export to Europe, the United States, South Korea, and Russia

  • Cardiovascular ingredient portfolio — Complementary to our Red Yeast Rice (Monacolin K) product line for comprehensive heart health formulations


GreenSky Bio — Professional Natural Plant Extract and Functional Ingredient Manufacturer Since 2004. For inquiries about nattokinase and other cardiovascular health ingredients, contact our team.

Related Products: Red Yeast Rice (Monacolin K) | Panax Ginseng Extract | Astaxanthin | Green Tea Extract (EGCG)


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