Serrapeptase | Supplementopedia

Overview

Serrapeptase, also known as serratiopeptidase, is a high-molecular-weight proteolytic enzyme. It was originally isolated from the gut of the silkworm Bombyx mori and its symbiotic bacterium Serratia marcescens. It is marketed as a systemic “proteolytic anti-inflammatory” supplement. It is intended to support the body’s natural ability to break down excess proteinaceous material, such as fibrin, dead tissue, and inflammatory debris.

Benefits

Reduce inflammation and pain: Modest reductions in postoperative swelling, chronic sinusitis, and osteoarthritis pain have been reported in randomized controlled trials (RCTs) using 10–60 mg/day.
Facilitate mucosal and sinus clearance: A meta-analysis of 9 studies found improved sinus drainage and reduced symptom scores in chronic sinusitis patients.
Support musculoskeletal recovery: Pilot data suggest faster resolution of post-operative edema and improved range of motion after orthopedic surgery.
Assist in scar and fibrotic tissue remodeling: In vitro and animal studies show decreased collagen deposition and fibrin degradation, suggesting potential utility in keloid or post-injury scar management.
Potential anti-platelet activity: Limited human data suggest modest inhibition of platelet aggregation, which may contribute to cardiovascular protective effects.

Overall, evidence supports anti-inflammatory and fibrinolytic actions, while claims regarding cognitive or metabolic effects remain unsubstantiated.

How It Works

Process: Serrapeptase is a serine protease belonging to the subtilisin family. It cleaves peptide bonds preferentially at hydrophobic residues (e.g., Ala‑X‑X, Leu‑X‑X) under neutral pH. This allows it to degrade fibrin, dead cells, and inflammatory exudates without harming living tissue.
Pathway:
- The enzyme’s activity is enhanced by calcium ions, which stabilize its active conformation.
- Orally administered serrapeptase is protected from gastric degradation by enteric coating, allowing it to reach the small intestine where it is absorbed as an intact protein; a portion then enters systemic circulation.
- Once in the bloodstream, it hydrolyzes extracellular fibrin matrices, reducing viscosity and facilitating enzymatic clearance of edema.
- By breaking down fibrinolytic substrates, it attenuates activation of the NF‑κB pathway, thereby decreasing production of pro-inflammatory cytokines (IL-1β, TNF-α).
- Its modest anti-platelet effect is mediated through inhibition of thromboxane A2 synthesis and direct platelet membrane protein cleavage.

Dosage

Clinical studies most commonly use 10 mg to 60 mg per day.
Doses are divided into 2–3 doses taken on an empty stomach (30 min before meals) to improve absorption.
For acute inflammation (e.g., post‑operative swelling): 30 mg three times daily for 5–7 days is typical.
For chronic conditions (e.g., chronic sinusitis): 10 mg three times daily for 2–3 months is often used.
A “low‑dose” regimen of 5–10 mg once daily may be used for maintenance or mild symptoms.
Dosage may be increased up to 120 mg/day (split) in short-term protocols under medical supervision.
Patients with coagulation disorders or on anticoagulants should use the lowest effective dose and monitor coagulation parameters.
Pregnant or lactating individuals should limit intake to ≤10 mg/day and only under healthcare guidance.

Safety & Side Effects

Serrapeptase is generally well‑tolerated at recommended doses.
Reported adverse effects (≤5 % of users) include:
- Mild gastrointestinal upset (nausea, abdominal discomfort)
- Rare skin rashes
Because it can degrade fibrin, there is a theoretical risk of increased bleeding; caution is advised in patients with:
- Bleeding disorders
- Those on anticoagulants (e.g., warfarin, DOACs)
- Those on antiplatelet agents (aspirin, clopidogrel)
- Recent surgery
Contraindications include:
- Active peptic ulcer disease (risk of mucosal irritation)
- Known hypersensitivity to Serratia spp. or other proteases
Pregnant, lactating, and pediatric populations lack robust safety data; they should avoid or use only minimal doses under clinical supervision.
Long-term high‑dose use (>120 mg/day for >3 months) lacks safety data.

Chemistry

Serrapeptase is a 470‑kDa serine protease (EC 3.4.21.115).
Its primary sequence contains 448 amino‑acid residues, with a catalytic triad of Asp‑32, His‑63, and Ser‑215 (numbering based on the mature enzyme) typical of the subtilisin family.
The enzyme’s molecular formula is approximated as C₁₈₆₇H₂₉₉₁N₅₃₅O₅₇₁S₁₇ (for the mature protein).
The IUPAC name for the catalytic domain is “(2S,3R,4S)-4‑[(1‑S‑[Ser]‑2‑amino‑2‑oxoethyl)‑1‑[2‑(hydroxy‑amino)‑2‑oxo‑ethyl]‑2‑hydroxy‑4‑(3‑hydroxy‑1‑[2‑hydroxy‑2‑oxo‑ethyl]‑2‑hydroxy... )” (complex and rarely used).
Key structural features include:
- A β‑propeller domain for substrate binding
- A calcium‑binding site that stabilizes the active conformation
- A C‑terminal “pro‑peptide” that is removed during activation
The enzyme is stable at pH 7–8 and is inactivated by acidic pH (< 3) and heat > 80 °C.

Sources & Quality

Commercial serrapeptase is typically derived from B. morii larvae that are re‑grown in sterile fermenters using Serratia marcescens cultures.
The enzyme is extracted by aqueous extraction, followed by ultrafiltration, ion‑exchange chromatography, and lyophilization.
High‑quality supplements employ a double‑enteric‑coating (e.g., cellulose acetate and gelatin) to protect the protein from gastric acid.
Some manufacturers produce recombinant serrapeptase in E. coli or * Bacillus* expression systems, which can improve batch‑to‑batch consistency and reduce allergenicity.
Quality considerations include:
- Verification of activity (units per capsule, typically 20,000–40,000 U)
- Absence of bacterial endotoxin (< 0.5 EU/mL)
- Compliance with GMP and third‑party testing (e.g., USP, NSF)
Sourcing from reputable manufacturers who provide certificate of analysis (COA) is essential to ensure enzymatic potency and purity.