What is serratiopeptidase?

Serratiopeptidase: A Proteolytic Enzyme with Limited Clinical Evidence

Serratiopeptidase is a bacterial metalloprotease with purported anti-inflammatory, anti-edemic, and analgesic properties, but lacks sufficient high-quality clinical evidence to support its widespread use for improving morbidity, mortality, or quality of life outcomes.

What is Serratiopeptidase?

Serratiopeptidase (also known as serrapeptase) is a proteolytic enzyme originally isolated from the intestine of the silkworm Bombyx mori, where it is produced by the bacterium Serratia marcescens. It has the following properties:

• It is classified as a bacterial metalloprotease 1
• It has proteolytic (protein-breaking) activity that gives it several potential therapeutic properties
• It is marketed as having anti-inflammatory, anti-edemic (reducing swelling), analgesic (pain-reducing), and fibrinolytic (clot-dissolving) effects 2

Purported Mechanisms of Action

Serratiopeptidase is claimed to work through several mechanisms:

• Breaking down fibrin, which thins fluids formed during inflammation 1
• Degrading inflammatory proteins and debris at inflammation sites
• Anti-biofilm activity that may enhance antibiotic effectiveness 1
• Fibrinolytic and caseinolytic properties that some suggest might have anti-atherosclerotic effects 2

FDA Status and Indications

According to the FDA label, serratiopeptidase is indicated for:

• Temporary relief of fussiness, tiredness, loss of appetite, minor aches or pains, occasional headache, nausea, or vomiting due to sensitivity to vaccination 3

However, it's important to note that serratiopeptidase is primarily sold as a dietary supplement in many countries, including the United States, and is not FDA-approved as a drug for specific medical conditions.

Clinical Evidence Assessment

The scientific evidence supporting serratiopeptidase is extremely limited:

• A 2013 systematic review evaluated 24 studies on the clinical efficacy of serratiopeptidase and found that most were of poor methodology 2
• Most studies were small, placebo-controlled trials with inadequate sample sizes
• Many studies lacked clear outcome definitions or specific dosing information
• Data on long-term safety and tolerability is notably absent 2

The systematic review concluded: "The existing scientific evidence for Serratiopeptidase is insufficient to support its use as an analgesic and health supplement." 2

Potential Applications (Based on Limited Evidence)

Despite limited evidence, serratiopeptidase has been used in various clinical specialties:

• Surgery, orthopedics, otorhinolaryngology, gynecology, and dentistry for anti-inflammatory effects
• Post-operative management to reduce swelling and pain
• Dental procedures, particularly after impaction surgery or maxillofacial trauma

Safety Concerns and Contraindications

Several important safety concerns exist:

• A case report documented spread of infection in a buccal space abscess after serratiopeptidase administration, suggesting its fibrinolytic activity may contribute to infection spread 4
• It should be used cautiously or avoided in cases of abscess due to this fibrinolytic activity
• Long-term safety data is lacking 2
• There are limited studies on drug interactions

Recent Research Developments

More recent research has suggested potential applications that require further investigation:

• Some researchers have proposed serratiopeptidase as a potential adjunctive treatment for COVID-19, though this remains highly speculative 5
• Researchers are exploring enhanced versions of the enzyme through protein engineering to address limitations like environmental sensitivity and poor cellular penetration 1
• Combination therapy with antibiotics has been studied to potentially reduce antibiotic resistance 1

Practical Recommendations

Based on the current evidence:

1. Serratiopeptidase should not be recommended as a primary treatment for inflammatory conditions due to insufficient high-quality evidence supporting its efficacy for improving mortality, morbidity, or quality of life outcomes.

2. For patients who inquire about serratiopeptidase:

   • Explain the limited scientific evidence supporting its use
   • Discuss that systematic reviews have found insufficient evidence for its efficacy
   • Recommend evidence-based alternatives for inflammation and pain management

3. If a patient is already taking serratiopeptidase:

   • Monitor for any adverse effects
   • Discontinue use if there are signs of infection spread or other adverse reactions
   • Ensure it's not being used as a replacement for proven medical therapies

4. Contraindications:

   • Avoid use in cases of abscess due to potential for infection spread
   • Use with caution in patients with bleeding disorders or those on anticoagulant therapy due to its fibrinolytic properties

Conclusion

While serratiopeptidase continues to be marketed and used for various inflammatory conditions, the scientific evidence supporting its efficacy and safety remains inadequate. Healthcare providers should prioritize evidence-based treatments with established benefits for improving patient outcomes.