What is the current evidence for the efficacy and safety of serrapeptase as a treatment option?

Serrapeptase Evidence Review

Current Evidence Quality and Limitations

The existing scientific evidence for serrapeptase is insufficient to support its routine clinical use, with most studies suffering from poor methodology, small sample sizes, and inadequately defined outcomes. 1

Positive Studies (Despite Methodological Limitations)

Ankle Sprain Study (2024)

• A prospective comparative study (n=76) demonstrated that serrapeptase 5 mg (two tablets three times daily for 10 days) was superior to paracetamol in reducing ankle joint edema in Grade II ankle sprains 2
• Edema reduction was measured using both Figure-of-Eight and water-displacement methods, showing statistically significant improvements on days 3 and 10 2
• Pain management (measured by VAS) did not differ significantly between serrapeptase and paracetamol 2
• Important caveat: This was a non-randomized comparative trial (Level II evidence), limiting the strength of conclusions 2

Venous Inflammatory Disease Study (1996)

• A controlled, randomized study (n=40) compared seaprose S (a similar proteolytic enzyme) to serratiopeptidase in superficial thrombophlebitis 3
• Serratiopeptidase 30 mg daily (two 5 mg tablets three times daily) for 14 days showed reductions in: spontaneous pain (63.3%), pain on pressure (57.6%), edema (56.2%), and erythema (58.3%) 3
• Efficacy was assessed as good or excellent in 65% of cases 3
• One patient experienced diarrhea requiring dosage adjustment 3

Mechanism of Action (Theoretical)

• Serrapeptase is a serine protease with reported affinity for cyclooxygenase (COX-I and COX-II), potentially reducing inflammatory mediators including interleukins, prostaglandins, and thromboxanes 4
• Possesses fibrinolytic and caseinolytic properties that theoretically contribute to anti-edemic effects 1, 4

Critical Safety Concern

Serrapeptase should be avoided in patients with active infections or abscesses due to its fibrinolytic activity, which can facilitate spread of infection into deeper tissue planes. 5

• A case report documented a buccal space abscess spreading into deeper muscular layers after serrapeptase administration in a 32-year-old male 5
• The infection resolved only after discontinuation of serrapeptase and appropriate surgical drainage 5

FDA-Approved Indication

The only FDA-recognized indication for serrapeptase is: "temporary relief of occasional headache, runny nose, nasal or sinus congestion, or dry or itchy skin due to sensitivity to phenolic compounds found in foods or other products" 6

Evidence Gaps

• No high-quality randomized controlled trials with adequate sample sizes exist 1
• Most studies lack clearly defined dosing protocols and treatment durations 1
• Long-term safety data is completely absent from the literature 1
• Data on tolerability and adverse effects is insufficient 1
• Claims regarding cardiovascular benefits (anti-atherosclerotic effects) lack evidence-based support 1

Clinical Bottom Line

While two small studies show potential benefit for edema reduction in ankle sprains 2 and venous inflammation 3, the overall body of evidence remains inadequate to recommend serrapeptase as a standard therapeutic agent. The methodological limitations of existing studies, combined with documented safety concerns regarding infection spread 5 and absence of long-term safety data 1, preclude evidence-based recommendations for routine clinical use.