Serrapeptase: Limited Evidence for Anti-Inflammatory Benefits
The existing scientific evidence for serrapeptase is insufficient to support its use as an analgesic or anti-inflammatory agent, with most clinical studies suffering from poor methodology, small sample sizes, and lack of long-term safety data. 1
FDA-Approved Indication
Serrapeptase is only FDA-approved for temporary relief of occasional headache, runny nose, nasal or sinus congestion, or dry/itchy skin due to sensitivity to phenolic compounds in foods or other products. 2 This extremely limited indication reflects the lack of robust clinical evidence for broader anti-inflammatory applications.
Conditions With Limited Positive Evidence
Despite widespread use across multiple specialties, only a handful of conditions show any documented benefit, all based on low-quality studies:
Post-Surgical Swelling (Strongest Limited Evidence)
Ankle surgery swelling: One prospective study (n=66) showed 50% reduction in post-operative ankle swelling by day 3 versus no reduction in control groups (p=0.013). 3 This represents the most methodologically sound evidence available, though the sample size remains small.
Maxillofacial surgery: A double-blind trial (n=174) in patients undergoing Caldwell-Luc antrotomy demonstrated significantly less buccal swelling in serrapeptase-treated patients versus placebo from day 1 through day 5 post-operatively (p<0.01 to p<0.05). 4
Ear, Nose, and Throat Inflammation
- A multi-center, double-blind trial (n=193) in acute or chronic ENT disorders showed significant symptom regression after 3-4 days of treatment compared to placebo, with more marked response in the serrapeptase group. 5 However, specific outcome measures were poorly defined.
Critical Limitations of Existing Research
The evidence base is fundamentally flawed across multiple dimensions: 1
- Methodological deficiencies: Most studies lack proper randomization, adequate blinding, or appropriate statistical power
- Unclear dosing: Many trials fail to specify exact dosing regimens or treatment duration
- Poorly defined outcomes: Primary endpoints are often subjective or not clearly pre-specified
- Missing safety data: Long-term tolerability and adverse event profiles are essentially undocumented 1
- Publication bias: Only 24 studies met basic inclusion criteria in systematic review, suggesting selective reporting 1
Conditions Lacking Evidence
Despite marketing claims and widespread prescribing in surgery, orthopedics, gynecology, and dentistry for anti-inflammatory effects, there is no credible evidence supporting serrapeptase for: 1, 6
- Arthritis or joint inflammation
- Chronic sinusitis or bronchitis
- Fibrocystic breast disease
- Carpal tunnel syndrome
- Cardiovascular disease prevention (despite promotion as health supplement for anti-atherosclerotic effects)
Clinical Bottom Line
Serrapeptase should not be recommended as a primary anti-inflammatory agent for any condition. 1 The enzyme's purported mechanism through cyclooxygenase inhibition and effects on inflammatory mediators (interleukins, prostaglandins, thromboxanes) remains theoretical rather than clinically validated. 6
If considering serrapeptase for post-operative swelling in ankle or maxillofacial surgery, recognize this represents off-label use based on decades-old, small studies that would not meet current standards for evidence-based practice. 3, 4 Conventional anti-inflammatory approaches with established safety profiles remain the standard of care.