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Serratiopeptidase - finding the evidence


Clinical bottom line

The evidence on serratiopeptidase being effective for anything is not based on a firm foundation of clinical trials.

Bandolier was recently sent an article published in the Daily Mail [1] by one of its readers. This reported the benefits of serratiopeptidase, an enzyme naturally occurring in silkworms, for the treatment of back pain. Serratiopeptidase is now commercially manufactured. Having never heard of this enzyme, Bandolier decided to see if there are any randomised, controlled trials.


PubMed and the Cochrane Library were searched using the terms ‘serratiopeptidase’ and ‘serrapeptase’.


The search yielded 34 articles with abstracts. Several were animal studies, letters, uncontrolled trials or those with inadequate randomisation, or case reports of adverse reactions. The Table shows the medical conditions for which randomised controlled trials were available, other study designs were not considered. There were no trials of serratiopeptidase for the treatment of back pain. Neither were there trials for the treatment of heart attack, stroke, asthma, or migraine also mentioned in the newspaper article as being possible indications.

Where there was randomised evidence trial quality was generally poor (Table 1 below). Studies were small, outcomes were poorly defined, and in some different medical conditions were mixed. Five studies were described as double blind: one was completely uninterpretable, three methodologically weak studies were positive, and one trial of apparent high quality was negative. This latter study compared serratiopeptidase, serraprose S or placebo in the treatment of chronic respiratory disease, with about 120 patients per group, and found no significant difference between groups for any outcome.


According to the newspaper article trial activity is ongoing, but to date there is no published evidence to support the use of serratiopeptidase. Existing trials are small and generally of poor methodological quality. The issue of safety cannot be ignored with use of biological agents.

  1. Stephens A. How silkworms have put an end to my back pain. Daily Mail, November 13, 2001.

Table 1: Trials of serratiopeptidase



Number of patients








  Back pain No randomised controlled trials              
  Carpel tunnel syndrome, migraine, asthma No randomised controlled trials              
Bracale et al, 1996 Superficial thrombophlebitis 40
(20 / group)
R Serra 10 mg x 3 daily
(6 tablets/day as 5 mg tabs)
Seaprose S 30 mg x 3 daily
(3 tablets/day)
14 days Improvement in specific symptoms eg pain, erythema Seaprose better than serra for all outcomes - no significance Randomisation failure - one group had significantly worse initial symptoms.
Small trial
No blinding
Kee et al, 1989 Breast engorgement 70
(35 / group)
R, single (observer) blind Serra - dose not specified Placebo 3 days Improvement in breast swelling & induration, and pain Serra significantly more effective than placebo Dose not specified
Duration short
60% placebo response rate
Tsuyama et al Postoperative & traumatic swelling 98 / group R & DB Serra - dose not specified Placebo
Not stated Global improvement for specific symptoms
% reduction in swelling
Serra significantly more effective than placebo at reducing pain & local heat Duration not stated
Don't provide info on swelling in abstract yet this is the objective of the paper!
Tachibana et al, 1984 Postoperative buccal swelling 174
(85 / group)
R & DB Serra 10 mg x 3 daily
(6 tablets/day)
Placebo 5 days Buccal swelling Serra significantly more effective than placebo Gave medication before & after operation
Measurement of swelling at baseline?
Esch et al, 1989 Postoperative & traumatic swelling 66
(22 / group)
R Serra - dose not specified Application of ice
Leg elevation & bed rest
Unclear Improvement in pain & swelling Serra significantly more effective at reducing swelling Dosenot stated
Duration unclear
No blinding
Small trial
Surachai et al Postoperative swelling (removal impacted molars) 40
(20 / group)
Not stated Serra 5 mg x 3 daily No medication 5 days Degree of facial swelling & maximum mouth opening No significant differences between groups Not stated whether randomised
No blinding
Small trial
Mazzone et al, 1990 Acute or chronic ear, nose or throat disorder 193
(about 96 / group)
R, DB Serra - dose not specified in mg, only as tablets Serr -2 tablets x 3 daily (dose in mg not specified) 7-8 days Reduction in symptoms Serra significantly more effective than placebo Dose in mg not specified
Mixed acute & chronic
Mixed disorders
Bellussi et al, 1984 Secretory otitis media 75 R & DB for 50 pts Unclear. Possibly Serra + bronchoplus Placebo Not stated Undefined global judgement
Numerous tests but outcomes unclear
Unclear which part of the trial the conclusions relate to Uninterpretable in terms of methodology, treatment given, outcomes, dosing & duration
Nagaoka et al, 1979 Chronic respiratory disease with difficult expectoration of sputum 125/group R, double dummy by description Serra 5 mg x 3 daily Seaprose S 5 mg x 3 daily

14 days Improvement in degree of difficulty of expectoration
Improvement in specific symptoms
No significant differences between groups Study design appears to be of good quality
Shimura et al, 1983 Chronic respiratory disease (not bronchial asthma) 40
(<10 / group)
R Serra - dose not specified Various mucolytic agents as comparators 7 days Relaxation of sputum viscoelasticity Serra produced significant changes in magnitude of relaxation & relaxation time No blinding
Fewer than 10 patients per group
Clinical relevance of outcomes? (break down of subunits of sputum structure)