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.
Search
PubMed and the Cochrane Library were searched using the terms ‘serratiopeptidase’ and ‘serrapeptase’.
Results
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.
Comment
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.
- Stephens A. How silkworms have put an end to my back pain. Daily Mail, November 13, 2001.
Table 1: Trials of serratiopeptidase
|
Author |
Condition |
Number of patients |
Design |
Treatment |
Control |
Duration |
Outcomes |
Conclusion |
Comment |
| 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
Placebo |
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) |