Serratiopeptidase: a systematic review of the existing evidence.

BACKGROUND: Serratiopeptidase is a proteolytic enzyme prescribed in various specialities like surgery, orthopaedics, otorhinolaryngology, gynaecology and dentistry for its anti-inflammatory, anti-edemic and analgesic effects. Some anecdotal reports suggest it to possess anti-atherosclerotic effects also, due to its fibrinolytic and caseinolytic properties. Despite being widely used there are few published studies regarding its efficacy. Thus, evidence regarding its clinical utility is needed.
OBJECTIVE: To evaluate the existing evidence regarding efficacy and safety of Serratiopeptidase in clinical practice. EVIDENCE ACQUISITION: A systematic review of all the published articles of Serratiopeptidase using Cochrane Library, PubMed, MEDLINE, Clinical Trials.gov, Google, Dogpile and a manual search of bibliographies was conducted from 1st May 2011 till 15th July 2012. Further emails were sent to all the leading pharmaceuticals who are manufacturing this enzyme preparation for any additional information. All studies related to Serratiopeptidase which included Randomised controlled trials (RCTs), meta-analysis of RCTs, placebo-controlled, single-blind, double-blind, open label, prospective trials as well as preclinical studies were screened and analysed. The scientific credibility of the studies was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) grading checklist. A total of 24 studies on clinical efficacy of Serratiopeptidase met the inclusion criteria. EVIDENCE SYNTHESIS: Serratiopeptidase search on Cochrane library revealed 16 results among which 9 were Cochrane Central Register of Controlled Trials 2011, issue 4 studies and 7 were Cochrane Central Register of Controlled trials 2012, issue 3 studies. Of these 16 results, 11 were RCTs on efficacy of Serratiopeptidase. PubMed search also revealed 74 results which showed 16 Clinical trials, out of which 9 were RCTs related to Serratiopeptidase. Bandolier online edition (retrieved on 1/5/2011) showed a review 'Serratiopeptidase-finding the evidence' which included 9 RCTs. The evidence supporting the use of Serratiopeptidase as anti-inflammatory and analgesic agent is based on clinical studies which are of poor methodology. Only few RCTs, which are usually placebo control, with a small sample size are there. The dose and duration of treatment was not specified in some studies, and the outcome of the study was not clearly defined in a few. Data on the safety and tolerability of Serratiopeptidase is lacking in these studies. LIMITATIONS: A thorough search of literature was done to include all the relevant studies but we may have unknowingly missed a few of those studies which have not been published or registered with any of these search engines. The clinical evidence obtained have been graded according to the "Scottish Intercollegiate Grading Network" checklist by two separate reviewers and then coordinated together to give the final grading. Any disagreement between the two reviewers was resolved by discussion with the third reviewer. This was done to minimise bias but still the risk of bias cannot be completely ruled out.
CONCLUSION: Serratiopeptidase is being used in many clinical specialities for its anti-inflammatory, anti-edemic and analgesic effects. It is even being promoted as a health supplement to prevent cardiovascular morbidity. The existing scientific evidence for Serratiopeptidase is insufficient to support its use as an analgesic and health supplement. The data on long-term safety of this enzyme is lacking. Evidence based recommendations on the analgesic, anti-atherosclerotic efficacy, safety and tolerability of Serratiopeptidase are needed.