What is serrapeptase
Serrapeptase is an extracellular metalloprotease enzyme isolated from enterobacterium Serratia marcescens Serratia sp. strain E-15 (one of the enteric bacilli in silk worm) 1). The microorganism Serratia marcescens Serratia sp. strain E-15 was originally isolated in the late 1960s from silk worm Bombyx mori L 2). Serrapeptase is presented in the silk worm intestine and allows the emerging moth to dissolve its cocoon. It is produced by purification mainly from fermentation of Serratia marcescens or Serratia sp. E 15. The Serrapeptase enzyme belongs to Serralysin group of enzymes and is known to cleave the peptides with linkages of Asn-Gln, CysSO3H-Gly, Arg-Gly, and Tyr-tyr as well as the bond between His-Leu, Gly-Ala, Ala-Leu, Tyr-leu, Gly-Gly, Phen-Tyr, and Tyr-Thr, showing broad substrate specificity 3). The Serrapeptase enzyme is absorbed through the intestine and transported directly into the blood stream 4). Serrapeptase should be enterically coated or else it may get destroyed by acid in the stomach before it gets into small intestine 5). Serrapeptase enzyme is believed to induce degradation of insoluble protein products like fibrin and inflammatory mediators. It reduces the viscosity of exudates facilitating drainage and alleviates pain by inhibiting the release of bradykinin 6).
Serrapeptase is also known as Serratiopeptidase (Serratia E-15 protease), serralysin, serratiapeptase, serratia peptidase or serrapeptidase, is a proteolytic enzyme preparation used is used either alone or in combination with other drugs to treat inflammation. Serrapeptase has been used in Europe and Asia for over 30 years, but is relatively new in the United States and Canada 7). Serrapeptase has powerful anti-inflammatory properties. Clinical studies have shown that Serrapeptase is effective in reducing swelling and edema and metabolizing scar tissues in the body 8) and particularly useful for post-traumatic swelling, breast engorgement during lactation 9) and bronchitis 10). Serrapeptase can digest dead tissue, blood clots, cysts, and arterial plaques 11). The anti-inflammatory properties of serrapeptase was first studied in Japan in 1967. Later during the 1970s these parenteral enzyme formulations were replaced by their enteric coated successors. During the 1980s and 1990s it was proposed by separate research conducted in Europe and Japan that serrapeptase is the most effective agent in reducing inflammation among all enzyme preparations.
Serrapeptase is used either alone or in combination with other drugs to treat inflammation. It is proved to be a superior alternative to traditional NSAIDS like diclofenac sodium and ketoprofen which have pronounced side effects.
Serrapeptase mechanism of anti-inflammatory effect is because of hydrolysis of histamine, bradykinin, and serotonin 12). Serrapeptase also has a proteolytic and fibrinolytic effect. This is achieved by dissolving the complement (specific proteins responsible for inflammation) and increasing the plasmin activity by inhibiting the plasmin inactivators 13). This anti-inflammatory activity of serrapeptase can be evaluated by Rat Paw Edema model, wherein edema is induced by Aerosil and the decrease in the thickness of the inflamed rat paw is measured using plethysmometer 14).
Serrapeptase contains 450 amino acids cleaved with the peptide bond having molecular weight of approximately 60 kDa. Serrapeptase is labile to heat, moisture, and pH of the environment. The enzyme has maximal activity at pH 9.0 and at temperature 40°C. Serrapeptase shows excellent stability at lower temperatures in the pH range from 5 to 10. Serrapeptase is unstable at 37°C in alkaline conditions. The enzyme is completely inactivated by heating at 55°C for 15 min.
What is serrapeptase good for?
Serrapeptase has been used to treat chronic sinusitis 15), carpal tunnel syndrome 16), sprains, torn ligaments, serous otitis media 17), osteoarthritis of the knee 18), osteoarticular infections 19), and postoperative inflammation 20). Serrapeptase was found to produce some relief in breast pain, induration and swelling, when compared to placebo in women with breast engorgement during lactation, with a fewer number of women experiencing slight to no improvement in overall breast engorgement, swelling and breast pain 21). However, the overall quality of the studies was found to be low due to limitations in study design and the small number of women in the included studies, thus there is insufficient evidence from published trials on Serrapeptase to justify widespread implementation as treatment for breast engorgement during lactation. More robust research is urgently needed on the treatment of breast engorgement during lactation.
Esch et al. 22) used serrapeptase for reduction of postoperative swelling in upper ankle joint surgery and concluded that significant reduction in swelling had been achieved post- operatively with the use of serrapeptase.
Al-Khateeb and Nusair 23) investigated the ability of serrapeptase to reduce post-operative pain, swelling and trismus after third molar surgery. There was a significant reduction in the pain intensity and extent of cheek swelling in the serrapeptase group at the 2nd, 3rd and 7th post-operative days. Another study by Chappi et al. 24) also indicated similar results in which the serrapeptase group showed significantly reduced trismus and swelling on the day 1, 3 and 5 post-operatively. However, this enzyme preparation did not exert an appreciable analgesic effect post-operatively 25). In the same study by Chappi et al. 26) showed serratiopeptidase 10 mg orally produced an appreciable anti-edema effect and had no apparent effect on rate of wound healing. Murugesan et al. 27) found that dexamethasone was more effective in reducing swelling and pain when compared with serratiopeptidase, however both had same effect on trismus.
Serrapeptase is a potent anti-inflammatory enzyme. Supplementing serrapeptase with NSAIDs has shown to have a favorable anti-inflammatory effect on the tissues of the body 28).
Possibly effective for:
- Facial swelling after surgery to clear the sinuses.
Insufficient evidence for:
- Chronic bronchitis. Developing research suggests that serrapeptase can significantly reduce coughing and thin secretions in people with chronic bronchitis after about 4 weeks of treatment.
- Sinus pain (sinusitis). Early research suggests that people with sinusitis who take serrapeptase have significantly reduced pain, nasal secretions, and nasal obstruction after 3-4 days of treatment.
- Hoarseness (laryngitis). Early research suggests that serrapeptase can significantly reduce pain, secretions, difficulty swallowing, and fever in people with laryngitis after 3-4 days of treatment.
- Sore throat (pharyngitis). Early research suggests that serrapeptase can significantly reduce pain, secretions, difficulty swallowing, and fever in people with sore throat after 3-4 days of treatment.
- Back pain.
- Rheumatoid arthritis.
- Carpel tunnel syndrome.
- Leg ulcers.
- Migraine headache.
- Tension headache.
- Pus accumulation (empyema).
- Fibrocystic breast disease.
- Inflammatory bowel disease (IBD) including ulcerative colitis and Crohn’s disease.
- Breast engorgement.
- Heart disease.
- Ear infections.
- Other conditions e.g. weight loss.
More evidence is needed to rate the effectiveness of serrapeptase for these uses.
For reducing swelling of the inside of the cheek after sinus surgery: 5-10 mg of serrapeptase 3 times on the day before surgery, once in the evening after surgery, and then 3 times daily for 5 days following surgery.
Serrapeptase side effects
Serrapeptase seems to be safe for adults when taken by mouth, short-term (up to 4 weeks). The long-term safety of serrapeptase is not known.
According to a review of the literature, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported as being associated exclusively with serrapeptase 29).
Special Precautions and Warnings
Pregnancy and breast-feeding: Not enough is known about the use of serrapeptase during pregnancy and breast-feeding. Stay on the safe side and avoid use.
Bleeding disorders: Serrapeptase might interfere with blood clotting, so some researchers worry that it might make bleeding disorders worse. If you have a bleeding disorder, check with your healthcare provider before using serrapeptase.
Surgery: Serrapeptase might interfere with blood clotting. There is a concern that it might increase bleeding during and after surgery. Stop using serrapeptase at least 2 weeks before a scheduled surgery.
Medications that slow blood clotting (Anticoagulant/Antiplatelet drugs interacts with serrapeptase
Serrapeptase might decrease blood clotting. Therefore, taking serrapeptase along with medications that also slow clotting might increase the chances of bruising and bleeding. Some medications that slow blood clotting include aspirin, clopidogrel (Plavix), diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, warfarin (Coumadin), and others.
References [ + ]
|1.||↵||Mali N, Wavikar P, Vavia P. Serratiopeptidase Loaded Chitosan Nanoparticles by Polyelectrolyte Complexation: In Vitro and In Vivo Evaluation. AAPS PharmSciTech. 2015;16(1):59-66. doi:10.1208/s12249-014-0201-0 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309803/|
|2.||↵||Gupte V, Luthra U. Analytical techniques for serratiopeptidase: A review. Journal of Pharmaceutical Analysis. 2017;7(4):203-207. doi:10.1016/j.jpha.2017.03.005. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790697|
|3.||↵||Hiroshi M., Kazuyuki M. Serralysin and related bacterial proteinases. Methods Enzymol. 1995;248:395–413|
|4.||↵||Bhagat S, Agarwal M, Roy V. Serratiopeptidase: A systematic review of the existing evidence. International Journal of Surgery. 2013;11(3):209–17.|
|5.||↵||Moriya N, Nakata M, Nakamura M, Takaoka M, Iwasa S, Kato K, et al. Intestinal absorption of serrapeptase™ (TSP) in rats. Biotechnol Appl Biochem. 1994;20(Pt1):101–08.|
|6.||↵||Mazzone A, Catalani M, Costanzo M, Drusian A, Mandoli A, Russo S, et al. Evaluation of serratia peptidase in acute or chronic inflammation of otorhinolaryngology pathology: a multicentre, double-blind, randomized trial versus placebo. J Int Med Res. 1990;18(5):379–88|
|7.||↵||Kotb E. Activity assessment of microbial fibrinolytic enzymes. Appl. Microbiol. Biotechnol. 2013;97:6647–6665|
|8.||↵||Yamasaki H., Tsuji H., Saeki K. Anti-inflammatory action of a protease, TSP, produced by Serratia. Folia Pharmacol. Jpn. 1967;63:302–314|
|9.||↵||The treatment of breast engorgement with Serrapeptase (Danzen): a randomised double-blind controlled trial. Singapore Med J. 1989 Feb;30(1):48-54. https://www.ncbi.nlm.nih.gov/pubmed/2688125|
|10.||↵||Chappi Mouneshkumar D., Suresh Kandagal V., Patil M.R. Comparison of clinical efficacy of methylprednisolone and serratiopeptidase for reduction of postoperative sequelae after lower third molar surgery. J. Clin. Exp. Dent. 1. 2015;7(2):197–202|
|11.||↵||Mazzone A., Catalani M., Costanzo M. Evaluation of Serratia-peptidase in acute or chronic inflammation of otorhinolaryngology pathology: a multicentre, double-blind, randomized trial versus placebo. J. Int. Med. Res. 1990;18:379–388.|
|12.||↵||Mali N, Wavikar P, Vavia P. Serratiopeptidase Loaded Chitosan Nanoparticles by Polyelectrolyte Complexation: In Vitro and In Vivo Evaluation. AAPS PharmSciTech. 2015;16(1):59-66. doi:10.1208/s12249-014-0201-0. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309803/|
|13.||↵||Jadav SP, Patel NH, Shah TG, Gajera MV, Trivedi HR, Shah BK. Comparison of anti-inflammatory activity of serratiopeptidase and diclofenac in albino rats. J Pharmacol Pharmacother. 2010;1(2):116. doi: 10.4103/0976-500X.72362 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3043339/|
|14.||↵||Fereidoni M, Ahmadiani A, Semnanian S, Javan M. An accurate and simple method for measurement of paw edema. J Pharmacol Toxicol Methods. 2000;43(1):11–4. doi: 10.1016/S1056-8719(00)00089-7 https://www.ncbi.nlm.nih.gov/pubmed/11091125|
|15.||↵||Evaluation of Serratia peptidase in acute or chronic inflammation of otorhinolaryngology pathology: a multicentre, double-blind, randomized trial versus placebo. Mazzone A, Catalani M, Costanzo M, Drusian A, Mandoli A, Russo S, Guarini E, Vesperini G. J Int Med Res. 1990 Sep-Oct; 18(5):379-88. https://www.ncbi.nlm.nih.gov/pubmed/2257960/|
|16.||↵||Panagariya A., Sharma A.K. A preliminary trial of serratiopeptidase in patients with carpal tunnel syndrome. J. Assoc. Physicians India. 1999;47:1170–1172. https://www.ncbi.nlm.nih.gov/pubmed/11225219|
|17.||↵||Effect of 2-(alpha-thenoylthio)propionylglycine in the treatment of secretory otitis media. Curr. Ther. Res.; VOL 36 ISS Sep 1984, P596-605|
|18.||↵||Klein G., Kullich W. Short-term treatment of painful osteoarthritis of the knee with oral enzymes. A randomized, double-blind study versus diclofenac. Clin. Drug Invest. 2000;19:15–23.|
|20.||↵||Kakinuma A., Moriya N., Kawahara K. Repression of fibrinolysis in scalded rats by administration of serratia protease. Biochem. Pharm. 1982;31:2861–2866. https://www.ncbi.nlm.nih.gov/pubmed/6753849|
|21.||↵||Mangesi L, Zakarija-Grkovic I. Treatments for breast engorgement during lactation. Cochrane Database of Systematic Reviews 2016, Issue 6. Art. No.: CD006946. DOI: 10.1002/14651858.CD006946.pub3. http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD006946.pub3/full|
|22.||↵||Esch PM, Gerngross H, Fatrian A. Reduction of post-operative swelling. Objective measurement of swelling of the upper ankle joint in treatment with serratipeptidase. A prospective study. Forstchre Med. 1989;107:67–8|
|23, 25.||↵||Effect of the proteolytic enzyme serrapeptase on swelling, pain and trismus after surgical extraction of mandibular third molars. Al-Khateeb TH, Nusair Y. Int J Oral Maxillofac Surg. 2008 Mar; 37(3):264-8. https://www.ncbi.nlm.nih.gov/pubmed/18272344/|
|24, 26.||↵||Chappi D. M, Suresh KV, Patil MR, et al. Comparison of clinical efficacy of methylprednisolone and serratiopeptidase for reduction of postoperative sequelae after lower third molar surgery. Journal of Clinical and Experimental Dentistry. 2015;7(2):e197-e202. doi:10.4317/jced.51868. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483323/|
|27.||↵||Murugesan K, Sreekumar K, Sabapathy B. Comparison of the roles of serratiopeptidase and dexamethasone in the control of inflammation and trismus following impacted third molar surgery. Indian J Dent Res. 2012;23:709–13 https://www.ncbi.nlm.nih.gov/pubmed/23649050|
|28.||↵||Evaluation of Serratia peptidase in acute or chronic inflammation of otorhinolaryngology pathology: a multicentre, double-blind, randomized trial versus placebo. Mazzone A, Catalani M, Costanzo M, Drusian A, Mandoli A, Russo S, Guarini E, Vesperini G. J Int Med Res. 1990 Sep-Oct; 18(5):379-88.|
|29.||↵||H Kanetomo, F Kazuyoshi, H Toshio. A case of Stevens-Johnson Syndrome induced by serratiopeptidase (Dasen). Skin Research. 1991;30(6):646–49|