Serrapeptase: Silkworm Enzyme

Heard about Serrapeptase, the proteolytic enzyme sometimes known as serratiopeptidase?  For over 30 years serrapeptase has been gaining wide acceptance in Europe and Asia as a potent analgesic and anti-inflammatory drug. 

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Serrapeptase has been used to promote wound healing and surgical recovery.  Recent Japanese patents even suggest that oral serrapeptase may help treat or prevent such viral diseases as AIDS and hepatitis B and C.  But perhaps its most spectacular application is in reversing cardiovascular disease.   In fact, serrapeptase appears so effective in unblocking carotid arteries that one researcher—Dr. Hans Nieper, the late, eminent internist from Hannover, Germany—called it a “miracle” enzyme.

Does this all sound a little too miraculous to be true? Read on. There’s a solid scientific rationale for each of these heath benefits, and they all have to do with the fact that serrapeptase is “proteolytic” (literally, protein-dissolving).

Proteolytic enzymes (also known as proteinases or peptidases) are ubiquitous in nature, being found in animals, plants, bacteria, and fungi. Human beings produce such well known peptidases as trypsin and chymotrypsin to help digest our food, but we also generate countless others to control virtually every regulatory mechanism in our bodies. For example, various peptidases are involved in initiating blood clotting (thrombogenesis) and also in dissolving clots (fibrinolysis); in evoking an immune response and quelling it; and in both promoting and halting inflammation. The mechanism in each case is the ability of the enzyme to cut or cleave a protein target into two or more pieces, usually at very specific cleavage sites. The same mechanism makes it possible for peptidases to inactivate HIV, the AIDS-associated virus, by pruning the viral proteins necessary for infectivity.

The medical use of enzymes as anti-inflammatory agents goes back many years. In the early 1950s it was discovered that intravenous trypsin could unexpectedly relieve the symptoms of many different inflammatory conditions, including rheumatoid arthritis, ulcerative colitis, and atypical viral pneumonia. Subsequently intramuscular enzyme injections were found to be beneficial in counteracting post-surgical swelling (edema), treating thrombophlebitis and lower back strain, and rapidly healing bruises caused by sports injuries.

At that time the mechanism of the anti-inflammatory effect remained obscure. Today it is believed to involve degradation of inflammatory mediators, suppression of edema, activation of fibrinolysis, reduction of immune complexes (antibody-antigen conglomerates), and proteolytic modification of cell-surface adhesion molecules which guide inflammatory cells to their targets.  (Such adhesion molecules are known to play an important role in the development of arthritis and other autoimmune diseases.) It’s also thought that the analgesic effect of proteolytic enzymes is due to their cleavage of bradykinin, a messenger molecule involved in pain signalling.  However, according to another theory, peptidases such as trypsin may be acting not as anti-inflammatory agents but rather as accelerants of the inflammatory process, thereby shortening its duration. Whatever the mechanism, many studies of proteolytic enzymes over the years have demonstrated their effectiveness in relieving pain and inflammation independently of steroids or nonsteroidal anti-inflammatory drugs (NSAIDs).

Fortunately we don’t need to rely on intramuscular injections any more to enjoy the benefits of proteolytic enzymes. Around 35 years ago researchers showed that enterically-coated enzymes such as trypsin, chymotrypsin, or bromelain were orally active. Oral proteolytic enzymes have been used successfully ever since for inflammatory conditions.  Recently the intestinal absorption of orally administered serrapeptase has also been demonstrated.16 To achieve an ideal therapeutic effect, however, it is essential that any enzyme preparation be properly enterically coated so as to release the enzymes in the intestines (where they can be absorbed) and not in the stomach (where they can be digested).

The proteolytic enzymes in common use today derive from bacteria (serrapeptase grown from Serratia marcescens cultures), plants (bromelain from pineapple stem and papain from papaya), and animal sources (trypsin and chymotrypsin from hogs or cattle). They’re all generally useful, but for many applications serrapeptase appears to be the most useful of them all.  In one study serrapeptase was compared to trypsin, chymotrypsin, and pronase (another microbial peptidase) in a rat model of scalding, which is known to induce abnormal activation of fibrinolysis. Serrapeptase was far more effective than any other enzyme in repressing fibrinolysis in this model, in agreement with its documented clinical efficacy as an anti-inflammatory agent.

By the way, in case you’ve got a good memory for details, you might have noticed that a few paragraphs back I said the activation of fibrinolysis, not its repression, is one of the likely anti-inflammatory mechanisms of serrapeptase. The truth is that serrapeptase, like other peptidases, can have seemingly contradictory effects at different times under different circumstances. The essential point of the study just cited is that serrapeptase and the other peptidases inhibited abnormal activation of fibrinolysis, and that this was a sign of their anti-inflammatory activity.

In other circumstances serrapeptase is definitely fibrinolytic, i.e., clot-busting, and it is this property that makes it so useful in treating cardiovascular disease. According to Dr. Hans Nieper serrapeptase taken daily for 12 to 18 months was sufficient to remove fibrous blockages from constricted coronary arteries, as confirmed in many of his patients by ultrasound examination.  But that’s still not the whole story—serrapeptase may well offer additional cardiovascular benefits not considered by Nieper. In particular, researchers have recently proposed that inflammation contributes to the development of arterial blockage. In one study, subjects with higher levels of CRP (C-reactive protein, a marker for systemic inflammation) were found to have a greater risk of future heart attack and stroke, independently of other risk factors such as smoking, high blood pressure, or cholesterol levels.18 Subjects with the highest levels of CRP who also used aspirin, however, showed dramatic decreases in their risk of heart attack, leading the researchers to speculate that the effectiveness of aspirin in preventing heart attack is due as much to its anti-inflammatory activity as to its anticlotting effects.

Serrapeptase, like aspirin, is both anti-inflammatory and anticlotting; unlike aspirin, however, serrapeptase can melt through existing fibrous deposits.  Serrapeptase also lacks the serious gastrointestinal side effects associated with chronic use of NSAIDs such as aspirin. This combination of properties makes serrapeptase just about the perfect remedy for warding off cardiovascular disease, better even than the proverbial aspirin a day. It’s beginning to look more and more as though Dr. Nieper was right—serrapeptase is indeed a “miracle” enzyme.

For optimal results in unclogging arteries Nieper suggests combining serrapeptase with other nutritional factors, including bromelain, magnesium orotate, carnitine, and selenium; see the information packet obtainable from the Brewer Library for more details.  To avoid possible pulmonary and ileal irritation, Nieper also recommends not exceeding a dose of about three tablets per day for long-term continuous use.

Because serrapeptase is a blood-thinning agent, it’s wise to consult your physician if you’re already taking any form of anticoagulant therapy (or, for that matter, if you suffer from any serious illness). Despite these cautions, however, serrapeptase has an excellent tolerability profile in general. The Japanese company that first developed serrapeptase, recommends up to six 5 mg tablets per day—two tablets three times a day, between meals—for short-term treatment of acute inflammation due to surgery, wound healing, sinusitis, cystitis, bronchial asthma, bronchitis, and breast engorgement in lactating women.


A preliminary trial of serrapeptase 
in patients with carpal tunnel syndrome.

Panagariya A, Sharma AK

Dept. of Neurology, SMS Medical College and Hospital, Jaipur.
J Assoc Physicians India 1999 Dec;47(12):1170-2

OBJECTIVES: This study was planned to assess the response of serrapeptase in patients with carpal tunnel syndrome (CTS). 

METHODS: Twenty patients with CTS were evaluated clinically. After baseline electrophysiological studies, these patients were given serrapetase10 mg twice daily with initial short course of nimesulide.  Clinical and electrophysiological reassessment was done after 6 weeks. 

RESULTS: Mean age was 43.9 years with male to female ratio of 1:2.33. Sixty five percent cases showed significant clinical improvement which was supported by significant improvement in electrophysiological parameters. Recurrence was reported in four cases. No significant side effect was observed. 

CONCLUSIONS: serrapeptase therapy may proved to be a useful alternative mode of conservative treatment.  Larger study may be further helpful to establish the role of serrapeptase in CTS.


Proteolytic enzymes: a new treatment strategy for prosthetic infections?

by Selan L, Berlutti F, Passariello C, Comodi-Ballanti MR, Thaller MC

Istituto di Microbiologia, Facolta di Farmacia, Universita La Sapienza, Rome, Italy.
Antimicrob Agents Chemother 1993 Dec;37(12):2618-21

Among the different mechanisms of bacterial resistance to antimicrobial agents that have been studied, biofilm formation is one of the most widespread.  This mechanism is frequently the cause of failure in the treatment of prosthetic device infections, and several attempts have been made to develop molecules and protocols that are able to inhibit biofilm-embedded bacteria.  We present data suggesting the possibility that proteolytic enzymes could significantly enhance the activities of antibiotics against biofilms.  Antibiotic susceptibility tests on both planktonic and sessile cultures, studies on the dynamics of colonization of 10 biofilm-forming isolates, and then bioluminescence and scanning electron microscopy under seven different experimental conditions showed that serrapetase greatly enhances the activity of ofloxacin on sessile cultures and can inhibit biofilm formation.


A New Method for Evaluating Mucolytic Expectorant Activity and its Application

II. Application to two proteolytic enzymes, serrapeptase and seaprose*

By Y. Kase, H. Seo, Y. Oyama, M. Sakata, K. Tomoda, K. Takahama, T. Hitoshi, Y. Okano, and T. Miyata

Arzneim.-Forsch. / Drug Res. 32 (1), Nr. 4 (1982)

From the Department of Chemico-Pharmacology. Faculty of Pharmaceutical Sciences, Kumamoto University, Kumamoto (Japan)

Summary: Using our new method described in a preceding paper, in vivo effects of two proteolytic enzymes such as serrapeptase and seaprose (SAP) on sputa collected from bronchitis rabbits were examined. Serrapeptase (20 mg/kg) and SAP (30 mg/kg) significantly reduced the viscosity of sputum (P < 0.05) at the 1-3-h periods and the 4-6-h periods, respectively, after intraduodenal administration. 50 mg/kg of serrapeptase also significantly decreased not only viscosity (P < 0.001) but also amount of freeze-dried substance (P < 0.05) of sputum at the 1-3-h periods, but SAP did not affect the amount of dried substance. Both enzymes significantly increased the volume of sputum, probably as the result of liquefaction. Thus, mucolytic expectorant activity of both enzymes can be demonstrated first by the reduction in viscosity and next by the increase in volume of sputa. However, the decrease in amount of freeze-dried substance is not always in accord with the reduction in viscosity.

1. Introduction

In this previous paper [1], we reported a new method which seems to be applicable to examine the in vivo effect of mucolytic expectorants. By the use of this method, the expectorant effect of a drug can be evaluated from the changes in both quantity and quality of sputa, which were quantitatively collected from the rabbits suffering from subacute bronchitis caused by long-term exposure to SO2 gas. The purpose of the present study is to ascertain whether this method is well applicable to the evaluation of mucolytic expectorant effect of the reference drugs as was expected, whose clinical efficacy was already well established. Two proteolytic enzymes, serrapeptase and seaprose, were chosen for such a purpose. Though their chemical properties differ, both enzymes have so far been used as the effective mucolytics in the treatment of various disorders related to viscous sputum or pus, and their efficacies have been war-ranted to be more potent and reliable than those of a-chymotrypsin and others. Therefore, they have widely been used not only in Japan but also in. some other countries. Nevertheless, the pharmacological evidence which sub-stantiates their clinical efficacies, in particular, mucolytic expectorant effect, is insufficient, though they exhibit potent mucolytic activity in in vitro experiments [2, 3]. Bromhexine, a representative of the expectorants, was used as a control drug, because its mechanism of action is quite different from that of proteolytic enzyme, that is, it does not exhibit in vitro mucolytic activity and its main effect is known only by the increase in the volume of respiratory tract fluid (RTF) when it was examined by Perry and Boyd's method [4-7] using normal healthy rabbits. Further pharmacological study, for instance, the acting mechanism of mucolytic expectorant effect of intraduodenally administered enzymes will be described in the subsequent paper.

2. Materials and methods

2.1. Animals and drugs

Male rabbits of New Zealand White-strain, weighing 1.8 to 2.5 kg, were used. Serrapeptase (Danzen*, hereafter abbreviated as SER), a proteolytic enzyme (endopeptidase) prepared from the culture broth of. genus Serratia sp. E-15 (one of enteric bacilli in silkworm) which comes as grayish powder, was provided


Evaluation of Serratia Peptidase in Acute or Chronic Inflammation of Otorhinolaryngology Pathology: a Multicentre, Double-blind, Randomized Trial versus Placebo

A. Mazzone1, M. Catalan2, M. Costanzo3, A. Drusian4, A. Mandol5, S. Russo6, E. Guarini7 and G. Vesperini8 

1Institute of Clinical Otorhinolaryngology, University of Naples, Naples, Italy; 
2Ear, Nose and Throat Department, 'Gradenigo' Hospital, Turin, Italy; 
3Ear, Nose and Throat Department, 'Villa Sofia' Hospital, Palermo, Italy; 
4Ear Nose and Throat Department, Treviso Regional Hospital, Treviso, Italy; 
5Ear, Nose and Throat Department, 'E. Fornaroli' Hospital, Magenta, Italy; 
6Ear, Nose and Throat Department, Lucca Hospital, Lucca, Italy; 
7Ear, Nose and Throat Department, Civil Hospital, Lecce, Italy; 
8Ear, Nose and Throat Department, 'Madonna del Soccorso' Hospital, San Benedetto del Tronto, Italy 

The efficacy and tolerability of Serratia peptidase were evaluated in a multi-centre, double-blind, placebo-controlled study of 193 subjects suffering from acute or chronic ear, nose or throat disorders. Treatment lasted 7 - 8 days, with the drug or placebo being administered at a rate of two tablets three times a day. After 3-4 days' treatment, significant symptom regression was observed in peptidase-treated patients. There was also a significant reduction in symptoms after 7 -8 days for patients in both treatment groups but the response was more marked in those patients receiving the active drug. Statistical comparison between the two groups confirmed the greater efficacy and rapid action of the peptidase against all the symptoms examined at both stages. Tolerance was found to be very good and similar for both groups. It is concluded that Serratia peptidase has anti-inflapimatory, anti-edemic and fibrinolytic activity and acts rapidly on localized inflammation. 

Received for publication 2 January 1990; accepted 16 January 1990.

Address for correspondence: A. Mazzone, MD, Institute of Clinical Otorhinolaryngology, University of Naples, Via Pansini 5, 80131 Naples, Italy. 


The use of enzymes with fibrinolytic, I proteolytic and anti-edemic activities has gained increasing support in recent years for the treatment of inflammatory ear, nose and throat (ENT) conditions1. Included among these enzymes is the Serratia peptidase (Danzen® ), a protease obtained from non-pathogenic enterobacteria of the genus Serratia. This proteolytic enzyme, which is available in tablet form to enable it to be absorbed from the intestinal lumen, has been shown lo induce intense fibrinolytic. anti-inflammatory, and anti-edemic activity in a number of tissues and results suggest that its anti-inflammatory activity may be of particular use for the treatment of localized or 'closed' forms of inflammation, such as those frequently found in ENT pathologies.' ^ Another important feature of Serratia peptidase is its effect on pain, the enzyme acting by inhibiting the release of pain-inducing amines, such as bradykinin, from inflammed tissue.1.7

     This peptidase induces fragmentation offibrinose aggregates and reduces the viscosity of exudates,"^ thus facilitating the drainage of these products of the inflammatory response and thereby promoting the tissue repair process, and clinical trials have confirmed that the use of Serratia peptidase resulted in fast resolution of the inflammatory process." ~ '° The aim of the present placebo-controlled multicentre study was to evaluate the efficacy and tolerability of the Serratia peptidase in the treatment of ENT inflammatory conditions.



Patients, who were recruited from ENT clinics throughout Italy, were all suffering from inherent acute or chronic inflammatory conditions. Any patients with serious concomitant conditions, such as severe renal and/or hepatic impairments, or who required additional drugs were excluded from the tnal, as this could interfere with evaluation of the parameters under examination, and the use of steroids, non-steroidal anti-inflammatory drugs and/or anti-inflammatory/analgesic agents was prohibited. Antibiotics were permitted when deemed necessary.


Indistinguishable tablets containing 5 mg Serratia peptidase or a placebo were provided in blister packs and patients were randomly assigned to receive two tablets of either drug, which they were instructed to take three times daily after meals for 7 -8 days.

Evaluation of treatment 
Clinical signs and symptoms were assessed on days 0, 3-4 and 7-8 of treatment on a scale of O-3 (0, absence of the symptoms: 3, maximum severity). Clinical parameters recorded were as follows: pain; quantity of secretion; difficulty in swallowing; nasal obstruction; anosmia; and body temperature. The appearance of the secretion was also recorded on a scale ofO-3 (0, normal; I, mucoid; 2, mucopurulent: 3, purulent). All evaluations were performed by an ENT specialist unaware of the treatment given.  

Evaluation of tolerability 
Tolerability of Serralia peptidase was evaluated on the basis of the presence, absence or severity of side-effects, recorded on the patients' data-collecting forms.

Statistical analysis
All data were analysed by the most appropriate statistical tests (^-test and Student's f-test).  


A total of 193 subjects (96 males, 97 females), aged between 12 and 77 years (mean ± SD 38 ± 15.7 years), with acute or chronic ENT pathologies were recruited to the trial. Of these 193 cases, 97 (43 males, 54 females; mean ± SD 37.3 ± 15.2 years) were placed in group A and 96 (53  


The treatment of breast engorgement with Serrapeptase (Danzen): a randomised double-blind controlled trial.

Kee WH, Tan SL, Lee V, Salmon YM.

Singapore Med J 1989 Feb;30(1):48-54

We evaluated an anti-inflammatory enzyme drug Danzen (Serrapeptase: Takeda Chemical Industries, Ltd.) on 70 patients complaining of breast engorgement. These patients were randomly divided into 2 groups, a treatment group and a placebo group. A single observer, unaware of the group the patients were in, assessed the severity of each of the symptoms and signs of breast engorgement before treatment was commenced, and daily for 3 days, during which therapy was administered. Danzen (Serrapeptase) was noted to be superior to placebo for improvement of breast pain, breast swelling and induration and while 85.7% of the patients receiving Danzen (Serrapeptase) had "Moderate to Marked" improvement, only 60.0% of the patients receiving placebo had a similar degree of improvement. "Marked" improvement was found in 22.9% of the treatment group and 2.9% of the placebo group. These differences were statistically significant (P less than 0.05). No adverse reactions were reported with the use of Danzen (Serrapeptase). Danzen (Serrapeptase) is a safe and effective method for the treatment of breast engorgement.


A multi-centre, double-blind study of serrapeptase versus placebo in post-antrotomy buccal swelling.

Tachibana M, Mizukoshi O, Harada Y, Kawamoto K, Nakai Y.

Pharmatherapeutica 1984;3(8):526-30

A multi-centre, double-blind, placebo-controlled trial was carried out to investigate the clinical efficacy of the anti-inflammatory enzyme serrapeptase in a total of 174 patients who underwent Caldwell-Luc antrotomy for chronic empyema. Eighty-eight patients received 10 mg serrapeptase 3 times on the day before operation, once on the night of the operation and 3 times daily for 5 days after operation; the other 86 received placebo. Changes in buccal swelling after operation were observed as a parameter of the response to treatment. The degree of swelling in the serrapeptase-treated patients was significantly less than that in the placebo-treated patients at every point of observation after operation up to the 5th day (p less than 0.01 to p less than 0.05). Maximal swelling throughout all the post-operative points of observation was also significantly smaller in size in the serrapeptase-treated group than in the placebo-treated group. No side-effects were reported.


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