A Potent Proteolytic Enzyme

The inflammatory response is an important mechanism for protecting the body from attack by invading organisms and faulty cells. In the case of immune dysregulation, the body loses its ability to differentiate between innocuous and potentially dangerous substances. This defective mechanism results in a wide array of autoimmune diseases such as allergies, psoriasis, rheumatoid arthritis, ulcerative colitis, uveitis, multiple sclerosis and some cancers.

Standard drug therapy for inflammatory-mediated diseases and trauma include steroids and non-steroidal anti-inflammatory agents (NSAIDs). Both classes of drugs offer temporary, symptomatic relief from swelling, inflammation and accompanying pain without treating the underlying condition. These drugs may also be immunosuppressive and cause dangerous side effects. The conscientious physician must weigh the benefits and long-term risks associated with the use of NSAIDs, especially in cases of rheumatoid arthritis. If left untreated, the inflammatory process itself can lead to limitation of joint function and destruction of bone, cartilage and articular structures.

NSAIDs are among the most widely prescribed drugs for rheumatoid arthritis and other inflammatory joint conditions. Their effects are mediated through inhibition of the biosynthesis of prostaglandins. They work by irreversibly blocking cyclooxygenase, the enzyme that catalyzes the reactions of arachidonic acid to endoperoxide compounds. The neurological and gastrointestinal side effects of these agents have been reviewed in considerable detail. All of the NSAIDs, with the exception of Cytotec, inhibit prostaglandin El, a local hormone responsible for gastric mucosai cytoprotection. A common side effect from these medications is gastric ulcers. More serious adverse reactions such as blood dyscrasias, kidney damage and cardiovascular effects have been noted. Most physicians rotate among the ten most widely prescribed NSAIDs, as soon as one causes side effects or stops working.

The search for a physiologic agent that offers anti-inflammatory properties without causing side effects may have ended with the discovery of the Serratia peptidase enzyme (Serrapeptase or SP). This anti-inflammatory agent is in wide clinical use throughout Europe and Asia as a viable alternative to salicylates, Ibuprofen (sold as an OTC in the U.S.) and the more potent NSAIDs. Unlike these drugs, SP is a naturally occurring, physiologic agent with no inhibitory effects on prostaglandins and devoid of gastrointestinal side effects.

SP is an anti-inflammatory, proteolytic enzyme isolated from the microorganism, Serratia El5. This enzyme is naturally present in the silkworm intestine and is processed commercially today through fermentation. This immunologically active enzyme is completely bound to the alpha 2 macroglobulin in biological fluids. Histologic studies reveal powerful anti-inflammatory effects of this naturally occurring enzyme.

The silkworm has a symbiotic relationship with the Serratia microorganisms in its intestine. The enzymes secreted by the bacteria in the silkworm’s intestine have a specific affinity to avital tissue and have no detrimental effect on the host’s living cells. By dissolving a small hole in the silkworm’s protective cocoon (avital tissue), the winged creature is able to emerge and fly away.

The discovery of this unique biological phenomenon led researchers to study clinical applications of the SP enzyme in man. In addition to its widespread use in arthritis, fibrocystic breast disease and carpal tunnel syndrome, researchers in Germany have used SP for atherosclerosis. SP helps to digest atherosclerotic plaque without harming the healthy cells lining the arterial wall.

Today, researchers consider atherosclerosis an inflammatory condition similar to other degenerative diseases. Some immunologists are even categorizing atherosclerosis as a benign tumor. Hardening and narrowing of the arterial wall is a cumulative result of microscopic trauma; inflammation occurs in the presence of oxidized lipids. SP doesn’t interfere with the synthesis of cholesterol in the body, but helps clear avital tissue from the arterial wall. It is important to note that cholesterol in its pure state is an antioxidant and a necessary component of the major organ systems in the body. The use of medications that block cholesterol biosynthesis may eventually damage the liver and compromise anti-oxidant status of the eyes, lungs and other soft tissues.

While studies with SP in the treatment of coronary artery disease are relatively new, a wealth of information exists regarding its anti-inflammatory properties. SP has been used as an anti-inflammatory agent in the treatment of chronic sinusitis, to improve the elimination of bronchopulmonary secretions, traumatic injury (e.g. sprains and torn ligaments), post-operative inflammation and to facilitate the therapeutic effect of antibiotics in the treatment of infections. In the urological field, SP has been used successfully for cystitis and epididymitis.

In a double-blind study, the anti-inflammatory enzyme, SP, was evaluated in a group of 70 patients with evidence of cystic breast disease. These patients were randomly divided into a treatment group and a placebo group. SP was noted to be superior to placebo for improvement of breast pain, breast swelling and in duration with 85.7% of the patients receiving SP reporting moderate to marked improvement. No adverse reactions were reported with the use of SP.

The mechanisms of action of SP at the sites of various inflammatory processes consist fundamentally of a reduction of the exudative phenomena and an inhibition of the release of the inflammatory mediators. This peptidase induces fragmentation of fibrinose aggregates and reduces the viscocity of exidates, thus facilitating drainage of these products of the inflammatory response and thereby promoting the tissue repair process. Studies suggest that SP has a modulatory effect on specific acute phase proteins, which are involved in the inflammatory process. This is substantiated by a report of significant reductions in C3 and C4 complement, increases in opsonizing protein and reductions in concentrations of haptoglobulin, which is a scavenger protein that inhibits lysosomal protease.

Carpal tunnel syndrome is a form of musculoligamentous strain caused by repetitive motion injury. Individuals who work at keyboard terminals are particularly susceptible to this condition. While surgery has been considered the first line treatment for carpal tunnel syndrome, recent studies reveal that the use of anti-inflammatory enzymes (e.g. SP and bromelain) in conjunction with vitamins B2 and B6 are also effective.

In a study of chronic bronchitis, conducted by a team of otolaryngolosits, the SP-treated group showed excellent results compared with the placebo group in the improvement of loosening sputum, frequency of cough and expectoration. Other improvements included the posterior nasal hydrorhea and rhinostenosis. The administration of SP reduces the viscosity of the nasal mucus to a level at which maximal transport can be achieved. It has also been demonstrated that the simultaneous use of the peptidase and an antibiotic results in increased concentrations of the antibiotic at the site of the infection.

SP digests non-living tissue, blood clots, cysts, and arterial plaque and inflammation in all forms. The late German physician Dr. Hans Nieper used serrapeptase to treat arterial blockage in his coronary patients. Serrapeptase protects against stroke and is more effective and quicker than EDTA chelation treatments in removing arterial plaque. He also reports that serrapeptase dissolves blood clots and causes varicose veins to shrink or diminish. Dr. Nieper told of a woman scheduled for hand amputation and a man scheduled for bypass surgery who both recovered quickly without surgery after treatment with serrapeptase.

Several research groups have reported on the intestinal absorption of SP. SP is well absorbed orally when formulated with an enteric coating. It is known that proteases and peptidases are only absorbed in the intestinal area. These enzymes are mobilized directly to the blood and are not easily detectible in urine. Other enzymes with structural similarities have been reported to be absorbed through the intestinal tract. Chymotrypsin is transported into the blood from the intestinal lumen. Horseradish peroxidase can cross the mucosal barrier of the intestine in a biologically and immunologically active form. Several studies have appeared so far which refer to the systemic effects of orally given proteases and peptidases (e.g. SP), such as repression of edema and repression of blood vessel permeability induced by histamine or bradykinin. These enzymes also affect the kallikreinkinin system and the complement system, thus modifying the inflammatory response. In vitro and in vivo studies reveal that SP has an aspecific, anti-inflammatory effect, superior to that of other proteolytic enzymes. A review of the scientific literature, including a series of controlled, clinical trials with large patient groups, suggests that Serrapeptase is useful for a broad range of inflammatory conditions. If one considers the fact that anti-inflammatory agents are among the most widely prescribed drugs, the use of a safe, proteolytic enzyme such as SP would be a welcome addition to the physician’s armamentarium of physiologic agents.