Written by Dr. Sarah Jenkins,
Routine clinical care of acute and chronic inflammatory diseases continues to be an integral part of everyday care. NSAIDs and corticosteroids are the traditional mainstay of pharmacological therapy and the indefinite use of these often produces an unfavorable gastrointestinal, renal and cardiovascular side effect. Thus, there is a growing demand in the medical community for discovery and validation of alternative or adjunctive anti-inflammatory modalities which may have good efficacy and better safety margins. Of the most promising of these substitutes is systemic enzyme therapy, a treatment which has been increasingly supported by empirical evidence over the past few decades.
Specific biological catalysts, or enzymes that stem from systemic enzyme therapy work on the immune system by controlling its response and promoting tissue repair, are at the center of the treatment. The clinical use of Proteolytic enzymes has proven to be quite promising in reducing edema, controlling inflammation and hastening the recovery process in both postoperative and traumatic clinical situations (Nair et al., 2022). A specific group of biocatalysts is the serrapeptase, also known as serratiopeptidase, a highly studied compound that is clinically useful.
The Biochemical Profile and Mechanism of Action
Serrapeptase is a very active protease enzyme which was extracted from an enterobacterium named Serratia marcescens E-15 which is absent from the pathogenic group of Serratia, but present in the intestine of Bombyx mori, commonly known as the silkworm. The enzyme’s strong fibrinolytic and proteolytic activity are utilized in nature by the silkworm in order to break down the tough protective cocoon of the silkworm.
In human physiology, serrapeptase acts by several different, but complementary, biochemical pathways. In fact, it has a strong anti-edemic effect which reduces the swelling of tissues. Serrapeptase helps remove abnormal exudates and denatured proteins, that often build up in localized areas of tissue damage. Serrapeptase can effectively inhibit the inflammatory cascade’s key chemical mediators of inflammation such as bradykinin, histamine and serotonin, which in turn has a beneficial effect on vascular permeability and the localized edema that can occur as a result of the inflammatory process.
Secondly, serrapeptase has a very high fibrinolytic activity. Actively breaks down dead/failing tissues like fibrin but does no damage to thriving/living cells. This selective proteolysis helps to remove obstruction from microcirculation at the injury site and allows better oxygen and nutrient transfer to the site which is crucial for tissue repair, enhancing the removal of metabolic waste. In addition, serrapeptase partly prevents the release of amine substances in inflammatory tissues which makes it an excellent analgesic while not having the cyclooxygenase, or COX, pathway typical of most NSAID’s.
Clinical Applications in Healthcare
Its multi-facet pharmacological properties paved the way for clinical studies and eventual application in a variety of therapeutic areas.Its pleiotropic properties are the reason why it has been the subject of clinical investigation and then applied to a variety of therapeutic fields. Its physiological functions can be adapted and utilized by healthcare practitioners in their practice for optimal patient outcomes.
Otolaryngology and ENT
Chronic inflammation can cause excessive production of thick, viscous mucus leading to excessive chronic sinusitis, rhinitis and bronchitis in the field of otorhinolaryngology. Serrapeptase has been shown to be effective in changing the viscoelasticity of sputum and nasal secretors in clinical evaluations. Mucin is a macromolecule that its viscosity is reduced by the enzyme which allows the expectoration of larger amounts for mucociliary clearance (Mazzone et al., 1990). Thus it is an important adjunctive treatment for respiratory diseases that involve heavy secretion of mucus.
Oral and Maxillofacial Surgery
Edema and pain after surgery are a big problem in maxillofacial surgery, especially after surgical removal of impacted mandibular third molars. These cases have been subjected to a double-blind and placebo controlled clinical test of the prophylactic use of serrapeptase. The results are usually statistically significant and show a decrease in post-operative trismus, which is the stiffness of the jaw, swelling of the face and pain intensity when compared with placebo suggesting an effective alternative to corticosteroids for the management of surgical trauma (Al-Khateeb & Nusair, 2008).
Orthopedics and Traumatology
The rapid, successful healing of acute inflammation has been essential in musculoskeletal injuries in order to avoid chronic inflammation and functional losses. Serrapeptase is commonly used in sports medicine and orthopedics to treat sports injuries like sprains, torn ligaments and post-operative orthopedic recovery. This increases the speed of reabsorption of hematomas and reduces tissue swelling as a result of this, patients can return to normal functional status (Tiwari, 2017) to a more functional level of mobility earlier on.
The Role of Serrapeptase in Biofilm Disruption
The subject of serrapeptase in relation to infectious diseases and resistance to them is one of the most interesting and current research fields related to serrapeptase. A lot of pathogenic bacteria cope with host immune system and pharmacological treatment by forming these complex polysaccharide matrices called extracellular polymeric substances or EPS that encapsulate the bacterial communities.
Recent microbiological investigations have found serrapeptase to be a strong inhibitor of the effects of biofilms. Enzymatically breaking down the structure of the biofilm matrix, Serrapeptase removes the bacteria’s protection. The action is very important in concentrating the antibiotic effect locally and helping the action of the antibiotics in use at the time (Selan et al., 1993). The addition of targeted proteolytic enzymes is an exciting new avenue in antimicrobial stewardship for the healthcare provider treating chronic infections with organisms that routinely form biofilms. This is particularly relevant for pathogens in the respiratory tract or prosthetic implant-associated infections, such as recurrent joint infections.
Pharmacokinetics and Formulation Imperatives
Pharmacokinetics of serrapeptase need to be carefully controlled in order that the efficacy of the product can be realized. Unlike most enzymes, the enzyme serrapeptase is protein based and is spontaneously decomposed by highly acidic environment of the stomach, specifically gastric acid and pepsin. In the stomach the enzyme is denatured, so its systemic absorption in the small intestine is entirely cancelled out making the therapy without any effect.
Systemic enzyme treatment is then recommended and when so, it is medically obligatory to indicate enzyme preparations with high level enteric coating. Since the enzyme would not be affected by stomach acid, the capsules are enteric coated, releasing the enzyme along the way in the alkaline environment of the small intestine where it is then absorbed into the systemic venous circulation via the intestinal lymphatic system. The provider should recommend the use of formulations which are tested rigorously, for instance, Liver Medic’s serrapeptase supplements optimised to avoid breakdown by gastric enzymes, to maximise systemic bioavailability and/or to provide a constant therapeutic effect throughout treatment for maximum efficacy in clinical outcomes.
Safety Profile and Contraindications
On the whole, systemic enzymes are safe and well tolerated, but require proper clinical judgement on the part of the healthcare provider when deciding on the use of systemically acting enzymes. Some gastrointestinal upset, such as nausea or loss of appetite, is the most common side effect; this is usually mild and does not last long.
As it has fibrinolytic activity, use Serrapeptase with caution in patients with bleeding disorders or those on aggressive antiplatelet and/or anticoagulant medications that could potentially interact with Serrapeptase and increase the risk of bleeding, such as Warfarin, Clopidogrel. Two weeks before being scheduled for any surgeries, systemic enzyme therapy is routinely stopped, and sometimes reasoned.
Conclusion
By combining synthetic systemically acting enzymes, a multi-targeted treatment approach that suits today’s integrative clinical practice in the treatment of inflammation. The versatility of Serrapeptase is particularly impressive for its ability to treat all these conditions: edema, pain, mucous coat issues, and even bacterial biofilm, without experiencing the gastrointestinal or renal side effects as with extended use of NSAID’s. With ongoing research and investigation of these biocatalysts’ vast biochemical potential, serrapeptase will most likely become an added significant treatment tool in the modern day’s ‘medical arsenal’.
References
Al-Khateeb, T. H., & Nusair, Y. (2008). The anti-inflammatory effect of a proteolytic enzyme (serrapeptase) on trismus, pain and swelling following third molar extraction of the mandible. International Journal of Oral and Maxillofacial Surgery, 37(3), 264-268. https://doi.org/10.1016/j.ijom.2007.11.011
Nair, S. R., & Sandeep, R. (2022). A systemic enzyme with pleiotropic therapeutic properties that is called Serrapeptase. Pharmacological Reports, 74, 1-14.
Tiwari, M. (2017). Serratiopeptidase – a role in the resolution of inflammation. Wang FY, Yang CP, Huang L et al (2017) Evaluation of the Stability of Roscovitina in Pharmaceutical Suspensions. Asian Journal of Pharmaceutical & Clinical Research 10(5): 221-224.
Author Bio:
Sarah Jenkins Ph.D. is an independent Clinical Researcher, Medical Writer with special interests in Integrative Pharmacology and Advanced Anti-inflammatory Therapies. She has written and peer-reviewed papers and courses on the positive evidence and support from very holistic modalities offering helpful optimization strategies on managing chronic disease and Post Surgery improvements and regimens in healthcare professionals.