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What is Crohn’s Disease? – Crohn’s and Systemic Enzymes

Treatment options with serious side effects have led to an increasing use of systemic enzyme therapy as a means to alleviate symptoms and improve quality of life. Certain proteolytic (protein digesting) enzymes have been identified to have extremely beneficial actions when applied to the inflammation and fibrin buildup related to this condition. Systemic enzymes, typically taken orally and on an empty stomach, enter directly into the blood stream. Enzymes can then circulate throughout the body, acting upon complexes in the blood as well as in tissues and organs.

Crohn’s Disease and Pain

Systemic enzymes have successfully demonstrated the ability to reduce signs of pain throughout the body. Serrapeptase, an enzyme extracted from silk worms, has been evaluated for its effectiveness in pain reduction and shown favorable results.

The use of systemic enzymes in treating pain throughout the body was evaluated in several clinical studies. Rheumatic conditions, including periarthritis of the shoulder, painful osteoarthritis of the knee and vertebral syndromes, were evaluated based on pain scores before and after treatment with proteolytic enzymes and non-steroidal anti-inflammatory drugs (NSAIDs). Evidence showed a statistical equivalence between oral enzyme therapy and conventional drug therapy in the ability to significantly reduce pain in various rheumatic diseases.1

Researchers in India conducted a study to assess the response of serrapeptase in patients with carpal tunnel syndrome (CTS). Twenty patients with CTS were evaluated clinically after six weeks of taking serrapeptase. Sixty-five percent showed significant clinical improvement, which was supported by improvement in electrophysiological parameters (measurements of nerve activity). The doctors concluded that serrapeptase therapy may prove to be a useful alternative conservative treatment .2

Another study was conducted comparing the efficacy of two proteolytic enzymes in the treatment of venous inflammatory disease. The efficacy of Serrapeptase and Seaprose S (a protease) was assessed using good or excellent results as the measure of effective treatment. Serrapeptase was effective in 65 percent of the cases compared to 85 percent for Seaprose S. Serrapeptase specifically demonstrated a 63 percent reduction in spontaneous pain and 57 percent reduction in pain on pressure. Though Seaprose S had better overall results, both enzymes were effective. It can thus be confirmed that both enzymes were effective in patients with inflammatory venous disease.3 (Note: Seaprose S has since been withdrawn from the market).

A prospective study was conducted on the effect of serrapeptase on post-operative swelling and pain of the ankle. In the serrapeptase group, the swelling decreased by 50 percent on the third post-operative day, while in the control groups (no treatment and treatment with ice) no reduction in swelling occurred. A decrease in pain correlated for the most part with the reduction in swelling. On the basis of these results, serrapeptase would appear to be an effective preparation for the post-operative reduction of swelling, in comparison with classical conservative measures, such as the application of ice.4

Crohn’s Disease and Inflammation

Reducing the amount of pain is only one aspect of how systemic enzymes can function. Chronic inflammation is often the root cause of a number of conditions and controlling the process can help alleviate symptoms.

One study compared blood laboratory values before and after supplementation of Exclzyme (a blend containing the proteolytic enzymes serrapeptase, bromelain, lipase, amylase and other proteases) in patients with inflammation related to rheumatic disease or trauma. Results showed a significant decrease in erythrocyte sedimentation rate (ESR), a long-term predictor of cardiovascular disease. ESR is a measurement comparable to C-reactive protein (CRP) levels in predicting risk of a cardiac event. However, ESR does not change as rapidly as does CRP, and CRP is not affected by other factors, as is ESR.5,6

Inflammatory marker reduction has been documented with the supplementation of serrapeptase.  The efficacy of serrapeptase was evaluated in a multi-centre, double-blind, placebo-controlled study of 193 subjects suffering from acute or chronic ear, nose or throat disorders. After 3-4 days of treatment, significant symptom regression was observed in serrapeptase-treated patients. Statistical comparison confirmed the greater efficacy of serrapeptase against all of the symptoms examined. It was concluded that serrapeptase has anti-inflammatory, anti-edemic and fibrinolytic activity, and acts rapidly on localized inflammation.7

Bromelain, a proteolytic enzyme extracted from pineapple, has also been found to be effective in reducing inflammation by blocking chemical signals called cytokines, which promote and increase inflammation.8,9 Research has also shown that bromelain disrupts the migration of neutrophils to an inflamed area, where they would otherwise propagate the process. One study measured a 50-85 percent decrease in the migration of neutrophils after bromelain treatment.10

Bromelain has also been evaluated specifically in relation to inflammatory bowel disease both in vitrousing colon biopsies from ulcerative colitis and Crohn’s disease patients, and in vivo being orally administered to rodent models. Evidence has shown that bromelain has the capacity to decrease colonic excretion of inflammatory markers –granulocyte colony stimulating factor, interferon (INF)-g, macrophage inhibitory protein (MIP)-1β, and tumor necrosis factor (TNF) – by inflamed tissue.8,11Exact mechanisms by which bromelain works have not yet been identified, however results indicate that this may be a potential approach to the treatment of inflammatory bowel disease.12

Crohn’s Disease and Wound Healing

Crohn’s disease patients experience an imbalance in immune response which can alter healing abilities, a fact that is detrimental to the elimination of ulcers in the intestines. Multiple studies have shown the effectiveness of serrapeptase in helping with proper wound healing.

A prospective study was conducted on the effect of serrapeptase on post-operative swelling and pain of the ankle. In the serrapeptase group, the swelling decreased by 50% on the third post-operative day, while in the control groups (no treatment and treatment with ice) no reduction in swelling occurred. A decrease in pain correlated for the most part with the reduction in swelling. On the basis of these results, serrapeptase would appear to be an effective preparation for the post-operative reduction of swelling, in comparison with the classical conservative measures, for example, the application of ice.13

An unusual clinical trial evaluated the effectiveness of serrapeptase in the elimination of a periprosthetic infection (an infection at the site of an implanted orthopedic device) in an in vivo animal model. Infections of slime-forming bacteria are especially difficult at these sites. Staphylococcus epidermidis was introduced at the prosthetic site in rats. After two weeks, infection persisted in 63.2% of animals in the no-treatment group; 37.5% of animals in an antibiotic-only group; and only 5.6% of animals in the serrapeptase-and-antibiotic group. The authors conclude that serrapeptase was effective at eradicating infection in this experimental animal model and may enhance antibiotic efficacy in the treatment of staphylococcal infections.14

Crohn’s Disease and Probiotics

Current research has found that probiotics, or live beneficial bacteria, can also play a large role in in reducing inflammation and symptoms of Crohn’s disease. Many bacterial strains have been evaluated for ability to normalize the properties of abnormal native microflora and reinforce various aspects of intestinal defense.

Probiotics inhibit microbial pathogen growth in the intestines by inhibiting their ability to attach to the gut and colonize.15 A study looked at the beneficial activity of Lactobacillus plantarum in an in vitro model of colon cells and demonstrated its ability to prevent adherence of a pathogenic E. coli strain, as well as increased the expression of protective proteins called mucins.16 Colonized probiotics ferment dietary fiber, and in doing so can induce pH and other chemical changes in the intestinal lumen (cavity) that also affect the inhibition of pathogen growth. 17.18 Additionally, short-chain fatty acids are released as a byproduct of bacterial fermentation display anti-inflammatory properties in the epithelial (intestinal lining) cells.19

Probiotics can stabilize the structure in the intestinal barrier and maintain rigidity in the tight junctions between epithelial cells. Lactobacillus GG was shown in multiple studies to stabilize the mucosal barrier, as well as inhibit the activation of proinflammatory cytokines that have been shown to be responsible for much of the cell death in the intestines related to Crohn’s.20,21,22 Mucosal samples from Crohn’s disease patients and controls were cultured with probiotic strains L. casei or L. bulgaricus and showed a significant decrease in the release of TNF-α, a cytokine strongly correlated with Crohn’s inflammation.23Probiotics can also stimulate the body’s innate defense mechanisms, as with the increased production of the antimicrobial peptide defensins in the intestines.24 As research continues to expand upon the use of probiotics with active Crohn’s disease, evidence continues to supports the use of oral probiotic supplements to help.


  1. Klein G, Kullich W. Reducing pain by oral enzyme therapy in rheumatic diseases. Wien Med Wochenschr. 1999; 149(21-22):577-80.
  2. Panagariya A, Sharma AK. A preliminary trial of serratiopeptidase in patients with carpal tunnel syndrome. J Assoc Physicians India. 2000; 48(11):1130.
  3. Bracale G, Selvetella L. Clinical study of the efficacy of and tolerance to seaprose S in inflammatory venous disease. Controlled study versus serratio-peptidase[Article in Italian] Minerva Cardioangiol. 1996; 44(10):515-24.
  4. Esch PM, Gerngross H, Fabian A. Reduction of postoperative swelling. Objective measurement of swelling of the upper ankle joint in treatment with serrapeptase– a prospective study (German). Fortschr Med. 1989; 107(4):67-8, 71-2. 
  5. Patki M. Study of anti-inflammatory and analgesic efficacy of Exclzyme ™ EN. J Orthopedics. 1999; 33(4):157-170. 
  6. Andresdottir MB, Sigfusson N, Sigvaldason H, Gundnason V. Erythrocyte Sedimentation Rate, an Independent Predictor of Coronary Heart Disease in Men and Women. Am J Epidemiol. 2003; 158(9):844-851. 
  7. Mazzone A, Catalani M, Costanzo M, 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. 
  8. Onken JE, Greer PK, Calingaert B, et al. Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro. Clin Immunol. 2008; 126(3):345-352. 
  9. Secor ER, Carson WF, Singh A, et al. Oral bromelain attenuates inflammation in an ovalbumin-induced murine model of asthma. Evid Based Complement Alternat Med. 2008; 5(1):61-69. 
  10. Fitzhugh DJ, Shan S, Dewhirst MW et al. Bromelain treatment decreases neutrophil migration to sites of inflammation. Clin Immunol. 2008; 128:66-74. 
  11. Hale LP, Greer PK, Trinh CT, Gottfried MR. Treatment with oral bromelain decreases colonic inflammation in the IL-10-deficient murine model of inflammatory bowel disease. Clin Immunol. 2005; 116(2):135-142. 
  12. Hale LP. Proteolytic activity and immunogenicity of oral bromelain within the gastrointestinal tract of mice. Intl Immunopharmaco. 2004; 4(2):255-64. 
  13. Esch PM, Gerngross H, Fabian A. Reduction of postoperative swelling. Objective measurement of the upper ankle joint in treatment with serrapeptase – a prospective study (German). Fortschr Med. 1989; 107(4):67-8, 71-2. 
  14. Mecikoglu M, Saygi B, Yildirim Y, et al. The effect of proteolytic enzyme serratiopeptidase in the treatment of experimental implant-related infection. J Bone Joint Surg Am. 2006; 88(6):1208-1214. 
  15. Bernet MF, Brassart D, Neeser JR, et al. Lactobacillus acidophilus LA 1 binds to cultured human intestinal cell lines and inhibits cell attachment and cell invasion by enterovirulent bacteria. Gut. 1994; 35:483–9. 
  16. Mack DR, Michail S, Wei S, et al. Probiotics inhibit enteropathogenic E coli adherence in vitro by inducing intestinal mucin gene expression. Am J Physiol1999; 276:G941–50. 
  17. Le Blay G, Michel C, Blottiere HM, et al. Prolonged intake of fructo-oligosaccharides induces a short-term elevation of lactic acid-producing bacteria and a persistent increase in cecal butyrate in rats. J Nutr. 1999; 129:2231–5. 
  18. Babakissa C, Colomb V, Andrieux C, et al. Luminal fermentation and colonocyte metabolism in a rat model of enteral nutrition. Dig Dis Sci. 2003; 48:1339–45. 
  19. Wilson AJ, Gibson PR. Short-chain fatty acids promote the migration of colonic epithelial cells in vitro. Gastroenterology1997; 113:487–96. 
  20. Isolauri E, Majamaa H, Arvola T, et al. Lactobacillus casei strain GG reverses increased intestinal permeability induced by cow milk in suckling rats. Gastroenterology1993; 105:1643–50. 
  21. Fabia R, Ar’Rajab A, Johansson ML, et al. The effect of exogenous administration of Lactobacillus reuteri R2LC and oat fiber on acetic acid-induced colitis in the rat. Scand J Gastroenterol1993; 28:155–62. 
  22. Bruewer M, Luegering A, Kucharzik T, et al. Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms. J Immunol2003; 171:6164–72. 
  23. Borruel N, Carol M, Casellas F, et al. Increased mucosal tumour necrosis factor alpha production in Crohn’s disease can be downregulated ex vivo by probiotic bacteria. Gut2002; 51:659–64. 
  24. Wehkamp J, Harder J, Wehkamp K, et al. NF-kappaB- and AP-1-mediated induction of human beta defensin-2 in intestinal epithelial cells by Escherichia coli Nissle 1917: a novel effect of a probiotic bacterium. Infect Immun2004; 72:5750–8.

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