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Proteolytic Enzyme Therapy

Enzymes are complex proteins that catalyze metabolic reactions throughout the body, and sufficient levels are required for optimizing many of the body’s functions.

 

Although the body produces its own supply of enzymes, the amount produced can vary from person to person and is affected by age, diet, biochemistry and stress.

 

Enzymes fall into three broad categories: metabolic enzymes, manufactured by cells to carry out various functions; digestive enzymes, primarily manufactured by the pancreas to digest foods and absorb nutrients and food enzymes; and exogenous (from outside the body) enzymes from plants and animals, also necessary for aiding and accelerating digestion.

 

Proteases and proteolytic enzymes play fundamental roles in multiple biological processes and are associated with a wide variety of pathological conditions, including cancer. Studies have demonstrated that systemic enzyme therapy significantly decreased tumor-induced and therapy-induced side effects and complaints such as nausea, gastrointestinal complaints, fatigue, weight loss, and restlessness and obviously stabilized the quality of life.

 

Studies have also highlighted the efficacy of systemic proteolytic enzyme therapy for a variety of uses, including maintaining normal inflammatory balance, nasal passage health, bronchial health, musculoskeletal health and exercise-related recovery. In vitro, animal and human data show that proteolytic enzyme therapies are capable of cleaving immune complexes, which are known inflammatory mediators.

Amri E, Mamboya. Papain, a Plant Enzyme of Biological Importance: A Review. Am J Biochem Biotechnol. 2012;8(2),99-104.

Atagi S, Sone S, Fukuta K, Ogura T. Inhibition by fibrin coagulation of lung cancer cell destruction by human interleukin-2-activated killer cells. Jpn J Cancer Res. 1992 Oct; 83(10):1088-94. 

Beard J. The action of trypsin upon the living cells of Jensen's mouse tumor. Br Med J 4, 140-141, 1906.

Beuth J, Braun JM. Modulation of murine tumor growth and colonization by bromelaine, an extract of the pineapple plant (Ananas comosum L.). In Vivo. Mar-Apr 2005;19(2):483-485.

Beuth J, Ost B, Pakdaman A, Rethfeldt E, Bock PR, Hanisch J, Schneider B. Impact of complementary oral enzyme application on the postoperative treatment results of breast cancer patients - results of an epidemiological multicentre retrolective cohort study. Cancer Chemother Pharmacol. 2001 Jul; 47 Suppl:S45-54.

Beuth, Josef. Proteolytic enzyme therapy in evidence-based complementary oncology: fact or fiction? Integrative cancer therapies 7, no. 4 (2008): 311-316.

Bhui K, Prasad S, George J, Shukla Y. Bromelain inhibits COX-2 expression by blocking the activation of MAPK regulated NF-kappa B against skin tumor-initiation triggering mitochondrial death pathway. Cancer Lett 2009 Sep 18;282(2):167-76. (Abstract)

Bhui K, Tyagi S, Prakash B, Shukla Y. Pineapple bromelain induces autophagy, facilitating apoptotic response in mammary carcinoma cells. Biofactors. 2010 Nov-Dec;36(6):474-82. (Abstract)

Braun, J. M., B. Schneider, and H. J. Beuth. Therapeutic use, efficiency and safety of the proteolytic pineapple enzyme Bromelain-POS® in children with acute sinusitis in Germany. In Vivo 19, no. 2 (2005): 417-421.

Brien S, Lewith G, Walker AF, et al. Bromelain as an adjunctive treatment for moderate-to-severe osteoarthritis of the knee: a randomized placebo-controlled pilot study. QJM. Dec 2006;99(12):841-850.

Bingle, áL, N. J. Brown, and C. E. Lewis. The role of tumour‐associated macrophages in tumour progression: implications for new anticancer therapies. The Journal of Pathology: A Journal of the Pathological Society of Great Britain and Ireland196, no. 3 (2002): 254-265.

Chabot JA, Tsai WY, Fine RL, et al. Pancreatic proteolytic enzyme therapy compared with gemcitabine-based chemotherapy for the treatment of pancreatic cancer. J Clin Oncol 28 (12): 2058-63, 2010.

Desser L, Rehberger A, Paukovits W. Proteolytic enzymes and amylase induce cytokine production in human peripheral blood mononuclear cells in vitro. Cancer Biother. Fall 1994;9(3):253-263. (Abstract)

Desser L, Rehberger A. Induction of tumor necrosis factor in human peripheral-blood mononuclear cells by proteolytic enzymes. Oncology. 1990;47(6):475-477. (Abstract) 

Desser, L.; Holomanova, D. et al. Oral therapy with proteolytic enzymes decreases excessive TGF-beta levels in human blood. Cancer Chemother Pharmacol. 2001; 47 Suppl.

Desser L, Rehberger A, Kokron E, et al. Cytokine synthesis in human peripheral blood mononuclear cells after oral administration of polyenzyme preparations. Oncology. Nov-Dec 1993;50(6):403-407. (Abstract)

Gass, Jonathan, Michael T. Bethune, Matthew Siegel, Andrew Spencer, and Chaitan Khosla. Combination enzyme therapy for gastric digestion of dietary gluten in patients with celiac sprue. Gastroenterology 133, no. 2 (2007): 472-480.

Gonzalez NJ, Isaacs LL. Evaluation of pancreatic proteolytic enzyme treatment of adenocarcinoma of the pancreas, with nutrition and detoxification support. Nutr Cancer 33 (2): 117-24, 1999. (Abstract)

Gunji Y, Gorelik E. Role of fibrin coagulation in protection of murine tumor cells from destruction by immune cells. Cancer Res 48: 5216–5221, 1988.

Gunji Y, Lewis J, Gorelik E. Fibrin formation inhibits the in vitro cytotoxic activity of human natural and lymphokine-activated killer cells. Blood Coagul Fibrinolysis. 1990 Dec; 1(6):663-72. (Abstract)

Johansson, Björn P., Oonagh Shannon, and Lars Björck. IdeS: a bacterial proteolytic enzyme with therapeutic potential. PLoS one 3, no. 2 (2008): e1692. (Abstract)

Kalra N, Bhui K, Roy P, et al. Regulation of p53, nuclear factor kappaB and cyclooxygenase-2 expression by bromelain through targeting mitogen-activated protein kinase pathway in mouse skin. Toxicol Appl Pharmacol. 2008 Jan 1;226(1):30-7. (Abstract)

 

Kamenicek, V.; Holan, P.; and Franek, P. Systemic enzyme therapy in the treatment and prevention of post-traumatic and postoperative swelling. Acta Chir Orthop Traumatol Cech. 2001; 68(1):45-49. (Abstract)

Klein, G.; Kullich, W. et al. Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomized study comparing oral enzymes with non-steroidal anti-inflammatory drugs. Clin Exp Rheumatol. 2006; 24(1):25-30.

López-Otín, Carlos, and Lynn M. Matrisian. Emerging roles of proteases in tumour suppression. Nature reviews cancer 7, no. 10 (2007): 800.

Massimiliano R, Pietro R, Paolo S, et al. Role of bromelain in the treatment of patients with pityriasis lichenoides chronica. J Dermatolog Treat. 2007;18(4):219-222. (Abstract)

Maurer HR. Bromelain: biochemistry, pharmacology and medical use. Cell Mol Life Sci 2001;58:1234-45. (Abstract) 

Minaev, S.V.; Nemilova, T.K.; and Knorring, G.I. Polyenzymatic therapy in prevention of adhesive processes in the abdominal cavity in children. Vestn Khir Im I I Grek. 2006. (Abstract) 

Novak JF, Trnka F. Proenzyme therapy of cancer. Anticancer Res. 2005 Mar-Apr;25(2A):1157-77.

Odell J. Oral Proteolytic Enzyme Therapy.

Onken JE, Greer PK, Calingaert B, et al. Bromelain treatment decreases secretion of proinflammatory cytokines and chemokines by colon biopsies in vitro. Clin Immunol. Mar 2008;126(3): 345-352.

Pandey S et al. Anti-inflammatory and immunomodulatory properties of Carica papaya. J Immunotoxicol. 2016;13(4),590-602.

Popiela T, Kulig J, Hanisch J, Bock PR. Influence of a complementary treatment with oral enzymes on patients with colorectal cancers - an epidemiological retrolective cohort study. Cancer Chemother Pharmacol. 2001 Jul; 47 Suppl:S55-63. (Abstract)

Rothman S, Liebow C, Isenman L. Conservation of digestive enzymes. Physiol Rev 82 (1): 1-18, 2002.

 

Siegel, Matthew, Michael T. Bethune, Jonathan Gass, Jennifer Ehren, Jiang Xia, Alexandre Johannsen, Tor B. Stuge, Gary M. Gray, Peter P. Lee, and Chaitan Khosla. Rational design of combination enzyme therapy for celiac sprue. Chemistry & biology 13, no. 6 (2006): 649-658.

Tysnes BB, Maurer HR, Porwol T, et al. Bromelain reversibly inhibits invasive properties of glioma cells. Neoplasia. Nov-Dec 2001;3(6):469-479.

Wald M, Olejar T, Sebkova V, et al. Mixture of trypsin, chymotrypsin and papain reduces formation of metastases and extends survival time of C57Bl6 mice with syngeneic melanoma B16. Cancer Chemother Pharmacol. Jul 2001;47 Suppl:S16-22.

Wald M, Závadová E, Poucková P, Zadinová M. Polyenzyme preparation Wobe-Mugos inhibits growth of solid tumors and development of experimental metastases in mice. Boubelik M.Life Sci. 1998; 62(3):PL43-8. (Abstract)

Walker AF, Bundy R, Hicks SM, Middleton RW. Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent fashion in an open study of otherwise healthy adults. Phytomedicine 2002;9:681-6.

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