Health Care Professional Information
Brand Name
Wobenzym ®, WOBE-MUGOS, Zymactive
Clinical Summary
Proteolytic enzyme (PE) treatments were first popularized in Germany in the 1960s for inflammation, osteoarthritis, autoimmune diseases, and viral infections. The products usually contain a mixture of pancreatin, papain, bromelain trypsin and chymotrypsin. Studies done in vitro and in mice have shown that PEs have immunomodulatory and tumoricidal properties (1) (2) (3) (4) (5) (6). Such effects are thought to result from degradation of abnormal immune complexes.
Oral administration of PEs to healthy volunteers resulted in an increase in release of reactive oxygen species (ROS) by polymorphonuclear leukocytes (7).
Although epidemiological studies suggest beneficial effects of PEs as adjuvants in patients with head and neck cancers (8), multiple myeloma (9), breast cancer (10), and cervical cancer (11), conflicting data do not support the findings (12). Further, results from a study involving patients with inoperable pancreatic cancer showed a decrease in overall survival and poorer quality of life with proteolytic enzymes compared to standard gemcitabine-based chemotherapy (14).
Reported adverse effects from use of PEs include mild to moderate gastrointestinal symptoms (13).
Food Sources
Pineapple stem is a good source of Bromelain. Papain is obtained from Papaya plant and fruits.
Purported Uses
- Cancer treatment
- Hepatitis C
- High cholesterol
- Immunomodulation
- Inflammation
- Viral infections
Constituents
May contain a combination of the following:
- Pancreatin
- Papain
- Bromelain trypsin
- Chymotrypsin
Mechanism of Action
Although the exact mechanism is not clear, PEs are thought to exert immunomodulatory effects by causing an increase in release of reactive oxygen species (ROS) by polymorphonuclear leukocytes (7) or by production of TNF and Interleukins IL-6 and IL-1B that cause cytotoxic effects (1) (2). Bromelain has been shown to lower the tumorigenic/metastatic capacities of Sarcoma L-1 cells (3). It also inhibited glioma cell migration and invasion by affecting expression of integrins, necessary for cellular migration and invasion (5). A study done in mice with B16 melanoma showed inhibition of metastasis when exposed to PEs by reduced expression of CD44 and CD54 molecules (6).
Adverse Reactions
- Gastrointestinal disturbance
- See also Bromelain
Literature Summary and Critique
Beuth J. et al. 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; 47(Suppl):S45-54.This study involved 649 breast cancer patients undergoing cancer treatment (radiation, chemo, or hormonal therapy) at 216 centres. Of these, 239 patients received an oral enzyme comprised of papain, trypsin, and chymotrypsin, whereas 410 received only conventional treatment. The results showed that symptoms such as infections, skin disorders, tumor pain, headache, and cachexia associated with cancer and cancer treatment were significantly less in patients who received oral enzyme. However, because of the short duration over which these observations were made, they are not conclusive. Randomized controlled trials are necessary to confirm these observations.
Gujral MS, et al. Efficacy of hydrolytic enzymes in preventing radiation therapy-induced side effects in patients with head and neck cancers. Cancer Chemother Pharmacol 2001; 47(Suppl):S23-S28.
One hundred patients with head and neck cancers receiving radiotherapy were randomized for this study. The test group received an oral enzyme made of papain, trypsin, and chymotrypsin, whereas the control group did not receive the enzyme or placebo. Researchers found statistically significant reduction in symptoms such as mucositis, dysphagia and skin reaction associated with radiotherapy. In addition, the number of patients progressing toward moderate and severe reactions was less in the test group compared to the control group. Another study with larger sample size is being performed to verify the above effects.
Martin T, et al. Does prophylactic treatment with proteolytic enzymes reduce acute toxicity of adjuvant pelvic irradiation? Results of a double-blind randomized trial. Radiotherapy and Oncology 2002; 65:17-22.
Fifty-six patients with an indication for pelvic radiation following surgery were randomized to receive an oral enzyme preparation or placebo. Patients were given four capsules three times a day of the enzyme three days before radiation and finishing on the last day of treatment. All patients received similar amounts of radiation. Results did not show any benefits of oral enzyme in reducing the toxic effects such as diarrhea, nausea, or vomiting from radiation.
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. 2010 Apr 20;28(12):2058-63.
Fifty-five patients with inoperable pancreatic cancer were enrolled in this controlled, observational study. Twenty-three patients chose gemcitabine-based chemotherapy, whereas 32 elected enzyme treatment that consisted of pancreatic enzymes, nutritional supplements, detoxification, and an organic diet. The two groups had no statistically significant differences in quality of life or pathology at enrollment. At one year time point, researchers observed an increase in overall survival (a 9.7 month difference in median survival) and better quality of life (P < .01) in patients who chose gemcitabine-based chemotherapy compared to those in the proteolytic enzyme group.
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References
- Desser L, Rehberger A, Paukovits W. Proteolytic enzymes and amylase induce cytokine production in human peripheral blood mononuclear cells in vitro. Cancer Biother 1994; 9(3):253-263.
- Desser L, Rehberger A.Induction of tumor necrosis factor in human peripheral-blood mononuclear cells by proteolytic enzymes. Oncology 1990; 47(6):475-477.
- Beuth J, Braun JM. Modulation of murine tumor growth and colonization by bromelaine, an extract of the pineapple plant (Ananas comosum L.) In Vivo 2005; 19(2):483-485.
- Desser L, Rehberger A, Kokron E, Paukovits W. Cytokine synthesis in human peripheral blood mononuclear cells after oral administration of polyenzyme preparations. Oncology 1993; 50(6):403-407.
- Tysnes BB, Maurer HR, Porwol T, Probst B, Bjerkvig R, Hoover F. Bromelain reversibly inhibits invasive properties of glioma cells. Neoplasia 2001; 3(6):469-479.
- Wald M, Olejar T, Sebkova V, Zadinova M, Boubelik M, Pouckova P. Mixture of trypsin, chymotrypsin and papain reduces formation of metastases and extends survival time of C57Bl6 mice with syngeneic melanoma B16. Cancer Chemother Pharmacol 2001; 47 Suppl:S16-S22.
- Zavadova E, Desser L, Mohr T. Stimulation of reactive oxygen species production and cytotoxicity in human neutrophils in vitro and after oral administration of a polyenzyme preparation. Cancer Biother 1995; 10(2):147-152.
- Gujral MS, Patnaik PM, Kaul R et al. Efficacy of hydrolytic enzymes in preventing radiation therapy-induced side effects in patients with head and neck cancers. Cancer Chemother Pharmacol 2001; 47 Suppl:S23-S28.
- Sakalova A, Bock PR, Dedik L et al. Retrolective cohort study of an additive therapy with an oral enzyme preparation in patients with multiple myeloma. Cancer Chemother Pharmacol 2001; 47 Suppl:S38-S44.
- Beuth J, Ost B, Pakdaman A et al. 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; 47 Suppl:S45-S54.
- Dale PS, Tamhankar CP, George D, Daftary GV. Co-medication with hydrolytic enzymes in radiation therapy of uterine cervix: evidence of the reduction of acute side effects. Cancer Chemother Pharmacol 2001; 47 Suppl:S29-S34.
- Martin T, Uhder K, Kurek R et al. Does prophylactic treatment with proteolytic enzymes reduce acute toxicity of adjuvant pelvic irradiation? Results of a double-blind randomized trial. Radiother Oncol 2002; 65(1):17-22.
- 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; 47 Suppl:S55-S63.
- 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. 2010;28(12):2058-63.
Consumer Information
How It Works
Bottom Line: Proteolytic enzymes have not been shown to treat cancer.
Proteolytic enzyme (PE) treatments were first used in Germany in the 1960s for inflammation, osteoarthritis, autoimmune diseases, and viral infections. The products usually contain a mixture of pancreatin, papain, bromelain trypsin and chymotrypsin. Laboratory studies have shown that PEs can affect the growth of cancer cells. Although PEs were reported to benefit patients with cancer, evidence from recent studies does not support such claims.
Gastrointestinal disturbance has been reported from use of PEs.
Purported Uses
- Inflammation
Observational studies suggest beneficial effects but clinical data are lacking. - Autoimmune diseases
This use is not backed by clinical data. - Viral infections
There is no scientific evidence to support this use. - Cancer treatment
Data from some observational studies suggest beneficial effects but randomized controlled trials are needed to verify such effects. - Hepatitis C
This use is not supported by scientific evidence.
Research Evidence
Cancer Treatment
An epidemiological study was conducted to observe the effects of an oral enzyme (made up of papain, trypsin and chymotrypsin) in patients with breast cancer. Out of 649 patients, 239 received the oral enzyme whereas 410 patients received only conventional treatment. Researchers found that symptoms such as infections, skin disorders, tumor pain, and headache resulting both from cancer and cancer treatments were less in patients who took the oral enzyme. Since the observations were made over a short period of time, more research is needed.
One hundred patients with head and neck cancers receiving radiotherapy participated in another study. Patients in the study group received three tablets of an oral enzyme (made of papain, trypsin and chymotrypsin) three times a day from 3 days prior to beginning radiotherapy until 5 days after completing radiotherapy. Patients in the control group did not receive the enzyme. Researchers found a reduction in symptoms such as mucositis (inflammation of mucus membrane), dysphagia (difficulty in swallowing) and skin reaction associated with radiotherapy in patients from the study group. Studies with more patients are needed to verify the above effects.
Another study involved 56 cancer patients who were given either four capsules of an oral enzyme preparation three times a day, three days before pelvic radiation and finishing on the last day of treatment or placebo. All patients received similar amounts of radiation. Results did not show any benefits of the oral enzyme in reducing the severe side effects such as diarrhea, nausea, or vomiting due to radiotherapy.
Fifty-five patients with inoperable pancreatic cancer were enrolled in this controlled, observational study. Twenty-three patients chose gemcitabine-based chemotherapy, whereas 32 elected enzyme treatment that consisted of pancreatic enzymes, nutritional supplements, detoxification, and an organic diet. The two groups had no significant differences in quality of life or pathology at enrollment. At one year time point, researchers observed an increase in overall survival and better quality of life in patients who chose gemcitabine-based chemotherapy compared to those in the proteolytic enzyme group.
Side Effects
- Gastrointestinal disturbance has been reported with use of proteolytic enzymes.
- See also Bromelain
Last updated: June 1, 2012
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