Proteolytic enzymes

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Proteolytic enzymes

For Patients & Caregivers

Proteolytic enzymes have not been shown to prevent or 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, recent studies do not support such claims. But they may be useful in reducing pain associated with moderate-to-severe knee osteoarthritis.

  • Inflammation
    Observational studies suggest beneficial effects but clinical data are lacking.
  • Autoimmune diseases
    Evidence is lacking to support this claim.
  • Viral infections
    Evidence is lacking to support this claim.
  • Cancer and treatment-related symptoms
    Data from clinical studies are conflicting
  • Hepatitis C
    Evidence is lacking to support this claim.

You are taking anticoagulants (Warfarin): Bromelain may increase bleeding risk due to its antithrombotic effects observed in laboratory experiments and in mice (17). But clinical relevance is not known.

See additional bromelain interactions.

  • Gastrointestinal disturbance
  • See also Bromelain
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For Healthcare Professionals

Wobenzym®, Wobe-Mugos®, Zymactive®

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. Preclinical studies indicate 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.

In clinical studies, oral administration of PEs to healthy volunteers resulted in immunomodulatory effects (7); and systemic therapy with a PE before and after exhaustive exercise increased maximal concentric strength, and had favorable effects on inflammatory, metabolic and immune biomarkers (18). In a randomized trial of subjects with moderate-to-severe knee osteoarthritis, oral PE was found to have comparable effectiveness as diclofenac in relieving pain and increasing function (19).

Although some clinical and epidemiological studies suggest beneficial effects with adjuvant PEs 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). A randomized controlled trial also failed to find sufficient evidence to support use of PEs for preventing mucositis (13). Further, results from a study involving patients with inoperable pancreatic cancer showed a decrease in overall survival and poorer quality of life with PEs compared with standard gemcitabine-based chemotherapy (14). But findings from two meta-analyses suggest that PEs may be useful for preventing acute radiation-induced skin reactions (20). More studies are needed to confirm such effects.

Pineapple stem is a good source of bromelain. Papain is obtained from the papaya plant and fruits.

  • Cancer
  • Cancer treatment-related symptoms
  • Hepatitis C
  • High cholesterol
  • Immunomodulation
  • Inflammation
  • Viral infections

PEs are thought to exert immunomodulatory effects by causing increased release of reactive oxygen species by polymorphonuclear leukocytes (7) or by production of tumor necrosis factor-alpha and interleukins IL-6 and IL-1B that cause cytotoxic effects (1) (2). The anti-angiogenic effects exhibited by papain in VEGF-activated human endothelial cells are concentration-dependent and likely due to interference with AKT, MEK1/2 and SAPK/JNK phosphorylation (15). 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). In B16 murine melanoma models, PEs inhibited metastasis by reducing expression of CD44 and CD54 molecules (6).

  • Mild to moderate gastrointestinal symptoms (16)
  • See also Bromelain

Anticoagulants (Warfarin): Bromelain may increase bleeding risk due to its antithrombotic effects observed in preclinical experiments (17). But clinical relevance is not known.

See additional bromelain interactions.


  1. 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.

  2. 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.

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

  4. 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. Jul 2001;47 Suppl:S23-28.

  5. 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. Jul 2001;47 Suppl:S38-44.

  6. Dale PS, Tamhankar CP, George D, et al. Co-medication with hydrolytic enzymes in radiation therapy of uterine cervix: evidence of the reduction of acute side effects. Cancer Chemother Pharmacol. Jul 2001;47 Suppl:S29-34.

  7. 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. Apr 20 2010;28(12):2058-2063.

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

  9. Chan RJ, Webster J, Chung B, Marquart L, Ahmed M, Garantziotis S. Prevention and treatment of acute radiation-induced skin reactions: a systematic review and meta-analysis of randomized controlled trials. BMC Cancer. 2014 Jan 31;14:53.

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