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⁾. Systemic therapy with 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 had effectiveness comparable to diclofenac in relieving pain and increasing function ⁽¹⁹⁾.

Although some clinical and epidemiological studies suggest benefit 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⁾.

Findings from two meta-analyses suggest that PEs may be useful for preventing acute radiation-induced skin reactions ⁽²⁰⁾, but more studies are needed to confirm such effects.