MD, PhD, MAE, FMedSci, FRSB, FRCP, FRCPEd.

A 2020 article that I just came across concluded with this rather remarkable statement:

High-dose enzyme therapy is a natural cancer protocol that has been highly successful in treating this much-feared disease.

Since we can find a plethora of similar claims on social media and elsewhere, it is high time, I think, to dedicate a post to this alleged cancer cure.

Enzyme therapy involves the administration of proteolytic enzymes by mouth. Proteolytic enzymes are large molecules that are nevertheless said to be absorbed in the gut before they are dispersed into different compartments of the body where they can be detected in various concentrations. Proteolytic enzymes (serine endopeptidases such as trypsin or chymotrypsin and cysteine endo-proteinases such as bromelain and papain or combinations of those enzymes) have long been available for diverse medical indications, including cancer. They are claimed to exert anticancer activities by restoring the reduced cytotoxic activity of patients’ sera.

Enzyme therapy has been subjected to experimental investigations and to a few studies in cancer patients. A systematic review claimed that, for plasmacytoma patients, systemic enzyme therapy was shown to increase the response rates, the duration of remissions, and the overall survival times.[1]

This statement is based on just one study. Here is its abstract[2]:

Purpose: To evaluate the impact of an additive therapy with an oral enzyme (OE) preparation given for more than 6 months additionally to standard combination chemotherapy (vincristine/melphalan/cyclophosphamide/prednisone (VMCP)- or methylprednisolone/ vincristine/CCNU/cyclophosphamide/melphalan (MOCCA)-regimen) in the primary treatment of patients with multiple myeloma stages I-III.

Methods: A cohort of 265 patients with multiple myeloma stages I-III was consecutively treated at our institution in two parallel groups (control group (n = 99): chemotherapy +/-OE for less than 6 months; OE-group (n = 166): chemotherapy + OE for more than 6 months). The median follow-up time in the stages I, II, and III for the OE-group was 61, 37, and 46.5 months, respectively; for the control group the respective values were 33, 51.5, and 31.5 months. The primary endpoint of the study was disease-specific survival. Secondary endpoints were response to therapy, duration of first response and side effects. The chosen method for evaluation was the technique of a retrolective cohort analysis with a concurrent control group. Survival analysis was performed by the Kaplan-Meier method and multivariate analysis was done with the Cox proportional hazards model.

Results: Significantly higher overall response rates and longer duration of remissions were observed in the OE-group. Primary responders showed a longer mean survival time than non-responders. Additive therapy with OE given for more than 6 months decreased the hazard of death for patients at all stages of disease by approximately 60%. Observation time was not long enough to estimate the median survival for patients at stages I and II; for stage III patients it was 47 months in the control group versus 83 months for the patients treated with OE (P = 0.0014) which means a 3-year gain of survival time. Significant prognostic factors for survival, in the Cox regression analysis, were stage of disease and therapy with OE. The OE-therapy was generally well tolerated (3.6% of patients with mild to moderate gastrointestinal symptoms).

Conclusion: OEs represent a promising new additive therapy in multiple myeloma which will be further evaluated in a randomized phase III trial in the USA.

My searches located no prospective clinical trials supporting the notion that enzyme therapy is an effective cancer cure for any type of human cancer. So, what about the bold statement quoted above? In my view, it is a dangerous and highly irresponsible claim that endangers the lives of many vulnerable cancer patients desperately looking for alternative cancer cures.

REFERENCES

[1] Beuth J. Proteolytic enzyme therapy in evidence-based complementary oncology: fact or fiction? Integr Cancer Ther. 2008 Dec;7(4):311-6. doi: 10.1177/1534735408327251. PMID: 19116226.

[2] Sakalová A, Bock PR, Dedík L, Hanisch J, Schiess W, Gazová S, Chabronová I, Holomanova D, Mistrík M, Hrubisko M. Retrolective cohort study of an additive therapy with an oral enzyme preparation in patients with multiple myeloma. Cancer Chemother Pharmacol. 2001 Jul;47 Suppl:S38-44. doi: 10.1007/s002800170008. PMID: 11561871.

4 Responses to Enzyme therapy for cancer?

  • Your link to Sakalova et al.’s paper just goes to your reference list. Here is a link to the abstract with the option of viewing the full paper for £29.95 for the benefit of anybody who has access through an academic library:

    https://link.springer.com/article/10.1007/s002800170008

    I had to read the abstract several times in order to work out what was going on. I think “retrolective” must be a misprint for “retrospective”, which does make me wonder about the quality of proofreading. There also appears to be some confusion about the difference between various survival measures – mean and median survival seem to be used interchangeably, and having defined the endpoint as disease-specific survival (DSS) they then talk about survival differences between the various groups without making it clear whether they are still referring to DSS, or whether they are now talking about overall survival (OS), which is a completely different thing.

    The chemotherapy regimens used struck me as rather strange, until I realised that the paper was nearly 20 years old, so given a median follow-up time for one of the groups of more than five years, the study was probably conducted 30 years or so ago. Myeloma / plasmacytoma treatment has moved on a bit since then. The authors claim a huge benefit (essentially a doubling of survival) for what is a cheap, easy and non-toxic adjunct to standard treatment, so if the results are as good as they claim then why have there never been any follow-up studies?

    The real problem with this study is how it was conducted. Essentially it appears to be a cohort study, with one cohort having received oral enzyme therapy (OE) for six months or more, and the other having received it for less than six months or not at all, this second cohort serving as the control. It is not at all clear why some patients received OE and some didn’t, nor indeed how much the duration of supplementation varied or why six months was chosen as a cut-off point (perhaps because it showed the largest effect when the data were examined?). All retrospective cohort studies by their nature are prone to bias (I use the word in the technical statistical sense, referring to the effect of an unidentified factor influencing the choice of treatment), and this is enough to explain any difference in outcome. For this reason they are not considered to be strong evidence. Such studies can only, therefore, be hypothesis-generating as a prelude to further, prospective randomised studies, and they should never form any basis for clinical practice.

    With regard to enzyme supplementation, enzymes are themselves proteins, and the proteolytic enzymes produced by our own digestive system break down any proteins into their constituent amino acids so that they can be absorbed, so any protein-based treatment (such as monoclonal antibodies) has to be given by systemic injection or intravenous infusion.

    I do know of one enzyme used in cancer treatment, asparaginase, which forms part of some leukaemia treatment regimens. However, that is a bit different from what is being discussed here.

    • Retrolective: Pertaining to data gathered without planning for the needs of an investigation.

      – A Dictionary of Epidemiology (5 ed.), Oxford University Press.

    • QFT:

      With regard to enzyme supplementation, enzymes are themselves proteins, and the proteolytic enzymes produced by our own digestive system break down any proteins into their constituent amino acids so that they can be absorbed, so any protein-based treatment (such as monoclonal antibodies) has to be given by systemic injection or intravenous infusion.

      Tx for the breakdown. IANAD and even I did a yeah-no at “enzymes by mouth”.

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