Enzyme Therapy Abstracts 1

© 

Proteolytic enzyme therapy in evidence-based complementary oncology: fact or fiction
            (Beuth, 2008) Download
Systemic enzyme therapy was recently subjected to experimental investigations and to rigorous clinical studies in cancer patients. The designs of the relevant clinical cohort studies followed the guidelines of Good Epidemiological Practice and represent level IIB in evidence-based medicine (EBM). Scientifically sound experimental in vitro and in vivo investigations are far advanced and document promising immunological, anti-inflammatory, anti-infectious, and antitumor/antimetastatic activities of proteolytic enzyme mixtures (containing trypsin, chymotrypsin, and papain) or bromelain. EBM level II clinical studies, which are accepted by the European Union to show safety and efficacy of medical treatments, were performed to evaluate the benefit of complementary systemic enzyme therapy in cancer patients suffering from breast and colorectal cancers and plasmacytoma. These studies 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. For plasmacytoma patients, complementary systemic enzyme therapy was shown to increase the response rates, the duration of remissions, and the overall survival times. These promising data resulted in an "orphan drug status" designation for a systemic enzyme product, which should motivate further studies on this complementary treatment.

Enzymes and cancer: a look toward the past as we move forward.
            (Block, 2008) Download
Several years ago, I was having lunch with a prominent German medical oncologist at a conference on cancer and CAM at the National Institutes of Health (NIH) in Washington, DC. I asked him what the most exciting thing in cancer CAM in Europe was at that time. “Enzymes,” he said. A bit surprised by his instantaneous response, I asked him what the second most exciting thing was. Again with no hesitation he blurted out, “More enzymes!”


 

Enzyme replacement therapy: conception, chaos and culmination.
            (Brady, 2003) Download
Soon after the enzymatic defects in Gaucher disease and in Niemann-Pick disease were discovered, enzyme replacement or enzyme supplementation was proposed as specific treatment for patients with these and related metabolic storage disorders. While relatively straightforward in concept, successful implementation of this approach required many years of intensive effort to bring it to fruition. Procedures were eventually developed to produce sufficient quantities of the requisite enzymes for clinical trials and to target therapeutic enzymes to lipid-storing cells. These achievements led to the development of effective enzyme replacement therapy for patients with Gaucher disease and for Fabry disease. These demonstrations provide strong incentive for the application of this strategy for the treatment of many human disorders of metabolism.

Pancreatic Enzyme Replacement Therapy: A Concise Review.
            (Brennan and Saif, 2019) Download
Pancreatic enzyme replacement therapy is safe and effective at treating pancreatic exocrine insufficiency. There are multiple causes of pancreatic exocrine insufficiency including chronic pancreatitis, cystic fibrosis and pancreatic cancer. Testing fecal elastase-1 level is useful for the diagnosis of pancreatic exocrine insufficiency. Starting doses of pancreatic enzyme replacement therapy should be at least 30-40,000 IU with each meal and 15-20,000 IU with snacks. pancreatic enzyme replacement therapy should be taken in divided doses throughout meals. Patients who do not respond to initial dosages should be evaluated for alternative etiologies and pancreatic enzyme replacement therapy optimized. Despite ease of use and benefit of pancreatic enzyme replacement therapy, challenges still remain clinically and this review hopes to provide a concise guide for clinicians.

Pancreatic proteolytic enzyme therapy compared with gemcitabine-based chemotherapy for the treatment of pancreatic cancer.
            (Chabot et al., 2010) Download
PURPOSE Conventional medicine has had little to offer patients with inoperable pancreatic adenocarcinoma; thus, many patients seek alternative treatments. The National Cancer Institute, in 1998, sponsored a randomized, phase III, controlled trial of proteolytic enzyme therapy versus chemotherapy. Because most eligible patients refused random assignment, the trial was changed in 2001 to a controlled, observational study. METHODS All patients were seen by one of the investigators at Columbia University, and patients who received enzyme therapy were seen by the participating alternative practitioner. Of 55 patients who had inoperable pancreatic cancer, 23 elected gemcitabine-based chemotherapy, and 32 elected enzyme treatment, which included pancreatic enzymes, nutritional supplements, detoxification, and an organic diet. Primary and secondary outcomes were overall survival and quality of life, respectively. Results At enrollment, the treatment groups had no statistically significant differences in patient characteristics, pathology, quality of life, or clinically meaningful laboratory values. Kaplan-Meier analysis found a 9.7-month difference in median survival between the chemotherapy group (median survival, 14 months) and enzyme treatment groups (median survival, 4.3 months) and found an adjusted-mortality hazard ratio of the enzyme group compared with the chemotherapy group of 6.96 (P < .001). At 1 year, 56% of chemotherapy-group patients were alive, and 16% of enzyme-therapy patients were alive. The quality of life ratings were better in the chemotherapy group than in the enzyme-treated group (P < .01). CONCLUSION Among patients who have pancreatic cancer, those who chose gemcitabine-based chemotherapy survived more than three times as long (14.0 v 4.3 months) and had better quality of life than those who chose proteolytic enzyme treatment.

Efficacy of Wobe-Mugos E for reduction of oral mucositis after radiotherapy : results of a prospective, randomized, placebo-controlled, triple-blind phase III multicenter study.
            (Dörr et al., 2007) Download
PURPOSE:  To investigate the efficacy and safety of Wobe-Mugos E (proteolytic enzymes) for amelioration of early side effects of radiotherapy for head-and-neck tumors, particularly oral mucositis. PATIENTS AND METHODS:  The study was a prospective, randomized, multicenter, placebo-controlled, triple-blind phase III study with parallel groups. 69 patients with carcinomas of the oropharynx or the oral cavity were enrolled between 1996 and 2000 in five centers; 54 of these were recruited in Dresden. Of the 69 patients, 61 (Dresden: 46) were available for analysis. The proteolytic enzymes tested (Wobe-Mugos E) comprised papain 100 mg, trypsin 40 mg, and chymotrypsin 40 mg. RESULTS:  Wobe-Mugos E was well tolerated. For the maximum mucositis scores, no statistically significant differences were found between the placebo and the verum group. The average mucositis score over weeks 1-6 revealed a significant difference in favor of the placebo arm, based on an earlier onset of mucositis in the Wobe-Mugos E group. CONCLUSION:  The present study failed to demonstrate any effect of treatment with Wobe-Mugos E on radiotherapy side effects in patients treated for head-and-neck tumors. In particular, there was no beneficial effect on radiation-induced early oral mucositis.


 

Enzyme replacement therapy for pancreatic insufficiency: present and future.
            (Fieker et al., 2011) Download
Pancreatic enzyme replacement therapy is currently the mainstay of treatment for nutrient malabsorption secondary to pancreatic insufficiency. This treatment is safe and has few side effects. Data demonstrate efficacy in reducing steatorrhea and fat malabsorption. Effective therapy has been limited by the ability to replicate the physiologic process of enzyme delivery to the appropriate site, in general the duodenum, at the appropriate time. The challenges include enzyme destruction in the stomach, lack of adequate mixing with the chyme in the duodenum, and failing to deliver and activate at the appropriate time. Treatment is begun when clinically significant malabsorption occurs resulting in steatorrhea and weight loss. Treatment failure is addressed in a sequential fashion. Current research is aimed at studying new enzymes and delivery systems to improve the efficiency of action in the duodenum along with developing better means to monitor therapy.

Evaluation of pancreatic proteolytic enzyme treatment of adenocarcinoma of the pancreas, with nutrition and detoxification support.
            (Gonzalez and Isaacs, 1999) Download
Historically, large doses of proteolytic enzymes, along with diet, nutritional supplements, and "detoxification" procedures, have been used in alternative therapies to treat all forms of cancer, without formal clinical studies to support their use. A 2-year, unblinded, 1-treatment arm, 10-patient, pilot prospective case study was used to assess survival in patients suffering inoperable stage II-IV pancreatic adenocarcinoma treated with large doses of orally ingested pancreatic enzymes, nutritional supplements, "detoxification" procedures, and an organic diet. From January 1993 to April 1996 in the authors' private practice, 10 patients with inoperable, biopsy-proven pancreatic adenocarcinoma were entered into the trial. After one patient dropped out, an 11th patient was added to the study (however, all 11 are considered in the data tabulation). Patients followed the treatment at home, under the supervision of the authors. As of 12 January 1999, of 11 patients entered into the study, 9 (81%) survived one year, 5 (45%) survived two years, and at this time, 4 have survived three years. Two patients are alive and doing well: one at three years and the other at four years. These results are far above the 25% survival at one year and 10% survival at two years for all stages of pancreatic adenocarcinoma reported in the National Cancer Data Base from 1995. This pilot study suggests that an aggressive nutritional therapy with large doses of pancreatic enzymes led to significantly increased survival over what would normally be expected for patients with inoperable pancreatic adenocarcinoma.


 

An Enzyme-Based Nutritional Protocol In Metastatic Cancer: Case Reports Of A Patient With Colon Cancer And A Patient With Lung Cancer.
            (Isaacs, 2019) Download
Context:  The author and others have previously published case reports demonstrating positive results in patients with cancer utilizing lifestyle modification which includes high doses of a product rich in pancreatic enzymes. Objective:  The study reports on outcomes of two patients utilizing this nutritional protocol, one with colon cancer metastatic to the liver and lung, another with lung cancer metastatic to the brain. Design:  Retrospective case studies. Setting:  The patients were seen in an outpatient clinic in New York City, and implemented their protocols in their homes in the United States of America. Participants:  The patients in these case reports are two men in their 60s. Intervention:  The patients were instructed in the self-administration of a nutritional protocol consisting of dietary modifications, a supplement protocol including high doses of a pancreas product naturally rich in enzymes, and detoxification including the use of coffee enemas. Outcome Measures:  Records were reviewed for evidence of prolonged survival and/or improvement or resolution of radiographically apparent disease. Results:  The patients experienced both prolongation of life and resolution of radiographically apparent disease. Conclusions:  While case reports cannot be considered as proof of efficacy, these cases added to others of patients treated with the same method would suggest that this is a viable option for those patients whose disease cannot be treated successfully with other modalities.

Contribution of pancreatic enzyme replacement therapy to survival and quality of life in patients with pancreatic exocrine insufficiency.
            (Layer et al., 2019) Download
The objective of this study was to analyze the current evidence for the use of pancreatic enzyme replacement therapy (PERT) in affecting survival and quality of life in patients with pancreatic exocrine insufficiency (PEI). Systematic searches of the literature were performed using the PubMed database. Articles were selected for inclusion if they reported findings from trials assessing the effects of PERT on quality of life, survival, malabsorption, growth parameters (such as height, body weight and body mass index), or gastrointestinal symptoms (such as abdominal pain, stool consistency and flatulence). PERT improved PEI-related malabsorption and weight maintenance in patients with cystic fibrosis, chronic pancreatitis, pancreatic cancer, and post-surgical states. In patients with chronic pancreatitis, PERT improved PEI-related symptoms and quality of life measures. Several small retrospective studies have also suggested that PERT may have a positive impact on survival, but long-term studies assessing this effect were not identified. PERT is effective for treating malnutrition and supporting weight maintenance, and it is associated with improved quality of life and possibly with enhanced survival in patients with PEI. However, there is evidence that not all patients with PEI receive adequate PERT. Future work should aim to assess the long-term effects of PERT on the survival of patients with PEI.

Systemic enzyme therapy in oncology: effect and mode of action.
            (Leipner and Saller, 2000) Download
Plant extracts with a high content of proteolytic enzymes have been used for a long time in traditional medicine. Besides proteolytic enzymes from plants, 'modern' enzyme therapy additionally includes pancreatic enzymes. The therapeutic use of proteolytic enzymes is partly based on scientific studies and is partly empirical. The aim of the current review is to provide an overview of clinical trials of systemic enzyme therapy in oncology, and to discuss the evidence for their possible mechanisms of action. Clinical studies of the use of proteolytic enzymes in oncology have mostly been carried out on an enzyme preparation consisting of a combination of papain, trypsin and chymotrypsin. This review of these studies showed that enzyme therapy can reduce the adverse effects caused by radiotherapy and chemotherapy. There is also evidence that, in some types of tumours, survival may be prolonged. The beneficial effect of systemic enzyme therapy seems to be based on its anti-inflammatory potential. However, the precise mechanism of action of systemic enzyme therapy remains unsolved. The ratio of proteinases to antiproteinases, which is increasingly being used as a prognostic marker in oncology, appears to be influenced by the oral administration of proteolytic enzymes, probably via an induction of the synthesis of antiproteinases. Furthermore, there are numerous alterations of cytokine composition during therapy with orally administered enzymes, which might be an indication of the efficacy of enzyme therapy. Effects on adhesion molecules and on antioxidative metabolism are also reviewed.

Effects of a systemic enzyme therapy in healthy active adults after exhaustive eccentric exercise: a randomised, two-stage, double-blinded, placebo-controlled trial.
            (Marzin et al., 2016) Download
BACKGROUND:  Systemic enzyme therapy may improve symptoms of exhaustive eccentric exercise due to anti-inflammatory properties. METHODS:  In a randomised, placebo-controlled, two-stage clinical trial, systemic enzyme therapy (Wobenzym) was administered for 72 hours before and 72 hours following a day on which subjects performed an exhaustive eccentric exercise (isokinetic loading of the quadriceps). Efficacy criteria (maximal strength and pain) and time points were selected to account for the multidimensional nature of exercise-induced muscle damage symptoms. Subjects were randomised in a crossover (stage I, n=28) and parallel group design (stage II, n=44). RESULTS:  Analysis of stage I data demonstrated a significant superiority (Mann-Whitney=0.6153; p=0.0332; one sided) for systemic enzyme therapy compared with placebo. Stage II was designed as a randomised controlled parallel group comparison. Heterogeneity (I CONCLUSION:  Systemic enzyme therapy before and after exhaustive eccentric exercise resulted in higher maximal concentric strength in the less strength-trained subjects (stage I) and in significant favourable effects on biomarkers (inflammatory, metabolic and immune) in all subjects. The application of these findings needs further evaluation.

[Effects of proteolytic enzyme therapy with Wobe Mugos against chemotherapy-induced toxicity in breast cancer patients - results of a pilot study].
            (Petru et al., 2010) Download
BACKGROUND:  Wobe Mugos(®) is an enzyme preparation containing the proteases trypsin and papain from the pancreatic calf and commonly used in complementary medicine. From non-randomized studies, its multiple favorable effects including the reduction of adverse events from radiotherapy and chemotherapy in oncology patients have been reported. METHODS:  Patients with invasive breast cancer receiving adjuvant or palliative chemotherapy between 2005 and 2006 and who were scheduled for at least two further cycles of this specific chemotherapy were included in this pilot study. A specific toxicity of at least grade 2 using the NCI common toxicity criteria which occurred during the preceeding cycle and was relevant to the patient was recorded. This specific toxicity, e.g. grade 2 emesis, was again evaluated after two analogously administered further chemotherapy cycles in which Wobe Mugos(®) had been coadministered. The hypothesis was that specific toxicites of individual patients will be reduced by this enzyme therapy. The majority of the 57 consecutive patients received palliative chemotherapy. Peroral enzyme therapy was coadministered with two uncracked coated tablets three times daily on all days of a chemotherapy cycle except on the day of chemotherapy administration. RESULTS:  Tolerability was good. Positive and neutral effects on toxicity parameters were observed in 11 and 42 patients, respectively, and a negative influence in 4 women. CONCLUSION:  We observed only a marginal influence of Wobe Mugos(®) in patients with breast cancer who had experienced at least a grade 2 toxicity in the preceding cycle and who received two further identical cycles of this chemotherapy in conjunction with the enzyme preparation. Randomized studies on homogenous patient populations are necessary.

 


 

References

Beuth, J (2008), ‘Proteolytic enzyme therapy in evidence-based complementary oncology: fact or fiction’, Integr Cancer Ther, 7 (4), 311-16. PubMed: 19116226
Block, KI (2008), ‘Enzymes and cancer: a look toward the past as we move forward.’, Integr Cancer Ther, 7 (4), 223-25. PubMed: 19116218
Brady, RO (2003), ‘Enzyme replacement therapy: conception, chaos and culmination.’, Philos Trans R Soc Lond B Biol Sci, 358 (1433), 915-19. PubMed: 12803925
Brennan, GT and MW Saif (2019), ‘Pancreatic Enzyme Replacement Therapy: A Concise Review.’, JOP, 20 (5), 121-25. PubMed: 31736680
Chabot, JA, et al. (2010), ‘Pancreatic proteolytic enzyme therapy compared with gemcitabine-based chemotherapy for the treatment of pancreatic cancer.’, J Clin Oncol, 28 (12), 2058-63. PubMed: 19687327
Dörr, W, T Herrmann, and Group Study (2007), ‘Efficacy of Wobe-Mugos E for reduction of oral mucositis after radiotherapy : results of a prospective, randomized, placebo-controlled, triple-blind phase III multicenter study.’, Strahlenther Onkol, 183 (3), 121-27. PubMed: 17340069
Fieker, A, J Philpott, and M Armand (2011), ‘Enzyme replacement therapy for pancreatic insufficiency: present and future.’, Clin Exp Gastroenterol, 4 55-73. PubMed: 21753892
Gonzalez, NJ and LL Isaacs (1999), ‘Evaluation of pancreatic proteolytic enzyme treatment of adenocarcinoma of the pancreas, with nutrition and detoxification support.’, Nutr Cancer, 33 (2), 117-24. PubMed: 10368805
Isaacs, LL (2019), ‘An Enzyme-Based Nutritional Protocol In Metastatic Cancer: Case Reports Of A Patient With Colon Cancer And A Patient With Lung Cancer.’, Altern Ther Health Med, 25 (4), 16-19. PubMed: 31202206
Layer, P, N Kashirskaya, and N Gubergrits (2019), ‘Contribution of pancreatic enzyme replacement therapy to survival and quality of life in patients with pancreatic exocrine insufficiency.’, World J Gastroenterol, 25 (20), 2430-41. PubMed: 31171887
Leipner, J and R Saller (2000), ‘Systemic enzyme therapy in oncology: effect and mode of action.’, Drugs, 59 (4), 769-80. PubMed: 10804034
Marzin, T, et al. (2016), ‘Effects of a systemic enzyme therapy in healthy active adults after exhaustive eccentric exercise: a randomised, two-stage, double-blinded, placebo-controlled trial.’, BMJ Open Sport Exerc Med, 2 (1), e000191. PubMed: 28879033
Petru, E, B Stranz, and C Petru (2010), ‘[Effects of proteolytic enzyme therapy with Wobe Mugos against chemotherapy-induced toxicity in breast cancer patients - results of a pilot study].’, Wien Med Wochenschr, 160 (19-20), 513-16. PubMed: 20972712