The Health Benefits Of Systemic Enzymes

No more “Shooting Rubber Bands” at the Moon

By Aftab J. Ahmed, Ph.D.
TOTAL HEALTH, Volume 22 Number 2


After many fits and starts, systemic enzymes have come into their own. A recent contribution to this publication bears testimony to the fact that multifarious health benefits of system enzymes have at long last begun to be better appreciated. (1) The insights garnered over many decades of work have finally yielded the conceptual scaffold which explicates, at least in cursory detail, the role of systemic enzymes in human health and disease.

List Of Digestive Enzymes
List Of Digestive Enzymes

 

The pedigree of research on systemic enzymes is just as longstanding as it is impressive, both in its reach and import. In its rudimentary forms, it dates back roughly 100 years. It is only relatively recently, however, the mode of action of systemic enzymes, from a clinical perspective, has been sufficiently elucidated to design molecular, pre-clinical and clinical studies for specific conditions.

Routinely, proteolytic enzymes from animal and plant sources, are used in combination. Whereas individual enzymes, such as trypsin, chymotrypsin, and papain, bromelain, pancreatin and others, have beneficial effects reported in the scientific literature, it is the combination of these enzymes that apparently confers synchrony, which makes them effective in a number of chronic, proliferative diseases. (for a detail review, see foot note 2) Thus their therapeutic effects in conditions such as arthritis and vascular health, as well as global effect on the immune system response, are rather well established. (3)

Of these, the immune system response to systemic enzyme therapy has been rather rigorously documented, especially if one takes the deleterious effects of inflammation into account. The immune system is one of the few most critical networks in the body and provides a powerful defense against intruding pathogens. What is less well fully appreciated, however, is the fact that it is also capable of bringing too much fire power to bear in clearing the infecting pathogens. In other words, the immune system could be likened to a high-wire act, either side of which spells serious health problems. Systemic enzymes provide one modality to keep the immune system in balance for most of the length of the wire.

Dysfunction of the immune system lies at the root of many an affliction. Thus immune system malfunction can precipitate autoimmune diseases, for example. The underlying phenomenon in autoimmunity is inflammation, which is a flare-up in protective defense launched by the immune system. Inasmuch as inflammation is a normal response, in disease it could trigger a cascade of reactions that progressively worsen the condition. Among its many manifestations, inflammation could increase the numbers of nonspecific circulating immune complexes, which can wreak havoc on the body. In addition, uncontrolled inflammation could increase fresh production of pro-inflammatory cytokines, which further intensify this raging inferno. Furthermore, persistent inflammation increases the absolute numbers of the so-called cell adhesion molecules that not only facilitate the communication between the errant cells but could also potentially initiate malignancy. Systemic enzymes, by virtue of their proteolytic activity, cleave these various offending agents and help restore a measure of normalcy to the aberrant cellular milieu. In that, proteolytic enzymes function quite like molecular vacuum cleaners in ridding the blood of the metabolic flotsam and jetsam, fortify the immune system will simultaneously bring the inflammation under control.

Inflammatory response is implicated in a variety of tissues and organs including, but not limited to, heart, brain, kidney, large intestine, pancreas, thyroid gland, tongue, urethra, optic nerve and skin. In fact, immune system dysfunction – and, indeed, inflammation – is known to play a significant role in the onset of carcinogenesis. Inasmuch as cancer is a complex disease in which a wide variety of environmental, genetic, cellular, metabolic and physiological factors contribute, more or less concurrently, to what presents as cancer, it is the breakdown of the immune system that, in the first instance, sets the stage for carcinogenesis. Of late, cumulative evidence suggest that system enzymes potentially could be used as a preventive therapy for those at risk to cancer or it can be employed to postpone, at least for a time, the appearance of clinically discernible malignancy. It can hardly be overemphasized that predisposition to cancer – hereditary in particular, but sporadic no less – the genetic luck of the draw, for which no cure is yet in sight. That notwithstanding, clinical data demonstrate that systemic enzymes may well have the ability to mitigate the harsh side effects of radiation and chemotherapy (3 and citations therein). Multiple myeloma is one of the cancers in which systemic enzymes have been recognized to have a beneficial effect. A specific European preparation compromised of papain, chymotrypsin and trypsin, has been successfully used as an adjunct to radiation and chemotherapy in the clinical management of multiple myeloma. (A) This preparation not only lessens the intensity of the side effects but also reduces severity of the symptoms which concomitant increase in life span and improves the quality of life of patients and, necessarily, of their families.

What is multiple myeloma, and how do proteolytic enzymes complement radiation and chemotherapy? Multiple myeloma is cancer of the plasma cells that are a type of white blood cells which, upon transformation to malignancy, proliferate rapidly. (4) Multiple myeloma is a relatively rare type of cancer with an incidence of three-to-four individuals of every 100,000 people. More men than women are afflicted with multiple myeloma and its incidence rises with advancing age. Myeloma is an incurable malignancy and treatment regimen with alkylating agents and glucocorticoids merely relieve symptoms. (5) Clinically, multiple myeloma patients present themselves with diffuse osteoporosis, bone pain and pathologic fractures along with lesions in bone that result in loss of height. This is due to the fact that plasma cells, which are antibody-producing cells, accumulate in the bone marrow, leading to marrow failure and bone destruction. (6)

Plasma cell growth is controlled and regulated by a complex network of growth factors, bone microenvironment and cell surface molecules that establish exquisite communication among various cell types in the bone marrow. The most important growth factor is the pro-inflammatory cytokine, interleukin {IL-}6, which is required for multiple myeloma cells. (7) It functions as a two-edge sword. It not only induces unbridled growth of plasma cells but it also fails to initiate their terminal differentiation. (8) In addition, multiple myeloma cells secrete another pro-inflammatory cytokine, IL-1-beta, which establishes a destructive cross talk with osteoclasts that are cell type responsible for bone breakdown. (6) Among other growth factors are interferon-gamma and tumor nectosis factor-alpha. By the same token cell adhesion molecules and other cell-surface antigens, are produced that allow the multiple myeloma cells to interact with the marrow microenvironment and thus complete the circle of this devastating process. (9)

The central role of IL-6 as a growth factor for multiple myeloma cells suggests that strategies to block its effect could provide therapeutic possibilities. (10) Conventionally, interferon-gamma has been used to inhibit the growth of multiple myeloma cells, at least in vitro. While a specific agent could be therapeutically designed to interfere with the action of IL-6, it is unlikely to help prevent the disease. Let alone cure it, since the growth of multiple myeloma critically depends on the support of the bone marrow microenvironment and one a defective anti-tumor immune response.

Systemic enzymes have been shown to down regulate pro-inflammatory cytokines while encouraging de novo induction of anti-inflammatory cytokines, such as interferongamma. (11) To an extent, that could explain the beneficial effects of protolytic enzymes in the clinical management of multiple myeloma. Needless to say, it is unlikely that in frank carcinogensis, systemic enzymes either alone or in conjunction with a standard therapy, would be able to arrest growth of a disease. Nonetheless, inclusion of systemic enzymes in standard therapies, such as VMCP and MOCCA, (B) decrease the amounts of IL-6, tumor necrosis factor-alpha and its receptors, which bespeaks their beneficial role. Hence the use of systemic enzymes as an adjuvant therapy in the management of multiple myeloma has considerable potential in both minimizing the side effect of chemotherapy and improving patients’ quality of life and, in some cases, even increasing survival rate.

The availability of the European systemic enzymes preparation in the United States is contingent upon the results of a Phase III clinical trail. A multi-center, randomized, placebo-controlled, double-blind trail is scheduled to begin in the United states in January of 2001, as the FDA reviews the trial protocol and makes a determination to accord the enzyme preparation and “orphan drug” status (FDA approval is now in place – see note at bottom of this page). (C) Status as an orphan drug in the clinical management of multiple myeloma will likely be the first step in the use of systemic enzymes as an adjunct to therapy for various types of cancer. It may even set the stage to evaluate more critically their potential in the management of other chronic diseases, such as cardiovascular conditions, neurodegeneration and other age-related diseases that arise because of compromised housekeep cellular functions with aging. This is largely due to the relative preponderance of proteolytic enzymes in the human body and ease of replenishment by oral administration, as much as the maintenance of supra-physiological homeostasis in the body. (12) Just a often as not, clinical management of chronic diseases may be akin to “shooting rubber bands” at the moon. Put differently, given the odds, cancer management may appear as a self-fulfilling prophecy. Since ever-lasting numbers of American as actively seeking out alternative therapeutic modalities, a reasonable combination of nutritive and pharmaceuticals may actually be shown to benefit the patients. The clinical trial to secure an orphan drug status for systemic enzyme is one such avenue that, if found efficacious, will ease the trauma of and devastation wreaked by cancer and, in due course, may not be as futile as shooting rubber bands at the moon.

Footnotes:

  • A. the enzyme preparation being referred is WOBE-MUGOS, a product of MUCOS Pharma, Germany. Composed of papain, trypsin and chymotrypsin, WOBE-MUGOS satisfies the stipulations of the German Dundes Gesundheitsamt and the USP XXI. WOBE_MUGOS remains active over a broad range of acidic and alkaline conditions [102].
  • B. After the diagnosis, multiple myeloma patients are first treated with melphalan and prednisone to relive pain, decrease the number of plasma cells in the bone marrow, and support renal function. Secondary therapies include treatment with interferon-gamma, high-dose dexamethosone and multidrug regimen such as VMCP (vinscristin, melphalan, cyclophosphamaide and prednisone) and MOCCA (methylprednisone, vincristiin, cyclophosphamide, melphalan and CCNU. Depending upon the severity of the symptoms, patients may also be put on ancillary regimen, including bisphosphonates, erythropoietin and acute hypercalcemia therapy.
  • C. Marlyn Nutraceuticals, Inc., based in Scottsdale, Arizona, is the applicant for orphan drug status for WOBE-MUGOS in the United States. In collaboration with its corporate partner MUCOS Pharma, it is sponsoring the Phase III clinical trial in the United States, which is anticipated to pave the way for WOBE-MUGOS to obtain orphan drug status by the FDA.

References:

  1. Kidd, P. “The Gonzales-Issacs Program,” totalhealth (2000), vol 22. pp. 19-21
  2. Klaschka, R. “New Perspectives in Tumor Therapy.” Forum-Medizin Verlagsgesellschaft mbH,, Graefelfing, Germany (1996)
  3. Wrba, H. and Pecheer, O. “Enzymes: A Drug of the Future,” EcoMed Verlagsgesellschaft, Landsberg/Lech, Germany (1997)
  4. Hallek, M., Bergsagel, P. and Anderson, K. “Multiple Myeloma: Increasing Evidence for a Multistep Transformation Process,” Blood (1998). Vol. 91 pp. 3-21
  5. Bataille, R., and Harousseau, J. L. “Multiple Myeloma,” N. Engl. J. Med. (1997). Vol. 336 pp. 1657-61
  6. Batille, R., Chappard, D., Marcelli, C., Dessauw, P., Balder, P., Sany, J. and Anexander C. “Recruitment of New Osteoblasts and Osteoclasts in the Earliest Critical Event in the Pathogenesis of Human Multiple Myeloma.” J. Clin. Invest. (1991). Vol. 88 pp. 62-9
  7. Caligaris-Cappio, F., Gregoretti, M., Ghia, P. and Bergui, L. “in vitro Growth of Human Multiple Myeloma: Implications for Biology and Therapy,” Hematl. Oncol. Clin. North Am. (1992). Vol 6 pp. 257-65
  8. Chauhan, D., Kharbanda, S., Ogata, A., Urashima. M., Teoh, G., Robertson, M., Kufe, D. and Anderson, K. “Interleukin-6 Inhibits Fas-Induced Apoptosis and SAP Kinase Activation in Multiple Myeloma Cells,” Blood (1997). Vol. 89 pp 227-31
  9. Filella, X., Blade, J., Guillermo, A., Molina, R., Rozman, C. and Ballesta, A. “Cytokines (IL-6, TNF-alpha, IL-1-alpha) and soluble Interleukin-2 Receptor as Serum Tumor Markers in Multiple Myeloma,” Cancer Detect. (1996) Vol. 20 pp 52-9
  10. Cheson, B. “Treatment Strategies for Multiple Myeloma,” ASCO Education Book (Spring 1997). P 115
  11. Sakalova, A., Dedik, L., Bazova, S., Hanisch, J. and Schiess, W. “Survival Analysis of an Adjuvant Therapy with Oral Enzymes in Multiple Myeloma Patients,” Br. J. Hematol. (1998). Vol 102 pp. 353-6
  12. Ahmed, A., “Metabolic Networks, Homeostasis, Pathogenesis, and Therapeutic Strategies,” in press. J. Theo. Biol. (2000)

These statements have not been evaluated by the Food & Drug Administration.

The following note was found on The Cancer Cure Foundation website – “FDA Grants Orphan Drug Status To Wobe-Mugos For Multiple Myeloma

SCOTTSDALE, AZ — August 10, 2000 — The FDA has approved the Orphan Drug application of Wobe-Mugos as an adjunct therapy for multiple myeloma. Wobe-Mugos is a combination of systemic enzymes, used successfully in Europe in conjunction with chemotherapy since 1977.

Numerous clinical trials have proven its efficacy in reducing the severity of symptoms, extending life span and improving the quality of life of multiple myeloma patients.

The orphan drug application was filed by Marlyn Nutraceuticals of Scottsdale, AZ. The company conducts extensive in-house research and also collaborates with numerous leading research institutions around the world to develop safe, effective and wholesome solutions to healthcare problems.

Each year, roughly 13,000 Americans develop multiple myeloma, an incurable form of cancer. The disease is characterized by the spread of cancerous B-Lymphocytes, the antibody-producing cells of the body. There is no cure. Currently, the only treatment is chemotherapy, and in some cases, bone marrow transplant.