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.

A Brief Overview Of The Gastrointestinal System

In order to heal or restore your body, it is important to make some very important nutritional changes. These alterations in your diet will be helping your body to cleanse away toxins, heal damaged or compromised tissues, restore normal functioning of your vital gastrointestinal mucosa and enzymes and facilitate the action of the nutritional supplements, homeopathic, etc., that have been recommended for you. Your understanding, willingness, and commitment to make these changes will be important keys in helping you to create health and well-being.

Gastrointestinal System
Gastrointestinal System

In order to achieve these healthy changes, it can be very helpful to take a closer look at how your body is designed and how it functions. Understanding some of the profound and miraculous changes that occur within your body can help you to deepen your overall understanding of your health and your unique health care needs. These understandings can also help you to better comprehend particular treatment protocols recommended. Research has proven that patients who take an active role in their health care get positive results much more quickly and easily.

Your gastrointestinal tract is a very important part of your body. It is responsible for harnessing energy that enables you to grow, to heal, to restore, and to live. Its many functions include digesting foods, absorbing nutrients, assimilating nutrients, and transporting waste products through and out of your body. The integrity of your gastrointestinal system plays a primary role in maintaining and sustaining your body. If any of the vital functions of your GI system are limited or imbalanced in any way, the rest of your body is also compromised. Without the necessary components and nutrients derived from food and its digestion and absorption, health and vitality would not be possible.

There are many factors that can compromise an individual’s gastro-intestinal functioning. These include but are not limited to: poor diet, certain medications, food allergies, stress, and lack of breast-milk as an infant. Other factors can include lack of exercise, genetics, certain disease processes, inadequate enzymatic activity, chronic exposure to environmental toxins, and poor water.

Digestive Process

The actual process of digestion begins in your mouth. As food is eaten, your teeth and jaws grind the food into smaller fragments. This process is called mastication. While the food is being chewed, it is mixed with digestive enzymes secreted by your salivary glands. These enzymes are responsible for breaking down starches in the foods that you eat. Starches include such foods as grains, breads, and cereals. As you chew or masticate, the larger bites of food become smaller fragments that are more easily broken down by the enzymes. It is for this reason that taking time to chew your food slowly and thoroughly is vital. Swallowing large chunks of food puts more stress on your stomach and other areas of the GI system that must work over-time which wastes energy to break down the food.

The food then moves down a long tube called the esophagus. Sometimes called the “food pipe,” the esophagus has wave-like contractions called peristalsis that propel the food toward the stomach. No digestion takes place in the esophagus.

The food then moves into the stomach. Strong contractions by the stomach churn the food. Cells in the walls of the stomach begins secreting digestive enzymes. These enzymes are called hydrochloric acid (HCI), pepsin, and protease. These substances are responsible for breaking down the food into even smaller fragments. The pH of the digestive enzymes are very acidic (1.0 – 3.0). The reason these enzymes are so acidic is to break down complex proteins, such as chicken and fish, into substances called amino acids. These amino acids can then be absorbed more easily into your bloodstream. The type of foods that you eat and the integrity of your digestive enzymes determines how long the food remains in your stomach. A piece of fruit, for example, is very easy to digest and may remain in your stomach for only 20-30 minutes. A steak, on the other hand, is a very complex food and may remain in your stomach for several hours. It takes a lot more time, energy, and enzymes for your stomach to break down complex foods.

The food, now called chyme, then moves out of the stomach and enters the portion of the small intestine called the duodenum. There are three major parts of the small intestine; the duodenum, the jejunum, and the ileum. The first portion of the small intestine, the duodenum, is perhaps the most important part of the small intestine. Within this area many vital absorption processes occur.

Once the acidic chyme moves into the duodenum, cells in the walls of the duodenum begin to secrete a mucosy substance designed to alkalinize the pH of the chyme. The delicate walls of the small intestine, unlike the stronger walls of the stomach, cannot tolerate acidic enzymes and sub-stances. To protect itself, it secretes the mucus that within a brief period of time raises the pH. It is important to note that stress can inhibit the release of this alkalinizing substance. When this occurs frequently, burning, pain, and ulcerations can occur in this area. As the process of alkalinizing the chyme is occurring, enzymes secreted from the pancreas and liver are also being secreted.

The pancreatic enzymes include amylase, protease, lipase, etc. These are responsible for breaking down complex foods, including fats, proteins, and carbohydrates into their basic elements. The liver produces bile that is stored in your gall bladder. The gall bladder secretes the bile into the small intestine. The bile has a detergent-type action that breaks down the fats into small fat globules to aid in fat digestion. Bile assists in the absorption of the fat-soluble vitamins A, D, E, F, and K and helps to assimilate calcium. Bile also converts beta-carotene to vitamin A. It promotes intestinal peristalsis as well, which helps to prevent constipation.

As the food particles move through the jejunum and ileum, absorption of nutrients, vitamins, and minerals occurs. This absorption process takes place through the walls of the small intestine. Molecules flow through the cell walls and enter the blood stream. Once in the bloodstream, they travel by way of the hepatic portal system to the liver. In the liver nutrients including iron and vitamins A, B12, and D are extracted from the bloodstream and stored for later use. The liver also plays a vital role in fat metabolism, in the synthesis of fatty acids from amino acids and sugars, in the production of lipoproteins, cholesterol, and phospholipids, and in the oxidation of fat to produce energy.

Excess food is converted to fat in the liver, which is then sent to the fatty tissues of the body for storage. The liver also acts as a detoxifier, regulates protein metabolism, and combines toxic substances including metabolic waste, insecticide residues, alcohol, drugs, and chemicals with other sub-stances that are less toxic. These substances are then excreted from the kidneys.

The waste products of the digestive and absorption processes then move into the large intestine. Depending upon the nature of the waste products and the length of time the waste products remain in the large intestine, very little absorption occurs. The primary functions of the large intestine include transport and removal of waste products through the rectum and reabsorption of water.