Enzyme Therapy

Enzymes have aptly been called the "Fountains of Life". They are biological catalysts that are ubiquitously found in nature and are responsible for the myriad reactions taking place in our bodies. Not only do they orchestrate the break down of complex molecules into simple molecules useful to our body, but they also regulate and control each and every process that keeps the body functioning harmoniously.

Consequently, their therapeutic applications are equally varied and as far-reaching, from digestive aids and nutritional supplements to treatment of pancreatic insufficiency in diseases such as chronic pancreatitis and even for the lysis of blood clots especially for treating cardio vascular diseases (streptokinase, tissue plasminogen activator, urokinase).

The following article takes a look at some of the varied applications of enzymes as therapeutic molecules.

Enzyme therapy is not new to us. Several evidences show that it has been in practice since times ancient. Enzyme therapy began with using enzymes from herbal origin for curing certain ailments. The enzyme papain is obtained from the leaves and fruit of the papaya plant Carica papaya while the enzyme bromelain is obtained from the pineapple plant stem Ananas comosus. These fruits or parts of plants have been used therapeutically by the ancient people of Central and South America. Pineapples have been used as a folk medicine by the natives of the tropics for centuries. The fruit has been put to multiple uses: as a digestive aid, as a cleansing agent to improve the texture of the skin and even to promote the healing of wounds (1). The enzyme ficin obtained from the fig plant has been employed for treating cancer since times ancient. This has been documented in the Bible (Second book of Kings, Chapter 20, Verse 7). In Europe, during the Middle Ages, early forms of enzyme therapy were practiced, in which topical enzyme preparations were used to heal ulcers and warts.

Beginning in the 1900s, proteolytic enzyme extracts of pancreas (pancreatin) were used systemically with some success for treating certain cancers. In the early 1950s it was discovered that intravenous trypsin was capable of relieving the symptoms of many different inflammatory conditions, including rheumatoid arthritis, ulcerative colitis, and atypical viral pneumonia. Subsequently intramuscular enzyme injections were found to be beneficial in counteracting post-surgical swelling (edema), treating thrombophlebitis and lower back strain, and rapidly healing bruises caused by sports injuries.

Later on pancreatic enzymes were added to mixtures of enzymes from plant origin. Initially enzyme therapy was followed empirically but over the years systematic scientific work has lead to elucidation of mode of action so as to support applications.

Since non-invasive routes of administration of drugs are preferred over invasive routes, soon, the possibility of developing oral formulations of proteolytic enzymes was explored. It is essential that any enzyme preparation be properly enterically coated so as to release the enzymes in the intestines, where they can be absorbed and not in the stomach where they can be degraded. Around 35 years ago it was shown that enterically coated enzymes are equally useful. Oral proteolytic enzymes have been used successfully ever since for treating inflammatory conditions. The intestinal absorption of orally administered serrapeptase has been demonstrated. to achieve an ideal therapeutic effect.

Thus, Modern Day systemic enzyme therapy involves orally administering high doses of mixtures of enzymes from plant, animal and microbial origin. Some of them include other constituents such as anti-oxidants as well.

Pioneering work in the field of Enzyme Therapy has been done in Germany independently, by Dr Hans Nieper, as well as Dr. Max Wolf along with the American Doctor, Dr Benitez. They successfully showed that mixtures of enzymes had positive effects in people with vascular diseases, lymphedema, certain viral infections, and in the healing of injuries and inflammations. They reached the conclusion that, in fact it is the deficiency of proteolytic enzymes that was a primary factor in premature aging. As we age, the level of proteolytic enzymes in our body is lowered. This leads to disturbance in the physiology and metabolism of the individual often leading to diseased conditions. Also this disturbed equilibrium deteriorates the immune status.

Effects of enzymes shown by Dr. Wolf and Dr. Benitez

Enzymes as digestive aids and dietary supplements:

The natural production of enzymes slows down as the body ages. Hence, selected enzymes are given as supplements to boost up the enzyme levels thereby normalizing enzyme levels and consequently metabolism and repair.

Enzymes as fibrinolytic agents:

Conventionally, streptokinase and tissue plasminogen activator or urokinase are being used as fibrinolytic agents following heart attack. The ability of other proteolytic enzymes such as serratiopeptidase to bring about fibrinolysis and digest arterial plaque makes them attractive molecules for cardiovascular disease.

Enzymes as mucolytic agents:

Proteolytic enzymes like bromelain and serratiopeptidase have shown mucolytic activity and thus have found use in treating respiratory tract diseases such as sinusitis and bronchitis. (22)

Enzymes as NSAIDS (non steroidal anti inflammatory drugs):

The anti-inflammatory activity of proteolytic enzymes has been attributed to several mechanisms. They can reduce the swelling on mucous membranes, decrease capillary permeability, dissolve blood clot-forming fibrin deposits and microthrombi. Enzymes reduce the viscosity of the blood and thus improve circulation. This consequently increases the supply of oxygen and nutrients to traumatized tissue, at the same time transporting harmful waste products away from it. Bromelain has been shown to inhibit platelet aggregation by using in vitro and in vivo models (21).

Proteolytic enzymes also help break down plasma proteins and cellular debris at the site of an injury into smaller fragments facilitating their passage through the lymphatic system and resulting in more rapid resolution of swelling. The net result is relief of pain and discomfort. Comparative studies in animal models for anti-inflammatory action of proteolytic enzymes with standard drugs such as phenylbutazone, hydrocortisone, indomethacin, and acetylsalicylic acid (aspirin) revealed that the enzymes were on par with the standard drugs and at times even superior (3).

Enzymes as healing agents:

Due to the above properties, enzymes act as excellent healing agents for minor musculoskeletal injuries, and accelerate recovery in surgeries and burns (14,15,16). Proteolytic enzymes have been of particular use to sportsmen for reducing bruising, swelling, pain and discomfort and improving healing thereby putting athletes back in action. Studies were conducted in Germany on hockey players and skiers to prove this and the enzyme formulations proved to be far more effective than non-steroidal anti-inflammatory drugs (NSAIDS) like ibuprofen and aspirin (1, 2).

Enzymes and heart disease

Due to their anti-inflammatory activity, proteolytic enzymes like bromelain have been found useful for cardiovascular disease such as atherosclerosis and coronary heart disease (17,19). The enzyme serratiopeptidase is anti-inflammatory as well as fibrinolytic making it very suitable as a drug for keeping away heart disease. It is a blood thinning agent without the side effects of conventional drug thinning agents like Aspirin.

Enzymes as analgesic agents:

It is also thought that the analgesic effect of proteolytic enzymes is due to their cleavage of bradykinin, a messenger molecule involved in pain signaling. However, according to another theory, peptidases such as trypsin may be acting not as anti-inflammatory agents but rather as accelerants of the inflammatory process, thereby shortening its duration.

Enzymes as novel antimicrobial agents:

Overuse and misuse of antibiotics is leading us towards a world in which there would be no effective treatment available for the very infections that were once upon a time curable. Besides, the steadily emerging antibiotic resistance, antibiotics have other limitations such as numerous side effects and toxicities. Therefore, there is a constant need for looking for new antimicrobials to combat these limitations.

Proteolytic enzymes are indeed quite amazing. They have been found to be useful against certain bacterial infections. Papain and trypsin inhibit the growth of pathogens whereas bromelain, trypsin and chymotrypsin are known to increase the bioavailability of antibiotics: when combined with antibiotics enzymes can increase the concentration of the drug at the site of infection leading to rapid control of infection. Synergistic action of enzyme - antibiotic mixtures could be an answer to the several problems associated with antibiotic therapy. This was proved using proteolytic enzymes in conjunction with Ampicillin, Tetracyclines and Trimethoprim. Enzyme - antibiotic combinations have proved to be of particular use for treatment of urinary tract infections.

Proteolytic enzymes also have activity against the otherwise difficult to treat fungi. Antiviral activity of different enzymes has been recorded.
At last, do we have an answer to the escalating drug resistance problems associated with bacteria, fungi and viruses?

Enzymes as immunomodulators:

Enzymes are an indispensable part of the regulatory mechanisms involved in the Immune System of our body. It has been found that enzymes can act as wonderful immunomodulators. They play a significant role in inflammation and other processes of the Immune System.

They are known to induce or enhance the production of cytokines such as tumour necrosis factor, interferon (IFN-g), interleukins such as IL-1, Il-6 (18).

They are known to bring about a 7-10 fold increase in the phagocytic activity of macrophages and in the potency of NK cells. Enzymes bring about proteolytic modification of cell-surface adhesion molecules, which play an important role in auto-immune diseases such as arthritis and guide inflammatory cells to their targets.

Circulating immune complexes are the primary causes of auto-immune diseases such as rheumatoid arthritis, glomerulonephritis, type 1 diabetes, multiple sclerosis etc. Proteolytic enzymes such as trypsin, chymotrypsin and papain are capable of preventing the formation of such complexes, facilitate the breaking up these complexes enhancing their lymphatic drainage.

A study of the immunological basis of protease therapy (trypsin, papain, chymotrypsin, bromelain) for type I diabetes revealed that the proteins present on T cells and antigen presenting cells changed along with changed cytokine profiles. The authors concluded that proteases have pleiotropic immunological effects and thus they potentially have an immunomodulatory role in chronic inflammatory diseases and Th-1 mediated oedema formation (12).

Enzymes as novel anticancer agents:

Studies have shown that enzyme therapy can reduce the adverse effects caused by radiotherapy and chemotherapy. The survival of patients with certain types of tumours may be prolonged with systemic enzyme therapy along with quality of life. Although, the exact role of enzymes is not clear, the beneficial role of enzymes has been attributed to the anti-inflammatory property of enzymes. (13). Other possibilities include digestion of adhesion molecules present on tumour cells and a possible role in differentiation of tumour cells (20). In general, proteolytic enzymes have been suggested as complementary therapy with the usual chemotherapeutic practices.

Safety issues and enzymes:

The long term safety of enzyme supplements has been explored in great details. The result is that enzymes are generally found to be highly safe and no toxic limit no matter how much you take or how long you take them. It is the lack of enzymes that causes problems, not taking too many. Enzyme action is highly specific and is well known and well characterized. Each enzyme has its own specific role and activity and has typical biochemical properties. Therefore there are few side effects. Healthy tissues and cells have natura mechanisms protecting them from enzyme action. The body is full of checks and balances including lots of enzyme inhibitors, which allow the enzymes to function properly without self-digestion. Enzymes are used for wound healing because they selectively degrade dead tissue and infected tissue wgile leaving the healing tissue growing. Enzymes are used to remove tumours: they attack the cancerous tissue and remove it while facilitating growth of healthy tissue. This built-in natural selective property of enzymes can be seen on surface wounds and tumours (Enzyme Therapy, Max Wolf). No known toxicity at any level of enzyme dosing in animal / human studies has been recorded. Animals survived large quantities of enzymes without damage so it has been impossible to find LD 50. Rats fed with human doses have shown no ill effects.

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