Chapter 71 Bromelain*
Proteolytic enzyme of Ananas comosus (family: Bromeliaceae)
Synonyms: bromelin, plant protease concentrate
Introduction
The pineapple plant (Ananas comosus) yields several proteolytic enzymes, including bromelain (from the stem and the fruit), ananain, and comosain,1 as well as several nonproteolytic enzymes such as amylase, peroxidase, and acid phosphatase.2 Most bromelain on the market is stem bromelain (which itself is composed of perhaps up to six different types of enzymes, including bromelain A and B).3 Bromelain is widely utilized in food processing to prepare precooked cereals, produce protein hydrolysates, chillproof beer, tenderize meat, etc.; in cosmetics; in diagnostic laboratories; and in pharmaceuticals.
Bromelain is a sulfur-containing enzyme, with an optimum pH activity between 3.0 and 8.0.4 Bromelain has endoproteolytic and catalytic activity and predominantly splits peptides, amides, as well as ester bonds involving lysine, alanine, tyrosine, glycine, and other basic amino acids.4
The extraction of bromelain is usually accomplished by fractionated ultra-filtration and subsequent lyophilization of the juice pressed from the stem of ripe pineapples (frequently from Ananas comosus of the cayenne variety). The molecular weight varies between 17,800 and 33,000 kDa.
Bromelain activity within the stem of the pineapple can vary widely depending on the age of the plant, as well as on the storage duration and conditions. A Thai study found that 3-year-old peeled pineapple stems contained substantially more activity than second and first year stems as measured in casein digesting units (CDU)—48.76% compared with 32.0% and 19.3%, respectively.5 In addition, storage duration before considerable loss of activity occurred was limited to 3 days at room temperature or 2 weeks in a room cooled to 5°C (41°F).5
Bromelain Supplements
Over 200 medical articles on bromelain’s therapeutic applications have been published since it was introduced as a therapeutic agent in 1957.6,7 Initially, many studies employed Ananase (Rorer), an enteric-coated bromelain tablet.
Bromelain is currently available in tablets, chewable tablets, capsules, powder, and ointment. Although available in individual enzyme form, supplemental bromelain is often combined with other enzymes, as well as various vitamins, minerals, and herbs, for wider application.
Bromelain activity is measured in “units”—and there are several types of units currently in use. The Food Chemicals Codex recognizes milk-clotting units (MCUs), although gelatin dissolving units (GDU), Federation Internationale du Pharmaceutiques units, and CDUs are also widely utilized. However, these measurement methods are neither interchangeable nor comparable. On the basis of their respective enzyme units, different grades of bromelain are available. Therefore, when purchasing bromelain, be aware of this fact.
Enteral Absorption (or Resorption)
For enzymes to be used systemically, they must reach the circulatory system and be conveyed to needy cells and organs. This means that oral enzymes must pass through the digestive system, into the small intestine, and pass through the brush border into the circulatory system. Further, this is a rationale for enterically coating the enzyme tablets so that they will not be broken down in the digestive tract before they reach the small intestine to pass into the bloodstream. This is also the rationale for consuming enzymes between meals. These enzymes can pass easily through the gut without involvement in food digestion, allowing more enzyme molecules to reach the small intestine, pass through the brush border and into the circulatory system, and be used systemically by needy organs and cells in the body.
In the past, it was widely assumed that large protein molecules—such as enzymes—could not survive the digestive process and be reabsorbed intact. However, numerous studies have demonstrated that bromelain—and other proteolytic enzymes—can be absorbed by the small intestine through a number of routes, pass into the bloodstream, and ultimately circulate throughout the body. Oral administration is effective, as is parenteral administration.8-11
Research on dogs indicated that levels of bromelain (after oral administration) peaked at 10 hours, and were still detectable after 48 hours, whereas intravenous infusion peaked in 50 minutes and was detectable for 5 hours.10
A randomized, controlled, double-blind study on humans demonstrated that the highest plasma concentration of bromelain was achieved at approximately 48 hours.12,13 A study of 19 men given 3 grams of oral bromelain daily indicated that the enzyme had a plasma half-life of 6 to 9 hours. Researchers estimated that within the 3- to 50-hour period, an average of 10.8 mcg of bromelain was present in plasma.13 In both animals and humans, studies indicated that up to 40% of the absorbed orally administered bromelain was absorbed intact.9-11 For an in-depth discussion of enzyme absorption, please refer to Chapter 111 on Pancreatic Enzymes in this book.
Factors Affecting Bromelain Activity
Bromelain, papain (from papaya), and ficin (from figs) are all sulfhydryl proteases and act similarly. Bromelain (from both stem and fruit) is inhibited by metallic ions (including cadmium, copper, iron, lead, and mercury), oxidizing agents (such as iodoacetate, methyl bromide, and hydrogen peroxide), and human serum (both in vivo and in vitro). Cysteine and magnesium activate commercial bromelain.8
As with all enzymes, bromelain’s activity can be inhibited by cold or increased by heat. Bromelain is a hydrolytic enzyme, so supplements should be taken with plenty of water to place the enzyme into solution.
Clinical Applications
Bromelain exerts a wide variety of therapeutic effects6-8:
• Cancer remission and prevention
• Induced pulmonary edema prevention
• Improved antibiotic absorption
During the process of aging, illness, or injury, the body’s production of pancreatic enzymes decreases in amount, concentration, and potency, thus allowing the growth of pathogenic cells (such as cancer cells). Pathogenic cells are constantly produced by the body; however, the enzymes manufactured by and circulating in the blood lyse the abnormal pathogenic cells, breaking them up and flushing them out of the body. Unfortunately, when weakened through aging, illness, or injury, the body’s capacity to overcome pathogens is diminished, resulting in illness.
Bromelain has long been used to improve digestion. However, when taken systemically, bromelain can also effectively speed healing from inflammatory diseases and conditions; inhibit cancer growth and metastasis; prevent the aggregation of blood platelets, and thereby help to prevent heart attacks, strokes, and other cardiovascular conditions; prevent intestinal attachment of Escherichia coli; improve the symptoms of dysmenorrhea; fight sinusitis; improve burn eschars and speed healing; improve skin appearance; and improve antibiotic and vitamin absorption.
Therefore, systemic enzyme therapy is essential for normal recovery of a sick or injured individual, to augment the body’s own production of pancreatic enzymes, and to stimulate the production of proteolytic enzymes in the pancreas.
Systemic Enzyme Therapy
When taken between meals, enzymes—such as bromelain—move through the digestive system and directly into the small intestine, passing through the brush border into the circulatory system and traveling to the damaged areas. In this way, the enzyme acts systemically. To be most effective, systemically, it is essential to take enzymes on an empty stomach (approximately 1-1/2 hours before or after a meal). However, when used for digestive therapy, enzymes should be ingested before meals (approximately 30 minutes before). See the section on “Dosage” in this chapter.
Aging
Unfortunately, the process of aging is accompanied by an increasingly wide variety of health problems, such as chronic disorders, cancer, cardiovascular disease, and arthritis. Further, the numbers of those over 65 are escalating. According to the U.S. Census Bureau, over 20% of the American population will be age 65 or older by the year 2050. That figure was only 12% in 2008.14
Most commonly, as it ages, the body loses resiliency and various degenerative diseases manifest, particularly after the age of 50. This is accompanied by a decline in hormone secretion, immune system function, and enzyme production, thus reducing the body’s effectiveness at fighting off foreign invaders. With aging, the body’s enzyme supply also diminishes in activity. The symptoms of aging could be, at least partially, the consequence of these enzymatic reductions. For example, the graying of hair has been attributed to a lack of tyrosinase or a loss of its activity level.
Unlike the known serious side effects of most prescription drugs, bromelain has been shown to effectively fight arthritis, high blood pressure, cancer, and many other disorders associated with aging, but without the serious and long-term side-effects of many drugs.
Bromelain is also effective in fighting the visual signs of aging, including wrinkles. Bromelain is widely incorporated into lotions, creams, scrubs, facial masks, and other skin care products, where it is believed to improve the skin’s appearance by removing dead skin cells.
Cancer
Bromelain delays metastases considerably, delays skin cancer, and is effectively used in adjunctive tumor therapy. There is also some indication that it has a direct effect on cancer cells.15
The increased understanding of immunology makes it evident that the solution to cancer is not to be found in chemotherapy or radiation therapy, but in the use of immunotherapy (such as systemic enzyme therapy). Pharmacologic and preclinical studies indicate that bromelain acts as an immunomodulator by inducing the production of distinct cytokines (such as interleukin-1β [IL-1β], IL-6, and IL-8, as well as tumor necrosis factor-γ), and by raising the impaired immunocytotoxicity of monocytes against tumor cells.8,15-19 These findings were recently partially confirmed in mammary tumor patients.16 Particularly encouraging are animal studies suggesting antimetastatic properties and inhibition of platelet aggregation associated with metastasis, as well as inhibition of invasiveness and growth of tumor cells. It is interesting to note that the antiinvasive activity might not depend on bromelain’s proteolytic activity.8,15,16
An in vitro study on bromelain and glioma (primary brain tumor) cells found that bromelain significantly and reversibly reduced the adhesion, migration, and invasion of glioma cells. Moreover, cell viability was not affected, even after treatment up to 3 months.20
In the United States, skin cancer is the most common form of cancer.21 It is generally agreed that exposure to ultraviolet rays increases an individual’s risk of skin cancer. To determine if bromelain could prevent skin cancer, researchers gave hairless mice 20 mg of bromelain per kilogram of body weight per day for 1 year and then subjected them to ultraviolet light for 15 minutes three times per week for the same period.22 After 1 year, only 40% of the bromelain group developed skin cancer (as opposed to 100% of the control group). In addition, it took the bromelain group twice as long to develop lesions. An earlier, 6-month study found that mice receiving 80 mg of bromelain per kilogram of body weight did not develop any abrasions after 2 months.23
Bromelain (and other proteolytic enzymes) appears useful in the treatment of cancer. A number of mechanisms seem to be responsible. Bromelain had a significant impact on monocytes, natural killer cells, and lymphocytes in a clinical study of 16 women with breast cancer.16 Regarding monocytic cytotoxicity, some 40% of the patients responded to bromelain with an increase of cytotoxicity from 7.8% to 54% (bMAK-cell activity).
Circulatory Disorders
Platelet aggregation is a major factor in atherogenesis and can result in heart attack, stroke, acute thrombophlebitis, transient ischemic attack, nightly leg cramps, edema, deep venous thrombosis, ecchymosis, and cellulitis. Research shows that bromelain is a potent inhibitor of platelet aggregation, both in vivo and in vitro.23-30 This could be due to its plasmin-increasing effects (plasmin is a proteolytic enzyme produced by the body whose job is to dissolve fibrin, a protein involved in blood clot formation).31 Further, research demonstrates that bromelain (in conjunction with potassium and magnesium) can be effective in treating angina pectoris.27
Researchers employed bromelain as an adjunct to analgesics in a double-blind study involving 73 patients with acute thrombophlebitis. All symptoms of inflammation, including pain, swelling, tenderness, redness, disability, and elevated skin temperature decreased.26 The common daily dose of bromelain (in this study and others) was 60 to 160 mg of 1200 MCU bromelain. Several researchers believe that doses of 400 to 800 mg are necessary in treating patients with thrombophlebitis (and many other conditions, as well).27 Researchers commented that poor study outcome was usually the result of inadequate dose strength and/or frequency of application.
Digestive Disorders
Bromelain can regulate digestion, alleviate symptoms of gastric and duodenal ulcers and ileitis, and can be used as enzyme substitution therapy after pancreatectomy.
Bromelain has a long history as a digestive aid. By the time Columbus and his men had “discovered” America, natives of Central and South America were already using bromelain-rich pineapple juice to cure bellyaches and improve digestion. As a proteolytic enzyme, bromelain aids in the digestion of protein foods. Because of bromelain’s wide pH activity, it is effective on substrates in the acidic stomach as well as the alkaline small intestine. Although bromelain alone is effective in treating pancreatic insufficiency (and is a proven substitute for trypsin or pepsin in cases of pancreatic insufficiency and postpancreatectomy),6 double-blind studies determined that it is particularly effective when combined with ox bile and pancreatin.32,33
Dysmenorrhea
Bromelain in combination with papain is an effective treatment for dysmenorrhea.34 Because bromelain decreases the spasms of a contracted cervix in tested patients, it is believed to be a smooth muscle relaxant. As yet unidentified substances in bromelain may be more beneficial in this regard than the bromelain protease, because when isolated and purified, the protease failed to produce a similar effect. Bromelain increases levels of prostaglandin-E (PGE1)-like compounds, while decreasing prostaglandins of the 2-series (such as PGE2 and PGF2a); this is hypothesized to be the basis for bromelain’s muscle relaxing ability.7
Immune Disorders
The understanding and treatment of immune disorders is becoming increasingly important in today’s society. Further, the immune and inflammatory systems are the two major factors in chronic disorders.
The lymphoid organs of the immune system are located throughout the body and are concerned with growth, development, and distribution of lymphocytes (white cells, which are key operatives of the immune system). These organs include the thymus, bone marrow, tonsils, lymph nodes, spleen, the appendix, adenoids, and Peyer’s patches.
Circulating immune complexes seem a major factor in all immune and autoimmune disorders. Various factors inhibit cellular immunity, but the most important elements seem to be these “blocking factors” (i.e., immune complexes) that cause immune suppression.
Autoimmune disorders occur when the body’s immune system mistakenly attacks healthy cells. There are dozens of such conditions, including rheumatoid arthritis and other rheumatic disorders, myasthenia gravis, type 1 diabetes mellitus, asthma, systemic lupus erythematosus, glomerulonephritis, and multiple sclerosis. Fortunately, an increasing number of studies have indicated that systemic enzyme therapy can reduce the severity of symptoms, more quickly resolving the condition because they stimulate the body’s own defenses, accelerate the inflammatory process, and break down pathogenic immune complexes from the tissues, bringing them into the bloodstream for elimination. Immune complexes are created when antigens and antibodies bind, forming a cluster that can lodge in tissues or circulate throughout the body, leading to inflammation and tissue damage. It is important to note that as systemic enzyme use liberates immune complexes from the tissues, increasing their presence in the bloodstream, symptoms may actually increase in severity; however, this is only temporary. When used in sufficient quantities, the enzymes can then degrade the immune complexes in the bloodstream (sometimes within a few hours), and the disease symptoms should subside.
Infections
Infections caused by bacteria, viruses, fungi, and parasites can frequently be the most challenging conditions to treat. Bromelain has proven effective in fighting numerous infections ranging from E. coli to bronchitis (see the section on “Respiratory Tract Diseases” later in this chapter).
The O157:H7 strain of E. coli is a particularly severe and potentially life-threatening bacterial infection that causes bloody diarrhea in humans. The E. coli enterotoxins gain a foothold by adhering to receptors on the intestinal mucosa. Preventing the attachment could also prevent the resulting diarrhea. Researchers administered a single dose of enterically coated protease granules (containing bromelain) to rabbits and then inoculated the animals with different strains of E. coli. Of those rabbits given the enzyme mixture and strain H10407, only one animal died, and none of the remaining rabbits developed diarrhea. In the group not inoculated with the enzyme mixture, 87% either developed severe diarrhea or died.35 Comparable results were obtained with other strains of E. coli.
Similar studies with bromelain have been conducted on piglets inoculated with K88 positive E. coli.36 An in vitro study on rabbit ileum found that bromelain was also 51% effective against cholera toxin.37
Bromelain is of particular benefit if treatment with antibiotics becomes necessary. Numerous clinical studies show that bromelain can increase serum levels of several antibiotics (including tetracycline, amoxicillin, and penicillin) in different body fluids (including blood, cerebral spinal fluid, mucus, sputum, and urine) and tissues (including appendix, gallbladder, ovary, epithelium, and uterus).38-40 In addition, researchers believe that bromelain itself possesses significant therapeutic effects. Studies tend to indicate that bromelain is as effective as antibiotics in treating bronchitis, perirectal abscess, pyelonephritis, cutaneous staphylococcus infection, and various infectious processes.8,38
Inflammatory Diseases and Conditions
Inflammatory conditions such as edema, rheumatoid arthritis, strains, sprains, bruises, fractures, and surgeries (oral, cosmetic, and general) all respond favorably to orally administered bromelain. Numerous studies have also noted bromelain’s ability to reduce pain, swelling, and bruising and improve rate of healing after various surgical procedures.8,41-44 Unlike the majority of nonsteroidal antiinflammatory drugs, there seems to be no indication that bromelain promotes bleeding.
Some of the earliest studies on bromelain involved athletic injuries. A 1960 study of boxers highlighted bromelain’s rehabilitative effects.43 Within 4 days of initiating bromelain treatment, 58 of 74 boxers experienced complete resolution of all signs of bruising. Complete clearance of bruising occurred in 8 to 10 days in the remaining 16 boxers receiving bromelain. At the end of 4 days, only 10 boxers in the control group demonstrated complete clearance of bruising, whereas clearance in the remaining 62 in the control group required 7 to 14 days. It is important to note that bromelain’s effect on pain reduction is probably not due to any direct analgesic effect, but rather to its ability to reduce tissue edema and inflammation.
Fifty-nine patients with muscle strains, contusions, ligament tears, and other injuries to the musculoskeletal system received 500 mg of bromelain three times daily, 30 minutes before meals.45 Results from this study and others indicated that the use of bromelain led to a rapid improvement of pain at rest and during motion, swelling, inflammation, and tenderness on palpation.46,47
Seventy-seven otherwise healthy subjects completed a study investigating bromelain’s effect on mild acute knee pain of less than 3 months’ duration.48 Two validated questionnaires (the Psychological Well-Being Index and the Western Ontario and McMaster Universities [WOMAC] Knee Health Index) were completed as a baseline and after 1 month of bromelain treatment (200 or 400 mg/day, allocated randomly to volunteers). In both bromelain groups, all WOMAC symptom scores decreased significantly compared with baseline. Reductions in the total symptom score were 41% for the low-dose group of bromelain recipients and 59% in the high-dose group. Additionally, those receiving 400 mg/day of bromelain experienced significantly greater improvement in total symptom score plus stiffness and physical function dimensions compared with those receiving low-dose (200 mg/day) bromelain. Both bromelain groups experienced a significant improvement in overall psychological well-being compared with baseline (researchers noted a dose-dependent relationship).
Surgery
Numerous studies indicate bromelain’s effectiveness at reducing postsurgical inflammation. In studies of patients who underwent oral surgery, Tassman et al41,42 concluded that, although postsurgical medication alone was effective, a regimen of presurgical and postsurgical bromelain was recommended to enhance the healing process.
A double-blind study of patients who underwent oral surgery found that bromelain was significantly superior to placebo in reduction of swelling (3.8 days compared with 7 days for the placebo). In addition, the duration of pain decreased to 5.1 days in the bromelain group compared with 8.1 days for the placebo group.42 Similar observations were made in studies of episiotomy cases. Bromelain reduced inflammation, pain, and edema. Further, preoperative administration of bromelain improved the potential positive effects.44,49
Antiinflammatory Action of Bromelain
Bromelain may function as an antiinflammatory by (1) activating proteolytic activity at the inflammation site; (2) lysing fibrin at the site; (3) depleting kininogen; and (4) inhibiting the biosynthesis of prostaglandins and the induction of PGE1 accumulation.7,17,50
As a proteolytic enzyme, bromelain demonstrates a delayed analgesic effect that involves the action of two mechanisms. Bromelain cleaves such inflammatory mediators as the kinins and prostaglandins, which directly stimulate the pain receptors. Further, bromelain supports the breakdown of plasmin protein and immune complexes that stem from the tissues by cleaving them directly and by stimulating their phagocytosis. The reduction of edema that subsequently follows leads to a relief of pressure and, secondarily, a reduction in pain, thus inhibiting bradykinin formation (a chemical mediator of inflammation) at the inflammation site.
Of these processes, the primary pharmacologic effects of bromelain are most likely plasmin activation and the decrease in kinin levels. The ability of bromelain to decrease inflammation has been documented in various clinical studies and experimental models.8,41-45,48,50-56 The inflammatory process is involved in numerous conditions, including infections and respiratory tract diseases. These conditions are covered separately within this chapter.
As mentioned in the “Cancer” section, bromelain functions as an immunomodulator and is able to increase levels of some cytokines, while reducing levels of others, thus leading to cytokine homeostasis and a reduction in inflammation.
Respiratory Tract Diseases
Bromelain’s efficacy in treating respiratory tract diseases seems to be due to its mucolytic activity.57 Bromelain appears to reduce sputum viscosity and possesses an antitussive effect in chronic bronchitis patients. Spirometric examination of patients before and after bromelain treatment indicated increased FEV1 (a measurement of the amount of air exhaled in a forced exhalation) and vital capacity, whereas residual volume was reduced. These favorable results were believed to be due to bromelain’s ability to function as a mucolytic and decrease bronchial secretions, thereby reducing respiratory congestion.
A double-blind study on patients with acute sinusitis found that 87% of those receiving bromelain experienced good to excellent results compared with 68% of the placebo group.58 Treatment with bromelain also appears to lead to a significantly faster recovery time.59
Bromelain has been found to exert antiinflammatory effects in allergic airway disease in murine models.60,61 Researchers hypothesize that it may be beneficial in treating human asthma.60,61
Skin Debridement
Severe burns leave dead and damaged tissue that can interfere with healing and potentially contaminate the wound. Removing the damaged or dead tissue (“debriding” the wound) exposes healthy tissue, promotes healing, and provides a clear foundation for skin grafting. Debridement can be accomplished surgically, chemically, or by using enzymes, which function without destroying the underlying, healthy tissue. Studies on a novel bromelain gel confirm its safety and efficacy in burn debridement.62,63
Bromelain is also effective in debriding contaminated tissue, as well as devitalized tissue from scars, wounds, and ulcers.
Dosage
When used as a digestive aid, bromelain should be taken just before a meal (no more than 30 minutes before eating). When used systemically, bromelain should be taken between meals, on an empty stomach (about 1-1/2 hours before or after a meal). The preparation’s potency will dictate dosage. Most bromelain currently marketed in the United States is between 600 and 2400 GDUs. A good dosage with which to begin might be 230 to 250 mg taken three to four times daily.
Side Effects and Contraindications
High doses (nearly 2 g) of bromelain have been administered with no apparent side effects.64 No lethal dose 50 (LD50) exists up to 10 g/kg, so it is deemed to be virtually nontoxic. Long-term use seems to be well-tolerated. As with most therapeutic agents, allergic reactions may occur with prolonged occupational exposure or in sensitive individuals; however, no significant side effects have been noted.65,66
No teratogenic studies have been conducted in humans, so bromelain should not be used by pregnant women. In addition, studies have not been conducted on the safety of using bromelain in nursing mothers.
Although no anaphylactic reactions have been reported, bromelain can induce gastrointestinal allergic and immunoglobulin-E–mediated respiratory reactions, as well as cross-react with papain, rye flour, wheat flour, birch pollen, and grass pollen.65,66 Although side effects are infrequently observed, bromelain sensitivity as manifested by skin rash or urticaria has occurred. Other possible but unconfirmed reactions include vomiting, nausea, metrorrhagia, menorrhagia, and diarrhea. Researchers hypothesize that bromelain’s ability to inhibit platelet aggregation may increase the risk of bleeding67; however, there are no studies to support this assertion.
Drug Interactions
There are few known interactions between bromelain and other medications. However, because bromelain is a potent inhibitor of platelet aggregation (both in vivo and in vitro),23-30 caution should be exercised when used with anticoagulants (blood thinners), including Jantoven, Lovenox, and warfarin, as well as over-the-counter nonsteroidal antiinflammatory drugs, including aspirin and ibuprofen. In addition, certain botanicals, including garlic, ginkgo biloba, and ginseng, may increase bleeding risk, so patients should be monitored when these are used in conjunction with bromelain.
Clinical studies show that bromelain can increase serum levels of several antibiotics (including tetracycline, amoxicillin, and penicillin) in body fluids and tissues.38-40 This can be helpful when attempting to improve an antibiotic’s efficacy; however, it is possible that there could be instances where elevated serum levels of antibiotics would be deleterious.
Any foods that contain protease inhibitors have the potential to decrease the proteolytic activity of bromelain. However, most of these foods (such as potatoes and soybeans) are rarely eaten raw (heat inactivates the protease inhibitors). In addition, many of the protease inhibitors found in these (and other) foods are trypsin inhibitors; however, bromelain contains no trypsin.
Conclusion
The future of oral enzyme therapy is already here; however, the rate at which this knowledge is utilized in restoring health to millions is deplorably slow. This concerns those scientists, doctors, biochemists, and pharmacists who recognize the potential of enzyme therapy. This chapter on bromelain and Chapter 111 on Pancreatic Enzymes have been written in the hope of hastening the day when enzyme therapy will be employed as a matter of course for every disorder in which it can be of assistance.
Bromelain has proven to be effective in treating the following diseases and conditions:
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For further information on enzymes and enzyme therapy, see the following:
Cichoke A.J. Enzymes: the sparks of life. Vancouver: Canada: Alive Books; 2002.
Cichoke A.J. Enzymes and enzyme therapy: how to jump start your way to lifelong good health, 2nd ed. New Canaan, CT: Keats; 2000.
Cichoke A.J. The complete book of enzyme therapy. New York: Avery Publishing; 1999.
Cichoke A.J. The back pain bible. Los Angeles: Keats; 1999.
Cichoke A.J. Bromelain: the active enzyme that helps us make the most of what we eat. New Canaan, CT: Keats; 1998.
Cichoke A.J. Enzymes: nature’s energizers. New Canaan, CT: Keats; 1997.
Cichoke A.J. Acute trauma and systemic enzyme therapy. Portland, OR: Seven C’s Publishing; 1993.
Cichoke A.J. A new look at chronic disorders and systemic enzyme therapy. Portland, OR: Seven C’s Publishing; 1993.
Cichoke A.J. A new look at enzyme therapy. Portland, OR: Seven C’s Publishing; 1993.