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Bromelain

  • Written by Shahrul
  • Updated on March 6, 2021


Plant Part Used

Proteolytic enzymes derived from pineapple stem.

Active Constituents

Sulfhydryl proteolytic enzymes (Bromelain A and B). (1) [span class=alert]

This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]

Introduction

Bromelain is a general name for a family of sulfhydryl proteolytic enzymes obtained from Ananas comosus, the pineapple plant. It is usually classified as either fruit bromelain or stem bromelain depending on its source, with all commercially available bromelain being derived from the stem. (2) These enzymes act on a wide variety of proteins, including food proteins, other enzymes, fibrin and plasminogen, and have been used for years in the food industry as meat tenderizers. (3)

In Europe, a patented tape has been developed containing bromelain that is used clinically for debriding wound eschar. (4) The German Commission E approves the use of bromelain in surgical swelling, particularly of the nasal sinuses. (5) Bromelain is used clinically in conditions such as soft tissue inflammation and arthritis, dyspepsia, and dysmenorrhea, as well as a digestive aid. (6)

Interactions and Depletions

Interactions

Dosage Info

Dosage Range

1-3 of the 500mg tablets, 3-4 times a day taken 30 minutes before meals.

Topically: Applied topically as a cream (35% bromelain in a lipid base); not recommended for more than 8-10 days.

Most Common Dosage

1-2 tablets (250-500mg), 3 times a day taken 30 minutes before meals. For anti-inflammatory benefits, use between meals, 1-3 tablets (250-500mg) up to 4 times a day.

Topically: Applied topically as a cream (35% bromelain in a lipid base); not recommended for more than 8-10 days.

Standardization

[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

The most current available medical and scientific literature indicates that this dietary supplement should be standardized to approximately 2,000 MCU/ tablet.
Note: One GDU (Gelatin Dissolving Unit) is equivalent to 1.5 MCU (Milk Clotting Units).

Uses

Frequently Reported Uses

  • Arthritis, Inflammation
  • Dyspepsia
  • Cardiovascular Support (Angioplasty, Angina, Bypass)

Other Reported Uses

  • Digestive Aid
  • Mucolytic
  • Anti-Inflammatory.
  • Anticoagulant
  • Chemotherapy Enhancing Effects

 

Toxicities & Precautions

General

Bromelain is reported safe in recommended dosages.

Allergy

The allergenic potential for proteolytic enzymes should not be underestimated. Bromelain may cause IgE-mediated respiratory allergies of both the immediate type and the late-phase of immediate type in sensitive individuals. (7) Bromelain was reported to cause allergic symptoms in approximately 28 percent of individuals with IgE allergic response to honey bee venom. (8)

Health Conditions

Based on pharmacology, use with caution in individuals with bleeding disorders. (9)

Side Effects

In large doses (up to 1,840mg), bromelain was reported to increase blood pressure in hypertensive patients. (10)

Pharmacology

Bromelain’s primary component is a sulfhydryl proteolytic fraction. (11) Bromelain also contains a peroxidase, acid phosphatase, several protease inhibitors, and organically bound calcium. Uses of bromelain include:

Inflammation: Bromelain is used as an anti-inflammatory and analgesic agent in treating the symptoms of arthritis. (12) , (13) , (14) The analgesic effects are reportedly due to inhibition of the arachidonic acid pathway of inflammation by selectively decreasing thromboxane generation, changing the ratio of thromboxane/prostacyclin (in favor of prostacyclin), and inhibiting PGE2 in addition to the direct effects on the nociceptors. (15) , (16) Other reported anti-inflammatory mechanisms of action of bromelain include inhibition of bradykinin at the site of inflammation via depletion of the plasma kallikrein system, and limiting the formation of fibrin by reduction of clotting cascade intermediates. (17) , (18) A few clinical trials in patients with arthritis reported statistical equivalence of pain reduction, whether they were treated with bromelain or diclofenac. (19)

A study evaluating rats with collagen-induced arthritis compared cyclosporin A therapy to an enzyme complex using a combination of both. The enzyme complex contained bromelain, trypsin and rutin. Ten mg/kg of cyclosporin A and 5mg/kg of cyclosporin A plus 300mg/kg of enzyme complex significantly inhibited changes in measures of inflammation and the destructive effects of arthritis. (20) Bromelain affects CCL4/MIP-1b chemokine secretion through mechanism whereby it reduces the amount contained in the inflamed tissues derived from inflammatory bowel disease (IBD) patients. (60) The breakdown of proteins by Bromelain is futher supported by the mechanism acting on cell-surface CD25 which will decrease CD4+T cells that contributes to anti-inflammatory benefits. (62) Bromelain plays a role in neutrophil migration by abrogating a particular cell surface known as CD128 receptor which prevents the union of leukocytes to blood vessels. (65)

A human study in 90 patients with oseoarthritis found that a combination of bromelain with trypsin and rutin was as effective as the NSAID diclofenac in reducing pain and associated symptoms of osteoarthritis. Another double blind, placebo controlled study in 47 adults with osteoarthritis of the knee found that use of bromelain for 12 weeks (800mg daily of placebo) improves WOMAC score from baseline significantly.

Platelet aggregation/Fibrinolysis: Bromelain has been reported to prevent platelet aggregation in vivo and in vitro. (21) In one study, bromelain was administered orally to 20 volunteers with a history of heart attack or stroke, or with high platelet aggregation values. (22) Bromelain was reported to decrease aggregation of blood platelets in 17 of the subjects and normalized values in 8 of the 9 subjects who previously had high aggregation values. In vitro studies have also demonstrated that bromelain inhibits platelet aggregation stimulated by ADP or epinephrine, as well as by prostaglandin precursors, in a dose-dependent manner. (23) Bromelain has been reported to stimulate the conversion of plasminogen to plasmin, resulting in increased fibrinolysis. (24) There is a possibility that bromelain can ‘expose’ the tumour cells because of fibrinolytic activity that reduces the soluble fibrin in circulation. (60) Bromelain also reduces platelet count which is significant in the haemostatic system whereby the formation of tumour-platelet aggregates can be prevented. (60) A laboratory animal study found that bromelain improves transport of heparin across the small intestine.
Antitumor: Several studies, both animal and human, indicate bromelain might have some antimetastatic ability. (25) , (26) In high dosages (over 1,000mg daily), bromelain has been combined with chemotherapeutic agents such as 5-FU and vincristine, resulting in tumor regression. (27) Bromelain was also reported to stimulate deficient monocytic cytotoxicity of mammary tumor patients, which may partially explain its proposed antitumor activity. (28)

Consumption of proteinases, including bromelain, trypsin and rutoside was found to form intermediate forms of alpha 2-macroglobulin. These intermediate forms had high affinity to TGF-beta, eliminating the TGF-beta effect on fibroblasts in cell culture. This demonstrates that treatment of cancers associated with high TGF-beta concentration may benefit from proteinase therapy. (29) It is believed bromelain plays a role in the modulating effect of neutrophils to produce reactive oxygen species (ROS) which is important for inhibition cancer cells although excess of ROS which cause oxidative stress might lead to DNA damage. (60) Bromelain plays a role in reducing the breakage of strand DNA by inhibiting Cox-2 and restrict the extracellular signal regulated protein which will reduce the percentage of tumour. (61)

Immune Modulation: Bromelain can reportedly induce cytokine production in human peripheral blood mononuclear cells. Use has been reported to lead to the production of tumor necrosis factor-alpha, interleukin-1-beta, and interleukin-6 in a time- and dose-dependent manner. (30) , (31) Bromelain has also been reported to remove T-cell CD4 molecules from lymphocytes and to affect T-cell activation (32) and to enhance macrophage production of INF-gamma-mediated nitric oxide and TNF-alpha. (33) In splenocyte cultures, T-cell receptor and anti-CD28 mediated T-cell proliferation was enhanced by bromelain, while IL-2 production was decreased. IL-2 production was also inhibited in highly purified CD4+ T-cells. (34) Another study has demonstrated immune system stimulation of phagocytosis, respiratory burst and killing (PBK) in blood samples using Candida albicans as target organism. (35)

Debridement of Wounds: Bromelain applied topically as a cream (35% bromelain in a lipid base) can reportedly be beneficial in the elimination of burn debris and in acceleration of healing. (36) A non-proteolytic component of bromelain may be responsible for this effect. This component, referred to as escharase, has no hydrolytic enzyme activity against normal protein substrates or various glycosaminoglycan substrates, and its activity varies greatly from preparation to preparation. (37)

Potentiation of Antibiotics: Antibiotic potentiation is a primary use of bromelain in some foreign countries. In humans, some undetermined activity of bromelain has been documented to increase blood and urine levels of antibiotics. (38) , (39) , (40) Several studies have reported increases in the serum level of tetracycline after oral ingestion of bromelain. (41) , (42) Bromelain combined with antibiotic therapy has been reported to be more effective than antibiotics alone in a variety of conditions including pneumonia, bronchitis, cutaneous staphylococcus infection, thrombophlebitis, cellulitis, pyelonephritis, perirectal and rectal abscesses, and sinusitis. (43) , (44)

Mucolytic: A decrease in the volume and purulence of sputum was reported with the use of bromelain in a clinical study of 124 patients hospitalized with chronic bronchitis, pneumonia, bronchopneumonia, bronchiectasis, or pulmonary abscesses. (45)

Digestive Aid: Bromelain has reportedly been used successfully as a digestive enzyme following pancreatectomy, in cases of exocrine pancreas insufficiency and in other intestinal disorders. (46) , (47) The combination of ox bile, pancreatin and bromelain is reportedly effective in lowering stool fat excretion in patients with pancreatic steatorrhea, resulting in a symptomatic improvement in pain, flatulence, and stool frequency. (48) Bromelain’s proteolytic activity has been reported effective for inflammatory bowel disease due to it’s anti-inflammatory effects and also since the enzymes are not affected by anti-bromelain IgG and remains within the gastrointestinal tract. (64)

Bromelain has been reported to heal gastric ulcers in laboratory animals. In an extensive study of the effect of bromelain on the gastric mucosa, it was found that bromelain reportedly increased the uptake of radioactive sulfur by 50 percent and glucosamine by 30-90 percent. (49) Increased uptake of these substances may allow the gastric mucosa to heal more rapidly. (50)

Surgical Procedures and Musculoskeletal Injuries: One of bromelain’s most common applications is in the treatment of inflammation and soft tissue injuries. It has been reported to speed healing of bruises and hematomas. (51) Treatment with bromelain following blunt injuries to the musculoskeletal system has resulted in a clear reduction in swelling, pain at rest and during movement, and tenderness. (52) Administration of bromelain pre-surgically can reportedly reduce the average number of days for complete disappearance of pain and inflammation. (53) , (54) In a dose dependent manner, bromelain was shown to be able to improve the mild acute knee pain on treatment groups although more studies need to be done to confirm. (63)

Cardiovascular and Circulatory Applications: Studies have reported that bromelain may minimize the severity of angina pectoris. (55) , (56) A drastic reduction in the incidence of coronary infarct after administration of potassium and magnesium along with 120-400mg of bromelain per day has been reported. (57) In a study involving 73 patients with acute thrombophlebitis, bromelain plus analgesics was reported to decrease symptoms of inflammation including pain, edema, tenderness, skin temperature, and disability. (58)

Another potential use for bromelain includes treatment of breast engorgement. A literature review evaluated numerous therapies for breast engorgement. Of the pharmacological therapies evaluated, a bromelain-trypsin complex as well as serrapeptase (Danzen), an anti-inflammatory agent, demonstrated significant improvement in engorgement symptoms over placebo, whereas oxytocin did not. (59)

References

  1. Kelly G. Bromelain: A literature review and discussion of its therapeutic uses. Alt Med Rev. Vol 1. Nov1996;(4):120-23.
  2. View Abstract: Gailhofer G, et al. Asthma caused by bromelain: an occupational allergy. Clin Allergy. Sep1988;18(5):445-50.
  3. View Abstract: Monograph:Bromelain. Altern Med Rev. Aug1998;3(4):302-5.
  4. View Abstract: Houck JC, et al. Isolation of an effective debriding agent from the stems of pineapple plants. Int J Tissue React. 1983;5(2):125-34.
  5. Blumenthal M, et al. Herbal Medicine: Expanded Commission E Monographs. Newton, MA: Integrative Medicine Communications;2000:33-35.
  6. View Abstract: Monograph:Bromelain. Altern Med Rev. Aug1998;3(4):302-5.
  7. View Abstract: Gailhofer G, et al. Asthma caused by bromelain: an occupational allergy. Clin Allergy. Sep1988;18(5):445-50.
  8. View Abstract: Tretter V, et al. Fucose alpha 1,3-linked to the core region of glycoprotein N-glycans creates an important epitope for IgE from honeybee venom allergic individuals. Int Arch Allergy Immunol. 1993;102(3):259-66.
  9. Blumenthal: The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines, 1st ed. American Botanical Council. 1998:94-95.
  10. Gutfreund AE, et al. Effect of oral bromelain on blood pressure and heart rate of hypertensive patients. Hawaii Med J. May1978;37(5):143-6.
  11. Kelly G. Bromelain: A literature review and discussion of its therapeutic uses. Alt Med Rev. Vol 1. Nov1996;(4):120-23.
  12. View Abstract: Taussig SJ, Batkin S. Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. J Ethnopharmacol. 1988;27:191-203.
  13. View Abstract: Rovenska E, et al. Enzyme and combination therapy with cyclosporin A in the rat developing adjuvant arthritis. Int J Tissue React. 1999;21(4):105-11.
  14. View Abstract: Walker AF, Bundy R, Hicks SM, Middleton RW. Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent fashion in an open study of otherwise healthy adults. Phytomedicine. Dec2002;9(8):681-6.
  15. View Abstract: Taussig SJ, et al. Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. J Ethnopharmacol. 1988;27:191-203.
  16. View Abstract: Felton GE. Fibrinolytic and antithrombotic action of bromelain may eliminate thrombosis in heart patients. Med Hypotheses. Nov1980;6(11):1123-33.
  17. View Abstract: Kumakura S, Tsurufuji S, Yamashita M. Effect of bromelain on kaolin-induced inflammation in rats. Eur J Pharmacol. 1988;150:295-301.
  18. View Abstract: Uchida Y, Katori M. Independent consumption of high and low molecular weight kininogens in vivo. Adv Exp Med Biol. 1986;198:113-118.
  19. View Abstract: Klein G, et al. Reducing pain by oral enzyme therapy in rheumatic diseases. Wien Med Wochenschr. 1999;149(21-22):577-80.
  20. View Abstract: Rovenska E, Svik K, Stancikova M, Rovensky J. Inhibitory effect of enzyme therapy and combination therapy with cyclosporin A on collagen-induced arthritis. Clin Exp Rheumatol. May2001;19(3):303-9.
  21. View Abstract: Metzig C, et al. Bromelain proteases reduce human platelet aggregation in vitro, adhesion to bovine endothelial cells and thrombus formation in rat vessels. In Vivo. Jan1999;13(1):7-12.
  22. Heinicke RM, et al. Effect of bromelain (Ananase) on human platelet aggregation. Experientia. Jul1972;28(7):844-5.
  23. View Abstract: Morita AH, et al. Chromatographic fractionation and characterization of the active platelet aggregation inhibitory factor from bromelain. Arch Int Pharmacodyn Ther. Jun1979;239(2):340-50.
  24. View Abstract: Ako H, et al. Isolation of a fibrinolysis enzyme activator from commercial bromelain. Arch Int Pharmacodyn Ther. Nov1981;254(1):157-67.
  25. Taussig SJ, Szekerczes J, Batkin S. Inhibition of tumor growth in vitro by bromelain, an extract of the pineapple plant (Ananas comosus). Planta Med. 1985;6:538-539.
  26. View Abstract: Batkin S, Taussig SJ, Szekerezes J. Antimetastatic effect of bromelain with or without its proteolytic and anticoagulant activity. J Cancer Res Clin Oncol. 1988;114:507-508.
  27. Gerard G. Anti-cancer therapy with bromelain. Agressologie. 1972;13:261-274.
  28. View Abstract: Eckert K, et al. Effects of oral bromelain administration on the impaired immunocytotoxicity of mononuclear cells from mammary tumor patients. Oncol Rep. Nov1999;6(6):1191-9.
  29. View Abstract: Lauer D, Muller R, Cott C, Otto A, Naumann M, Birkenmeier G. Modulation of growth factor binding properties of alpha2-macroglobulin by enzyme therapy. Cancer Chemother Pharmacol. Jul2001;47(Suppl):S4-9.
  30. View Abstract: Desser L, Rehberger A, Paukovits W. Proteolytic enzymes and amylase induce cytokine production in human peripheral blood mononuclear cells in vitro. Cancer Biother. 1994;9:253-263.
  31. View Abstract: Desser L, et al. Cytokine synthesis in human peripheral blood mononuclear cells after oral administration of polyenzyme preparations. Oncology. Nov1993;50(6):403-7.
  32. View Abstract: Munzig E, Eckert K, Harrach T, et al. Bromelain protease F9 reduces the CD44 mediated adhesion of human peripheral blood lymphocytes to human umbilical vein endothelial cells. FEBS Lett. 1995;351:215-218.
  33. View Abstract: Engwerda CR, Andrew D, Murphy M, Mynott TL. Bromelain activates murine macrophages and natural killer cells in vitro. Cell Immunol. May2001;210(1):5-10.
  34. View Abstract: Engwerda CR, Andrew D, Ladhams A, Mynott TL. Bromelain modulates T cell and B cell immune responses in vitro and in vivo. Cell Immunol. May2001;210(1):66-75.
  35. View Abstract: Brakebusch M, Wintergerst U, Petropoulou T, Notheis G, Husfeld L, Belohradsky BH, et al. Bromelain is an Accelerator of Phagocytosis, Respiratory Burst and Killing of Candida albicans by Human Granulocytes and Monocytes. Eur J Med Res. May2001;6(5):193-200.
  36. Klaue P, Dilbert G, Hinke G, et al. Tier-experimentelle untersuchungen zur enzymatischen lokalbehandlung subdermaler verbrennungen mit bromelain. Therapiewoche. 1979;29:796-799.
  37. View Abstract: Houck JC, Chang CM, Klein G. Isolation of an effective debriding agent from the stems of pineapple plants. Int J Tissue React. 1983;5:125-134.
  38. Tinozzi S, Venegoni A. Effect of bromelain on serum and tissue levels of Amoxycillin. Drugs Exptl Clin Res. 1978;4:39-44.
  39. Renzinni G, Varengo M. The absorption of tetracycline in combination with bromelain by oral application. Arzneim-Forsch. 1972;22:410-412.
  40. Luerti M, Vignali ML. Influence of bromelain on penetration of antibiotics in uterus, salpinx and ovary. Drugs Exp Clin Res. 1978;4:45-48.
  41. Bradbrook ID, et al. The effect of bromelain on the absorption of orally administered tetracycline. Br J Clin Pharmacol. Dec1978;6(6):552-4.
  42. Lucchi R, et al. Chronic infections of the lower respiratory tract. Antibiotic therapy. Results of a double-blind study: tetracycline-HCl as a monosubstance versus tetracycline and bromeline. ZFA (Stuttgart). Apr1980;56(11):807-12.
  43. Hunter RG, Henry GW, Heinicke RM. The action of papain and bromelain on the uterus. Am J Ob Gyn. 1957;73:867-873.
  44. Neubauer RA. A plant protease for potentiation of and possible replacement of antibiotics. Exp Med Surg. 1961;19:143-160.
  45. View Abstract: Schafer A, Adelman B. Plasmin inhibition of platelet function and of arachidonic acid metabolism. J Clin Invest. 1985;75:456-461.
  46. Knill-Jones RP, et al. Comparative double blind experience of a polyenzymatic preparation in chronic pancreatic insufficiency. Acta Gastroenterol Belg. Sep1973;36(9):489-504.
  47. Knill-Jones RP, Pearce H, Batten J, et al. Comparative trial of Nutrizym in chronic pancreatic insufficiency. Brit Med J. 1970;4:21-24.
  48. Balakrishnan V, Hareendran A, Sukumaran Nair C. Double-blind cross-over trial of an enzyme preparation in pancreatic steatorrhea. J Asso Phys Ind. 1981;29:207-209.
  49. Seligman B. Bromelainan anti-inflammatory agentthrombophlebitis. No toxicity. Angiology. 1962;13:508-510.
  50. Felton G. Does kinin released by pineapple stem bromelain stimulate production of prostaglandin E1-like compounds? Hawaii Med J. 1976;2:39-47.
  51. Blonstein JL. Control of swelling in boxing injuries. Practitioner. 1960;185:78.
  52. View Abstract: Masson M. Bromelain in blunt injuries of the locomotor system. A study of observed applications in general practice. Fortschr Med. 1995;113:303-306.
  53. Tassman GC, Zafran JN, Zayon GM. A double-blind crossover study of a plant proteolytic enzyme in oral surgery. J Dent Med. 1965;20:51-54.
  54. Tassman GC, Zafran JN, Zayon GM. Evaluation of a plant proteolytic enzyme for the control of inflammation and pain. J Dent Med. 1964;19:73-77.
  55. Taussig SJ, Nieper HA. Bromelain: its use in prevention and treatment of cardiovascular disease, present status. J IAPM. 1979;6:139-151.
  56. Nieper HA. Effect of bromelain on coronary heart disease and angina pectoris. Acta Med Empirica. 1978;5:274-278.
  57. Nieper HA. Decrease of the incidence of coronary heart infarct by Mg- and K-orotate and bromelain. Acta Med Empirica. 1977;12:614-618.
  58. Seligman B. Oral bromelains as adjuncts in the treatment of acute thrombophlebitis. Angiology. 1969;20:22-26.
  59. View Abstract: Snowden HM, Renfrew MJ, Woolridge MW. Treatments for breast engorgement during lactation (Cochrane Review). Cochrane Database Syst Rev. 2001;2:CD000046.
  60. Katya Chobotova, Ann B. Vernallis, Fadzilah Adibah Abdul Majid. Bromelain’s activity and potential as an anti-cancer agent: Current evidence and perspectives. Cancer Letters, Volume 290, Issue 2, 28 April 2010, Pages 148-156
  61. Kulpreet Bhui, Sahdeo Prasad, Jasmine George, Yogeshwer Shukla. Bromelain inhibits COX-2 expression by blocking the activation of MAPK regulated NF-kappa B against skin tumor-initiation triggering mitochondrial death pathway. Cancer Letters, Volume 282, Issue 2, 18 September 2009, Pages 167-176
  62. Eric R. Secor Jr.,Anurag Singh, Linda A. Guernsey, Jeff T. McNamara, Lijun Zhan, Nilanjana Maulik, Roger S. Thrall. Bromelain treatment reduces CD25 expression on activated CD4+ T cells in vitro International Immunopharmacology, Volume 9, Issue 3, March 2009, Pages 340-346
  63. A.F. Walker, R.Bundy, S.M. Hicks, R.W. Middleton. Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent fashion in an open study of otherwise healthy adults. Phytomedicine, Volume 9, Issue 8, 2002, Pages 681-686
  64. Laura P. Hale. Proteolytic activity and immunogenicity of oral bromelain within the gastrointestinal tract of mice. International Immunopharmacology, Volume 4, Issue 2, February 2004, Pages 255-264
  65. Jane E. Onken, Paula K. Greer, Brian Calingaert, Laura P. Hale. Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro. Clinical Immunology, Volume 126, Issue 3, March 2008, Pages 345-352

in this scope
Malaysian Herbal Monograph​
Medicinal Herbs & Plants Monographs​
Traditional Chinese Medicine Herbs (Professional Data)
Herbal Medicines Compendium (HMC) - U.S​

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