About Herbs, Botanicals & Other Products

Scientific Name
Sulphydryl proteolytic enzyme, cysteine-proteinase
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Brand Name

Ananase, Dayto Anase, Traumanase

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Clinical Summary

An enzyme obtained from the stem of pineapple, bromelain belongs to a group of plant-derived proteolytic enzymes that also includes papain, and has a wide range of applications. In vitro and some in vivo studies demonstrate its anti-inflammtory (15) (16) properties. Bromelain reduces serum fibrinogen levels, supports fibrinolysis and has been investigated for its debriding effects on burn wounds (1). In addition, it may be useful for treating some skin conditions (2). Bromelain reduces mild, acute knee pain in a dose-dependent fashion (3). Studies of bromelain’s pain relieving effect on patients with arthritis yielded mix results (4) (5) (6).

Studies done in vitro and in mice have shown that bromelain has chemopreventive (19) (25) and antitumorigenic effects (20) (26). Bromelain and other proteolytic enzymes were used as adjuvants in cancer treatments (7) (8) (9). It also increased the survival indices of animals bearing leukemia, sarcoma, lung, breast, and ascetic tumors (10); however, the anticancer effects of bromelain have not been evaluated in clinical trials.

Theoretically, bromelain may interfere with anticoagulation therapy and increase bleeding risk due to its antithrombotic effects. Bromelain also inhibits cytochrome P450 (CYP) 2C9 activity (12).

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Food Sources

Pineapple

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Purported Uses
  • Arthritis
  • Bruises
  • Burns
  • Cancer prevention
  • Cancer treatment
  • Circulatory disorders
  • Edema
  • Indigestion
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Mechanism of Action

Proteolytic removal of cell surface molecules by bromelain may account for some of its activities. Studies show that bromelain prevents platelet aggregation and adhesion of platelets to blood vessel endothelial cells as well as improves ischemia-reperfusion injury (13). It can act as an anti-inflammatory agent by reducing levels of prostaglandin E2 and thromboxane A2 (9). In addition, bromelain inhibits neutrophil migration in response to IL-8 during inflammation (14) and decreases pro-inflammatory chemokine and cytokine secretion (15) (16). Topical application of bromelain may be used for the skin debridement of burns (1).
Oral enzymes such as bromelain have been proposed as additive agents for cancer therapy (8). Proposed mechanisms include down-regulation of the immunosuppressive cytokine, TGF-beta (7), direct inhibition of tumor cell growth, modulation of immune cell function, modulation of cell adhesion molecules (CAMs), and the effects on platelet aggregation and thrombosis mentioned above (8) (9). Studies does in mice showed that bromelain induced apoptosis-related proteins along with inhibition of NF-kappaB-driven Cox-2 expression by blocking the MAPK and Akt/protein kinase B signaling in DMBA-TPA-induced skin tumors (20).
Bromelain also induces the expression of autophagy-related proteins, light chain 3 protein B II (LC3BII), and beclin-1 thereby facilitating apoptosis in mammary carcinoma cells (26).

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Pharmacokinetics

Absorption
Orally administered bromelain is absorbed intact through the intestine. Because of its proteolytic activity, about 50% of bromelain is rapidly complexed with an antiproteinase, namely alpha-2-macroglobulin (AMG). Proteolytic activity is maintained within this protective molecule, but reduced. In a recent human study, plasma half-life was determined to be 6-9 hours. Orally administered bromelain is absorbed at a rate of 40% in animal studies.
Distribution
Bromelain is distributed in the blood and plasma.
Metabolism/Excretion
The pathways of metabolism and excretion are not fully known.
(11)

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Adverse Reactions

Reported: Allergic reactions (21) (22).

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Herb-Drug Interactions

Cytochrome P450 2C9: Bromelain inhibits CYP2C9 activity and can affect metabolism of its substrates (12).
Antibiotics/Tetracyclines: Bromelain may increase blood and urine levels (23).
Anticoagulants: Bromelain may increase bleeding risk due to its antithrombotic effects (24).

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Literature Summary and Critique

Klein G, et al. Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs. Clin Exp Rheumatol. 2006;24(1):25-30.
Phlogenzyme (PE), a combination therapy including bromelain (90 mg), trypsin (48 mg), and rutoside (100 mg), was compared with a standard non-steroidal anti-inflammatory drug (NSAID), diclofenac (DC; 50 mg), in this double-blind, randomized study of 90 osteoarthritis patients. Participants were either given PE (2 tablets t.i.d.) or DC (1 tablet b.i.d.) for 6 weeks, and the Western Ontario and McMaster Osteoarthritis Index (WOMAC) dimensions and the Lequesne’s index were used to measure pain, joint stiffness, and physical function. Both PE and DC improved pain, joint stiffness, and physical function to similar levels, and patients receiving PE reported a small increase in drug tolerability. These results indicate that PE may be a useful alternative to NSAID therapy for osteoarthritis patients. Because PE is a combination therapy, the effects of bromelain alone were not determined.

Desser L, et al. Oral therapy with proteolytic enzymes decreases excessive TGF-beta levels in human blood. Cancer Chemother Pharmacol 2001;47suppl:S10-S15.
The effect of a combination of oral proteolytic enzymes (OET) containing papain, bromelain, trysin and chymotrypsin on the levels of cytokin-transforming growth factor-beta (TGF-beta) was studied. Overproduction of TGF-beta is involved in chronic inflammation and delayed wound healing and is associated with adverse effects from chemo- and radiationtherapy. 52 patients with rheumatoid arthritis, osteomyelofibrosis or herpes zoster were recruited. 78 healthy volunteers served as controls. OET were shown to reduce TGF-beta1 only in patients with elevated TGF-beta1 concentration (> 50 ng/ml serum). This study was well designed and has a relatively high level of statistical significance. However, it included other OET in addition to bromelain, leaving the possibility that the outcome was due to a synergy of all the OET. The effect of bromelain alone was not identified.

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References
  1. Klasen HJ. A review on the non-operative removal of necrotic tissue from burn wounds. Burns 2000;26:207-22.
  2. Massimiliano R, Pietro R, Paolo S, et al. Role of bromelain in the treatment of patients with pityriasis lichenoides chronica. J Dermatolog Treat. 2007;18(4):219-222.
  3. Walker AF, et al. Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent fashion in an open study of otherwise healthy adults. Phytomedicine 2002 Dec;9(8):681-6.
  4. Klein G, Kullich W, Schnitker J, et al. Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs. Clin Exp Rheumatol. Jan-Feb 2006;24(1):25-30.
  5. Kerkhoffs GM, Struijs PA, de Wit C, et al. A double blind, randomised, parallel group study on the efficacy and safety of treating acute lateral ankle sprain with oral hydrolytic enzymes.Br J Sports Med. Aug 2004;38(4):431-435.
  6. Brien S, Lewith G, Walker AF, et al. Bromelain as an adjunctive treatment for moderate-to-severe osteoarthritis of the knee: a randomized placebo-controlled pilot study.QJM. Dec 2006;99(12):841-850.
  7. Desser L,et al. Oral therapy with proteolytic enzyes decreases excessive TGF-beta levels in human blood. Cancer Chemother Pharmacol 2001;47:S10-5.
  8. Desser L, Zavadova E, Herbacek I. Oral enzymes as additive cancer therapy. Int J Immunotherapy. 2001;17(2-3-4):153-161.
  9. Maurer HR. Bromelain: biochemistry, pharmacology and medical use. Cell Mol Life Sci 2001;58:1234-45.
  10. Baez R, Lopes MT, Salas CE, et al. In vivo antitumoral activity of stem pineapple (Ananas comosus) bromelain. Planta Med. Oct 2007;73(13):1377-1383.
  11. Castell JV, et al. Intestinal absorption of undegraded proteins in men: presence of bromelain in plasma after oral intake. Am J Physiol 1997;273:G139-46.
  12. Hidaka M, Nagata M, Kawano Y, et al. Inhibitory effects of fruit juices on cytochrome P450 2C9 activity in vitro. Biosci Biotechnol Biochem. Feb 2008;72(2):406-411.
  13. Juhasz B, Thirunavukkarasu M, Pant R, et al. Bromelain induces cardioprotection against ischemia-reperfusion injury through Akt/FOXO pathway in rat myocardium.Am J Physiol Heart Circ Physiol. Mar 2008;294(3):H1365-1370.
  14. Fitzhugh DJ, Shan S, Dewhirst MW, et al. Bromelain treatment decreases neutrophil migration to sites of inflammation. Clin Immunol. Jul 2008;128(1):66-74.
  15. Onken JE, Greer PK, Calingaert B, et al. Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro. Clin Immunol. Mar 2008;126(3):345-352.
  16. Secor ER, Carson WF, Singh A, et al. Oral Bromelain Attenuates Inflammation in an Ovalbumin-induced Murine Model of Asthma. Evid Based Complement Alternat Med. Mar 2008;5(1):61-69.
  17. Herr SM. Herb-Drug Interaction handbook, 2nd ed. Nassau (NY): Church Street Books; 2002
  18. Taussig SJ, Batkin S. Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. J Ethnopharmacol 1988 Feb-Mar;22(2):191-203.
  19. Bhui K, Prasad S, George J, Shukla Y. Bromelain inhibits COX-2 expression by blocking the activation of MAPK regulated NF-kappa B against skin tumor-initiation triggering mitochondrial death pathway. Cancer Lett 2009 Sep 18;282(2):167-76.
  20. Kalra N, Bhui K, Roy P, et al. Regulation of p53, nuclear factor kappaB and cyclooxygenase-2 expression by bromelain through targeting mitogen-activated protein kinase pathway in mouse skin. Toxicol Appl Pharmacol. 2008 Jan 1;226(1):30-7.
  21. Raison-Peyron N, Roulet A, Guillot B, Guilhou JJ. Bromelain: an unusual cause of allergic contact cheilitis. Contact Dermatitis. 2003 Oct;49(4):218-9.
  22. Nettis E, Napoli G, Ferrannini A, Tursi A. IgE-mediated allergy to bromelain. Allergy. 2001 Mar;56(3):257-8.
  23. Bradbrook IK, Morrison PJ, Rogers HJ. The effect of bromelain on the absorption of orally administered tetracycline. Br J Clin Pharmacol. 1978;6:552-4.
  24. Metzig C, Grabowska E, Eckert K, Rehse K, Maurer HR. Bromelain proteases reduce human platelet aggregation in vitro, adhesion to bovine endothelial cells and thrombus formation in rat vessels in vivo. In Vivo. 1999 Jan-Feb;13(1):7-12.
  25. Hale LP, Chichlowski M, Trinh CT, Greer PK. Dietary supplementation with fresh pineapple juice decreases inflammation and colonic neoplasia in IL-10-deficient mice with colitis. Inflamm Bowel Dis. 2010 Dec;16(12):2012-21.
  26. Bhui K, Tyagi S, Prakash B, Shukla Y. Pineapple bromelain induces autophagy, facilitating apoptotic response in mammary carcinoma cells. Biofactors. 2010 Nov-Dec;36(6):474-82.
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How It Works

Bottom Line: Bromelain is a digestive aid. It has not been shown to treat or prevent cancer or other serious medical conditions.

Bromelain, obtained from the stem of the pineapple, is an enzyme that breaks down protein molecules. In laboratory experiments, bromelain prevented several steps of blood clotting and decreased some substances that cause inflammation. Bromelain increases the absorption of antibiotics and when used topically, helps remove dead and damaged tissue from burns. Bromelain can help digestion and absorption in patients with digestive tract cancers. Anticancer activity has not been studied in humans.

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Purported Uses
  • To treat arthritis
    Laboratory studies show that bromelain reduces the levels of some substances that cause inflammation, but results from clinical trials are mixed.
  • To treat burns of the skin
    Laboratory evidence supports this use, but clinical trails have not been conducted to show that bromelain can treat burns.
  • To prevent and treat cancer
    Laboratory studies suggested bromelain has anticancer activities. But these effects have not been confirmed in humans.
  • To treat circulatory disorders
    Laboratory studies show that bromelain can prevent the formation of blood clots, but there is no proof from clinical trials that it can treat circulatory disorders.
  • To reduce swelling and edema
    Laboratory studies show that bromelain reduces the levels of substances in the body that cause inflammation. Clinical trials have yet to be conducted.
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Research Evidence

Rheumatoid arthritis, osteomyelofibrosis or herpes zoster (shingles):
Bromelain was studied in combination with other proteases (papain, trypson, and chymotrypsin) in 78 healthy volunteers and 52 patients with rheumatoid arthritis, osteomyelofibrosis or herpes zoster. Before and after therapy, the researchers measured blood levels of TGF-beta, a substance involved in chronic inflammation, delayed wound healing, and side effects from chemo- and radiation therapy. The enzymes were found to reduce levels of TGF-beta, but only in the patients who had elevated TGF-beta blood levels to begin with. However, it is possible that this outcome was due to an additive effect of all four enzymes, and it is still unclear whether bromelain alone would have any effect.

In a clinical study that included 90 osteoarthritis patients, Phlogenzyme (PE), a therapy that contains bromelain as well as other components, was compared with a standard non-steroidal anti-inflammatory drug, diclofenac (DC). Participants were either given PE or DC for 6 weeks after which pain, joint stiffness, and physical function were measured. Both PE and DC improved pain, joint stiffness, and physical function similarly, and patients receiving PE reported a small increase in drug tolerability. Therefore, PE may be a useful alternative to taking NSAIDs for osteoarthritis; however, because PE is a combination therapy, the action of bromelain alone is not known.

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Patient Warnings
  • This product is regulated by the FDA as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. This product may not contain the labeled amount or may be contaminated. In addition, it may not have been tested for safety or effectiveness.
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Do Not Take If
  • You are taking warfarin or other blood thinners (Bromelain may increase the risk of bruising and bleeding).
  • You are taking Tetracycline antibiotics (Bromelain may increase blood and urine levels).
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Side Effects
  • Allergic reactions have been reported.
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Special Point

Bromelain may increase blood levels of antibiotics by increasing their absorption in the intestine.

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Dosage (Inside MSKCC Only)
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E-mail your questions and comments to aboutherbs@mskcc.org.
Last updated: September 30, 2011