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Bromelain

Bromelain

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For Patients & Caregivers

How It Works

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.

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.

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).

Side Effects
  • Allergic reactions have been reported.

Special Point

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

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For Healthcare Professionals

Brand Name
Ananase, Dayto Anase, Traumanase

Scientific Name
Sulphydryl proteolytic enzyme, cysteine-proteinase

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-inflammatory (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). It was also shown to reduce post-operative pain and swelling, and improve quality of life (27). 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).

Food Sources

Pineapple

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

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).

Adverse Reactions

Reported: Allergic reactions (21) (22).

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).

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.

  27. Majid OW, Al-Mashhadani BA. Perioperative bromelain reduces pain and swelling and improves quality of life measures after mandibular third molar surgery: a randomized, double-blind, placebo-controlled clinical trial. J Oral Maxillofac Surg. 2014 Jun;72(6):1043-8.

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