Bromelain

Purported Benefits, Side Effects & More
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Bromelain

Purported Benefits, Side Effects & More
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Bromelain

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For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.

What is it?

Bromelain has anti-inflammatory properties, but has not been shown to treat or prevent cancer.

Bromelain is an enzyme that breaks down protein molecules and is obtained from pineapple stems. In lab experiments, bromelain prevented blood clotting and decreased inflammation.

Studies in humans are limited. When used topically in clinical settings, it helps remove dead and damaged tissue from burns. Although bromelain is sometimes taken orally to help digestion and absorption, studies are lacking. It also has not been studied for effects on cancer in humans.

Bromelain may increase the absorption of some antibiotics.

What are the potential uses and benefits?
  • To treat arthritis
    Lab studies suggest bromelain can reduce inflammation, but results from clinical trials are mixed.
  • To treat skin burns
    Studies in humans support this use in clinical settings.
  • To prevent and treat cancer
    Lab studies suggest bromelain has anticancer activities, but these effects have not been studied in humans.
  • To improve circulation
    Lab studies suggest that bromelain can prevent blood clots, but there is no proof from clinical trials that it can treat circulatory disorders.
  • To reduce swelling
    Small clinical studies suggest that bromelain helps reduce swelling.
What are the side effects?

Allergic reactions have been reported.

What else do I need to know?

Do Not Take if:

  • You are taking warfarin or other blood thinners: Preclinical studies suggest bromelain may increase the risk of bruising and bleeding.
  • You are taking tetracycline antibiotics: Bromelain may increase blood and urine levels of these drugs.

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

Bromelain is a proteolytic enzyme obtained from pineapple stems that has a range of applications. Preclinical data suggest it has anti-inflammatory properties (15) (16), reduces serum fibrinogen levels, supports fibrinolysis, and has debriding effects on burn wounds (1).

Clinical findings reported safety and effectiveness of a bromelain-based product for burn (28) and chronic wound (33) debridement although a case series suggests it may not be useful for diabetic foot burns (32). Other small studies suggest benefit for treating specific skin conditions (2), improving acute knee pain (3), and for alleviating postoperative pain, swelling and bleeding (27) (29) (30) (34). However, data on whether it can reduce inflammation (35) or relieve arthritis pain are mixed (4) (5) (6), and it does not appear to reduce fibrinogen or influence other cardiovascular disease risk factors (31).

Bromelain demonstrated chemopreventive (19) (25) and antitumorigenic effects (10) (20) (26) in preclinical studies. A formulation of alpha-Lipoic acid, Boswellia serrata, methylsulfonylmethane and bromelain improved symptoms of aromatase inhibitor-associated arthralgia in early breast cancer postmenopausal patients (36). A case report of prostate cancer patients found adjunctive use of bromelain with immunotherapy reduced PSA levels and stabilized the disease (37). Well-designed randomized trials are needed to evaluate the anticancer potential of bromelain.

Food Sources

Pineapple

Purported Uses and Benefits
  • Arthritis
  • Burns
  • Cancer
  • Circulation
  • Swelling
Mechanism of Action

Proteolytic removal of cell surface molecules by bromelain may account for some of its activities. Preclinical studies suggest it prevents platelet aggregation and adhesion to blood vessel endothelial cells (13). Anti-inflammatory effects are attributed to reduced 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).

Oral enzymes such as bromelain have been proposed as additive agents for cancer therapy (8). Proposed mechanisms include downregulation of the immunosuppressive cytokine TGF-beta (7), direct inhibition of tumor cell growth, modulation of immune cell function and cell adhesion molecules, and the effects on platelet aggregation and thrombosis mentioned above (8) (9). Experiments with murine models suggest bromelain induces apoptosis-related proteins and inhibits NF-kappaB-driven Cox-2 expression by blocking MAPK and Akt/protein kinase B signaling (20). Bromelain also induced expression of autophagy-related proteins, light chain 3 protein B II, and beclin-1, thereby facilitating apoptosis in mammary carcinoma cells (26).

Adverse Reactions

Allergic reactions have been reported following use of bromelain (21) (22) (38). 

Herb-Drug Interactions

CYP450 2C9: In vitro studies suggest bromelain inhibits CYP2C9 activity and may affect the metabolism of substrate drugs (12). Clinical relevance has yet to be determined.
Antibiotics/tetracyclines: Bromelain may increase blood and urine levels of these drugs (23).
Anticoagulants: Preclinical studies suggest bromelain may increase bleeding risk due to its antithrombotic effects (24). Clinical relevance has yet to be determined.

Dosage (OneMSK Only)
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.
  28. Rosenberg L, Shoham Y, Krieger Y,et al. Minimally invasive burn care: a review of seven clinical studies of rapid and selective debridement using a bromelain-based debriding enzyme (Nexobrid®). Ann Burns Fire Disasters. 2015 Dec 31;28(4):264-274.
  29. de A C Almeida R, de Sousa Lima FCM, do E Vasconcelos BC. Is bromelain an effective drug for the control of pain and inflammation associated with impacted third molar surgery? Systematic review and meta-analysis. Int J Oral Maxillofac Surg. 2018 Sep 14. pii: S0901-5027(18)30349-7.
  30. Bormann KH, Weber K, Kloppenburg H, et al. Perioperative Bromelain Therapy after Wisdom Teeth Extraction - A Randomized, Placebo-Controlled, Double-Blinded, Three-Armed, Cross-Over Dose-Finding Study. Phytother Res. 2016 Dec;30(12):2012-2019.
  31. Ley CM, Ni Q, Liao X, Gao HL, Robinson N. Bromelain and cardiovascular risk factors in diabetes: An exploratory randomized, placebo controlled, double blind clinical trial. Chin J Integr Med. 2016 Oct;22(10):728-37.
  32. Berner JE, Keckes D, Pywell M, et al. Limitations to the use of bromelain-based enzymatic debridement (NexoBrid(®)) for treating diabetic foot burns: a case series of disappointing results. Scars Burn Heal. Jan-Dec 2018;4:2059513118816534.
  33. Shoham Y, Shapira E, Haik J, et al. Bromelain-based enzymatic debridement of chronic wounds: Results of a multicentre randomized controlled trial.  Wound Repair Regen. 2021 Nov;29(6):899-907.
  34. Babazade H, Mirzaagha A, Konarizadeh S. The effect of bromelain in periodontal surgery: a double-blind randomized placebo-controlled trial.  BMC Oral Health. 2023 May 13;23(1):286. 
  35. Pereira IC, Sátiro Vieira EE, de Oliveira Torres LR, et al. Bromelain supplementation and inflammatory markers: A systematic review of clinical trials.  Clin Nutr ESPEN. 2023 Jun;55:116-127.
  36. Bonomo P, Greto D, Terziani F, Becherini C, Visani L, Livi L. Use of an alfa-lipoic, Methylsulfonylmethane, Boswellia serrata and Bromelain dietary supplement (OPERA®) for aromatase inhibitors-related arthralgia management (AIA): a prospective phase II trial (NCT04161833).  Med Oncol. 2022 Jun 6;39(8):113. 
  37. Dalgleish AG, Liu WM. The role of immune modulation and anti-inflammatory agents in the management of prostate cancer: A case report of six patients.  Oncol Lett. 2022 Jun 7;24(2):247. 
  38. Kutlu Ö, Demirbaş A, Elmas ÖF, Güvenç U, Metin A. Fixed drug eruption: A new side effect of bromelain. Contact Dermatitis. 2021 Jan;84(1):51-52. 
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