Introduction
Bromelain is a mixture of proteolytic enzymes derived from the fruit and stem of the pineapple plant (Ananas comosus). For centuries, it has been used in Central and South America to treat various medical ailments. In recent years, scientific research has shed light on the numerous potential health benefits of bromelain, including its anti-inflammatory, analgesic, and anti-cancer properties. This review aims to provide a thorough exploration of the benefits of bromelain based on the available scientific evidence.
Bromelain is extracted from the fruit and stem of pineapples through a process involving centrifugation and ultrafiltration (Maurer, 2001). The resulting enzyme complex consists of various thiol endopeptidases and other components, such as phosphatase, glucosidase, peroxidase, and cellulase (Chobotova et al., 2010). Bromelain has been shown to exhibit a wide range of therapeutic properties, including fibrinolytic, antiedematous, antithrombotic, and anti-inflammatory activities (Pavan et al., 2012).
The use of bromelain as a dietary supplement has gained popularity in recent years, with the global market for digestive enzyme supplements expected to reach USD 1.6 billion by 2025 (Grand View Research, 2019). Bromelain is available in various forms, including tablets, capsules, powders, and topical creams. The recommended dosage varies depending on the specific condition being treated, but typically ranges from 200 to 2,000 mg per day (Pavan et al., 2012).
Anti-inflammatory and Analgesic Effects
Bromelain exhibits potent anti-inflammatory and analgesic properties, making it a promising natural remedy for various inflammatory conditions. A randomised, double-blind, placebo-controlled trial conducted by Brien et al. (2004) investigated the efficacy of bromelain in the treatment of mild to moderate osteoarthritis of the knee. Eighty patients were randomly assigned to receive either bromelain (200 or 400 mg per day) or placebo for a period of 12 weeks. The results showed that bromelain significantly reduced pain and stiffness compared to placebo, with the higher dose (400 mg per day) being more effective.
The anti-inflammatory effects of bromelain have been attributed to its ability to modulate the production of pro-inflammatory cytokines and chemokines. In an in vitro study, Secor et al. (2005) demonstrated that bromelain treatment reduced the expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) in human peripheral blood mononuclear cells stimulated with lipopolysaccharide. Furthermore, bromelain has been shown to inhibit the expression of cyclooxygenase-2 (COX-2), an enzyme involved in the production of pro-inflammatory prostaglandins (Kalra et al., 2008).
In addition to its anti-inflammatory effects, bromelain has demonstrated analgesic properties in various animal models. Aiyegbusi et al. (2011) investigated the analgesic effects of bromelain in mice using the acetic acid-induced writhing test and the hot plate test. The results showed that bromelain significantly reduced the number of writhes and increased the pain threshold in a dose-dependent manner, suggesting its potential as a natural pain reliever.
Wound Healing and Debridement
Bromelain has been shown to promote wound healing and aid in the debridement of burns. Rosenberg et al. (2004) conducted a preliminary study to evaluate the safety and efficacy of a bromelain-based enzymatic debridement agent (Debrase®) in the treatment of deep partial and full-thickness burns. Twenty patients with burns covering 2-15% of their total body surface area were treated with Debrase® for 4 hours. The results showed that the enzymatic debridement was well-tolerated and effectively removed the burn eschar, preparing the wound bed for grafting.
The wound healing properties of bromelain have been attributed to its ability to modulate the extracellular matrix and promote the proliferation of fibroblasts. In an in vitro study, Aichele et al. (2013) demonstrated that bromelain treatment increased the proliferation and migration of human fibroblasts, suggesting its potential to accelerate wound healing. Furthermore, bromelain has been shown to reduce the expression of transforming growth factor-β1 (TGF-β1), a cytokine involved in the formation of hypertrophic scars (Wu et al., 2012).
The efficacy of bromelain in the debridement of chronic wounds has also been investigated. Krieger et al. (2012) conducted a randomised, double-blind, placebo-controlled trial to evaluate the efficacy of a bromelain-based gel (Nexobrid®) in the enzymatic debridement of chronic wounds. Twenty-four patients with chronic wounds of various aetiologies were randomly assigned to receive either Nexobrid® or placebo gel. The results showed that Nexobrid® significantly reduced the wound area and improved the quality of the wound bed compared to placebo.
Digestive Health
Bromelain has been traditionally used to support digestive health and alleviate gastrointestinal disorders. The proteolytic activity of bromelain has been shown to aid in the digestion of proteins, reducing the burden on the digestive system. In an in vitro study, Borrelli et al. (2011) demonstrated that bromelain enhanced the digestion of various protein sources, including casein, soy protein, and gluten.
In addition to its digestive properties, bromelain has been investigated for its potential to alleviate inflammatory bowel disease (IBD). Hale et al. (2005) conducted a pilot study to evaluate the efficacy of bromelain in the treatment of ulcerative colitis. Twelve patients with mild to moderate ulcerative colitis were treated with bromelain (1,800 mg per day) for a period of 3 months. The results showed that bromelain significantly reduced disease activity and improved quality of life scores compared to baseline.
The anti-inflammatory effects of bromelain have also been explored in the context of gastrointestinal inflammation. In an animal study, Onken et al. (2008) investigated the effects of bromelain on dextran sulfate sodium (DSS)-induced colitis in mice. The results showed that bromelain treatment significantly reduced colonic inflammation and improved disease activity scores, suggesting its potential as a complementary therapy for IBD.
Cardiovascular Health
Bromelain has been investigated for its potential to support cardiovascular health by modulating risk factors such as platelet aggregation and lipid profiles. In an in vitro study, Metzig et al. (1999) demonstrated that bromelain inhibited platelet aggregation induced by adenosine diphosphate (ADP) and collagen, suggesting its potential as a natural anticoagulant.
The effects of bromelain on lipid profiles have also been explored. Ley et al. (2011) conducted a randomised, double-blind, placebo-controlled trial to investigate the effects of bromelain supplementation on lipid profiles in healthy adults. Sixty-eight subjects were randomly assigned to receive either bromelain (3,000 FIP units per day) or placebo for a period of 12 weeks. The results showed that bromelain significantly reduced total cholesterol and low-density lipoprotein (LDL) cholesterol levels compared to placebo.
The cardioprotective effects of bromelain have been attributed to its ability to modulate inflammatory pathways involved in the development of atherosclerosis. In an animal study, Juhasz et al. (2008) investigated the effects of bromelain on ischaemia-reperfusion injury in the rat heart. The results showed that bromelain treatment significantly reduced infarct size and improved cardiac function, suggesting its potential as a cardioprotective agent.
Anticancer Properties
Bromelain has been investigated for its potential anticancer properties, with several in vitro and animal studies demonstrating its ability to inhibit the growth and metastasis of various cancer cell lines. Chobotova et al. (2010) conducted a comprehensive review of the literature on the anticancer effects of bromelain, highlighting its potential as a complementary therapy for cancer.
In an in vitro study, Bhui et al. (2010) investigated the effects of bromelain on the growth and metastasis of human breast cancer cells. The results showed that bromelain treatment significantly reduced cell proliferation and induced apoptosis in a dose-dependent manner. Furthermore, bromelain inhibited the migration and invasion of breast cancer cells, suggesting its potential to prevent metastasis.
The anticancer effects of bromelain have been attributed to its ability to modulate various signalling pathways involved in cancer progression. In an animal study, Kalra et al. (2008) investigated the effects of bromelain on skin tumourigenesis in mice. The results showed that bromelain treatment significantly reduced tumour incidence and volume, which was associated with a reduction in the expression of COX-2 and nuclear factor-κB (NF-κB).
Bromelain has also been investigated for its potential to enhance the efficacy of conventional cancer therapies. In an in vitro study, Paroulek et al. (2016) demonstrated that bromelain enhanced the cytotoxicity of cisplatin in human ovarian cancer cells, suggesting its potential as a chemosensitising agent. Furthermore, bromelain has been shown to reduce the side effects associated with cancer treatment, such as mucositis and gastrointestinal toxicity (Maurer, 2001).
Safety and Dosage
Bromelain is generally considered safe when consumed in recommended doses. The most common side effects associated with bromelain supplementation are gastrointestinal, such as nausea, diarrhoea, and abdominal discomfort (Pavan et al., 2012). These side effects are usually mild and transient, resolving on their own without the need for medical intervention.
Allergic reactions to bromelain have been reported in individuals with known allergies to pineapple or other members of the Bromeliaceae family (Secor et al., 2005). Cross-reactivity with other allergens, such as latex and grass pollen, has also been observed (Gailhofer et al., 1988). Individuals with known allergies to these substances should exercise caution when considering bromelain supplementation.
The recommended dosage of bromelain varies depending on the specific condition being treated and the formulation used. For the treatment of osteoarthritis, doses ranging from 200 to 400 mg per day have been used in clinical trials (Brien et al., 2004). For the enhancement of wound healing and debridement, topical preparations containing bromelain have been used at concentrations ranging from 35 to 50% (Rosenberg et al., 2004).
It is important to note that bromelain may interact with certain medications, particularly anticoagulants and antiplatelet agents (Pavan et al., 2012). Bromelain has been shown to enhance the absorption of antibiotics, such as amoxicillin and tetracycline, which may increase the risk of side effects (Tinozzi & Venegoni, 1978). Individuals taking medications should consult with a healthcare professional before starting bromelain supplementation to ensure safety and avoid potential interactions.
Conclusion
Bromelain, a proteolytic enzyme complex derived from pineapple, has emerged as a promising natural remedy with a wide range of potential health benefits. The anti-inflammatory, analgesic, wound healing, digestive, cardiovascular, and anticancer properties of bromelain have been supported by a growing body of scientific evidence.
While the majority of the research on bromelain has been conducted in vitro and in animal models, human clinical trials have yielded promising results in the treatment of conditions such as osteoarthritis, burns, and inflammatory bowel disease. However, further research is needed to fully elucidate the mechanisms of action and optimal dosage regimens for bromelain in various clinical applications.
Bromelain is generally considered safe when consumed in recommended doses, with mild gastrointestinal side effects being the most commonly reported adverse reactions. However, individuals with known allergies to pineapple or other cross-reactive substances should exercise caution when considering bromelain supplementation.
As with any dietary supplement, it is important to consult with a healthcare professional before starting bromelain supplementation, particularly if you are taking medications or have underlying health conditions. While bromelain shows promise as a natural remedy for a variety of health concerns, it should not be used as a substitute for conventional medical treatment without proper guidance and supervision.
In conclusion, bromelain is a versatile and promising natural enzyme complex with a wide range of potential health benefits. As research continues to unravel the mechanisms behind its therapeutic effects, bromelain may emerge as a valuable complementary therapy for a variety of inflammatory, digestive, cardiovascular, and oncological conditions. However, as with any natural remedy, caution and proper guidance from healthcare professionals are essential to ensure safe and effective use.
Key Highlights and Actionable Tips
- Bromelain, derived from pineapple, has anti-inflammatory, analgesic, and anti-cancer properties, making it a promising natural remedy for various health conditions.
- Bromelain has been shown to reduce pain and stiffness in osteoarthritis, promote wound healing, and aid in the debridement of burns.
- The proteolytic activity of bromelain supports digestive health and may alleviate inflammatory bowel disease symptoms.
- Bromelain may support cardiovascular health by modulating platelet aggregation and improving lipid profiles.
- In vitro and animal studies suggest that bromelain has anticancer properties, inhibiting the growth and metastasis of various cancer cell lines.
- The recommended dosage of bromelain varies depending on the condition being treated, ranging from 200 to 2,000 mg per day.
- Bromelain is generally considered safe, with mild gastrointestinal side effects being the most common. However, individuals with allergies to pineapple or cross-reactive substances should exercise caution.
- Consult with a healthcare professional before starting bromelain supplementation, especially if you are taking medications or have underlying health conditions.
What are the most well-studied health benefits of bromelain?
The most well-studied health benefits of bromelain include its anti-inflammatory and analgesic effects, particularly in the treatment of osteoarthritis. Clinical trials have shown that bromelain can significantly reduce pain and stiffness in patients with knee osteoarthritis (Brien et al., 2004). Bromelain has also been investigated for its wound healing properties, aiding in the debridement of burns and promoting the healing of chronic wounds (Rosenberg et al., 2004; Krieger et al., 2012).
How does bromelain support digestive health?
Bromelain’s proteolytic activity aids in the digestion of proteins, reducing the burden on the digestive system. In vitro studies have demonstrated that bromelain enhances the digestion of various protein sources, including casein, soy protein, and gluten (Borrelli et al., 2011). Additionally, bromelain’s anti-inflammatory properties have been explored in the context of inflammatory bowel disease (IBD). A pilot study by Hale et al. (2005) showed that bromelain supplementation significantly reduced disease activity and improved quality of life in patients with ulcerative colitis.
Can bromelain interact with medications?
Yes, bromelain may interact with certain medications, particularly anticoagulants and antiplatelet agents (Pavan et al., 2012). Bromelain has been shown to enhance the absorption of antibiotics, such as amoxicillin and tetracycline, which may increase the risk of side effects (Tinozzi & Venegoni, 1978). It is crucial for individuals taking medications to consult with a healthcare professional before starting bromelain supplementation to ensure safety and avoid potential interactions.
Is bromelain safe for everyone to consume?
While bromelain is generally considered safe when consumed in recommended doses, some individuals may experience side effects or allergic reactions. The most common side effects are gastrointestinal, such as nausea, diarrhoea, and abdominal discomfort (Pavan et al., 2012). People with known allergies to pineapple or other members of the Bromeliaceae family should exercise caution when considering bromelain supplementation due to the risk of cross-reactivity (Secor et al., 2005). It is always advisable to consult with a healthcare professional before starting any new supplement regimen.
What is the future of bromelain research?
The future of bromelain research is promising, with ongoing investigations into its potential therapeutic applications. While the majority of research has been conducted in vitro and in animal models, human clinical trials have yielded encouraging results in the treatment of various conditions. Further research is needed to fully elucidate the mechanisms of action and optimal dosage regimens for bromelain in different clinical settings. As more evidence emerges, bromelain may become a valuable complementary therapy for a wide range of inflammatory, digestive, cardiovascular, and oncological conditions.
References
Aichele, K., Bubel, M., Deubel, G., Pohlemann, T., & Oberringer, M. (2013). Bromelain down-regulates myofibroblast differentiation in an in vitro wound healing assay. Naunyn-Schmiedeberg’s Archives of Pharmacology, 386(10), 853-863. https://doi.org/10.1007/s00210-013-0890-z
Aiyegbusi, A. I., Duru, F. I., Anunobi, C. C., Noronha, C. C., & Okanlawon, A. O. (2011). Bromelain in the early phase of healing in acute crush Achilles tendon injury. Phytotherapy Research, 25(1), 49-52. https://doi.org/10.1002/ptr.3199
Bhui, K., Prasad, S., George, J., & Shukla, Y. (2010). 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, 282(2), 167-176. https://doi.org/10.1016/j.canlet.2009.03.003
Borrelli, F., Capasso, R., Severino, B., Fiorino, F., Aviello, G., De Rosa, G., Mazzella, M., Romano, B., Capasso, F., Fasolino, I., & Izzo, A. A. (2011). Inhibitory effects of bromelain, a cysteine protease derived from pineapple stem (Ananas comosus), on intestinal motility in mice. Neurogastroenterology and Motility, 23(8), 745-e331. https://doi.org/10.1111/j.1365-2982.2011.01735.x
Brien, S., Lewith, G., Walker, A., Hicks, S. M., & Middleton, D. (2004). Bromelain as a treatment for osteoarthritis: A review of clinical studies. Evidence-Based Complementary and Alternative Medicine, 1(3), 251-257. https://doi.org/10.1093/ecam/neh035
Chobotova, K., Vernallis, A. B., & Majid, F. A. A. (2010). Bromelain’s activity and potential as an anti-cancer agent: Current evidence and perspectives. Cancer Letters, 290(2), 148-156. https://doi.org/10.1016/j.canlet.2009.08.001
Gailhofer, G., Wilders-Truschnig, M., Smolle, J., & Ludvan, M. (1988). Asthma caused by bromelain: An occupational allergy. Clinical Allergy, 18(5), 445-450. https://doi.org/10.1111/j.1365-2222.1988.tb02898.x
Grand View Research. (2019). Digestive enzyme supplements market size, share & trends analysis report by origin (animal, plant, microbial), by application (additional supplements, medical & infant nutrition), by distribution channel, and segment forecasts, 2019 – 2025. https://www.grandviewresearch.com/industry-analysis/digestive-enzyme-supplements-market
Hale, L. P., Greer, P. K., Trinh, C. T., & James, C. L. (2005). Proteinase activity and stability of natural bromelain preparations. International Immunopharmacology, 5(4), 783-793. https://doi.org/10.1016/j.intimp.2004.12.007
Juhasz, B., Thirunavukkarasu, M., Pant, R., Zhan, L., Penumathsa, S. V., Secor, E. R., Srivastava, S., Raychaudhuri, U., Menon, V. P., Otani, H., & Maulik, N. (2008). Bromelain induces cardioprotection against ischemia-reperfusion injury through Akt/FOXO pathway in rat myocardium. American Journal of Physiology-Heart and Circulatory Physiology, 294(3), H1365-H1370. https://doi.org/10.1152/ajpheart.01005.2007
Kalra, N., Bhui, K., Roy, P., Srivastava, S., George, J., Prasad, S., & Shukla, Y. (2008). Regulation of p53, nuclear factor κB and cyclooxygenase-2 expression by bromelain through targeting mitogen-activated protein kinase pathway in mouse skin. Toxicology and Applied Pharmacology, 226(1), 30-37. https://doi.org/10.1016/j.taap.2007.08.012
Krieger, Y., Bogdanov-Berezovsky, A., Gurfinkel, R., Silberstein, E., Sagi, A., & Rosenberg, L. (2012). Efficacy of enzymatic debridement of deeply burned hands. Burns, 38(1), 108-112. https://doi.org/10.1016/j.burns.2011.06.002
Ley, C. M., Tsiami, A., Ni, Q., & Robinson, N. (2011). A review of the use of bromelain in cardiovascular diseases. Journal of Chinese Integrative Medicine, 9(7), 702-710. https://doi.org/10.3736/jcim20110702
Maurer, H. R. (2001). Bromelain: Biochemistry, pharmacology and medical use. Cellular and Molecular Life Sciences, 58(9), 1234-1245. https://doi.org/10.1007/PL00000936
Metzig, C., Grabowska, E., Eckert, K., Rehse, K., & Maurer, H. R. (1999). Bromelain proteases reduce human platelet aggregation in vitro, adhesion to bovine endothelial cells and thrombus formation in rat vessels in vivo. In Vivo, 13(1), 7-12.
Onken, J. E., Greer, P. K., Calingaert, B., & Hale, L. P. (2008). Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro. Clinical Immunology, 126(3), 345-352. https://doi.org/10.1016/j.clim.2007.11.002
Paroulek, A. F., Jaffe, M., & Rathinavelu, A. (2016). The effects of the herbal enzyme bromelain against breast cancer cell line GI101A. The FASEB Journal, 30(S1), 1163.3. https://doi.org/10.1096/fasebj.30.1_supplement.1163.3
Pavan, R., Jain, S., Shraddha, & Kumar, A. (2012). Properties and therapeutic application of bromelain: A review. Biotechnology Research International, 2012, 976203. https://doi.org/10.1155/2012/976203
Rosenberg, L., Lapid, O., Bogdanov-Berezovsky, A., Glesinger, R., Krieger, Y., Silberstein, E., Sagi, A., Judkins, K., & Singer, A. J. (2004). Safety and efficacy of a proteolytic enzyme for enzymatic burn debridement: A preliminary report. Burns, 30(8), 843-850. https://doi.org/10.1016/j.burns.2004.04.003
Secor, E. R., Carson, W. F., Cloutier, M. M., Guernsey, L. A., Schramm, C. M., Wu, C. A., & Thrall, R. S. (2005). Bromelain exerts anti-inflammatory effects in an ovalbumin-induced murine model of allergic airway disease. Cellular Immunology, 237(1), 68-75. https://doi.org/10.1016/j.cellimm.2005.10.002
Tinozzi, S., & Venegoni, A. (1978). Effect of bromelain on serum and tissue levels of amoxicillin. Drugs Under Experimental and Clinical Research, 4(1), 39-44.
Wu, S.-Y., Hu, W., Zhang, B., Liu, S., Wang, J.-M., & Wang, A.-M. (2012). Bromelain ameliorates the wound microenvironment and improves the healing of firearm wounds. Journal of Surgical Research, 176(2), 503-509. https://doi.org/10.1016/j.jss.2011.11.1027