Bromelain

Bromelain is a combination of several thiol endopeptidases, a mixture of enzymes from the protease family and other compounds obtained from the fruit, stem and/or root of the pineapple, hence the synonym pineapple enzyme. These are sulfhydryl-containing cysteine proteases (glycoproteins). Originally, the term bromelain referred specifically to the enzyme mixture obtained from the stem, the fruit stalks, of Ananas cosmosus (Fam Bromeliaceae). Bromelain is poorly soluble in water and hardly soluble in ethanol and ether. The enzyme develops its optimum proteolytic activity in the pH 4 - 10 range.

The extracts obtained from pineapple are also called bromelain, which in addition to the cysteine proteases also contain papain-like endopeptidases, several protease inhibitors, a peroxidase, acid phosphatase and organically bound calcium.

Commission E-monography: acute swelling conditions, post-operative, post-traumatic, especially facial area, paranasal sinuses.

Empirical medicine: sports injuries, traumatic edema, thrombophlebitis, rheumatoid arthritis, digestive complaints in pancreatic insufficiency.

Studies: anti-inflammation and cartilage protection in osteoarthritis and rheumatoid arthritis.

On December 14, 2018, the European Commission granted MUCPharm Pty Ltd, United Kingdom, orphan drug designation for bromelain for the treatment of pseudomyxoma peritonei.

Bromelain has an anti-inflammatory, decongestant, analgesic and cartilage-protective effect.

Clinical studies have demonstrated the anti-inflammatory, chondroprotective effect of bromelain, especially in osteoarthritis and rheumatoid arthritis. The mechanism of action is based on the downregulation of the expression of inflammatory cytokines (tumor necrosis factor (TNF)-α, IL-1β, IL-6, IL-8, IL-1β and interferon γ in synovial fibroblasts) and NF-κB and MAPK signaling. The concomitant analgesic effect is due to the reduction of vascular permeability to bradykinin with a reduction in the formation of bradykinin. The levels of superoxide dismutase, catalase and prolidase are lowered. In animal models, the degradation of cartilage matrix in inflamed cartilage has been demonstrated (Pothacharoen P et al. 2021; Savadjan SA et al. 2023).

Bromelain and the enzymes supplied exogenously with it are partially absorbed as intact proteins via the gastrointestinal tract. In humans, measurable concentrations of bromelain-specific proteases can be detected using quantitative determination methods proportional to the administered dose (Castell 1997). The highest bromelain blood concentrations are found approx. 1 hour after oral administration. In the blood, bromelain is rapidly complexed to alpha2-macroglobulin (AMG), although the specific enzyme activity is retained (Kelly GS -1996; Maurer HR 2001). The bromelain effects are already detectable 20-60 minutes after oral application and subside after approx. 24 hours.

Bromelain effects are described as anti-oedematous, anti-inflammatory, antithrombotic and fibrinolytic (Cooreman WM-1976, Leipner J et al.2001, Taussig SJ 1998). The large number of preclinical, pharmacological, animal and cell experimental findings provide a sound scientific basis for further randomized and controlled clinical intervention studies.

The monopreparation bromelain was monographed by Commission E in 1994 with suggestions for dosage and indications.

• Systemic use: Medicinally, bromelain preparations are preferably used as adjunctive therapy for diseases with inflammatory, post-traumatic and post-operative soft tissue edema. They are therefore also of medical interest, especially in sports medicine and traumatology. In the treatment of sports injuries with post-traumatic swelling and edema, bromelain administration represents an alternative to therapy with non-steroidal anti-inflammatory drugs (NSAIDs).
• Post-operative swelling for 4-5 days

Studies support its use in joint inflammation such as rheumatoid arthritis and psoriatic arthritis.

Furthermore:

• Substitution therapy for digestive disorders
• Technically, the drug is used in the pre-treatment of meat (softening effect).

In addition to allergic reactions, occasional gastrointestinal symptoms such as diarrhea and stomach discomfort have been described as temporary side effects.

Prolongation of bleeding time, reduction of platelet aggregation.

Discontinue before planned operations!

Initial dose 4x40mg/p.o./day; maintenance dose 4x20mg/p.o./day.

Bromelain Pos 1 Kps contains 500 F.I.P. units, corresponding to 56.25-95 mg bromelain

Taking anticoagulants. Possible hypersensitivity to bromelain. Pregnancy, lactation (no clinical information available). Planned surgery

Possible increase of the bleeding tendency with simultaneous therapy with anticoagulants and platelet aggregation inhibitors.

Monopreparations:

• Bromelain-POS®, Traumanase®, Traumanase forte®, Wobenzym mono® (D), Bromelain-R.A.N®.

Combination preparations:

• Innovazym® , Phlogenzym®, Wobenzym®, DOG TG.

Bromelain is used medicinally both as a mono-preparation and as a combination preparation.

1. Castell JV et al. (1997) Intestinal absorption of undegraded proteins in men: presence of bromelain in plasma after oral intake. Am J Physiol 273 139-146.
2. Chandler DS et al. (1998) Bromelain protects piglets from diarrhea caused by oral challenge with K88 positive enterotoxigenic Escherichia coli. Gut 43: 196-202.
3. Cooreman WM etg al. (1976) Bromelain, biochemical and pharmacological properties. Pharm Acta Helv 51: 73-97.
4. Kelly GS (1996) Bromelain: A literature review and discussion of its therapeutic applications. Alt Med Rev 1: 243-257.
5. Leipner J et al. (2001) Therapy with proteolytic enzymes in rheumatic disorders. Bio Drugs 15: 779-789.
6. Maurer A (1996) On the bioavailability of bromelain containing in two different formulas after multiple oral dosage. Eur J Clin Pharmacol 50: 549.
7. Maurer HR (2001) Bromelain: biochemistry, pharmacology and medical use. Cell Mol Life Sci 58: 1234-1245.
8. Pavan R et al. (2012) Properties and therapeutic application of bromelain: a review. Biotechnol Res Int:976203.
9. Rathnavelu V et al. (2016) Potential role of
10. bromelain in clinical and therapeutic applications. Biomed Rep 5:283-288.
11. Taussig SJ et al. (1988) Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. J Ethnopharmacol 22:191-203.
12. Wenigmann M. (2017) Phytotherapy medicinal drugs, phytopharmaceuticals, application. Urban & Fischer, p. 90
13. Pothacharoen P et al. (2021) Bromelain Extract Exerts Antiarthritic Effects via Chondroprotection and the Suppression of TNF-α-Induced NF-κB and MAPK Signaling. Plants (Basel). 23;10:2273. doi: 10.3390/plants10112273. PMID: 34834636; PMCID: PMC8625807.
14. Savadjan SA et al (2023) The effects of bromelain on osteoarthritis symptoms: A systematic review. Journal of Shahrekord University of Medical Sciences 25:149-155. DOI:10.34172/jsums.2023.789
15. Varilla C et al. (2021) Bromelain, a Group of Pineapple Proteolytic Complex Enzymes (Ananas comosus) and Their Possible Therapeutic and Clinical Effects. A Summary. Foods. 23;10(10):2249. doi: 10.3390/foods10102249. PMID: 34681298; PMCID: PMC8534447.