Bromelain (Protease from Pineapple)

Overview

Bromelain is a mixture of proteolytic enzymes (primarily cysteine‑type proteases) extracted from the stem and fruit of Ananas comosus (pineapple). In dietary supplements, it is used primarily for its ability to hydrolyze proteins, which underlies its anti‑inflammatory, digestive-support, and tissue-repair properties.

Benefits

Anti‑inflammatory & analgesic: Oral bromelain reduces edema and pain in postoperative and musculoskeletal injuries (e.g., sinus surgery, osteoarthritis).
Digestive aid: Improves protein digestion and alleviates functional dyspepsia; a 500 mg dose increased protein absorption by ~20 % in healthy volunteers.
Immune modulation: In vitro and animal studies show decreased cytokine (IL‑1β, TNF‑α) production and enhanced neutrophil migration, suggesting a role in immune homeostasis.
Wound‑healing & tissue remodeling: Topical and oral bromelase accelerate collagen turnover, beneficial in pressure‑ulcer and burn recovery.
Cardiovascular support: Modest reductions in platelet aggregation and fibrinogen levels have been reported, which may lower thrombotic risk.
Potential anticancer activity: Laboratory studies demonstrate apoptosis induction in certain cancer cell lines, though human evidence is still limited.

How It Works

Catalytic Action: Bromelain’s catalytic core contains a catalytic cysteine residue that cleaves peptide bonds at the carbonyl side of lysine, arginine, and other neutral residues.
Tissue Remodeling: By hydrolyzing extracellular matrix proteins (collagen, fibrin), it facilitates tissue remodeling and reduces edema.
Eicosanoid Modulation: The enzyme inhibits cyclo‑oxygenase (COX‑1/2) and reduces prostaglandin E₂ synthesis, thereby dampening inflammation.
Digestive Enhancement: In the gut, bromelase cleaves dietary proteins into smaller peptides and amino acids, enhancing absorption and stimulating release of gastrointestinal hormones (e.g., cholecystokinin) that stimulate pancreatic enzyme secretion.
Kallikrein‑Kinin System: Systemically, bromelain can influence the kallikrein‑kinin system, leading to decreased bradykinin‑mediated vascular permeability.
Antithrombotic Effect: Its ability to cleave fibrinogen and fibrin interferes with platelet aggregation, contributing to its antithrombotic effect.

Dosage

Typical Oral Dosage: Oral bromelain supplements range from 200 mg to 1,200 mg per day, divided into 2–3 doses.
Digestive Support: 200–400 mg taken with meals is common.
Anti‑inflammatory/Post‑surgical: 500–800 mg taken 30 min before meals or 2–3 × daily for 2–4 weeks is widely reported.
High‑Dose Regimens: High‑dose regimens (1,000–1,200 mg/day) have been studied for osteoarthritis and sinusitis, but should be introduced gradually.
Protein-Rich Meals: When used with protein‑rich meals, a lower dose (150–300 mg) taken at the start of the meal may maximize protein‑digestive benefits while minimizing gastrointestinal upset.
Research/Therapeutic Protocols: For research or therapeutic protocols, dosing is individualized and may depend on body weight (≈10 mg/kg) and the specific clinical outcome.

Safety & Side Effects

General Tolerance: Bromelain is generally well‑tolerated.
Mild Adverse Effects: Mild adverse effects include gastrointestinal irritation, diarrhea, and occasional rash.
Contraindications:
- Active bleeding disorders
- Recent major surgery
- Pregnancy (insufficient data) – thus avoid high doses (>1 g/day) in these populations.
Drug Interactions:
- Potentiates the antiplatelet/anticoagulant effect of aspirin, clopidogrel, warfarin, and heparin, increasing bleeding risk.
- May enhance absorption of antibiotics (e.g., amoxicillin) and some chemotherapeutics.
Allergies: Persons with allergy to pineapple may experience hypersensitivity.
Cautions:
- Use caution in children under 12 y (lack of dosing data).
- Use caution in people with peptic ulcer disease due to possible increased gastric acid secretion.
Discontinuation: Discontinue if severe abdominal pain or persistent diarrhea occurs.

Chemistry

Type: Bromelain is a cysteine protease.
Molecular Weight: ~24 kDa (≈ 23,200 Da).
Primary Structure: Consists of ~ 210 amino‑acid residues.
Active Site: The catalytic triad Cys‑27, His‑159, and Asn‑175 (numbering varies by isoform) forms the active site.
Enzyme Family: The enzyme belongs to the MEROPS family C1 (papain‑like).
Glycosylation: The enzyme is glycosylated (≈ 10 % carbohydrate).
pH Optimum: The enzyme has a pH optimum.

Sources & Quality

Source: Commercial bromelain is extracted mainly from pineapple stem (≈ 70 % of total yield) because the stem contains higher protease activity than the fruit.
Extraction Process:
- Aqueous extraction
- pH‑adjusted precipitation
- Ultrafiltration to isolate the protein fraction
- Freeze‑drying to produce a stable powder.
Recombinant Expression: Some manufacturers use recombinant expression in Pichia pastoris or E. coli to achieve consistent enzyme activity, but most dietary supplements rely on vegetal extraction.
Quality Considerations:
- Activity units (e.g., 1,000 GDU/g – “gelatin‑digesting units”)
- Protease activity per capsule
- Third‑party testing for purity (absence of heavy metals, pesticide residues)
- Standardized activity.
GMP Facilities: Good‑manufacturing‑practice (GMP) facilities provide the most reliable products.