Table 1.
Summary of studies assessing the effectiveness of bromelain as a treatment for osteoarthritis of the knee
| Authors | Study design | n+ | Dosage | Condition | Treatment period | Follow up | Adverse events | Primary outcome | Conclusion |
|---|---|---|---|---|---|---|---|---|---|
| Cohen & Goldman (24) | Uncontrolled series of case reports | 29 | 60–160 mg/day bromelain | Moderate to severe arthritis (25 RA; 2 OA; 10 A and RA; and 1 gout) | 3 weeks to 13 months | When soft tissue swelling | None reported | Soft tissue swelling and pain | Reduction in soft tissue swelling in 72.4% |
| Leipner et al. (25). Series of unpublished studies in OA involving PhlogenzymTM (PHL), WobenzymTM (WOB), Wobenzym NTM (WOB-N). Studies investigating OA of knee are reported | (i) placebo controlled DB RCT | (ii) 60 (ref. 31) | PHL 3 × 2 tabs/day (540 mg/day bromelain) versus placebo | Arthrosis of the knee (57%) or hip (43%) | 3 weeks | NK | No SAE reported. Two ADR reported in PHL group | Sum score of various pain (active, pressure, rest, night) and dysfunction (four point category scale) measures | Similar reduction in primary outcome for both groups. NS group differences. Drop out n = (1 PHL) |
| (ii) placebo controlled DB RCT | (ii) 60 (ref 32) | PHL 3 × 2 tabs/day (540 mg/day bromelain) versus placebo | OA of the knee joint | 3 weeks | NK | No SAE reported. Two ADR reported in PHL group | Lequesne index | Reduction in primary outcome for both groups; NS group differences. Drop out n = 3 (1 PHL) | |
| (iii) Comparative DB, RCT | (ii) 60 (ref 38) | PHL 3 × 2 tabs/day (540 mg/day bromelain) versus DF (100–150 mg/day) | OA of the knee joint | 3 weeks | NK | No SAE reported. One ADR (0 PHL; 1 DF) | Lequesne index | Similar reduction in primary outcome for both groups. NS group differences. Drop out n = 1 (0 PHL) | |
| (iv) Comparative DB, RCT | (iv) 60 (ref 45) | WOB 3 × 4 tabs/day (540 mg/day bromelain) versus DF (100–150 mg/day) | OA of the knee joint | 3 weeks | NK | No SAE reported but 30 ADR (15 WOB; 15 DF) | Lequesne index | Similar reduction in primary outcome for both groups. NS group differences. Drop out n = 2 (1 WOB) | |
| Singer and Oberleitner (26) | Comparative DB, RCT | 80 | WOB 4 × 7 tabs/day (945 mg/day bromelain) versus DF (100 mg) | OA of the knee joint | 4 weeks | 4 weeks | No SAE reported. 22 ADR (13 WOB) Mainly GI but allergic skin reaction in n = 1 | Mobility and pain (five point scale) in morning | Equivalence not tested but similar reductions in primary outcome for both groups. NS group differences. Drop outs n = 12 (8 WOB; 4 DF) |
| Klein & Kullich (27) | Comparative DB, RCT | 73 | PHL 3 × 2 tabs/day (540 mg/day bromelain) versus DF (100–150 mg/day) | Knee OA | 3 weeks | 4 weeks | 1 in 36 (2.8%) (headache probably not related) | Lequesne index (pain and function) | Reduction in pain indices by 80% sustained at 4 weeks post treatment. Equivalence was identified at week 3 (Mann Whitney = 0.47) and week 7 (Mann Whitney = 0.55) |
| Singer et al. (28) | Comparative DB, RCT | 68 (ref 37) | PHL 3 × 2 tabs/day (540 mg/day bromelain) versus DF (100–150 mg/day) | OA of the knee joint | 3 weeks | 4 weeks | No SAE reported. 14 ADR (7 PHL; 7 DF) | Lequesne index and sum of pain scores | PHL group showed significant > reduction compared to DF for both Lequesne (P = 0.017) and sum of pain scores (P = 0.047). Drop out n = 5 (3 PHL) |
| Tilwe et al. 2001 (29) | Comparative SB, RCT | 50 | PHL 4 × 7 tabs/day (1890 mg/day bromelain) versus DF (100–150 mg/day) | Arthritis of the knee | 3 weeks | 4 weeks | ‘well tolerated’; specific AE not reported. | Likert scale to assess pain | Equivalence not tested. Reduction in pain (NS), tenderness (P < 0.05) and swelling (NS) in both groups. Joint tenderness was significantly greater (P < 0.05) in PHL group than DF group |
| Walker et al. (30) | Open. Dose ranging | 77 | BromelinTM 200 or 400 mg/day | Mild, acute knee pain | 4 weeks | 4 weeks | No SAE. Minor AE (n = 19) mainly GI | WOMAC i.e. total score, pain, stiffness and function | Significant WOMAC total score at both doses (P = 0.0001 for 200 mg; P = 0.000001 for 400 mg). Significant difference between groups for total score [(P = 0.036), stiffness (0.026), physical function (0.021), well-being.] |
+Citations quoted in this column refer to references contained within publications listed in the first column.
PHL, Phlogenzym; WOB, Wobenzym; DF, diclofenac; DB, double blind; SB, single blind; RCT, randomised controlled trial; AE, adverse event; SAE, serious adverse event; ADR, adverse drug reaction; GI, gastrointestinal; WOMAC, Western Ontario McMaster University Arthritis Index; NK, not known; NS, not significant.
BromelinTM contains bromelain 200 mg per tablet. PhlogenzymTM each tablet contains proteolytic enzymes in the following doses: bromelain (90 mg), trypsin (48 mg), rutin (100 mg). WobenzymTM, each tablet contains: bromelain (45 mg), papain (60 mg) trypsin (24 mg), chymotrypsin (1 mg), pancreatin (100 mg), lipase (100 mg), amylase (100 mg), rutin (50 mg).