Improved WOMAC score following 16-week treatment with bromelain for knee osteoarthritis

Clin Rheumatol. 2016 Oct;35(10):2531-40. doi: 10.1007/s10067-016-3363-1. Epub 2016 Jul 28.


Treatment with bromelain-containing enzyme preparation for 3-4 weeks is effective for treatment of knee osteoarthritis (OA). Here, we aimed to assess 16-week treatment with bromelain in mild-to-moderate knee OA patients. We performed a randomized, single-blind, active-controlled pilot study. Forty knee OA patients were randomized to receive oral bromelain (500 mg/day) or diclofenac (100 mg/day). Primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) analyzed by Wilcoxon signed rank test. Secondary outcome was the short-form 36 (SF-36). Plasma malondialdehyde (MDA) and nitrite were measured as oxidative stress markers. There was no difference in WOMAC and SF-36 scores compared between bromelain and diclofenac groups after 4 weeks. At week 4, the improvement of total WOMAC and pain subscales from baseline was observed in both groups; however, two patients given diclofenac had adverse effects leading to discontinuation of diclofenac. However, observed treatment difference was inconclusive. At week 16 of bromelain treatment, the patients had improved total WOMAC scores (12.2 versus 25.5), pain subscales (2.4 versus 5.6), stiffness subscales (0.8 versus 2.0), and function subscales (9.1 versus 17.9), and physical component of SF-36 (73.3 versus 65.4) as compared with baseline values. OA patients had higher plasma MDA, nitrite, and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated whole blood but lower plasma α-tocopherol than control subjects. Plasma MDA and LPS-stimulated PGE2 production were decreased at week 16 of bromelain treatment. Bromelain has no difference in reducing symptoms of mild-to-moderate knee OA after 4 weeks when compared with diclofenac.

Keywords: Bromelain; Diclofenac; Knee osteoarthritis; Malondialdehyde; SF-36; WOMAC.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Biomarkers / blood
  • Bromelains / therapeutic use*
  • Diclofenac / therapeutic use
  • Female
  • Humans
  • Male
  • Malondialdehyde / blood
  • Middle Aged
  • Osteoarthritis, Knee / diagnosis
  • Osteoarthritis, Knee / drug therapy*
  • Oxidative Stress / drug effects
  • Pilot Projects
  • Severity of Illness Index
  • Single-Blind Method
  • Symptom Assessment
  • Treatment Outcome


  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers
  • Diclofenac
  • Malondialdehyde
  • Bromelains