Geranylgeranylacetone protects against diclofenac-induced gastric and small intestinal mucosal injuries in healthy subjects: a prospective randomized placebo-controlled double-blind cross-over study

Digestion. 2009;80(4):260-6. doi: 10.1159/000236032. Epub 2009 Oct 16.


Background and aims: Little information is available regarding the prevention and treatment of small intestinal mucosal injuries caused by non-steroidal anti-inflammatory drugs (NSAIDs). We planned a pilot study to investigate the protective effects of geranylgeranylacetone (GGA) against NSAID-induced small intestinal injuries using video capsule endoscopy (VCE).

Subjects and methods: Ten healthy male volunteers took oral GGA 300 mg/day (regimen A) or placebo (regimen B) in addition to diclofenac 75 mg/day + rabeprazole 20 mg/day for 7 days. We conducted a cross-over trial of regimens A and B with a 2-week washout period. All subjects underwent VCE before and after each administration period, and were evaluated for NSAID-induced gastric and small intestinal mucosal lesions.

Results: The number of mucosal lesions (erosions, ulcers and a red spot with possible bleeding) detected in both stomach and small bowel changed between prior to and immediately after administration period, with significantly fewer lesions for regimen A after administration period (mean +/- SD A:B = 2.6 +/- 3.2:9.5 +/- 8.5; p = 0.027).

Conclusions: Combination therapy with GGA and rabeprazole reduced the incidence of gastroenteropathy induced by 1-week administration of diclofenac. Our findings suggest this therapy as a candidate for protecting patients on long-term NSAID therapy.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles / therapeutic use
  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Ulcer Agents / therapeutic use*
  • Capsule Endoscopy
  • Cross-Over Studies
  • Diclofenac / adverse effects*
  • Diterpenes / therapeutic use*
  • Double-Blind Method
  • Humans
  • Male
  • Peptic Ulcer / chemically induced
  • Peptic Ulcer / diagnosis
  • Peptic Ulcer / prevention & control*
  • Prospective Studies
  • Rabeprazole
  • Young Adult


  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Anti-Inflammatory Agents, Non-Steroidal
  • Anti-Ulcer Agents
  • Diterpenes
  • Diclofenac
  • Rabeprazole
  • geranylgeranylacetone