Abstract #3003: Preventing cancer in the colon: effect of ginger on markers of inflammation in gut mucosa

Purpose: Colorectal Cancer (CRC) is the third most prevalent cancer with over 148,000 cases and almost 50,000 deaths estimated in 2008. Between 60 to 70% of all CRC cases are diagnosed at late stages when 5-year survival rates average less than 10 to 40%. Consequently, prevention of CRC with low toxicity agents could lead to considerable decrease in CRC morbidity and mortality. In vitro studies, murine models and trials in humans using drugs that inhibit cyclooxygenase enzymes (COX1 & COX2) indicate that up-regulation of inflammatory eicasanoids and in particular prostaglandin E2 (PGE2) are early events in the development of CRC. Ginger (Zingiber officinale) and its constituent\#8217;s gingerols and shogaols have demonstrated down regulation of COX1 and COX2, apoptosis in CRC cell lines and decreased incidence and multiplicity of adenomas in rats. We conducted a study to determine if ginger extract standardized to 5% gingerols could decrease the concentration of PGE2, 5-hydroxyeicosatetraenoic acid (5-HETE), 12-hydroxyeicosatetraenoic acid (12-HETE), 13-hydroxyoctadecadienoic acid (13-HODE) and 15-hydroxyeicosatetraenoic acid (15-HETE) in the gut mucosa of healthy volunteers. Secondary aims included the evaluation of, toxicity, blinding and adherence. Methods: We randomized 17 participants to placebo and 16 to 2.0 g ginger for 28 days; with mean age of 33.9±11.5, 63.1% white and 48.5% male. Once randomized, we performed a baseline flexible sigmoidoscopy (Flex sig.) and a day 28 Flex sig. to obtain rectal biopsies. A liquid chromatography mass spectrometry (LC/MS/MS) method was conducted on the biopsies to simultaneously determine PGE2, 5-HETE, 12-HETE, 15-HETE and 13-HODE. Results: Mean PGE2 % change from baseline was increased by 26.49 ± 95.97% for placebo and decreased by -27.97 ± 37.94% for ginger (p=0.05) and the number of participants that had \#8805;10% decrease of PGE2 was 62.5% in the placebo group and 92.9% in the ginger group (p=0.05). There was no significant difference in mean change of 5-HETE (p=0.61), 12-HETE (p=0.52), 15-HETE (p=0.16) and 13-HODE (p=0.35) as standardized to arachidonic acid (AA), but there was a borderline significant difference in PGE2 (p=0.10) in favor of ginger. There was no difference between the groups in terms of total AEs (p=0.55) or specific types of AEs such as gastrointestinal AEs (p=0.71). Participants randomized to ginger were able to correctly guess their assignment 87.5% compared to the placebo arm, who correctly guessed their assignment 48% (p=0.02). Participants indicated that how the capsule tasted was the most common (43.3%) reason for guessing their assignment and this assessment differed significantly by treatment group (p=0.01). Conclusion: Ginger was able to decrease PGE2 levels compared to placebo when taken for 28 days. Ginger also appears both tolerable and safe when taken for 28 days at a 2.0 g dose. Further investigation in people at high risk for CRC seems warranted. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3003.