Pharmacodynamic action and colonic levels of curcumin in humans with resectable colorectal cancer primaries Giuseppe Garcea, David P. Berry, John Jameson, Adam Scott, Ricky Sharma, Cathy Richards, Ashley Dennison, Will Steward, Andreas Gescher. University of Leicester, Leicester, UK; Department of Hepatobiliary Surgery, Leicester, UK; Department of Colorectal Surgery, Leicester, UK; Department of Pathology, Leicester, UK. Curcumin, a constituent of the spice turmeric is a potent antioxidant with chemopreventive properties in several rodent models of carcinogenesis. In the MIN/+ mouse model of familial adenomatous polyposis, 0.2% dietary curcumin reduced the number of adenomas at mucosal concentrations of 111 nmol/g (Perkins et al, Cancer Epidemiol. Biomarkers & Prev 2002; 11: 535-540). In this animal model, dietary curcumin reduced the levels of malondialdehyde-DNA (M1G) adduct, which reflects oxidative DNA changes. Little is known about the metabolism, distribution and pharmacodynamics of curcumin in humans. We tested the hypothesis that pharmacologically active levels of curcumin can be achieved in the gastrointestinal tract of humans by oral dosing. Patients with resectable colorectal cancer received curcumin capsules (0.45g, 1.8 g or 3.6 g, 4 patients per dose level) daily for 7 days, the last dose having been ingested 6 h prior to surgery. Samples of peripheral and portal blood, normal and malignant colorectal tissue and bile were obtained before and after treatment. Curcumin and its metabolites were analyzed by HPLC and M1G levels by immunoslotblot (Perkins et al, Cancer Epidemiol. Biomarkers & Prev 2002; 11: 535-540). Curcumin was not found in the bile and only trace levels were recovered in the peripheral circulation after the highest dose, and only at the 1 h time point. In contrast, in portal blood curcumin was still detectable 7 h following administration. The concentrations of curcumin in normal and malignant colorectal tissue were 12.8 ± 2.9 and 7.6 ± 3.3 nmol/g, respectively, after the 3.6 g dose, and 19.6 ± 1.5 and 6.7 ± 0.6 nmol/g, respectively, after 1.8 g. Trace levels of curcumin glucuronide and sulphate were detected in the colorectal mucosa and portal blood. M1G levels measured by immunoslotblot were 4.6 ± 1.7 and 2.6 ± 1.0 adducts per 107 nucleotides in human malignant and normal colorectal tissue, respectively (p<0.01 by ANOVA). Administration of curcumin (3.6 g) decreased M1G levels in malignant colorectal tissue significantly to 1.3 ± 0.6 adducts per 107 nucleotides (p<0.001), but it did not appear to affect M1G levels in normal mucosa. This the first time that the effect of curcumin on M1G levels in humans has been analyzed and the results suggest that moderate doses of curcumin can achieve pharmacologically efficacious levels in the colorectum. Curcumin should be considered for phase II evaluation as a colorectal cancer chemopreventive agent. AACR Abstract Number: 4790, 2003 AACR Abstract #R2699, 2003 AACR Abstract #R2722, 2003 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.