Introduction: Anthocyanins, polyphenolic phytochemicals which render fruit and vegetables bright red or blue, possess anticarcinogenic properties in preclinical models of carcinogenesis. These effects are putatively mediated via suppression of cyclooxygenase-2, induction of apoptosis, interference with the mitogen-activated protein kinase pathway and antioxidant effects. Intestinal adenoma numbers in ApcMinmice were reduced by 30% when their diet was supplemented with a standardised bilberry extract (0.3%) containing 15 anthocyanins (Cooke et al, Int J Cancer 2006, 119, 2213). We are testing the hypothesis that consumption of a standardised bilberry extract generates pharmacodynamically active levels of anthocyanins in the plasma and tissue of patients with primary colorectal cancer or colorectal hepatic metastases.
 Methods: Patients are consented to provide pre-treatment blood, urine and tissue samples during routine colonoscopy/staging laparoscopy. They receive a seven day course of a standardised bilberry extract, at one of three dose levels (367, 733 or 1100 mg anthocyanins/day) prior to surgery. During surgery, tissue, blood and urine samples are obtained. Anthocyanin levels are measured by HPLC(Cooke et al, J Agricult Food Chem 2006, 54, 7009), and biomarkers of chemopreventive activity are assessed.
 Results: Thirteen patients, 9 with colon cancer and 4 with liver metastases have completed the trial to date. Consumption of up to 1100 mg of anthocyanins per day has been safe and well tolerated. HPLC analysis yielded levels of anthocyanins in the plasma near the limit of detection. Mean anthocyanin concentrations in the urine were 1.1, 1.6 and 1.8 µg/ml in patients receiving the low, medium or high dose, respectively.
 Conclusion: Ingestion of high doses of a standardised bilberry extract for seven days is safe and yields measurable quantities of anthocyanins in human plasma and urine.

99th AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA