Consumption of the Putative Chemopreventive Agent Curcumin by Cancer Patients: Assessment of Curcumin Levels in the Colorectum and their Pharmacodynamic Consequences
Cancer Epidemiol Biomarkers Prev. 2005; 14(1):120-25.
Curcumin in animal models has shown to reduce the levels of oxidative DNA adduct M1G and expression of COX-2 enzyme.
To test the hypothesis that pharmacologically active levels of Curcumin can be achieved in colorectum tissue of humans by oral consumption to effect the levels of M1G and COX-2 proteins.
12 subjects suffering from colorectal carcinoma with tumor location in ascending / transverse colon, sigmoid and rectal colon were recruited. The subjects were divided in three groups of 4 per group and administered Curcumin C3 Complex® in the form of capsule of 450 mg each. The three groups were given doses of 1, 4 or 8 capsules per day, translating to 450, 1800 or 3600 mg of Curcumin daily, for 7 days before surgery. The Curcumin and its conjugates were analyzed in tissue and plasma as well as the levels of COX-2 proteins and M1G adducts were analyzed in colorectal tissue.
- Levels of Curcumin in normal and malignant colorectal tissue ranged from 7 to 20 nmol/g tissue.
- In patients receiving 1.8 or 3.6 g Curcumin, the concentration of Curcumin measured was 21.7±8.2 and 6.8±3.7 nmol/g in right and left colon respectively.
- Colorectal mucosa of 7 out of 8 patients who received 1.8 g or 3.6 g of Curcumin exhibited Curcumin sulphate and 2 patients on highest dose exhibited Curcumin glucuronide.
- Researchers were not able to detect the reduced metabolites such as hexahydrocurcumin and hexahydrocurcuminol in the intestinal tissue.
- Administration of Curcumin did not affect the M1G levels in normal colorectal mucosa while it caused a decrease in adduct levels in malignant colorectal mucosa.
Based on the results obtained, the authors were able to conclude that a dose of 1.8 g of Curcumin might actually have achieved the statistically significant reduction of M1G levels. Study also shows that a dosage of 3.6 g is safe in humans and negative targeting of Curcumin could be a considerable advantage. Further, concentrations of Curcumin achieved in colorectal mucosa are consistent with levels needed to exert chemopreventive activity.