A dose escalation study was conducted to determine the maximum tolerated dose and safety of a single dose of a standardized curcuminoid formulation (C3 Complex™, Sabinsa Corporation) in healthy volunteers. Participants received escalating doses of 500 to 12,000 mg. Seven of 24 subjects experienced minimal toxicity, which was not dose-related. No curcumin was detected in serum at doses up to 8,000 mg, while low levels were found in two subjects at 10,000 or 12,000 mg. The study found that curcumin tolerance at high single oral doses appears excellent. However, systemic bioavailability of curcumin or its metabolites may not be essential for colorectal cancer chemoprevention, warranting further investigation. Curcumin, derived from turmeric, has broad anticarcinogenic potential but poor bioavailability. Despite this, it is safe in animal and human studies. The study used a standardized powder extract, which showed minimal toxicity up to 12,000 mg. However, curcumin activity as measured by HPLC was 66% less than a pure curcumin powder, suggesting differences in bioavailability based on formulation. The study highlights the need to determine the biologically effective dose for chemoprevention, as poor bioavailability limits systemic cancer preventive activity. Higher doses may be required to overcome intestinal metabolism and achieve systemic effects. Further research is needed to assess curcumin's direct effects on colonic mucosa and its efficacy as a colorectal cancer chemopreventive agent.A dose escalation study was conducted to determine the maximum tolerated dose and safety of a single dose of a standardized curcuminoid formulation (C3 Complex™, Sabinsa Corporation) in healthy volunteers. Participants received escalating doses of 500 to 12,000 mg. Seven of 24 subjects experienced minimal toxicity, which was not dose-related. No curcumin was detected in serum at doses up to 8,000 mg, while low levels were found in two subjects at 10,000 or 12,000 mg. The study found that curcumin tolerance at high single oral doses appears excellent. However, systemic bioavailability of curcumin or its metabolites may not be essential for colorectal cancer chemoprevention, warranting further investigation. Curcumin, derived from turmeric, has broad anticarcinogenic potential but poor bioavailability. Despite this, it is safe in animal and human studies. The study used a standardized powder extract, which showed minimal toxicity up to 12,000 mg. However, curcumin activity as measured by HPLC was 66% less than a pure curcumin powder, suggesting differences in bioavailability based on formulation. The study highlights the need to determine the biologically effective dose for chemoprevention, as poor bioavailability limits systemic cancer preventive activity. Higher doses may be required to overcome intestinal metabolism and achieve systemic effects. Further research is needed to assess curcumin's direct effects on colonic mucosa and its efficacy as a colorectal cancer chemopreventive agent.