The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 6 No.
4 • September 2003
Curcumin in Phase I Clinical Trial Prevention of Cancer
A 2001 paper reported on the results of a phase I clinical trial of curcumin to reduce the risk of or prevent cancer in patients with high-risk conditions, including: (1) recently resected urinary bladder cancer; (2) arsenic Bowen’s disease of the skin; (3) uterine cervical intraepithelial neoplasm; (4) oral leukoplakia; and (5) intestinal metaplasia of the stomach. Thus, this was not a trial of the ability of curcumin to prevent cancer in healthy individuals, but in those who have already had cancer (and are at risk of recurrence) or have premalignant lesions.
Curcumin is the major component (about 40%) of turmeric, a spice commonly used in foods, especially those of India. In India and China, curcumin has been said to be long used as a medicinal herb. Evidence suggests that curcumin acts on stages of initiation, promotion, and progression of carcinogenesis.
A total of 25 patients were enrolled in this study. The subjects took curcumin once in the morning on an empty stomach. Since a previous small-series human study used 500 mg/day for 7 days without observing any toxicity, and a commonly consumed diet in India may contain as much as 100 mg/day of curcumin, the authors chose 500 mg/day as the starting dose. The patients were then moved up into the next dose level (1000, 2000, 4000, 8000, and 12,000 mg/day) as soon as at least two patients at a given level had completed the 3-month treatment and no more than one patient had experienced any equal to or greater than grade II toxicity. Tissue samples were taken from the indicator lesions before and at completion of the 3-month treatment with curcumin.
No toxicity was observed up to 8000 mg/day. However, it was not possible to increase patients to the next level (12,000 mg/day) because the bulky volume of the tablets was unacceptable.
The authors found that curcumin was not well absorbed from the GI tract. The peak serum concentration was only 1.77 µM even at the 8000-mg/day dose. However, these researchers had earlier found in an animal study that curcumin was rapidly biotransformed to dihydrocurcumin and tetrahydrocurcumin and that these compounds were later converted to monoglucuronide conjugates. They suggest that some of the metabolites may retain the pharmacologic properties of curcumin, so the relatively low serum concentrations in the patients in this trial may not reflect the entire beneficial activity of the oral curcumin.
After 3 months in this study, they found histologic improvement in 7 out of 25 patients with these various high-risk and premalignant lesions. They note the need for further phase IIb studies with placebo control for individual lesions to confirm the findings of this study. The authors recommend an oral dose of 6000–8000 mg/day of curcumin in the phase II study. However, since this would be a study of high-risk individuals, 6000–8000 mg/day of curcumin would be an excessive dose for a healthy individual taking curcumin as a supplement; we suggest 200 mg/day.
Experiments on mice genetically engineered to express human amyloid-beta protein (and that develop a condition resembling Alzheimer’s) show a delayed onset with curcumin supplementation, but an accelerated onset if they take too much. Curcumin, like most antioxidants, becomes a pro-oxidant if taken at excessive levels. More is not always better, and it is the dose that makes the poison.
- Cheng et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or premalignant lesions. Anticancer Res 21:2895-2900 (2001).