Dose escalation of a curcuminoid formulation.
BACKGROUND
Curcumin is the major yellow pigment extracted from turmeric, a commonly-used spice in India and Southeast Asia that has broad anticarcinogenic and cancer chemopreventive potential. However, few systematic studies of curcumin's pharmacology and toxicology in humans have been performed.


METHODS
A dose escalation study was conducted to determine the maximum tolerated dose and safety of a single dose of standardized powder extract, uniformly milled curcumin (C3 Complextrade mark, Sabinsa Corporation). Healthy volunteers were administered escalating doses from 500 to 12,000 mg.


RESULTS
Seven of twenty-four subjects (30%) experienced only minimal toxicity that did not appear to be dose-related. No curcumin was detected in the serum of subjects administered 500, 1,000, 2,000, 4,000, 6,000 or 8,000 mg. Low levels of curcumin were detected in two subjects administered 10,000 or 12,000 mg.


CONCLUSIONS
The tolerance of curcumin in high single oral doses appears to be excellent. Given that achieving systemic bioavailability of curcumin or its metabolites may not be essential for colorectal cancer chemoprevention, these findings warrant further investigation for its utility as a long-term chemopreventive agent.
Lao
Christopher D
CD
Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan, 2150 CCGC, Ann Arbor, MI 48109-0930, USA. clao@umich.edu
Ruffin
Mack T
MT
Normolle
Daniel
D
Heath
Dennis D
DD
Murray
Sandra I
SI
Bailey
Joanne M
JM
Boggs
Martha E
ME
Crowell
James
J
Rock
Cheryl L
CL
Brenner
Dean E
DE
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D000970:Antineoplastic Agents / Q000633:toxicity; D001682:Biological Availability; D003474:Curcumin / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010936:Plant Extracts / Q000633:toxicity*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D010936:Plant Extracts; D003474:Curcumin