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Published in: BMC Complementary Medicine and Therapies 1/2006

Open Access 01-12-2006 | Research article

Dose escalation of a curcuminoid formulation

Authors: Christopher D Lao, Mack T Ruffin IV, Daniel Normolle, Dennis D Heath, Sandra I Murray, Joanne M Bailey, Martha E Boggs, James Crowell, Cheryl L Rock, Dean E Brenner

Published in: BMC Complementary Medicine and Therapies | Issue 1/2006

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Abstract

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 (C 3 Complex™, 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.

Conclusion

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.
Literature
1.
go back to reference Mukhopadhyay A, Basu N, Ghatak N, Gujral PK: Anti-inflammatory and irritant activities of curcumin analogues in rats. Agents Actions. 1982, 12 (4): 508-515. 10.1007/BF01965935.CrossRefPubMed Mukhopadhyay A, Basu N, Ghatak N, Gujral PK: Anti-inflammatory and irritant activities of curcumin analogues in rats. Agents Actions. 1982, 12 (4): 508-515. 10.1007/BF01965935.CrossRefPubMed
2.
go back to reference Srimal RC, Dhawan BN: Pharmacology of diferuloyl methane (curcumin), a non-steroidal anti-inflammatory agent. J Pharm Pharmacol. 1973, 25 (6): 447-452.CrossRefPubMed Srimal RC, Dhawan BN: Pharmacology of diferuloyl methane (curcumin), a non-steroidal anti-inflammatory agent. J Pharm Pharmacol. 1973, 25 (6): 447-452.CrossRefPubMed
3.
go back to reference Rao CV, Rivenson A, Simi B, Reddy BS: Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compound. Cancer Res. 1995, 55 (2): 259-266.PubMed Rao CV, Rivenson A, Simi B, Reddy BS: Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compound. Cancer Res. 1995, 55 (2): 259-266.PubMed
4.
go back to reference Huang MT, Smart RC, Wong CQ, Conney AH: Inhibitory effect of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res. 1988, 48 (21): 5941-5946.PubMed Huang MT, Smart RC, Wong CQ, Conney AH: Inhibitory effect of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res. 1988, 48 (21): 5941-5946.PubMed
5.
go back to reference Huang MT, Lou YR, Ma W, Newmark HL, Reuhl KR, Conney AH: Inhibitory effects of dietary curcumin on forestomach, duodenal, and colon carcinogenesis in mice. Cancer Res. 1994, 54 (22): 5841-5847.PubMed Huang MT, Lou YR, Ma W, Newmark HL, Reuhl KR, Conney AH: Inhibitory effects of dietary curcumin on forestomach, duodenal, and colon carcinogenesis in mice. Cancer Res. 1994, 54 (22): 5841-5847.PubMed
6.
go back to reference Aggarwal BB, Kumar A, Bharti AC: Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 2003, 23 (1A): 363-398.PubMed Aggarwal BB, Kumar A, Bharti AC: Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 2003, 23 (1A): 363-398.PubMed
7.
go back to reference Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY: Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001, 21 (4B): 2895-2900.PubMed Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY: Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001, 21 (4B): 2895-2900.PubMed
8.
go back to reference Sharma RA, McLelland HR, Hill KA, Ireson CR, Euden SA, Manson MM, Pirmohamed M, Marnett LJ, Gescher AJ, Steward WP: Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res. 2001, 7 (7): 1894-1900.PubMed Sharma RA, McLelland HR, Hill KA, Ireson CR, Euden SA, Manson MM, Pirmohamed M, Marnett LJ, Gescher AJ, Steward WP: Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res. 2001, 7 (7): 1894-1900.PubMed
9.
go back to reference Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS: Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998, 64 (4): 353-356.CrossRefPubMed Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS: Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998, 64 (4): 353-356.CrossRefPubMed
11.
go back to reference Heath DD, Pruitt MA, Brenner DE, Rock CL: Curcumin in plasma and urine: quantitation by high-performance liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2003, 783 (1): 287-295.CrossRefPubMed Heath DD, Pruitt MA, Brenner DE, Rock CL: Curcumin in plasma and urine: quantitation by high-performance liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2003, 783 (1): 287-295.CrossRefPubMed
12.
go back to reference Clinical development plan: curcumin. J Cell Biochem Suppl. 1996, 26: 72-85. Clinical development plan: curcumin. J Cell Biochem Suppl. 1996, 26: 72-85.
13.
go back to reference National Toxicology Program, Report TR 427, Turmeric Oleoresin. 1992 National Toxicology Program, Report TR 427, Turmeric Oleoresin. 1992
14.
go back to reference Soni KB, Kuttan R: Effect of oral curcumin administration on serum peroxides and cholesterol levels in human volunteers. Indian J Physiol Pharmacol. 1992, 36 (4): 273-275.PubMed Soni KB, Kuttan R: Effect of oral curcumin administration on serum peroxides and cholesterol levels in human volunteers. Indian J Physiol Pharmacol. 1992, 36 (4): 273-275.PubMed
15.
go back to reference Satoskar RR, Shah SJ, Shenoy SG: Evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation. Int J Clin Pharmacol Ther Toxicol. 1986, 24 (12): 651-654.PubMed Satoskar RR, Shah SJ, Shenoy SG: Evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation. Int J Clin Pharmacol Ther Toxicol. 1986, 24 (12): 651-654.PubMed
16.
go back to reference Deodhar SD, Sethi R, Srimal RC: Preliminary study on antirheumatic activity of curcumin (diferuloyl methane). Indian J Med Res. 1980, 71: 632-634.PubMed Deodhar SD, Sethi R, Srimal RC: Preliminary study on antirheumatic activity of curcumin (diferuloyl methane). Indian J Med Res. 1980, 71: 632-634.PubMed
17.
go back to reference Holder GM, Plummer JL, Ryan AJ: The metabolism and excretion of curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) in the rat. Xenobiotica. 1978, 8 (12): 761-768.CrossRefPubMed Holder GM, Plummer JL, Ryan AJ: The metabolism and excretion of curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) in the rat. Xenobiotica. 1978, 8 (12): 761-768.CrossRefPubMed
18.
go back to reference Wahlstrom B, Blennow G: A study on the fate of curcumin in the rat. Acta Pharmacol Toxicol (Copenh). 1978, 43 (2): 86-92.CrossRef Wahlstrom B, Blennow G: A study on the fate of curcumin in the rat. Acta Pharmacol Toxicol (Copenh). 1978, 43 (2): 86-92.CrossRef
19.
go back to reference Ireson CR, Jones DJ, Orr S, Coughtrie MW, Boocock DJ, Williams ML, Farmer PB, Steward WP, Gescher AJ: Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine. Cancer Epidemiol Biomarkers Prev. 2002, 11 (1): 105-111.PubMed Ireson CR, Jones DJ, Orr S, Coughtrie MW, Boocock DJ, Williams ML, Farmer PB, Steward WP, Gescher AJ: Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine. Cancer Epidemiol Biomarkers Prev. 2002, 11 (1): 105-111.PubMed
20.
go back to reference Ravindranath V, Chandrasekhara N: Metabolism of curcumin--studies with [3H]curcumin. Toxicology. 1981, 22 (4): 337-344. 10.1016/0300-483X(81)90027-5.CrossRefPubMed Ravindranath V, Chandrasekhara N: Metabolism of curcumin--studies with [3H]curcumin. Toxicology. 1981, 22 (4): 337-344. 10.1016/0300-483X(81)90027-5.CrossRefPubMed
21.
go back to reference Ravindranath V, Chandrasekhara N: Absorption and tissue distribution of curcumin in rats. Toxicology. 1980, 16 (3): 259-265. 10.1016/0300-483X(80)90122-5.CrossRefPubMed Ravindranath V, Chandrasekhara N: Absorption and tissue distribution of curcumin in rats. Toxicology. 1980, 16 (3): 259-265. 10.1016/0300-483X(80)90122-5.CrossRefPubMed
22.
go back to reference Ravindranath V, Chandrasekhara N: In vitro studies on the intestinal absorption of curcumin in rats. Toxicology. 1981, 20 (2-3): 251-257. 10.1016/0300-483X(81)90056-1.CrossRefPubMed Ravindranath V, Chandrasekhara N: In vitro studies on the intestinal absorption of curcumin in rats. Toxicology. 1981, 20 (2-3): 251-257. 10.1016/0300-483X(81)90056-1.CrossRefPubMed
23.
go back to reference Pan MH, Huang TM, Lin JK: Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos. 1999, 27 (4): 486-494.PubMed Pan MH, Huang TM, Lin JK: Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos. 1999, 27 (4): 486-494.PubMed
24.
go back to reference Ireson C, Orr S, Jones DJ, Verschoyle R, Lim CK, Luo JL, Howells L, Plummer S, Jukes R, Williams M, Steward WP, Gescher A: Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2 production. Cancer Res. 2001, 61 (3): 1058-1064.PubMed Ireson C, Orr S, Jones DJ, Verschoyle R, Lim CK, Luo JL, Howells L, Plummer S, Jukes R, Williams M, Steward WP, Gescher A: Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2 production. Cancer Res. 2001, 61 (3): 1058-1064.PubMed
Metadata
Title
Dose escalation of a curcuminoid formulation
Authors
Christopher D Lao
Mack T Ruffin IV
Daniel Normolle
Dennis D Heath
Sandra I Murray
Joanne M Bailey
Martha E Boggs
James Crowell
Cheryl L Rock
Dean E Brenner
Publication date
01-12-2006
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2006
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/1472-6882-6-10

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