Prolonged Biologically Active Colonic Tissue Levels of Curcumin Achieved After Oral Administration—A Clinical Pilot Study Including Assessment of Patient Acceptability

Glen R.B Irving,Stewart Sale,David P Berry,Edwina N Scott,Andrew S Miller,Ines Kralj-Hans,Lynne M Howells,Susan K Clark,William P Steward,Andreas J Gescher,Karen Brown,Robert G Britton,Wendy S Atkin,David Hemingway,Donald J.L Jones

doi:10.1158/1940-6207.capr-12-0281

Abstract

Curcumin, the main constituent of turmeric, is suspected to possess cancer chemopreventive properties. Pharmacokinetic and pharmacodynamic parameters have been reported, but few data exist describing whether methodologies are suitably robust for curcuminoid detection in colonic biopsy specimens. Information on the acceptability of prolonged administration of daily curcumin is not available. This is of vital importance to implement chemoprevention strategies. This study aimed to quantify levels of curcuminoids in colorectal mucosa of patients undergoing colorectal endoscopy or surgical resection and to obtain information on the acceptability and compliance with daily curcumin. Curcumin C3 complex (2.35 g) was administered to patients once daily for 14 days before endoscopic biopsy or colonic resection. Safety and tolerance were monitored. Analysis of curcuminoids in plasma, urine, and colonic mucosa was conducted by ultraperformance liquid chromatography (UPLC)-UV with characterization by liquid chromatography/tandem mass spectrometry (LC/MS-MS). Twenty-four of 26 patients commencing curcumin completed the course. Six patients reported mild gastrointestinal adverse events. Curcuminoids were detectable in nine of 24 plasma samples, 24 of 24 urine samples, and in the colonic mucosa of all 23 biopsied participants. Mean tissue levels were 48.4 μg/g (127.8 nmol/g) of parent curcuminoids. The major conjugate, curcumin glucuronide, was detectable in 29 of 35 biopsies. High levels of topical curcumin persisted in the mucosa for up to 40 hours postadministration. Sixteen participants (67%) stated that they would take curcumin long-term should it be of proven benefit. In summary, pharmacologically active levels of curcumin were recovered from colonic mucosa. The regimen used here seems safe, and patients support its use in long-term trials.

Highlights

Curcumin, the major constituent of the spice turmeric, has been the subject of increasing interest as having the potential to prevent and treat colorectal cancer [1] and may be of benefit in cardiovascular [2] and Alzheimer’s disease [3]
It is unclear from these investigations how much of the curcumin recovered from the gut mucosa reflects material loosely adherent to the mucosal surface, as compared with agent absorbed into the tissue, which may elicit pharmacologic activity
Participants Twenty-eight patients were recruited into this study, with 18 recruited at the University Hospitals of Leicester (UHL) and 10 at St Mark’s Hospitals (SMH)

Summary

Introduction

The major constituent of the spice turmeric, has been the subject of increasing interest as having the potential to prevent and treat colorectal cancer [1] and may be of benefit in cardiovascular [2] and Alzheimer’s disease [3] It has shown chemopreventive activity in a variety of in vitro cell-based systems and in vivo preclinical models [4,5,6]. The lower dose produced colonic tissue concentrations of curcumin of an order of magnitude associated with pharmacologic effects, both in cells in vitro and in rodents in vivo [17] It is unclear from these investigations how much of the curcumin recovered from the gut mucosa reflects material loosely adherent to the mucosal surface, as compared with agent absorbed into the tissue, which may elicit pharmacologic activity

Objectives

Methods

Results

Conclusion