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

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 mg/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. Cancer Prev Res; 6(2); 119-28. Ó2012 AACR.

The Molecular Basis for the Pharmacokinetics and Pharmacodynamics of Curcumin and Its Metabolites in Relation to Cancer

“…In support of this, a preceding study in rats by the same group revealed that, 24 hour after per gavage administration of 400 mg of curcumin, approximately 40% of curcumin was present in the gastrointestinal tract and that curcumin levels in blood, liver, and kidneys were below the limit of detection (,5 mg/ml or g tissue, equivalent to 13 mM) (Ravindranath and Chandrasekhara, 1980). Furthermore, relatively high curcumin concentrations have been found in colorectal mucosa of patients after oral intake (Garcea et al, 2005;Carroll et al, 2011;Irving et al, 2013) and in feces as well as intestinal and colonic mucosa in rats after 1 week of dietary curcumin intake (Perkins et al, 2002). Given the very low curcumin levels in healthy tissue, it is likely that the accumulation of curcumin in nonenteral tumor tissue will follow a similar pattern.…”

“…Clinical trials have reported patient discontent and withdrawal of patients from the high dosage cohorts solely due to the discomfort they experienced when ingesting a large amount of curcumin pills Irving et al, 2013).…”

Photopreventive Effect and Mechanism of AZD4547 and Curcumin C3 Complex on UVB-Induced Epidermal Hyperplasia

“…C3 complex, collectively known as curcuminoids, is a standardized preparation (Sabinsa) of three curcuminoids-curcumin (76.07%), demethoxycurcumin (DMC; 20.28%), and bisdemethoxycurcumin (3.63%). The safety and efficacy of C3 complex is established in clinical trials (6)(7)(8). DMC and bisdemethoxycurcumin, natural demethoxy derivatives of curcumin, possess anti-inflammatory, and antiproliferative properties and are more stable than curcumin in serum (9).…”

Curcumine (Turmeric – Curcuma longa) as a Supportive Phytotherapeutic Treatment in Oncology

“…Z těchto studií vyplývá, že při per os podání se kurkumin dostává do střevní tkáně v množství, které může mít bio logický účinek [25], a je v ní detekovatelný i 40 hod po jeho posledním podání. Prokázána byla také bezpeč-nost a dobrá tolerance kurkuminu až do dávky 3,6 g denně, u ně kte rých pa cientů byla ale léčba provázena slabými gastrointestinálními obtížemi [26,27].…”