The dark side of curcumin

Abstract

Curcumin is a yellow-orange pigment obtained from the plant Curcuma longa.The powdered rhizome of this plant, called turmeric, is a common ingredient in curry powders and has a long history of use in traditional Asian medicine for a wide variety of disorders.In the last decade a large number of reports have been published on the beneficial effects of curcumin, and it has repeatedly been claimed that this natural product is efficient and safe for the prevention and treatment of several diseases including cancer.[1][2][3] It is not surprising, therefore, that curcumin is currently sold as a dietary supplement and that numerous clinical trials are ongoing or recruiting participants to evaluate curcumin activity.But there is accumulating evidence that curcumin may not be so effective and safe.Because such evidence is not generally acknowledged, the purpose of this letter is to briefly review the negative properties of curcumin so that they can be balanced against its beneficial effects.Most of the evidence that supports the therapeutic potential of curcumin is mainly based on in vitro studies in which curcumin was tested at concentrations in the micromolar range.Several reports have demonstrated, however, that the plasma concentrations of curcumin in people taking relatively high oral doses of this compound are very low, typically in the nanomolar range (reviewed in Ref. 4).For instance, a recent study examined the pharmacokinetics of a curcumin preparation in 12 healthy human volunteers 0.25-72 hr after an oral dose of 10 or 12 g.Using a high-performance liquid chromatography assay with a limit of detection of 50 ng mL À1 , only 1 subject had detectable free curcumin at any of the time points assayed.5 The fact that curcumin also undergoes extensive metabolism in intestine and liver 6,7 means that high concentrations of curcumin cannot be achieved and maintained in plasma and tissues after oral ingestion.This is a major obstacle for the clinical development of this agent and suggests that the therapeutic potential of oral curcumin is limited.The low clinical efficiency of curcumin in the treatment of several chronic diseases such as Alzheimer's disease and cardiovascular diseases has been discussed recently.8 As far as cancer is concerned, in vitro studies have demonstrated that cancer cells do not die unless they are exposed to curcumin concentrations of 5-50 lM for several hours.4,9,10 Because of its poor bioavailability, these concentrations are not achieved outside the gastrointestinal tract when curcumin is taken orally.Because of its extensive metabolism in intestine and liver, these concentrations cannot