More research is needed to establish the benefit-risk profile of curcumin

Authors


More research is needed to establish the benefit-risk profile of curcumin

Dear Editor,

We thank Kurien et al.1 for their interest and comments on our recent publication entitled “The dark side of curcumin.”2 Curcumin is the major constituent of the spice turmeric, which is obtained from the rhizome of the plant Curcuma longa and has a long history of use in traditional Asian medicine. Many studies have been published in recent years on the beneficial effects of curcumin, and it has repeatedly been claimed that this dietary agent is efficient and safe for the prevention and treatment of several diseases including cancer. As a result, curcumin has entered clinical trials and is also readily available as a dietary supplement. As there is accumulating evidence challenging the view that curcumin is effective and nontoxic, and because such evidence is not generally acknowledged, the purpose of our previous letter was to review the negative properties of curcumin. Our conclusion was that future research is needed to establish the benefit-risk profile of curcumin and that, meanwhile, it is important to recognized the negative properties of curcumin so that its use is not based on unbalanced information.2

One of the most worrying aspects of curcumin is its ability to induce DNA alterations, because the induction of DNA alterations is a common event in carcinogenesis.2 Several reports have shown that curcumin can induce DNA damage and chromosomal alterations both in vitro and in vivo,3–11 and some evidence of carcinogenic activity has been reported.12, 13 In their letter to the Editor, Kurien et al. challenge the idea of curcumin inducing DNA damage and, therefore, its potential carcinogenicity. The authors observe that, when curcumin is dissolved in water, it does not bind or intercalate into DNA, and suggest that the DNA alterations observed in previous reports may be artifacts caused by the solvents in which curcumin was dissolved. For instance, the authors focus on a work by Goodpasture and Arrighi3 in which turmeric (dissolved in ethanol) induced DNA alterations in several mammalian cell lines. Kurien et al. discuss that it is not clear whether these DNA alterations are because of curcumin alone, curcumin plus ethanol, or ethanol alone.

After electrophoresing DNA on agarose gels, Kurien et al. placed the gels in a solution of the intercalating agent ethidium bromide, in a solution of curcumin dissolved in water, or in a solution of curcumin dissolved in other solvents such as ethanol. The gels were then visualized by ultraviolet light at a wave length at which curcumin fluoresces. The authors observed that the DNA was stained by the ethidium bromide solution but not by the curcumin solutions, and conclude that curcumin does not bind or intercalate into DNA. Because DNA binding and intercalation often leads to DNA damage, the authors suggest that the DNA damage observed in previous studies could have been caused by the organic solvents in which curcumin was dissolved.

We believe that the conclusions of Kurien et al. are not supported by a robust experimental approach. The authors dissolved turmeric in hot water and reached a concentration of curcumin that was estimated to be 7.4 μg/ml. This concentration of curcumin is relatively low and, assuming that their experimental approach is appropriate for detecting DNA binding and intercalation activity, it is possible that a higher concentration of curcumin could have shown activity. The authors could have supported their hypothesis by showing that curcumin is inactive when it is dissolved in water but active when it is dissolved in organic solvents such as ethanol. However, they show that curcumin was also inactive when it was dissolved in ethanol. These data do not support the idea that the DNA alterations observed in cells exposed to curcumin are caused by the organic solvents in which it was dissolved. In addition, even if curcumin does not bind or intercalate into DNA, curcumin can still induce DNA alterations through an indirect mechanism. Curcumin has been shown to generate reactive oxygen species (ROS) in cells,5, 10, 14–17 and ROS are known to induce DNA alterations.18–21

In brief, we do not believe that the data presented by Kurien et al. either invalidate previous studies showing that curcumin induces DNA alterations or challenge our conclusion that it is reasonable to acknowledge the negative properties of curcumin until future research establishes its benefit-risk profile.

Yours sincerely,

Estefanía Burgos-Morón, José Manuel Calderón-Montaño, Concepción Pérez-Guerrero, Miguel López-Lázaro.

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