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We greatly appreciate the interest of Gescher et al. in our manuscript and the opportunity to respond to their correspondence. We understand their concerns that our study did not present levels of parent curcumin, which is considered to play a major role of anticancer effects of this agent.
We observed in a rat model that Theracurmin® could increase the parent curcumin level as well as conjugated curcumin level (unpublished data). Unfortunately, however, we could not detect parent curcumin levels in human subjects after administration of 210 mg of Theracurmin® or 8 g of unformulated curcumin manufactured by Sabinsa Corporation (Piscataway, NJ, USA), which were also used in other clinical trials [2, 3]. We believe that the parent curcumin level in our study was less than 0.5 ng/mL, which is the lower limit of detection in our LC-MSMS system. Supporting our observation, Vareed et al. [5] reported that they failed to detect parent curcumin levels even after administration of 12 g of Sabinsa curcumin. Similarly, Garcea et al. [1] could detect only trace amounts of parent curcumin after the administration of 3.6 g of Sabinsa curcumin.
On the other hand, several researchers have proposed that conjugated curcumin can show its activity after deconjugation at the target sites [5] and that conjugated curcumin itself has some important biological functions [4].
Therefore, we believe that an increase in conjugated curcumin levels achieved by Theracurmin® can potentially improve the efficacy of this agent in human subjects, and several clinical trials are now underway to verify this hypothesis.
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Kanai, M., Matsumoto, S., Otsuka, Y. et al. In response. Cancer Chemother Pharmacol 70, 489 (2012). https://doi.org/10.1007/s00280-012-1928-5
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DOI: https://doi.org/10.1007/s00280-012-1928-5