Plasma concentrations of curcumin in individuals using curcumin with adjuvants or lipid formulated curcumin supplements: a real world cohort

The spice curcumin and its metabolites have been linked to many beneficial health effects. These effects have, thus far, not been duplicated in independent research most likely due to low plasma concentrations of curcumin. Despite the many reports, the public’s interest in curcumin continues to grow and many people use curcumin in daily life. Moreover, companies seize the popularity of curcumin and claim that their formulations increase systemic expose of curcumin. In this independent study we determined the plasma concentration of curcumin after oral intake in daily life to determine if the systemic exposure is sufficient to achieve beneficial health effects. We used a validated HPLC-MS/MS assay to determine the plasma concentration of curcumin and its metabolites in 47 individuals (patient or healthy) using their own curcumin formulations. Through questionnaires, we assessed which other supplements and (self-)medication(s) were used. The concentrations of curcumin and its metabolites were analyzed in plasma samples collected just before and 1.5 h after curcumin intake. Each sample was pretreated with and without β-glucuronidase to determine the levels of conjugated and unconjugated curcumin. After oral intake of the curcumin supplement, plasma concentrations of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin ranged between 2 and 4 nM. Use of adjuvants like piperine did not result in higher curcumin plasma concentrations. Adding β-glucuronidase to the plasma sample increased curcumin plasma levels from below LLQ to 25.3 ng/mL, however still below any plasma concentration to which a beneficial health effect can be expected. The observed plasma concentration of unchanged curcumin remained several orders below the concentration of 2-100 μg/mL used in in vitro studies. Therefore, our study confirms the low plasma levels of curcumin and indicates the need to be critical towards the claimed beneficial systemic health effects of current curcumin supplement use in daily life among patients and healthy individuals. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NL5931 ### Funding Statement The authors received no specific funding for this work. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol was reviewed and approved by the Ethics committee of the Amsterdam UMC, location Academic Medical Centre, The Netherlands. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All relevant data are within the manuscript and its Supporting Information files.