Pharmacokinetics of a Single Dose of Turmeric Curcuminoids Depends on Formulation: Results of a Human Crossover Study

Abstract

Background: Curcuminoids from turmeric rhizome have significant health benefits but low bioavailability.

Objectives: To assess the pharmacokinetics of a novel natural turmeric dried colloidal suspension compared with 4 other turmeric formulations (including a standardized extract) at their respective recommended dosages.

Methods: Thirty healthy men and women (18 to 45 y old) were enrolled in a randomized, open-labeled, crossover trial, and sequentially consumed single oral doses of standard turmeric extract (1500 mg), liquid micellar preparation (1000 mg), piperine-curcuminoid combination (1515 mg), phytosome formulation (1000 mg), or the dried colloidal suspension (300 mg). Eleven blood samples were obtained over 24 h, plasma was extracted with or without deconjugation with β-glucuronidase or sulfatase, and ultra-high-pressure liquid chromatography/tandem MS was used to quantify the 3 parent curcuminoids and 12 metabolites. Classical pharmacokinetics parameters were derived.

Results: The total AUC values of unconjugated curcuminoids were highly variable within participants, with no significant differences between formulations. However, the AUC values for total curcuminoids (including all metabolites) showed significant product effects. Indeed, the micellar preparation delivered higher levels of total curcuminoids than any other formulation (8540 ng·h/mL), reaching significance when compared with the dried colloidal suspension and standard extract (6520 and 5080 ng·h/mL, respectively). After dose normalization, both micellar and dried colloidal formulations showed significantly higher AUC levels than the standard extract (respectively 136 and 72.9, compared with 3.7 ng·h/mL/mg). Total curcuminoid absorption levels were also significantly higher for the dried colloidal suspension when compared with either piperine or phytosome formulations. Interestingly, no significant differences were observed between the piperine-curcuminoid combination and the standard extract. No serious adverse events were reported.

Conclusions: The administration of a low dose of the novel natural dried colloidal suspension provided high unconjugated and conjugated curcuminoid absorption, with significant beneficial differences when compared with the high dose of standard extract.This trial was registered at clinicaltrials.gov as NCT03621865.

Keywords: Curcuma longa; absorption; curcumin; curcuminoids; metabolism; metabolites; relative bioavailability.

© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1

Chemical structures of curcuminoids from turmeric extract and principal phase I and phase II metabolites.

FIGURE 2

Schematic representation of study procedures. Participants were provided turmeric-free dinner the night before through home delivery. After a 12-h overnight fast, they were welcomed at the study site and prepared for blood draw and product consumption. Participants were asked to stay at the study site during the day and were provided turmeric-free lunch (after the 4-h time point) and snack (after the 8-h time point) before being allowed to leave. Water was not permitted 1 h before or after product administration but was allowed at all other times ad libitum. The last turmeric-free dinner, before the 24-h time point, was provided through home delivery. After a 12-h overnight fast, participants were asked to come back for a last blood draw corresponding to the last time point (24 h).

FIGURE 3

Clinical study CONSORT diagram. A total of 42 volunteers were screened, of which 12 did not meet the inclusion/exclusion criteria. Thirty participants were enrolled and completed the study. No participants discontinued the intervention, were lost to follow-up, or were excluded from the data analysis. No serious adverse events were reported.

FIGURE 4

Twenty-four hour kinetics of plasma total curcuminoids after consumption of a single dose of the turmeric formulations STE, TEP, PHYT, NOV, and TPG by healthy human participants. (A) Concentrations of total curcuminoids; and (B) dose-normalized concentrations of total curcuminoids determined using UHPLC-tandem MS. Observed means ± SD on the ITT population, n = 30 for each formulation. Total curcuminoids = curcumin + curcumin sulfate + curcumin glucuronide + DMC + DMC sulfate + DMC glucuronide + BDMC + BDMC glucuronide + BDMC sulfate + THC + THC sulfate + THC glucuronide + HHC + HHC glucuronide + HHC sulfate. BDMC, bisdemethoxycurcumin; DMC, desmethoxycurcumin; HHC, hexahydrocurcumin; ITT, intent-to-treat; NOV, liquid micellar formulation; PHYT, phytosome formulation; STE, standard turmeric extract; TEP, piperine-curcuminoids combination; THC, tetrahydrocurcumin; TPG, Turmipure Gold formulation; UHPLC, ultra-high-pressure liquid chromatography.

FIGURE 5

AUC 0–24h of plasma total curcuminoids after consumption of a single dose of the turmeric formulations STE, TEP, PHYT, NOV, and TPG by healthy human participants. (A) AUC 0–24h of total curcuminoids; and (B) dose-normalized AUC 0–24h of total curcuminoids determined using UHPLC-tandem MS. Boxplot representing the group medians, 25th and 75th percentiles, minima, and maxima of observed means on the ITT population, n = 30 for each formulation. †Significantly different from the reference STE product, P < 0.0001. $,#Significantly different compared with the TPG product: $P < 0.05, #P < 0.0001. Total curcuminoids = curcumin + curcumin sulfate + curcumin glucuronide + DMC + DMC sulfate + DMC glucuronide + BDMC + BDMC glucuronide + BDMC sulfate + THC + THC sulfate + THC glucuronide + HHC + HHC glucuronide + HHC sulfate. BDMC, bisdemethoxycurcumin; DMC, desmethoxycurcumin; HHC, hexahydrocurcumin; ITT, intent-to-treat; NOV, liquid micellar formulation; PHYT, phytosome formulation; STE, standard turmeric extract; TEP, piperine-curcuminoids combination; THC, tetrahydrocurcumin; TPG, Turmipure Gold formulation; UHPLC, ultra-high-pressure liquid chromatography.