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.

Increasing Post‐Digestive Solubility of Curcumin Is the Most Successful Strategy to Improve its Oral Bioavailability: A Randomized Cross‐Over Trial in Healthy Adults and In Vitro Bioaccessibility Experiments

“…In the current clinical trial, all formulations were without adverse effects when given as a single oral dose of 207 mg curcumin, which is in agreement with previous single and repeated dose clinical trials using even higher doses of curcumin during longer durations in the form of micelles, [ 8,20,21,24 ] γ‐cyclodextrin complexes, [ 9 ] liposomes, [ 10,25 ] phytosomes, [ 9,11,20,22,26 ] together with piperine, [ 6,20,27 ] or as native powder. [ 8,9,11,20–22 ]…”

“…In previous clinical trials, native and formulated curcumin were shown to be safe even at higher doses. [ 8,9,11,20 ]…”

“…Their successes (e.g., fold‐increase in the area under the plasma concentration‐time curve (AUC)) depend not only on the better absorption of the studied formulation, but also on the bioavailability of native curcumin as control, with its low blood concentrations often automatically resulting in increases in AUC for the studied formulations. [ 17 ] Attempts to compare the results from different trials through dose‐normalization by calculating the “bioavailability per mg formulation” (e.g., AUC mg –1 curcumin) [ 18–20 ] are flawed, because they require that each milligram administered results in the same increase in curcumin concentrations. Such a reproducible linear relationship between the dose administered and the blood concentration or bioavailability achieved, respectively, does not exist, as can be easily deduced from plotting the published pharmacokinetic data for curcumin from human trials ( Figure 1 , Tables S1 and S2, Supporting Information); data summarized from.…”

Curcumin in Retinal Diseases: A Comprehensive Review from Bench to Bedside

“…The observation that plasma exposure to THC post-infusion does not decrease as much as for curcumin suggested that curcumin cleared rapidly from the plasma into tissues is still being metabolized into THC post-infusion. Another study [ 64 ] compared the pharmacokinetic profile of a novel natural dried-turmeric colloidal suspension with four other turmeric formulations at their recommended doses, including a standardized extract, a combination-containing piperine, a phytosome formulation and a liquid micellar preparation. Thirty healthy men and women were enrolled in this randomized open-labelled crossover trial.…”

Safety of tetrahydrocurcuminoids from turmeric (Curcuma longa L.) as a novel food pursuant to Regulation (EU) 2015/2283

“…Tetrahydrocurcumin is one of the metabolites of curcumin, produced in vivo through Phase I metabolism in the liver by hepatic reductases. Similar to other reduced curcumin metabolites, tetrahydrocurcumin is conjugated with glucuronide (via glucuronyltransferases) or sulfate (via sulfotransferases), resulting in tetrahydrocurcumin glucuronoside (about 30% (Fança‐Berthon et al, 2021 )) or corresponding monosulfate. Excretion occurs primarily via the biliary system and, to a lesser extent, via the urinary system (Holder et al, 1978 ; Heger et al, 2014 ; Jäger et al, 2014 ).…”