Micellar Curcumin: Pharmacokinetics and Effects on Inflammation Markers and PCSK‐9 Concentrations in Healthy Subjects in a Double‐Blind, Randomized, Active‐Controlled, Crossover Trial

Abstract

Scope: Preclinical models have demonstrated the anti-inflammatory and lipid-lowering effects of curcumin. Innovative formulations have been developed to overcome the poor bioavailability of native curcumin. The study hypothesizes that the bioavailability of micellar curcumin is superior to native curcumin and investigates the potential anti-inflammatory and proprotein convertase subtilisin/kexin type 9 (PCSK9) concentration lowering effects. Methods and results: In this double-blind, randomized, crossover trial, 15 healthy volunteers receive micellar or native curcumin (105 mg day −1 ) for 7 days with a ≥7 days washout period. Curcumin and metabolite concentrations are quantified by highperformance liquid chromatography with fluorescence detection (HPLC-FD), and pharmacokinetics are calculated. To analyze anti-inflammatory effects, blood samples (baseline, 2 h, 7 days) are stimulated with 50 ng mL −1 lipopolysaccharides (LPS). Interleukin (IL)-6, tumor-necrosis factor (TNF-𝜶), and PCSK9 concentrations are quantified. Micellar curcumin demonstrates improved bioavailability (≈39-fold higher maximum concentrations, ≈14-fold higher area-under-the-time-concentration curve, p < 0.001) but does not reduce pro-inflammatory cytokines in the chosen model. Subjects receiving micellar curcumin have significantly lower PCSK9 concentrations (≈10% reduction) after 7 days compared to baseline (p = 0.038). Conclusion: Micellar curcumin demonstrates an improved oral bioavailability but does not show anti-inflammatory effects in this model. Potential effects on PCSK9 concentrations warrant further investigation.

The Pharmacokinetics of Individual Conjugated Xanthohumol Metabolites Show Efficient Glucuronidation and Higher Bioavailability of Micellar than Native Xanthohumol in a Randomized, Double‐Blind, Crossover Trial in Healthy Humans

“…In a similar trial comparing native versus micellar curcumin, significantly higher fasting curcumin concentrations were observed after intake of the micellar compared to the native formulation at days 3 and 7. [ 25 ] The differences may be explained by differences in the solubilities of the compounds. The lipid‐soluble curcumin is insoluble in water and dependent on conjugation with glucuronic acid and sulfates for its excretion, whereas XN is slightly soluble in water and can thus be more easily excreted.…”

The Incorporation of Curcuminoids in Gamma‐Cyclodextrins Improves Their Poor Bioaccessibility, Which Is due to Both Their Very Low Incorporation into Mixed Micelles and Their Partial Adsorption on Food

“…[ 17 ] Some studies suggest dCUR and bdCUR could also exert biological effects/health benefits. [ 18–22 ] Several clinical trials, whose primary focus was to compare CUR bioavailability from different turmeric formulations, also reported dCUR and bdCUR bioavailabilities, [ 2–11 ] which have been suggested by some to be higher than that of CUR. [ 2,3 ]…”

“…[1,2] These are also usually found in turmeric extracts, albeit at slightly different relative concentrations (CUR: 80.0 ± 1.9%, dCUR: 17.1 ± 1.4%, bdCUR: 2.9 ± 0.6%; mean ± SEM calculated from ref. [2][3][4][5][6][7][8][9][10][11]). Turmeric is widely used as a spice, particularly in Asian cuisine, but it has also long been used as a traditional medicine.…”

“…[17] Some studies suggest dCUR and bdCUR could also exert biological effects/health benefits. [18][19][20][21][22] Several clinical trials, whose primary focus was to compare CUR bioavailability from different turmeric formulations, also reported dCUR and bdCUR bioavailabilities, [2][3][4][5][6][7][8][9][10][11] which have been suggested by some to be higher than that of CUR. [2,3] Curcuminoids are lipids (the computed log octanol/water partition coefficients of CUR, dCUR, and bdCUR are around 3.2) and they display poor solubility in the aqueous environment of the gastrointestinal tract.…”

Prospects for the use of curcumin as an additional treatment for multiple sclerosis

“…М е х а н и з м ы д е й с т в и я к у р к у м и н а п р и Р С Куркумин -природный полифенол, содержащийся в корне растения Curcuma longa. Куркумин обладает различными видами фармакологической активности, в частности противовоспалительной, нейропротекторной, антиоксидантной, противоопухолевой, а также противомикробной [8,9]. Широкий диапазон фармакологических эффектов куркумина является типичным для группы полифенолов и, вероятно, связан с особенностями их химической структуры.…”