The enhanced bioavailability of free curcumin and bioactive-metabolite tetrahydrocurcumin from a dispersible, oleoresin-based turmeric formulation

Abstract

Background: Curcuminoids have been widely studied for human health and disease applications, yet bioavailability remains a hurdle to actualizing all the benefits ascribed to them. The lack of standardization in analysis method, confusion about what constitutes an ideal analyte, and conflicting thoughts around dosing strategies have made it difficult to draw parity between bioavailability and bioactivity and establish a baseline for formulation comparisons. Methods: This randomized double-blinded, 2-way cross over, single oral dose, comparative bioavailability study differentially evaluates curcumin at the time of its absorption and along various biotransformation pathways, to include free curcumin, the readily usable form of curcumin; individual and composite totals of curcumin and its analogues as exogenously cleaved conjugates, for example, total curcumin, total demethoxycurcumin (DMC), total bisdemethoxycurcumin (BDMC), and total curcuminoids respectively; and the bioactive metabolite of curcumin, total tetrahydrocurcumin (THC). As a primary study objective, the relative bioavailability of CURCUGEN, a novel dispersible, 50% curcuminoids-concentrated turmeric extract was compared to the standard curcumin reference product, curcuminoids 95% standardized extract (C-95), using the maximum concentration ( C max ), and area under the curve (AUC 0-t ) of free curcumin, total curcumin, total DMC, total BDMC and the curcumin active metabolite, as total THC. Results: The evaluation of free curcumin demonstrated that the C max and AUC 0-t of the CURCUGEN was 16.1 times and 39 times higher than the C max and AUC 0-t of C-95. Furthermore, total curcumin, total DMC, total BDMC, and total curcuminoids resulted in AUC 0-t of the CURCUGEN at 49.5-, 43.5-, 46.8-, and 52.5-fold higher than C-95, respectively. The relative bioavailability of CURCUGEN for total THC was found to be 31 times higher when compared to C-95. Conclusion: As the first human pharmacokinetics study to apply best-practice recommendations and pharmaceutically-aligned guidance in the comprehensive evaluation of a novel curcuminoids formulation, we have established the novelty of said formulation while better standardizing for the common variances and discrepancies between curcuminoids and their derivatives in the literature and commercial marketing, alike.

Review of Curcumin and Its Different Formulations: Pharmacokinetics, Pharmacodynamics and Pharmacokinetic-Pharmacodynamic Interactions

“…A study in healthy volunteers compared the pharmacokinetics of Curcugen (a novel dispersible 50% curcuminoid extract) with standard extract (i.e., 95% curcuminoids). Curcugen was 16.9-, 39-, 49.5-, 43.5-, 46.8-, and 52.5-fold higher than C-95 in terms of AUC0-t, Cmax, total curcumin, total DMC, total BDMC and total curcuminoids, respectively, as well as 31-fold higher relative bioavailability [66]. In another study comparing the pharmacokinetics of nano-curcumin with free curcumin (500 mg/kg dose) in rats, it was found that the concentration of free curcumin in the plasma, liver, kidney, and colon was higher than nano-curcumin.…”

Superior Bioavailability of a Novel Curcumin Formulation in Healthy Humans Under Fasting Conditions

“…3-5%), and THC being the major metabolite of curcumin [7]. We measured the plasma levels of CUR, DMC, BDMC, and THC which are known to be responsible for the diverse bioactivity of curcuminoids [8,[24][25][26][27] and represented the data for total curcuminoids. Our study results showed that the plasma concentrations of total curcuminoids and its bioavailability were significantly higher for both doses (250 and 500 mg) of CU?…”

“…Major components of curcuminoids include curcumin (CUR), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC), with CUR being up to 77% of the total curcuminoid content [4][5][6]. Tetrahydrocurcumin (THC) is a primary metabolite of curcumin that has better aqueous solubility, chemical stability, bioavailability, and antioxidative activity [7,8].…”

Phytochemicals in Skeletal Muscle Health: Effects of Curcumin (from Curcuma longa Linn) and Sulforaphane (from Brassicaceae) on Muscle Function, Recovery and Therapy of Muscle Atrophy

“…The novel CURCUGEN, a dispersible formulation with 50% curcuminoids—concentrated turmeric extract—demonstrated that the relative bioavailability of total tetrahydrocurcumin was 31 times higher compared to the standard curcumin reference product, curcuminoid 95% standardized extract (C-95). In addition, CURGUGEN had C max and the area under de curve (AUC0-t) was 16.1 times higher and 39 times higher than that of C-95 [ 29 ]. Furthermore, Curcuwin Ultra+ (CU+), a novel formulation designed to protect curcuminoids from intestinal degradation, demonstrated a significant higher total systemic exposure and C max for total curcuminoids compared with 95% turmeric extract (TUR 1800).…”