Berberine is a plant-origin quaternary isoquinoline alkaloid with a vast array of biological activities, including antioxidant and blood-glucose- and blood-lipid-lowering effects. However, its therapeutic potential is largely limited by its poor oral bioavailability. The aim of this study was to investigate the in vitro solubility and Caco-2 cell permeability followed by pharmacokinetic profiling in healthy volunteers of a new food-grade berberine delivery system (i.e., Berberine LipoMicel^®). X-ray diffractometry (XRD), in vitro solubility, and Caco-2 cell permeability indicated higher bioavailability of LipoMicel Berberine (LMB) compared to the standard formulation. Increased aqueous solubility (up to 1.4-fold), as well as improved Caco-2 cell permeability of LMB (7.18 × 10⁻⁵ ± 7.89 × 10⁻⁶ cm/s), were observed when compared to standard/unformulated berberine (4.93 × 10⁻⁶ ± 4.28 × 10⁻⁷ cm/s). Demonstrating better uptake, LMB achieved significant increases in AUC_0–24 and C_max compared to the standard formulation (AUC: 78.2 ± 14.4 ng h/mL vs. 13.4 ± 1.97 ng h/mL, respectively; p < 0.05; C_max: 15.8 ± 2.6 ng/mL vs. 1.67 ± 0.41 ng/mL) in a pilot study of healthy volunteers (n = 10). No adverse reactions were reported during the study period. In conclusion, LMB presents a highly bioavailable formula with superior absorption (up to six-fold) compared to standard berberine formulation and may, therefore, have the potential to improve the therapeutic efficacy of berberine. The study has been registered on ClinicalTrials.gov with Identifier NCT05370261.

Randomized clinical trials (RCT) and observational studies have highlighted the importance of flavonoid consumption for human health. Several studies have associated a high intake of dietary flavonoids with (a) enhanced metabolic and cardiovascular health, (b) enhanced cognitive and vascular endothelial functions, (c) an improved glycemic response in type 2 diabetes mellitus, and (d) a reduced risk of breast cancer in postmenopausal women. Since flavonoids belong to a broad and diverse family of polyphenolic plant molecules—with more than 6000 compounds interspersed in the human diet—researchers are still uncertain whether the intake of single, individual polyphenols or a large combination of them (i.e., synergistic action) can produce the greatest health benefits for humans. Furthermore, studies have reported a poor bioavailability of flavonoid compounds in humans, which presents a major challenge for determining their optimal dosage, recommended intake, and, consequently, their therapeutic value. Especially because of their scarce bioavailability from foods—along with the overall declining food quality and nutrient density in foods—the role of flavonoid supplementation may become increasingly important for human health. Although research shows that dietary supplements can be a highly useful tool to complement diets that lack sufficient amounts of important nutrients, some caution is warranted regarding possible interactions with prescription and non-prescription drugs, especially when taken concurrently. Herein, we discuss the current scientific basis for using flavonoid supplementation to improve health as well as the limitations related to high intakes of dietary flavonoids.

This study aimed to evaluate the blood concentrations of quercetin in healthy participants after the administration of different formulations in single‐ and multiple‐dose phases. Ten healthy adults (males, 5; females, 5; age 37 ± 11 years) participated in a diet‐controlled, crossover pilot study. Participants received three different doses (250 mg, 500 mg, or 1000 mg) of quercetin aglycone orally. In the single‐dose study, blood concentrations (AUC_0–24 and C_max) of standard quercetin were compared with those of LipoMicel®—a food‐grade delivery form of quercetin. In the multiple‐dose study, blood concentrations of formulated quercetin were observed over 72 h, after repeated doses of LipoMicel (LM) treatments. The AUC_0–24 ranged from 77.3 to 1128.9 ng·h/ml: LM significantly increased blood concentrations of quercetin by 7‐fold (LM 500) compared to standard quercetin, when tested at the same dose, over 24 h (p < 0.001); LM administered at a higher dose (LM 1000) achieved 15‐fold higher absorption (p < 0.001); LM tested at half a dose of standard quercetin increased concentration by approx. 3‐fold (LM 250). Quercetin blood concentrations were attained over 72 h. The major metabolites measured in the blood were methylated, sulfate, and glutathione (GSH) conjugates of quercetin. Significant differences in concentrations between quercetin conjugates (sulfate vs. methyl vs. GSH) were observed (p < 0.001). Data obtained from this study suggest that supplementation with LipoMicel® is a promising strategy to increase the absorption of quercetin and its health‐promoting effects in humans. However, due to the low sample size in this pilot study, further research is still warranted to confirm the observations in larger populations. This trial is registered with NCT05611827.