Bioenhancer‐Driven Modulation of Membrane Dynamics Improves B‐Vitamin Uptake in Caco‐2 Cells

Abstract

Enhancing the bioavailability of B vitamins can increase their biological efficacy while reducing resource use in supplement production. Bioavailability can be improved through strategies such as microencapsulation, micellization, or the application of plant-derived bioenhancers. However, the influence of these approaches on B vitamin absorption remains largely unclear. In this study, we investigated the effects of various bioenhancers, including ginger, turmeric, black pepper, and spearmint, in both non-micellized and micellized formulations on vitamin B uptake using a Caco-2 enterocyte cell model. Our results indicated that tailored combinations of bioenhancers, particularly in micellized form, increased the cellular uptake of vitamins B1, B5, B6, and B7. Analysis of vitamin B transporter gene expression revealed no direct transcriptional effects of the bioenhancer formulations. Untargeted metabolomics revealed bioenhancer-dependent alterations in lipid and amino acid metabolism, suggesting that cellular adaptations are linked to membrane organization. Finally, single-molecule fluorescence microscopy demonstrated that bioenhancer application increased the diffusion of a membrane-anchored model protein, suggesting that changes in membrane fluidity may contribute to the improved vitamin B uptake observed. These findings provide new insight into the cellular mechanisms underlying the increase in vitamin bioavailability and highlight the potential application of natural bioenhancers in optimized vitamin formulations.