Fat-soluble vitamin intestinal absorption: Absorption sites in the intestine and interactions for absorption

Highlights

• Vitamin A, D, E and K display different absorption sites in mouse intestine.

• Vitamin E may prevent vitamin A oxidation and increases its intestinal absorption.

• Vitamin D, E and K common uptake pathways would explain the competitions observed.

Abstract

The interactions occurring at the intestinal level between the fat-soluble vitamins A, D, E and K (FSVs) are poorly documented. We first determined each FSV absorption profile along the duodenal–colonic axis of mouse intestine to clarify their respective absorption sites. We then investigated the interactions between FSVs during their uptake by Caco-2 cells. Our data show that vitamin A was mostly absorbed in the mouse proximal intestine, while vitamin D was absorbed in the median intestine, and vitamin E and K in the distal intestine. Significant competitive interactions for uptake were then elucidated among vitamin D, E and K, supporting the hypothesis of common absorption pathways. Vitamin A also significantly decreased the uptake of the other FSVs but, conversely, its uptake was not impaired by vitamins D and K and even promoted by vitamin E. These results should be taken into account, especially for supplement formulation, to optimise FSV absorption.

Introduction

Vitamins are essential nutrients that ensure optimal growth, reproduction and function. They have been categorised based on solubility as water- (Bs and C) and fat-soluble (FSVs), which are, in turn, classed as four groups of compounds, specifically A, D, E and K (Table 1). As the body cannot synthesise vitamins, or at least insufficient vitamin D, adequate amounts have to be provided by the diet. However, the fundamental mechanisms involved in the absorption of FSVs are still unclear. Initially, Hollander et al. (Hollander, 1981) provided most of the evidence concerning FSV absorption. They suggested that vitamins E and D were absorbed by passive diffusion (Hollander et al., 1975, Hollander and Truscott, 1976) while vitamins A and K were absorbed via carrier-dependent proteins (Hollander, 1973, Hollander and Muralidhara, 1977). However, recent studies have reconsidered these assumptions, and have shown that absorption mechanisms are more complex than previously described: passive diffusion occurs at high concentrations of these compounds, while protein-mediated transport occurs at dietary doses (Reboul & Borel, 2011). Our recent work shows that vitamin D intestinal uptake is not just passive, but also involves cholesterol transporters, such as SR-BI (Scavenger Receptor class B type I), CD36 (Cluster Determinant 36) and NPC1-L1 (Niemann–Pick C1-Like 1) (Reboul et al., 2011). In the same way, SR-BI was shown to mediate tocopherol uptake in both Caco-2 and mouse models (Reboul et al., 2006), as well as NPC1-L1 (Narushima, Takada, Yamanashi, & Suzuki, 2008). The proteins involved in vitamin A and K membrane transport into the enterocyte remain unidentified.

Interestingly, several food component-vitamin interactions have been previously reported. We first showed that phytosterols inhibited vitamin D incorporation into micelles (Goncalves et al., 2011). Inhibition of α-tocopherol uptake was also observed in Caco-2 cells in the presence of different compounds, such as the phenolic naringenin, carotenoids and γ-tocopherol (Reboul et al., 2007), and vitamin D uptake was impaired by α-tocopherol (Reboul et al., 2011) and phytosterols (Goncalves et al., 2011). Another study has shown that FSVs could have antagonist interactions affecting their intestinal absorption in vivo. Indeed, in chicks fed with high dietary levels of vitamin A (retinyl palmitate) during 24 days, plasma α-tocopherol levels were significantly depressed compared to chicks fed control vitamin A (Sklan & Donoghue, 1982).

After investigating FSV absorption in mouse intestine, our aim was to identify the competitive or synergistic interactions between vitamins A, D, E and K at a key step of intestinal absorption, i.e. during their uptake by the enterocyte.