Fatty acid/monoglyceride type and amount modulate fat-soluble vitamin absorption from mixed assemblies in mice.

We investigated the effects of fatty acid/ monoglyceride type and amount on the absorption of fat-soluble vitamins. Micelles or vesicles made with either caprylic acid (CA) + monocaprylin (MC) or oleic acid (OA) + monoolein (MO) at low or high concentrations were infused in bile duct-ligated mice. Retinol + retinyl ester and γ-tocopherol intestinal mucosa contents were higher in mice infused with CA + MC than with OA + MO (up to + 350 % for vitamin A and up to + 62 %, for vitamin E; p < 0.05). Cholecalciferol intestinal mucosa content was the highest in mice infused with micelles with CA + MC at 5 mg/mL (up to + 105 %, p < 0.05). Retinyl ester plasma response was higher with mixed assemblies formed at low concentration of FA + MG compared to high concentration (up to + 1212 %, p < 0.05), while no difference in cholecalciferol and γ-tocopherol plasma responses were measured. No correlation between size or zeta potential and vitamin absorption was found. The impact of FA and MG on fat-soluble vitamin absorption thus differs from one vitamin to another and should be considered to formulate adequate vitamin oral or enteral supplements.

Vitamin D metabolism is altered during aging alone or combined with obesity in male mice.

Aging and obesity are associated with a decrease in plasma 25-hydroxyvitamin D (25(OH)D) levels. In the context of a growing aging population and the rising incidence of obesity, we hypothesized that aging process, either independently or in combination with obesity, could influence vitamin D (VD) metabolism, consequently resulting in the reduced 25(OH)D plasma concentrations. C57BL/6JRJ young (6 months) and old (23 months) mice fed with control (CD) or high fat diet (HF) were compared. Plasma and adipose concentration of cholecalciferol and 25(OH)D and mRNA expression of genes coding for the main VD actors were analyzed. Aging was associated with a decrease in plasma 25(OH)D levels, whereas combined effect of obesity and aging did not generate a cumulative effect on plasma 25(OH)D levels. The mRNA expression of Cyp27a1, Cyp3a11, and Cyp2j6 were decreased in the liver during aging. Together, these regulations could explain the reduced 25-hydroxylation. Interestingly, the lack of cumulative reduction of 25(OH)D in aged and obese mice could be related to the strong induction of Cyp2j6. In kidneys, a complex modulation of Cyp27b1 and Cyp24a1 could contribute to the reduced 25-hydroxylation in the liver. In white adipose tissue, an induction of Cyp2r1 was observed during aging and obesity, together with an increase of 25(OH)D quantity, suggesting an exacerbated storage that may participated to the reduced plasma 25(OH)D levels. These findings support the notion that aging alone or combined with obesity, induces regulation of VD metabolism in the organs, beyond the classical reduction of epidermal VD precursor, which may contribute to the decrease in 25(OH)D levels.

Carotenoids in familial hypobetalipoproteinemia disorders: Malabsorption in Caco2 cell models and severe deficiency in patients.

BACKGROUND: Familial hypobetalipoproteinemias (FHBL) are rare genetic diseases characterized by lipid malabsorption. We focused on abetalipoproteinemia (FHBL-SD1) and chylomicron retention disease (FHBL-SD3), caused by mutations in MTTP and SAR1B genes, respectively. Treatments include a low-fat diet and high-dose fat-soluble vitamin supplementations. However, patients are not supplemented in carotenoids, a group of lipid-soluble pigments essential for eye health. OBJECTIVE: Our aim was to evaluate carotenoid absorption and status in the context of hypobetalipoproteinemia. METHODS: We first used knock-out Caco-2/TC7 cell models of FHBL-SD1 and FHBL-SD3 to evaluate carotenoid absorption. We then characterized FHBL-SD1 and FHBL-SD3 patient status in the main dietary carotenoids and compared it to that of control subjects. RESULTS: In vitro results showed a significant decrease in basolateral secretion of α- and ß-carotene, lutein, and zeaxanthin (-88.8 ± 2.2 % to -95.3 ± 5.8 %, -79.2 ± 4.4 % to -96.1 ± 2.6 %, -91.0 ± 4.5 % to -96.7 ± 0.3 % and -65.4 ± 3.6 % to -96.6 ± 1.9 %, respectively). Carotenoids plasma levels in patients confirmed significant deficiencies, with decreases ranging from -89 % for zeaxanthin to -98 % for α-carotene, compared to control subjects. CONCLUSION: Given the continuous loss in visual function despite fat-soluble vitamin treatment in some patients, carotenoid supplementation may be of clinical utility. Future studies should assess the correlation between carotenoid status and visual function in aging patients and investigate whether carotenoid supplementation could prevent their visual impairment.

Can the Substitution of Milk with Plant-Based Drinks Affect Health-Related Markers? A Systematic Review of Human Intervention Studies in Adults.

The consumption of plant-based drinks (PBDs) in substitution for cow's milk (CM) is increasing due to concerns for human and planet health and animal welfare. The present review aims to analyze the main findings from intervention trials investigating the effect of PBDs in comparison with CM on markers of human health. Suitable articles published up to July 2022 were sourced from PubMed and Scopus databases. A total of 29 papers were collected, with 27 focusing on soy drinks (1 of which also evaluated the effects of an almond drink), while only 2 focused on rice drinks. Among studies focused on soy drinks, the most investigated factors were anthropometric parameters (n = 13), the lipid profile (n = 8), markers of inflammation and/or oxidative stress (n = 7), glucose and insulin responses (n = 6) and blood pressure (n = 4). Despite some evidence of a beneficial effect of PBDs, especially for the lipid profile, it was not possible to draw any overall conclusions due to some conflicting results. As well as the low number of studies, a wide heterogeneity was found in terms of the characteristics of subjects, duration and markers, which reduces the strength of the available results. In conclusion, further studies are needed to better elucidate the effects of substituting CM with PBDs, especially in the long term.

Validation of Knock-Out Caco-2 TC7 Cells as Models of Enterocytes of Patients with Familial Genetic Hypobetalipoproteinemias.

Abetalipoproteinemia (FHBL-SD1) and chylomicron retention disease (FHBL-SD3) are rare recessive disorders of lipoprotein metabolism due to mutations in MTTP and SAR1B genes, respectively, which lead to defective chylomicron formation and secretion. This results in lipid and fat-soluble vitamin malabsorption, which induces severe neuro-ophthalmic complications. Currently, treatment combines a low-fat diet with high-dose vitamin A and E supplementation but still fails in normalizing serum vitamin E levels and providing complete ophthalmic protection. To explore these persistent complications, we developed two knock-out cell models of FHBL-SD1 and FHBL-SD3 using the CRISPR/Cas9 technique in Caco-2/TC7 cells. DNA sequencing, RNA quantification and Western blotting confirmed the introduction of mutations with protein knock-out in four clones associated with i) impaired lipid droplet formation and ii) defective triglyceride (-57.0 ± 2.6% to -83.9 ± 1.6%) and cholesterol (-35.3 ± 4.4% to -60.6 ± 3.5%) secretion. A significant decrease in α-tocopherol secretion was also observed in these clones (-41.5 ± 3.7% to -97.2 ± 2.8%), even with the pharmaceutical forms of vitamin E: tocopherol-acetate and tocofersolan (α-tocopheryl polyethylene glycol succinate 1000). MTTP silencing led to a more severe phenotype than SAR1B silencing, which is consistent with clinical observations. Our cellular models thus provide an efficient tool to experiment with therapeutic strategies and will allow progress in understanding the mechanisms involved in lipid metabolism.

Impact of pulses, starches and meat on vitamin D and K postprandial responses in mice.

In vitro experiments showed that i) phytates, tannins and saponins from pulses can alter vitamin D and K bioavailability and ii) meat decreased vitamin D bioaccessibility by impairing its stability during digestion. We aimed to confirm these results in vivo by force-feeding mice with emulsions containing either potatoes or semolina or chickpeas or meat. Vitamin D and K plasma responses decreased after a gavage with chickpeas or meat compared with potatoes (-62 % and -67 %, respectively for vitamin D, -40 % and -64 %, respectively for vitamin K; p < 0.05). Vitamin D and K intestinal contents were also reduced in mice force-fed with chickpeas or meat compared with potatoes (from -64 to -83 % and from -76 to -84 %, respectively for vitamin D and from -7 to -59 % and from -7 to -90 %, respectively for vitamin K; p < 0.05). The results confirm that chickpea and meat compounds can decrease vitamin D and K bioavailability.

Vitamin A deficiency during the perinatal period induces changes in vitamin A metabolism in the offspring. The regulation of intestinal vitamin A metabolism via ISX occurs only in male rats severely vitamin A-deficient.

PURPOSE: 1) To test the hypothesis of the existence of a perinatal vitamin A (VA) programming of VA metabolism and to better understand the intestinal regulation of VA metabolism. METHODS: Offspring from rats reared on a control (C) or a VA-deficient (D) diet from 6 weeks before mating until offspring weaning, i.e., 7 weeks after mating, were themselves reared on a C or D diet for 19 weeks, resulting in the following groups: C-C (parents fed C-offspring fed C), D-C, C-D and D-D. VA concentrations were measured in plasma and liver. ß-Carotene bioavailability and its intestinal conversion rate to VA, as well as vitamin D and E bioavailability, were assessed after gavages with these vitamins. Expression of genes involved in VA metabolism and transport was measured in intestine and liver. RESULTS: C-D and D-D had no detectable retinyl esters in their liver. Retinolemia, hepatic retinol concentrations and postprandial plasma retinol response to ß-carotene gavage were higher in D-C than in C-C. Intestinal expression of Isx was abolished in C-D and D-D and this was concomitant with a higher expression of Bco1, Scarb1, Cd36 and Lrat in males receiving a D diet as compared to those receiving a C diet. ß-Carotene, vitamin D and E bio-availabilities were lower in offspring receiving a D diet as compared to those receiving a C diet. CONCLUSION: A VA-deficient diet during the perinatal period modifies the metabolism of this vitamin in the offspring. Isx-mediated regulation of Bco1 and Scarb1 expression exists only in males severely deficient in this vitamin. Severe VA deficiency impairs ß-carotene and vitamin D and E bioavailability.

Proteins involved in fat-soluble vitamin and carotenoid transport across the intestinal cells: New insights from the past decade.

It is now well established that vitamins D, E, and K and carotenoids are not absorbed solely through passive diffusion. Broad-specificity membrane transporters such as SR-BI (scavenger receptor class B type I), CD36 (CD36 molecule), NPC1L1 (Niemann Pick C1-like 1) or ABCA1 (ATP-binding cassette A1) are involved in the uptake of these micronutrients from the lumen to the enterocyte cytosol and in their secretion into the bloodstream. Recently, the existence of efflux pathways from the enterocyte back to the lumen or from the bloodstream to the lumen, involving ABCB1 (P-glycoprotein/MDR1) or the ABCG5/ABCG8 complex, has also been evidenced for vitamins D and K. Surprisingly, no membrane proteins have been involved in dietary vitamin A uptake so far. After an overview of the metabolism of fat-soluble vitamins and carotenoids along the gastrointestinal tract (from the mouth to the colon where interactions with microbiota may occur), a focus is placed on the identified and candidate proteins participating in the apical uptake, intracellular transport, basolateral secretion and efflux back to the lumen of fat-soluble vitamins and carotenoids in enterocytes. This review also highlights the mechanisms that remain to be identified to fully unravel the pathways involved in fat-soluble vitamin and carotenoid intestinal absorption.

Antinutritional factors, nutritional improvement, and future food use of common beans: A perspective.

Common bean seeds are an excellent source of protein as well as of carbohydrates, minerals, vitamins, and bioactive compounds reducing, when in the diet, the risks of diseases. The presence of bioactive compounds with antinutritional properties (e.g., phytic acid, lectins, raffinosaccharides, protease inhibitors) limits, however, the bean's nutritional value and its wider use in food preparations. In the last decades, concerted efforts have been, therefore, made to develop new common bean genotypes with reduced antinutritional compounds by exploiting the natural genetic variability of common bean and also applying induced mutagenesis. However, possible negative, or positive, pleiotropic effects due to these modifications, in terms of plant performance in response to stresses or in the resulting technological properties of the developed mutant genotypes, have yet not been thoroughly investigated. The purpose of the perspective paper is to first highlight the current advances, which have been already made in mutant bean characterization. A view will be further provided on future research directions to specifically explore further advantages and disadvantages of these bean mutants, their potential use in innovative foods and representing a valuable genetic reservoir of combinations to assess the true functional role of specific seed bioactive components directly in the food matrix.

Bioaccessibility and uptake by Caco-2 cells of carotenoids from cereal-based products enriched with butternut squash (Cucurbita moschata L.).

Enriching cereals-based products with bioactive compounds is a valuable strategy to improve product quality. We studied carotenoid bioaccessibility and intestinal uptake from a pumpkin-enriched porridge, cookies and sponge cakes by using in vitro digestion coupled with Caco-2 cell uptake. Among the carotenoids recovered in different products, α-carotene was the most important abundant one. However, lutein displayed a significantly higher bioaccessibility compared to α-carotene and ß-carotene in baked products (up to 10.28% compared to 1.22% and 0.88%, respectively). α-Carotene was the only carotenoid recovered in Caco-2 cells after micelle incubation. Cookie micelles led to the highest percentage of α-carotene cell uptake (2.33% and 1.38% for cookies with butter and cookies with vegetable oil, respectively) compared to the other baked products, followed by dry pumpkin puree micelles (1.31%). Overall, our data show that both bioaccessiblity and cell uptake of carotenoids from cereal-based products are variable and highly depend on food formulation and structure.

Reduction of pulse "antinutritional" content by optimizing pulse canning process is insufficient to improve fat-soluble vitamin bioavailability.

Some bioactive compounds found in pulses (phytates, saponins, tannins) display antinutritional properties and interfere with fat-soluble vitamin bioavailability (i.e., bioaccessibility and intestinal uptake). As canned chickpeas are consumed widely, our aim was to optimize the chickpea canning process and assess whether this optimization influences fat-soluble vitamin bioavailability. Different conditions during soaking and blanching were studied, as was a step involving prior germination. Proteins, lipids, fibers, vitamin E, lutein, 5-methyl-tetrahydro-folate, magnesium, iron, phytates, saponins and tannins were quantified. Bioaccessibility and intestinal uptake of vitamin D and K were assessed using in vitro digestion and Caco-2 cells, respectively. Significant reductions of phytate, saponin and tannin contents (-16 to -44%), but also of folate content (up to -97%) were observed under optimized canning conditions compared with the control. However, bioaccessibility and cellular uptake of vitamin D and K remained unaffected after in vitro digestion of test meals containing control or optimized canned chickpeas.

ß-Carotene Bioavailability and Conversion Efficiency Are Significantly Affected by Sex in Rats: First Observation Suggesting a Possible Hormetic Regulation of Vitamin A Metabolism in Female Rats.

SCOPE: To study the effect of variation in dietary vitamin A (VA) content on its hepatic and intestinal metabolism. METHODS AND RESULTS: Adult female and male rats are fed with diets containing 400, 2300, or 9858 IU kg-1 VA for 31-33 weeks. VA concentrations are measured in plasma and liver. Bioavailability and intestinal conversion efficiency of ß-carotene to VA are assessed by measuring postprandial plasma ß-carotene and retinyl palmitate concentrations after force-feeding rats with ß-carotene. Expression of genes involved in VA metabolism, together with concentrations of RBP4, BCO1, and SR-BI proteins, are measured in the intestine and liver of female rats. Plasma retinol concentrations are lower and hepatic free retinol concentrations are higher in females than in males. There is no effect of dietary VA content on ß-carotene bioavailability and its conversion efficiency, but bioavailability is higher and conversion efficiency is lower in females than in males. The expression of most genes exhibited a U-shaped dose response curve depending on VA intake. CONCLUSIONS: ß-Carotene bioavailability and conversion efficiency to VA are affected by the sex of rats. Results of gene expression suggest a hormetic regulation of VA metabolism in female rats.

The Complex ABCG5/ABCG8 Regulates Vitamin D Absorption Rate and Contributes to its Efflux from the Intestine.

SCOPE: Most people are vitamin D insufficient around the world. Vitamin D intestinal absorption should thus be optimized. The role of the ATP-binging cassette G5/G8 (ABCG5/G8) heterodimer in vitamin D intestinal efflux is investigated. METHODS AND RESULTS: Both cholecalciferol and 25-hydroxycholecalciferol apical effluxes are increased by ABCG5/G8 overexpression in human Griptite cells. Mice deficient in ABCG5/G8 at the intestinal level (I-Abcg5/g8-/- mice) display an accumulation of cholecalciferol in plasma in females and in liver in males compared to control animals. I-Abcg5/g8-/- mice display a delay in cholecalciferol postprandial response after gavage compared with controls. 25-Hydroxycholecalciferol transfer from plasma to lumen is observed in vivo in intestine-perfused mice, and the lack of intestinal ABCG5/G8 complex induces a decrease in this efflux, while vitamin D bile excretion remains unchanged. CONCLUSION: Overall, it is showed for the first time that the ABCG5/G8 heterodimer regulates the kinetics of absorption of dietary vitamin D by contributing to its efflux back to the lumen, and that it also participates in vitamin D transintestinal efflux.

Vitamin A Deficiency during the Perinatal Period and First Weeks of Life Modifies Vitamin A and Lipid Postprandial Metabolism in Both Female and Male Young Rats.

SCOPE: The effect of vitamin A deficiency on vitamin A and lipid postprandial metabolism in young rats is addressed, considering the effect of sex. METHODS AND RESULTS: Sprague-Dawley rats are fed either 400 UI.kg-1 vitamin A diet (vitamin A-deficient (VAD) diet) or 2300 UI.kg-1 vitamin A (control diet), before being mated. Mothers receive the same VAD or control diet during gestation and lactation. Offspring receive the same diet than mothers until 8 weeks of age. VAD diet-fed female and male offspring display a severe vitamin A deficiency with no body weight or glucose tolerance defects. Fasting plasma triglyceride concentrations are decreased in VAD diet-fed animals compared to controls (p < 0.05). Retinyl ester postprandial responses after vitamin A gavage, expressed as area under the curves, are not different in VAD diet-fed and control animals, although retinyl ester postprandial peak is significantly delayed (p < 0.05) in VAD diet-fed rats. Lipids also accumulate in the distal part of the intestine after gavage and [1-13 C]-oleate postprandial response is decreased in VAD diet-fed males. CONCLUSION: Vitamin A deficiency modulates both vitamin A absorption rate and lipid postprandial metabolism, which can partly explain the altered fasting lipid status observed in VAD diet-fed offspring.

Pulses Twice a Week in Replacement of Meat Modestly Increases Diet Sustainability.

The French food-based dietary guidelines recommend eating pulses at least twice a week and to reduce meat consumption. This study assessed the impact on the sustainability characteristics (nutrition, cost, environment) of individual diets of meeting the pulse guideline. Dietary data of 2028 adults from the Esteban survey were completed with the nutritional content (considering bioavailability on iron, zinc and protein), price and environmental impacts of foods. When the pulse guideline (i.e., 57 g/day) was not met, two substitution scenarios raised the quantity of pulses to the recommended level, in replacement of an equivalent portion of (i) starches or (ii) meat. Only 9.6% of the participants reached the pulse guideline. Diet sustainability characteristics improved with the meat scenario (nutritional indicators improved; diet cost, greenhouse gas emissions and acidification decreased), while several indicators deteriorated with the starches scenario. Zinc available for absorption slightly decreased in both scenarios while iron available for absorption decreased in the meat scenario only. Increasing pulse consumption to two portions/week could modestly improve the sustainability of diets when pulses replace meat but not starches. Cultural acceptability of that substitution still needs to be proven, and iron and zinc status of individuals at risk of deficiency should be monitored.

One-Step Extraction of Olive Phenols from Aqueous Solution Using ß-Cyclodextrin in the Solid State, a Simple Eco-Friendly Method Providing Photochemical Stability to the Extracts.

The extraction of phenolic compounds from olive mill wastes is important, not only to avoid environmental damages, but also because of the intrinsic value of those biophenols, well-known for their high antioxidant potential and health benefits. This study focuses on tyrosol (Tyr) and hydroxytyrosol (HT), two of the main phenolic compounds found in olive mill wastes. A new, simple, and eco-friendly extraction process for the removal of phenolic compounds from aqueous solutions using native ß-cyclodextrin (ß-CD) in the solid state has been developed. Several ß-CD/biophenol molar ratios and biophenol concentrations were investigated, in order to maintain ß-CD mostly in the solid state while optimizing the extraction yield and the loading capacity of the sorbent. The extraction efficiencies of Tyr and HT were up to 61%, with a total solid recovery higher than 90% using an initial concentration of 100 mM biophenol and 10 molar equivalents of ß-CD. The photochemical stability of the complexes thus obtained was estimated from ∆E*ab curve vs. illumination time. The results obtained showed that the phenols encapsulated into solid ß-CD are protected against photodegradation. The powder obtained could be directly developed as a safe-grade food supplement. This simple eco-friendly process could be used for extracting valuable biophenols from olive mill wastewater.

Mechanisms of absorption of vitamin D3 delivered in protein nanoparticles in the absence and presence of fat.

Novel protein-based nanovehicles offer alternatives to fat for delivery of lipophilic bioactives (nutraceuticals and drugs), yet they raise important questions regarding the bioavailability and absorption mechanism of the bioactive without fat. To provide answers, we chose vitamin D3 (VD3) as a model lipophilic-nutraceutical, re-assembled casein-micelles (rCM) as model protein-based nanovehicles, and non-fat yoghurt as a model food. We prepared three yoghurt formulations: 3% fat with VD3 dissolved in milk-fat, non-fat and 3% fat, both latter enriched with VD3 within rCM. Following in vitro digestion, VD3 retention and bioaccessibility were high (∼90% and ∼70%, respectively) in all formulations. VD3 uptake by Caco-2 cells was three-fold higher (p < 0.005) in the non-fat yoghurt enriched with VD3 in rCM compared with enriched fat-containing yoghurts. SR-BI, CD36 and NPC1L1 transporters were involved in VD3 absorption irrespective of the composition. Thus, our findings demonstrate that protein nanovehicles may improve VD3 bioavailability, without altering its absorption mechanism compared to that from fat.

Evaluation of vitamin D bioaccessibility and mineral solubility from test meals containing meat and/or cereals and/or pulses using in vitro digestion.

In this study, we evaluated vitamin D and mineral (iron, zinc, magnesium) transfer to the bolus aqueous phase during the digestion of meals with/without pulses. We performed in vitro digestions using test meals made either of i) beef and/or semolina and/or chickpeas, or of ii) potatoes supplemented or not with fibers, phytates, tannins and saponins. Chickpea presence led to a decrease in vitamin D bioaccessibility (-56%, p ≤ 0.05) and mineral solubility (-28% for iron, p ≤ 0.05) compared with meals with beef and/or semolina only. This effect was largely compensated for vitamin D by the fact that this vitamin was more stable during digestion of meals based on plant foods only than of meals with beef. Tannins were the most deleterious compounds for iron solubility, while phytates and tannins decreased vitamin D bioaccessibility. Agronomical or technical solutions to selectively decrease the amount in pulses of compounds that affect micronutrient bioavailability should be further explored.

In vitro solubilization of fat-soluble vitamins in structurally defined mixed intestinal assemblies.

The structures of fed state intestinal assemblies containing bile components, dietary fat, and fat-soluble vitamins are not well known, although they are involved in lipid transport. In this study, several methods were used to investigate structural transitions upon various dietary lipids or various fat-soluble vitamins incorporation in bile intestinal assemblies. In particular, DLS and turbidimetry were used to study transition points as a function of component concentration, and cryo-TEM and SAXS were used to resolve assembly structures at microscopic and supramolecular scales, respectively. Results showed that increasing the concentration of dietary lipids in bile assembly induced a transition from core-shell micelles to unilamellar vesicles (except with caprylate lipids, always yielding micelles). In these specific assemblies, increasing the concentration of a fat-soluble vitamin either induced a systematic structural transition, defining a solubilization capacity (α-tocopherol or phylloquinone), or induced a structural transition only in micelles (retinol), or did not induce any structural transition up to very high concentrations (cholecalciferol). Using SAXS data, ideal molecular organizations are proposed for assemblies in the absence or presence of α-tocopherol.

P-glycoprotein (ABCB1) is involved in vitamin K efflux.

ABCB1 (P-glycoprotein/MDR1) is a multidrug efflux transporter that has previously been involved in cholesterol and vitamin D metabolism. Our aim was to explore whether ABCB1 is also involved in vitamin K efflux. Vitamin K apical efflux was significantly decreased in presence of ABCB1 inhibitor in Caco-2 cells (-20.4%; p < 0.05) and increased in Griptite cells overexpressing ABCB1 (+40.7%; p < 0.05). In vivo, the vitamin K postprandial response was higher in male Abcb1-/- mice after gavage compared to control animals (+115%; p < 0.05), but was unchanged in female mice. Finally, a vitamin K transintestinal efflux and a biliary vitamin K efflux were observed, but the specific involvement of ABCB1 could not be confirmed in these pathways. Overall, we showed for the first time that ABCB1 is involved in enterocyte vitamin K efflux in both cell and mouse models and regulates vitamin K absorption in mice.