Carotenoids are C-30 or C-40 based pigments with antioxidant/anti-inflammatory properties, some possessing vitamin A activity. Their dietary intake, especially within fruits and vegetables, has been associated with a decreased risk of chronic diseases, including type-2 diabetes, cardiovascular diseases, age-related macular degeneration, and several types of cancer. However, their bioavailability is wide ranging and is affected by numerous factors. Recent findings showing that the intestinal absorption of carotenoids involves proteins have raised new relevant questions about factors that can affect their bioavailability. It is therefore opportune to present a current overview of this topic.Scope and approach: This review begins by exploring what is known, as well as what is unknown, about the metabolism of carotenoids in the human upper gastrointestinal tract and then presents a methodical evaluation of factors assumed to affect carotenoid bioavailability. Key findings and conclusions : Numerous unanswered questions remain about the metabolism of carotenoids in the intestinal lumen and about the factors affecting their absorption efficiency. These gaps need to be filled to be able to better understand individual, variable responses to these compounds so as to promote guidelines towards personalized dietary recommendation in order to increase carotenoid absorption efficiency and hence their health effects. Two main conclusions can be drawn. First, the efficiency of carotenoid absorption is affected by several dietary factors (e.g. food matrix, fat, and fat-soluble micronutrients). Second, carotenoid bioavailability also depends on host-related factors, e.g. diseases, life-style habits, gender and age, as well as genetic variations including single nucleotide polymorphisms

Carotenoid dietary intake and their endogenous levels have been associated with a decreased risk of several chronic diseases. There are indications that carotenoid bioavailability depends, in addition to the food matrix, on host factors. These include diseases (e.g. colitis), life‐style habits (e.g. smoking), gender and age, as well as genetic variations including single nucleotide polymorphisms that govern carotenoid metabolism. These are expected to explain interindividual differences that contribute to carotenoid uptake, distribution, metabolism and excretion, and therefore possibly also their association with disease risk. For instance, digestion enzymes fostering micellization (PNLIP, CES), expression of uptake/efflux transporters (SR‐BI, CD36, NPC1L1), cleavage enzymes (BCO1/2), intracellular transporters (FABP2), secretion into chylomicrons (APOB, MTTP), carotenoid metabolism in the blood and liver (LPL, APO C/E, LDLR), and distribution to target tissues such as adipose tissue or macula (GSTP1, StARD3) depend on the activity of these proteins. In addition, human microbiota, e.g. via altering bile‐acid concentrations, may play a role in carotenoid bioavailability. In order to comprehend individual, variable responses to these compounds, an improved knowledge on intra‐/interindividual factors determining carotenoid bioavailability, including tissue distribution, is required. Here, we highlight the current knowledge on factors that may explain such intra‐/interindividual differences.

There is uncertainty regarding carotenoid intake recommendations, because positive and negative health effects have been found or are correlated with carotenoid intake and tissue levels (including blood, adipose tissue, and the macula), depending on the type of study (epidemiological vs intervention), the dose (physiological vs supraphysiological) and the matrix (foods vs supplements, isolated or used in combination). All these factors, combined with interindividual response variations (eg, depending on age, sex, disease state, genetic makeup), make the relationship between carotenoid intake and their blood/tissue concentrations often unclear and highly variable. Although blood total carotenoid concentrations <1000 nmol/L have been related to increased chronic disease risk, no dietary reference intakes (DRIs) exist. Although high total plasma/serum carotenoid concentrations of up to 7500 nmol/L are achievable after supplementation, a plateauing effect for higher doses and prolonged intake is apparent. In this review and position paper, the current knowledge on carotenoids in serum/plasma and tissues and their relationship to dietary intake and health status is summarized with the aim of proposing suggestions for a “normal,” safe, and desirable range of concentrations that presumably are beneficial for health. Existing recommendations are likewise evaluated and practical dietary suggestions are included.

β-Carotene intake and tissue/blood concentrations have been associated with reduced incidence of several chronic diseases. Further bioactive carotenoid-metabolites can modulate the expression of specific genes mainly via the nuclear hormone receptors: retinoic acid receptor- and retinoid X receptor-mediated signalling. To better understand the metabolic conversion of β-carotene, inter-individual differences regarding β-carotene bioavailability and bioactivity are key steps that determine its further metabolism and bioactivation and mediated signalling. Major carotenoid metabolites, the retinoids, can be stored as esters or further oxidised and excreted via phase 2 metabolism pathways. In this review, we aim to highlight the major critical control points that determine the fate of β-carotene in the human body, with a special emphasis on β-carotene oxygenase 1. The hypothesis that higher dietary β-carotene intake and serum level results in higher β-carotene-mediated signalling is partly questioned. Alternative autoregulatory mechanisms in β-carotene / retinoid-mediated signalling are highlighted to better predict and optimise nutritional strategies involving β-carotene-related health beneficial mediated effects.

Blood concentration of vitamin A (VA), which is present as different molecules, i.e., mainly retinol and provitamin A carotenoids, plus retinyl esters in the postprandial period after a VA-containing meal, is affected by numerous factors: dietary VA intake, VA absorption efficiency, efficiency of provitamin A carotenoid conversion to VA, VA tissue uptake, etc. Most of these factors are in turn modulated by genetic variations in genes encoding proteins involved in VA metabolism. Genome-wide association studies (GWAS) and candidate gene association studies have identified single nucleotide polymorphisms (SNPs) associated with blood concentrations of retinol and β-carotene, as well as with β-carotene bioavailability. These genetic variations likely explain, at least in part, interindividual variability in VA status and in VA bioavailability. However, much work remains to be done to identify all of the SNPs involved in VA status and bioavailability and to assess the possible involvement of other kinds of genetic variations, e.g., copy number variants and insertions/deletions, in these phenotypes. Yet, the potential usefulness of this area of research is exciting regarding the proposition of more personalized dietary recommendations in VA, particularly in populations at risk of VA deficiency.

Recent data have shown that interindividual variability in the bioavailability of vitamins A (β-carotene), D, and E, and carotenoids (lutein and lycopene), as well as that of phytosterols, is modulated by single nucleotide polymorphisms (SNPs). The identified SNPs are in or near genes involved in intestinal uptake or efflux of these compounds, as well as in genes involved in their metabolism and transport. The phenotypic effect of each SNP is usually low, but combinations of SNPs can explain a significant part of the variability. Nevertheless, results from these studies should be considered preliminary since they have not been validated in other cohorts. Guidelines for future studies are provided to ensure that sound associations are elucidated that can be used to build consolidated genetic scores that may allow recommended dietary allowances to be tailored to individuals or groups by taking into account the multiloci genotypic signature of people of different ethnic origin or even of individuals.