ABSTRACT The distribution of fat-soluble compounds (including antioxidants) in follicular fluid (FF) remains sparsely documented in relation to in vitro fertilization (IVF) outcomes and existing studies have reported diverging associations. This study aimed to describe plasma and FF concentrations of fat-soluble micronutrients in women undergoing IVF and to analyze their adjusted associations with ovarian function, embryo development and pregnancy outcomes. In 2021-2022, plasma and FF samples were collected from 82 women (first IVF cycle) at oocyte puncture, along with lifestyle data covering the three preceding months. Eleven compounds (two tocopherols, three xanthophylls, five carotenes and retinol) were quantified. All compounds were detected in both compartments (lowest in FF) except phytoene, undetectable in FF. Plasma and FF α-tocopherol concentrations were positively associated with plasma estradiol levels before oocyte puncture (both p<0.01) while FF α-carotene and lycopene were inversely associated with plasma progesterone concentrations (p=0.01 and 0.02, respectively). Plasma phytofluene and phytoene were positively associated with mature oocyte rate (p=0.03 and p=0.01, respectively), while FF retinol was negatively associated (p=0.03). Carotenes, tocopherols and retinol were inversely associated with later IVF outcomes: fertilization rate (p<0.001 for plasma γ-tocopherol, 0.02 for FF retinol), top-quality embryo (p=0.02 for plasma phytofluene), biochemical pregnancy at day 7 post-embryo transfer (p=0.05 for plasma α-tocopherol, 0.02 for plasma α-carotene), clinical pregnancy (p=0.03 for plasma α-tocopherol, 0.01 for plasma phytoene) and live birth (p=0.04 for plasma α-tocopherol, 0.02 for plasma phytoene). Plasma and FF γ-tocopherol were positively associated with embryo fragmentation (both p<0.05). Finally, among xanthophylls, only plasma β-cryptoxanthin was positively associated with plasma progesterone concentrations (p=0.02). Our findings of heterogeneous associations between tocopherols, carotenes, retinol and IVF outcomes across the stages of IVF suggest a beneficial effect limited to early outcomes and support a complex and context-dependent role of these compounds in female reproduction.

Adipose tissue is a major storage site for provitamin A carotenoids (proVA CAR)-mainly β-carotene (BCAR), α-carotene (ACAR), and β-cryptoxanthin (BCRY). However, the determinants of their concentrations in this tissue remain poorly understood. This study aimed to identify genetic variants associated with adipose tissue proVA CAR concentrations. Periumbilical adipose tissue samples were collected on six occasions in 43 healthy adult males and proVA CAR concentrations were quantified by HPLC. Participants were genotyped for 2,398 SNPs in 44 candidate genes involved in CAR and lipid metabolism, and genetic associations were assessed using partial least squares (PLS) regression. Adipose tissue proVA CAR concentrations ranked as BCAR > ACAR > BCRY, with CV ranging from 54 to 66%. PLS regression models integrating fasting plasma proVA CAR concentrations and SNPs explained 69, 59, and 67% of the variability in BCAR, ACAR, and BCRY concentrations, respectively. In a multivariate PLS regression model, the main determinants of proVA CAR concentrations were fasting plasma BCAR and ACAR concentrations and four SNPs-rs4694627 (CXCL8), rs7558381 (IRS1), rs709157 and rs1152004 (PPARG). Interindividual variability in adipose tissue proVA CAR concentrations is partly explained by genetic variation in genes involved in CAR and lipid metabolism. Clinical Trial Registry: ClinicalTrials.gov registration number NCT02100774.

Dietary fiber could inhibit β-carotene bioaccessibility by restricting its release from the food matrix, interfering with digestive enzyme activities, binding bile salts, or modifying viscosity and other physicochemical properties of the digesta. In this study, we investigated whether high methoxyl pectin (HMP), a soluble dietary fiber found in fruits/vegetables and an additive for the food industry would impact β-carotene bioaccessibility under various physiological digestive conditions, following the INFOGEST gastrointestinal model. Concentrations of pancreatin plus bile salts and shear forces (simulated by varying water bath rounds/min. and glass bead addition) were modified in the presence (1.15 mg/mL digesta) and absence of HMP. Endpoints measured in the digesta included β-carotene bioaccessibility, surface tension, viscosity, micelle size, zeta potential, and triglyceride lipolysis. Adding HMP reduced overall bioaccessibility of β-carotene from 32.1±6.2% to 24.1±5.7% (p<0.001). All other parameters also had a significant impact on the bioaccessibility of β-carotene, that is, bile/pancreatin concentration (p<0.001), water bath shaking speed (p<0.001), and glass beads (p = 0.001). Surface tension, viscosity, and micelle size were less strongly affected by HMP addition (p<0.05), though not triglyceride lipolysis. The inhibitory effect of HMP varied depending on bile/pancreatin concentration and shear-forces, with strongest reductions when β-carotene bioaccessibility was highest at onset.

Background and objectives: Lycopene (LYC) is a carotenoid obtained primarily from tomatoes and tomato-based products. LYC displays potent antioxidant properties and its intake and circulating concentrations have been associated with a reduced risk of prostate and breast cancers as well as cardiovascular diseases. Following absorption, it is mainly stored in adipose tissue, which accounts for approximately two-thirds of total body stores, where it may influence processes such as oxidative stress and inflammation. However, the factors determining LYC concentration in adipose tissue remain poorly understood. This study aimed to characterize the interindividual variability of adipose tissue LYC concentration and identify single nucleotide polymorphisms (SNPs) associated with it. Methods: Forty-three healthy adult males (mean age: 32.0 ± 2.0 year; mean BMI: 23.0 ± 0.3 kg m-2) underwent whole-genome genotyping. Periumbilical adipose tissue samples were collected on six occasions (in the fasting state and 8 h after consumption of three different standardized meals), and plasma and adipose tissue LYC concentrations were quantified by HPLC. Forty-three candidate genes potentially involved in LYC metabolism were selected, and the association of 3786 SNPs from these genes with adipose tissue LYC concentration was assessed using partial least squares regression. Results: Adipose tissue LYC concentration showed marked interindividual variability (CV = 55%). Adipose tissue and fasting plasma LYC concentrations were significantly, but moderately, correlated (Pearson's r = 0.37; 95% CI: 0.07-0.61). An internally validated PLS regression model consisting of 17 SNPs in 11 genes-ABCA1, APOB, CD36, ELOVL5, GRAMD1C, INSIG2, IRS1, ISX, PPARG, SOD2, and TCF7L2-explained 55% of the variability in adipose tissue LYC concentration (adjusted R2). Conclusions: Adipose tissue LYC concentration displays high interindividual variability, which can be explained in part by genetic variants in genes involved in carotenoid and lipid metabolism. Clinical trial registry: ClinicalTrials.gov registration number NCT02100774.

Intracellular trafficking of fat-soluble vitamins in enterocytes remains poorly understood. Recent studies have implicated Aster proteins in the non-vesicular transport of cholesterol and carotenoids from the brush border membrane to the endoplasmic reticulum, alongside an endocytic pathway. Here, we investigated the role of these two pathways in the transport of vitamins A, D, and E. In cultured human intestinal cells, Aster inhibition did not affect retinol esterification, confirming that retinol can reach the endoplasmic reticulum via an Aster-independent pathway. Conversely, Aster inhibition significantly reduced the basolateral secretion of both α-tocopherol and cholecalciferol without altering their uptake. Combined inhibition of Aster and NPC1L1 did not further decrease the secretion of vitamins E and D, indicating a shared pathway. In contrast, dual inhibition of Aster and SR-BI led to an additional reduction in the secretion of vitamins E and D. Inhibition of endocytosis markedly decreased the secretion of vitamins D and E, as well as the esterification of vitamin A. In mice, Aster inhibition lowered vitamin E bioavailability, while in humans, five SNPs in GRAMD1B gene correlated with vitamin D bioavailability. This work provides the first evidence of the involvement of Aster proteins and endocytosis in intestinal fat-soluble vitamin absorption.

Neurodevelopmental psychiatric diseases such as schizophrenia or affective disorders share common symptomatic dimensions, in particular reward processing dysfunctions, associated with dysregulation of dopamine (DA) transmission. Retinoic acid (RA) homeostasis, the active metabolite of vitamin A, is altered across psychiatric disorders but whether impaired developmental RA signaling impacts the functionality of DA-related reward processing at adulthood remains poorly explored. Herein, we found that vitamin A (i.e., retinol) deficiency (VAD) from gestation to adulthood potentiates instrumental responding in motivational tasks and increases choice impulsivity in male, but not female mice. These behavioral alterations in males are coherent with reduced DA transporter (DAT) expression in the midbrain and increased mesolimbic DA dynamics associated with instrumental responding. In accordance, chemogenetic inhibition of midbrain DA neurons normalizes motivational performance in VAD males. Our results support that developmental VAD induces sex-specific reward processing alterations at adulthood through hyperactivity of the mesolimbic DA pathway. Such findings reinforce the idea that RA signaling is an important modulator of the brain reward system by shaping DA transmission.

Black soldier fly larvae (BSFL), Hermetia illucens, can efficiently convert biowaste into high-quality protein for the feed industry. However, biowaste can contain several chemical hazards and their fate in BSFL remain largely unexplored, even though they can pose a threat for both the insect sector and the higher levels of the trophic chain. The purpose of this study was to evaluate the chemical contamination of BSFL reared on authorized biowaste (wheat bran, carrots, apricots, salad) or unauthorized biowaste in the EU (school canteen and supermarket biowaste). PFAS were not quantifiable in the substrates in contrast with persistent organic pollutants, pesticides and trace metal elements. The chlormequat pesticide was the only pesticide quantified in BSFL (15 µg/kg), slightly above the maximum residue limit in the EU for feed (10 µg/kg). Concentrations of PCBs and PCDD/Fs in BSFL were below the maximum limit (ML) but bioaccumulation factors up to 5 were obtained. As and Cd were highly bioaccumulated with concentrations approaching the ML for Cd (0.5 mg/kg) or 8 times below for As (ML = 2 mg/kg). The unauthorized substrate samples tested led to higher chemical safety risks in BSFL, with 10 times higher concentrations of As than in BSFL reared on authorized substrates and the presence of PCDD/Fs and PCBs. The concentrations of chemical contaminants in animal products consumed by humans such as eggs were estimated using transfer models when animals were fed with BSFL reared on unauthorized substrates. The concentrations were below the maximum limits in all cases.

The nutritional and market values of black soldier fly larvae (BSFL) can be improved by enriching them with compounds of interest. It has recently been shown that these larvae can bioaccumulate fat-soluble vitamins and carotenoids under optimal rearing conditions. Based on these preliminary results, the aim was to determine whether BSFL can be significantly enriched in these compounds when raised under conditions usually used by breeders such as preliminary substrate fermentation. BSFL were raised on EU-authorized substrates, i.e. plant biowastes, and EU-unauthorized biowastes from school canteens and supermarkets. Vitamins A, E and D, as well as 10 carotenoids were quantified by HPLC-DAD in the substrates and larvae. Although BSFL mass were lower in the apricot (85 ± 4 mg) group compared to the control group (121 ± 8 mg), the dry weight, total protein and lipid content of all the groups were not different. Most compounds present in the fermented substrates were found in the larvae, but in lower concentrations than those observed under the optimal rearing conditions, e.g. β-carotene in larvae reared on carrots 9.6 ± 0.4 mg/kg FW vs98 ± 17 mg/kg, respectively. Regarding unauthorized substrates, they allowed larvae to bioaccumulate wider variety of micronutrients than other substrates, although in smaller quantities. Thus, raising BSFL under standard industrial breeding conditions makes it possible to obtain larvae enriched in micronutrients, without impacting their total protein and lipid content. However, the rearing conditions must be optimized if higher concentrations of these micronutrients in the larvae are wanted and further studies are necessary to confirm the results of this exploratory study.

Following a request from the French Directorate General for Health, ANSES was asked to deliver a scientific opinion on the state of the evidence on the prevention of neural tube defects (NTDs) by increasing vitamin B9 intake. The opinion estimates the prevalence of NTDs in France using data collected between 2012 and 2021 from five French registries reporting a mean prevalence of 13.5 per 10 000 births. The efficacy of vitamin B9 supplementation and food fortification was evaluated by conducting systematic reviews of human studies. The opinion also provides a comparative analysis of international vitamin B9 fortification strategies, followed by simulations to assess fortification levels and their potential to reduce inadequate vitamin B9 intake in France. The Expert Committee and ANSES concluded that fortifying flour (both refined and whole grain) with 200 μg of folic acid per 100 g would enable 90% of women to meet the Dietary Reference Value for adults and ensure a mean intake exceeding the adequate intake of 600 μg/day of dietary folate equivalents during pregnancy. However, this measure would not replace the recommendation for women to take a folic acid supplement (400 μg/day) from the moment they try to conceive until 12 weeks of pregnancy. ANSES further recommended initiating a public consultation of all the stakeholders.

This document presents the opinion of the French Agency for Food, Environmental and Occupational Health & Safety (ANSES), established from the work of its Working Group on Vegetarian diets and validated by its Expert Committee on Human Nutrition. ANSES issued an internal request to establish dietary guidelines for people who follow a diet that excludes some or all foods of animal origin. Firstly, ANSES conducted a systematic review of the scientific literature to identify epidemiological links between health and various types of vegetarian diets. This systematic review showed that the risk of developing type 2 diabetes is lower with vegetarian than with non-vegetarian diets. With a lower level of evidence, vegetarians are less likely than non-vegetarians to develop certain diseases, such as ischaemic heart disease, ovulation disorders, certain types of cancer (prostate, stomach, blood) and certain ophthalmological and gastro-intestinal diseases. However, they are at greater risk of bone fractures and hypospadias (congenital malformation of the urethra). The epidemiological studies examined showed that vegetarians have a less favourable nutritional status in iron, iodine and vitamins B12 and D, and a poorer calcium and phosphorus balance than non-vegetarians. Vegans also have a less favourable nutritional status in vitamin B2. ANSES then used dietary optimisation to identify combinations of food groups (state variables) enabling the set objectives to be met, i.e. to reduce nutritional and toxicological risks, while deviating as little as possible from current consumption habits. All the nutritional and toxicological constraints and the criteria (minimisations or maximisations) made it possible to take account of the risks associated with nutrient intakes or exposure to contaminants, as well as the expected nutritional benefits. The systematic review and establishment of dietary guidelines using an optimisation tool show that the lacto-ovo-vegetarian diet requires particular attention regarding certain nutrients for which requirements in terms of vitamin D and eicosapentaenoic and docosahexaenoic fatty acids may not be met. The risk of requirements not being met by the lacto-ovo-vegetarian diet is greater than that associated with the diet of non-vegetarian populations. In addition, lacto-ovo-vegetarians limiting their intake of milk and fresh dairy products may not be able to cover their vitamin B12 requirements. Furthermore, with the vegan diet, which excludes all foods of animal origin, it is difficult to meet the dietary reference value for zinc in men.

Vitamin A (VA) supplementation has been recommended for pregnant women at-risk of deficiency, and is widely applied to children under 5 in developing countries. We addressed the effect of excessive VA exposure during pregnancy, lactation and first weeks of life on VA, vitamin E and lipid metabolism in rat offspring. Sprague-Dawley female rats were fed either a 2300 IU.kg-1 VA diet (control diet) or a 9858 IU.kg-1 VA diet (vitamin A supplemented diet - VAS diet) and mated with males fed the control diet. Weanlings were fed the same diet as their mothers until they were 8 weeks old. Organs and adipose tissue were collected from half of the offspring after fasting. The other half was force-fed an oil-in-water emulsion containing retinyl palmitate and [1,1,1-13C3]triolein. VAS-fed female and male offspring displayed a significant accumulation of VA in the liver (18 and 32 times more retinyl esters than respective controls, p < 0.0001) and VAS-fed males exhibited higher plasma retinol concentrations (+ 42.8 ± 6.6% compared to control males, p = 0.0011). Fasting plasma triglyceride concentration was higher for both VAS-fed females and males (+ 44.6 ± 6.8%, p = 0.0007 and + 58.8 ± 20.2%, p = 0.0343, compared to their respective controls). Lipid absorption was increased in VAS-fed males (+ 60.9% of [1-13 C]oleate absorption at 1.5 h post-gavage, p < 0.0001). Overall, our data show that VA overexposure disbalances VA status and detrimentally impacts lipid metabolism in offspring.

Carotenoids, including β-carotene, lutein and lycopene, the 3 main carotenoids present in our body, are lipophilic phytochemicals associated with several health benefits. Dietary fibre may influence the bioavailability of carotenoids by altering their release from the food matrix and their solubilisation into mixed micelles during digestion and thus their subsequent absorption by enterocytes. We examined the dose-dependent influence of major soluble (pectin, guar, alginate, fructooligosaccharides,) and insoluble dietary fibres (cellulose, type-2 resistant starch) at nutritional relevant doses (0, 30 and 90 mg per 26 ml) added for digestion, containing also pure β-carotene, lutein or lycopene (at 75 μg) solubilized in peanut oil. Following in vitro gastrointestinal digestions, carotenoid bioaccessibility, selected physico-chemical parameters (viscosity, surface tension, ζ-potential and micelle size) and free fatty acid release were evaluated. β-Carotene bioaccessibility was reduced by 90 mg of alginate and pectin, from 29.1% to 11.8% and 17.9%, respectively (p < 0.001), while other fibres had no overall significant impact. For lutein, only pectin decreased its bioaccessibility, from 58.3% to 26.0% (p < 0.001), while for lycopene, the reduction in bioaccessibility was from 7.2% (control) to 5.4% for pectin (p < 0.05), 4.1% for alginate (p = 0.001) and 4.8% for guar (p < 0.05) for 90 mg. This negative effect was associated with altered physico-chemical properties, with soluble, gel-forming fibres (vs. non-gel-forming fibres) in general increasing viscosity, reducing surface tension and absolute ζ-potential and in part micelle size, and hampering triglyceride digestion by up to 54.3% for guar (90 mg) vs. controls. Thus, soluble, gel-forming dietary fibres hampered carotenoid bioaccessibility, also depending on carotenoid type, while insoluble and non-gel-forming dietary fibres showed no negative effect on bioaccessibility.

Black soldier fly larvae (BSFL) are a sustainable source of protein for feed but they can also be a sustainable source of some phytochemicals due to their ability to bioaccumulate them. Knowing that ergosterol in mushrooms can be chemically converted to vitamin D2 (VD2) under ultraviolet B (UVB) exposure, the aim was to investigate whether BSFL can bioaccumulate ergosterol and whether larvae ergosterol can be converted into VD2 under UVB exposure. Method: BSFL were reared on mushrooms for 2 weeks and then exposed to UVB (2.7 mW/cm2/s for up to 5 h). Ergosterol, VD2 and vitamin D3 (VD3) were quantified by HPLC in mushrooms and larvae. Main results: larvae non-exposed to UVB did not contain any detectable amount of VD2 or VD3. Larvae reared on mushrooms bioaccumulated ergosterol (702 f 95 mg/Kg FW in larvae vs 444 f 56 mg/Kg in mushrooms). Larvae reared on mushrooms and then exposed to UVB for 1 h contained high concentrations of VD2 but also of VD3 (46 f 2 and 10.9 f 0.5 mg/Kg FW, respectively). Conclusions: BSFL can bioaccumulate ergosterol. UVB exposure of ergosterol-enriched BSFL results in VD2 but also in VD3 rich BSFL. The maximal VD concentration obtained in BSFL was about 23 times higher than cod liver oil, the food known to be richest in VD. These results suggest that VD-enriched BSFL could be used to supplement the nutrition of certain livestock with VD, or be valued as a functional ingredient. This procedure has been patented (PCT/EP2024/074854).

The postprandial period is marked by increased plasma inflammatory biomarkers and heightened adipose tissue inflammation. Consumption of tomato-based products has been linked to reduced inflammation, potentially lowering the risk of cardiometabolic diseases. This study investigated the addition of tomato puree to a high-fat meal (HFM) on postprandial inflammation in healthy men. Thirty-nine healthy men participated in a randomized crossover trial (NCT02100774). Two meals were given: a HFM and the same HFM with 100 g tomato puree (TPM). Blood samples and adipose tissue biopsies were taken at various timepoints to measure inflammatory markers. TPM reduced plasma tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and C-C motif chemokine ligand (CCL)-2, and gene expression of TNFA, IL6, IL1B, and CCL5 in adipose tissue. In contrast, HFM increased IL-1β, CCL2, and adipose gene expressions of IL6, IL1B, and CCL2. Variations and net incremental area under the curve (iAUCsnet) between groups showed significantly lower inflammatory markers in TPM, except for plasma CCL2 and CCL5 expression. Incorporating tomato puree in HFM reduces both systemic and adipose tissue inflammation during the postprandial period. These findings suggest that tomato-based products may contribute to the reduction of postprandial inflammation, potentially explaining their cardiometabolic benefits.

Background: Adipose tissue vitamin A (VA), that is, mainly retinol (RET) and its esters, comes from preformed VA and proVA carotenoids present in our food. Adipose tissue VA acts as hormonal cue maintaining essential aspects of adipocyte biology, which includes fat mobilization and catabolism, energy balance, and glucose homeostasis, and it is thus of particular interest to study its determinants, including genetic ones. Objectives: This study aimed to identify genetic variations associated with adipose tissue VA concentration. Methods: Forty-two healthy male adults received, in a randomized crossover design, 3 test meals. Periumbilical adipose tissue samples were collected on 6 occasions, that is, at fast and 8 h after consumption of each meal. RET concentration was measured in both plasma and the adipose tissue following saponification. Participants were genotyped using whole-genome microarrays. A total of 1305 single nucleotide polymorphism (SNPs) in or near 27 candidate genes were included for univariate analysis. Partial least squares (PLS) regression was carried out to find the best combination of SNPs associated with the interindividual variability in adipose tissue RET concentration. Results: Adipose tissue RET concentration was not associated with plasma RET concentrations (r = -0.184, P = 0.28). Interindividual variability of adipose tissue RET concentration was high (coefficient of variation = 62%). Twenty-nine SNPs were significantly (P < 0.05) associated with adipose tissue RET concentration and a PLS regression model identified 16 SNPs as explanatory variables of this concentration. The SNPs were in or near peroxisome proliferator activated receptor gamma, retinoid X receptor alpha, signaling receptor and transporter of retinol, cluster of differentiation 36, free fatty acid receptor 4, aldehyde dehydrogenase 1 family member A1, monoglyceride lipase, diacylglycerol O-acyltransferase 2, and polycystic kidney disease 1-like 2. Conclusions: A combination of 16 SNPs has been associated with the interindividual of adipose tissue VA concentration in humans. This trial was registered at clinicaltrials.gov as NCT02100774.

This study aimed to characterize the concentrations of lutein and zeaxanthin in human adipose tissue, evaluate interindividual variation and investigate potential genetic associations.

Several studies have linked the intake of lycopene and/or tomato products with improved metabolic health under obesogenic regime. The aim was to evaluate the differential impact of supplementations with several tomato genotypes differing in carotenoid content and subjected to different irrigation levels on obesity-associated disorders in mice. In this study, 80 male C57BL/6JRj mice were assigned into 8 groups to receive: control diet, high fat diet, high fat diet supplemented at 5 % w/w with 4 tomato powders originating from different tomato genotypes cultivated under control irrigation: H1311, M82, IL6-2, IL12-4. Among the 4 genotypes, 2 were also cultivated under deficit irrigation, reducing the irrigation water supply by 50 % from anthesis to fruit harvest. In controlled irrigation treatment, all genotypes significantly improved fasting glycemia and three of them significantly lowered liver lipids content after 12 weeks of supplementation. In addition, IL6-2 genotype, rich in β-carotene, significantly limited animal adiposity, body weight gain and improved glucose homeostasis as highlighted in glucose and insulin tolerance tests. No consistent beneficial or detrimental impact of deficit irrigation to tomato promoting health benefits was found. These findings imply that the choice of tomato genotype can significantly alter the composition of fruit carotenoids and phytochemicals, thereby influencing the anti-obesogenic effects of the fruit. In contrast, deficit irrigation appears to have an overall insignificant impact on enhancing the health benefits of tomato powder in this context, particularly when compared to the genotype-related variations in carotenoid content.