The Kraft Heinz Company global nutrition targets for the innovation and reformulation of food and beverages: Current and future directions.

Reformulating packaged foods has the potential to improve the nutrient density of the global diet. The present perspective illustrates The Kraft Heinz Company's approach to product (re)formulation to develop healthier product lines that are lower in saturated fats, total sugars, and sodium, and contain health promoting components. Here we present the rationale for The Kraft Heinz Company's global nutrition targets used for the global innovation and renovation of foods and beverages. The global nutrition targets use a category specific approach to set maximum levels for the main nutrients of public health concern: saturated fat, total sugars and sodium, taking into account product characteristics (typical portion size, eating occasion, role in the diet, etc.) as well as regulatory, technological, sensory and safety constraints. Benchmarking examples illustrate how the nutrition targets are positioned within the United States, France, and Australia. These global nutrition targets serve as part of The Kraft Heinz Company's environmental, social and governance nutrition commitments and demonstrates how the food industry is improving the nutritional value of packaged foods and beverages both now and into the future.

Are Front-of-Pack Nutrition Labels Influencing Food Choices and Purchases, Diet Quality, and Modeled Health Outcomes? A Narrative Review of Four Systems.

Front-of-Pack Nutrition labels (FOPNLs) aim to improve consumers' food purchases and prompt product reformulation by the food and beverage industry. Despite their widespread use, the effectiveness of FOPNL in achieving these goals is still a matter of debate. This review has gathered 65 original studies exploring the performances of four widely used FOPNLs (Multiple Traffic Light, Warning signs, Nutri-Score and Health Star Rating). Although FOPNLs have been associated with healthier food purchases, the magnitude of improvements was small and dependent on study settings. Any associated health effects were modeled rather than observed. None of the four FOPNLs clearly outperformed the other ones on any outcome. Few studies dealt with the impact of FOPNL on product reformulation. Some of those studies, but not all, found small reductions in energy, sodium, sugar and saturated fat content of foods in some food categories. Although global trends point to a small favorable effect of FOPNL, this conclusion is subject to caution since the evidence is inconsistent and comes from a wide variety of contexts and study designs. There remain numerous research gaps, notably with regard to the optimal characteristics of FOPNLs, the durability of FOPNL effects on consumer behaviors, and any possible unexpected consequences.

A Slight Adjustment of the Nutri-Score Nutrient Profiling System Could Help to Better Reflect the European Dietary Guidelines Regarding Nuts.

The consumption of nuts remains low among European populations despite widespread inclusion as a recommended food group across European dietary guidelines. Front-of-Pack nutrition labelling systems are designed to support consumers make healthier choices and to stimulate product improvement, thus representing a pivotal opportunity to reduce the gap between intakes and recommendations. This study examined how the Nutri-Score algorithm treats nuts and nut-containing products and tested whether slight adjustments could better recognise and motivate nut inclusion in foods and diets. The nutritional score (ScN) and corresponding Nutri-Score letter of 68 nuts and nut-containing products were calculated, using the initial algorithm and slight adjustments, where nut weight was doubled (S1), saturated fats (S2) or energy (S3) from nuts were discounted, or saturated fats were replaced by the saturated fats/lipid ratio (S4). The correlation between the nuts' content and the ScN was moderate for the initial algorithm (R2 = 0.34) and S1 (R2 = 0.36), but improved for S2, S3 and S4 (R2 = 0.54, 0.55 and 0.52, respectively). Four plain nuts, initially labelled as "B" or "C" obtained a Nutri-Score "A" with S2, S3 and S4. Slight adjustments could better align the Nutri-Score with food-based dietary guidelines, reassure consumers on healthfulness of nuts and nut-containing products, whilst incentivising the inclusion of nuts in diverse foods.

Ultra-processed foods: how functional is the NOVA system?

BACKGROUND: In the NOVA classification system, descriptive criteria are used to assign foods to one of four groups based on processing-related criteria. Although NOVA is widely used, its robustness and functionality remain largely unexplored. We determined whether this system leads to consistent food assignments by users. METHODS: French food and nutrition specialists completed an online survey in which they assigned foods to NOVA groups. The survey comprised two lists: one with 120 marketed food products with ingredient information and one with 111 generic food items without ingredient information. We quantified assignment consistency among evaluators using Fleiss' κ (range: 0-1, where 1 = 100% agreement). Hierarchical clustering on principal components identified clusters of foods with similar distributions of NOVA assignments. RESULTS: Fleiss' κ was 0.32 and 0.34 for the marketed foods (n = 159 evaluators) and generic foods (n = 177 evaluators), respectively. There were three clusters within the marketed foods: one contained 90 foods largely assigned to NOVA4 (91% of assignments), while the two others displayed greater assignment heterogeneity. There were four clusters within the generic foods: three clusters contained foods mostly assigned to a single NOVA group (69-79% of assignments), and the fourth cluster comprised 28 foods whose assignments were more evenly distributed across the four NOVA groups. CONCLUSIONS: Although assignments were more consistent for some foods than others, overall consistency among evaluators was low, even when ingredient information was available. These results suggest current NOVA criteria do not allow for robust and functional food assignments.

The simplified nutrient profiling system (SENS) adequately ranks foods in relation to the overall nutritional quality of diets: a validation study.

BACKGROUND/OBJECTIVES: We aimed to validate the simplified nutrient profiling system (SENS) algorithm based on its ability to rank foods across the four SENS classes in relation to overall nutritional quality of both observed diets and nutritionally optimized diets. SUBJECTS/METHODS: Foods and beverages from the French nutritional composition database were classified according to SENS. Diets consumed by French adults in the latest national dietary survey (>19 years, n = 1719) were divided into four nutritional quality levels, and average daily frequencies (number of portions per day) of foods from the four SENS classes were compared between the four levels. Then, for each individual observed diet, one iso-caloric and nutritionally adequate diet was optimized, and variations in daily frequencies of foods from each SENS class between observed and optimized diets were estimated. RESULTS: In observed diets, as overall nutritional quality level of diet increased, daily frequency increased for Class-1 foods (3.5 to 8.7 portions/d) and decreased for Class-4 foods (6.8 to 3.0 portions/day). From observed to optimized diets, daily frequency increased for Class-1 foods for 98.4% of individuals and decreased for Class-4 foods for 94.2% of individuals. Class-2 and Class-3 foods also followed patterns that fit the expected ranking. CONCLUSIONS: Results from two WHO-recommended validation approaches showed that the SENS algorithm adequately ranks foods according to their contribution to overall nutritional quality of diets, which is a pre-requisite to use for simplified nutritional labeling in Europe.

The SENS algorithm-a new nutrient profiling system for food labelling in Europe.

BACKGROUND/OBJECTIVES: In response to the European regulation on nutrition and health claims, France proposed in 2008 the SAIN,LIM profiling system that classifies foods into four classes based on a nutrient density score called 'SAIN', a score of nutrients to limit called 'LIM', and one primary threshold on each score. We present here the SENS algorithm, a new nutrient profiling system adapted from the SAIN,LIM to be operational for simplified nutrition labelling in line with the European regulation on food information to consumers. SUBJECTS/METHODS: The main changes made to SAIN,LIM to get SENS were to introduce food categories and sub-categories ('Beverages', 'Added Fats' and 'Other Solid Foods' sub-categorised into 'cereals', 'cheese', 'other dairy products', 'eggs', 'fish' and 'others'), reduce the number of nutrients, introduce category-specific nutrients and category-specific weighting for some nutrients, replace French recommendations with European reference intakes, and add secondary thresholds. Each food and non-alcoholic beverage from the 2013-CIQUAL French composition database (n = 1065) was assigned one SENS class. Distribution of foods according to the four SENS classes was described by food groups (n = 26). RESULTS: The SENS classification was consistent with the recommendations to consume large amounts of whole grains, vegetables and fruits, and moderate intake of fats, sugars, meats, caloric beverages and salt. For most groups (19/26), foods were distributed across at least three SENS classes. CONCLUSIONS: The SENS is a nutrition-sensitive system that discriminates foods between and within food categories. It preserves the strengths of the initial SAIN,LIM while making it operational for simplified nutrition labelling in Europe.

From the SAIN,LIM system to the SENS algorithm: a review of a French approach of nutrient profiling.

Nutrient profiling aims to classify or rank foods according to their nutritional composition to assist policies aimed at improving the nutritional quality of foods and diets. The present paper reviews a French approach of nutrient profiling by describing the SAIN,LIM system and its evolution from its early draft to the simplified nutrition labelling system (SENS) algorithm. Considered in 2010 by WHO as the 'French model' of nutrient profiling, SAIN,LIM classifies foods into four classes based on two scores: a nutrient density score (NDS) called SAIN and a score of nutrients to limit called LIM, and one threshold on each score. The system was first developed by the French Food Standard Agency in 2008 in response to the European regulation on nutrition and health claims (European Commission (EC) 1924/2006) to determine foods that may be eligible for bearing claims. Recently, the European regulation (EC 1169/2011) on the provision of food information to consumers allowed simplified nutrition labelling to facilitate consumer information and help them make fully informed choices. In that context, the SAIN,LIM was adapted to obtain the SENS algorithm, a system able to rank foods for simplified nutrition labelling. The implementation of the algorithm followed a step-by-step, systematic, transparent and logical process where shortcomings of the SAIN,LIM were addressed by integrating specificities of food categories in the SENS, reducing the number of nutrients, ordering the four classes and introducing European reference intakes. Through the French example, this review shows how an existing nutrient profiling system can be specifically adapted to support public health nutrition policies.

Iron for Africa-Report of an Expert Workshop.

Scientific experts from nine countries gathered to share their views and experience around iron interventions in Africa. Inappropriate eating habits, infections and parasitism are responsible for significant prevalence of iron deficiency, but reliable and country-comparable prevalence estimates are lacking: improvements in biomarkers and cut-offs values adapted to context of use are needed. Benefits of iron interventions on growth and development are indisputable and outweigh risks, which exist in populations with a high infectious burden. Indeed, pathogen growth may increase with enhanced available iron, calling for caution and preventive measures where malaria or other infections are prevalent. Most African countries programmatically fortify flour and supplement pregnant women, while iron deficiency in young children is rather addressed at individual level. Coverage and efficacy could improve through increased access for target populations, raised awareness and lower cost. More bioavailable iron forms, helping to decrease iron dose, or prebiotics, which both may lower risk of infections are attractive opportunities for Africa. Fortifying specific food products could be a relevant route, adapted to local context and needs of population groups while providing education and training. More globally, partnerships involving various stakeholders are encouraged, that could tackle all aspects of the issue.

A review of total & added sugar intakes and dietary sources in Europe.

Public health policies, including in Europe, are considering measures and recommendations to limit the intake of added or free sugars. For such policies to be efficient and monitored, a precise knowledge of the current situation regarding sugar intake in Europe is needed. This review summarizes published or re-analyzed data from 11 representative surveys in Belgium, France, Denmark, Hungary, Ireland, Italy, Norway, The Netherlands, Spain and the UK. Relative intakes were higher in children than in adults: total sugars ranged between 15 and 21% of energy intake in adults and between 16 and 26% in children. Added sugars (or non-milk extrinsic sugars (NMES), in the UK) contributed 7 to 11% of total energy intake in adults and represented a higher proportion of children's energy intake (11 to 17%). Educational level did not significantly affect intakes of total or added sugars in France and the Netherlands. Sweet products (e.g. confectionery, chocolates, cakes and biscuits, sugar, and jam) were major contributors to total sugars intake in all countries, genders and age groups, followed by fruits, beverages and dairy products. Fruits contributed more and beverages contributed less to adults' total sugars intakes than to children's. Added sugars were provided mostly by sweet products (36 to 61% in adults and 40 to 50% in children), followed by beverages (12 to 31% in adults and 20 to 34% in children, fruit juices excluded), then by dairy products (4 to 15% in adults and 6 to 18% in children). Caution is needed, however, as survey methodologies differ on important items such as dietary data collection, food composition tables or estimation of added sugars. Cross-country comparisons are thus not meaningful and overall information might thus not be robust enough to provide a solid basis for implementation of policy measures. Data nevertheless confirm that intakes of total and added sugars are high in the European countries considered, especially in children, and point to sweet products and beverages as the major contributors to added sugar intakes.

Influence of the Lactotripeptides Isoleucine-Proline-Proline and Valine-Proline-Proline on Systolic Blood Pressure in Japanese Subjects: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The lactotripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) have been shown to decrease systolic blood pressure (SBP) in several populations, but the size of the effect varies among studies. We performed a meta-analysis including all published studies to evaluate the SBP-lowering effect of IPP/VPP in Japanese subjects more comprehensively. METHODS AND FINDINGS: Eligible randomized controlled trials were searched for within four bibliographic databases, including two Japanese ones. Eighteen studies (including a total of 1194 subjects) were included in the meta-analysis. A random effect model using the restricted maximum likelihood (REML) estimator was used for the analysis. The analysis showed that consumption of IPP/VPP induced a significant reduction in SBP as compared with placebo in Japanese subjects, with an estimated effect of -5.63 mm Hg (95% CI, -6.87 to -4.39, P<0.0001) and no evidence of publication bias. A significant heterogeneity between series was evident, which could be explained by a significant influence of the baseline blood pressure status of the subjects, the effect of IPP/VPP on SBP being stronger in hypertensive subjects (-8.35 mm Hg, P<0.0001) than in non-hypertensive subjects (-3.42mm Hg, P<0.0001). Furthermore, the effect of IPP/VPP on SBP remained significant when limiting the analysis to series that tested the usual doses of IPP/VPP consumed daily (below 5 mg/d), with estimated effects of -6.01 mm Hg in the overall population and -3.32 mm Hg in non-hypertensive subjects. CONCLUSIONS: Results from this meta-analysis show that IPP/VPP lactotripeptides can significantly reduce office SBP in Japanese subjects with or without overt hypertension, and for doses that can potentially be consumed as an everyday supplement. This suggests that these peptides could play a role in controlling blood pressure in Japanese subjects. The systematic review protocol was published on the PROSPERO register (CRD42014014322).

Consumption Patterns of Fruit and Vegetable Juices and Dietary Nutrient Density among French Children and Adults.

BACKGROUND: Fruit and vegetable consumption is a marker of higher-quality diets; less is known about the contribution of 100% fruit and vegetable juices (FVJ) to diet quality. OBJECTIVE: To explore FVJ consumption patterns in relation to dietary nutrient density among French children (aged 3-14 years old) and adults (≥21 years old). METHODS: Analyses were based on the nationally representative 2013 CCAF (Comportements et Consommations Alimentaires en France) survey of 1930 respondents, stratified by age group, FVJ consumption, and socioeconomic status (SES). Dietary nutrient density was based on the Nutrient Rich Food (NRF9.3) index, adjusted for gender and age. RESULTS: Mean total consumption of fruits and vegetables was 2.6 servings/day for children and 3.8 servings/day for adults. Mean population consumption of FVJ was 83 mL/day for children and 54.6 mL/day for adults, equivalent to 0.4 servings/day and 0.3 servings/day respectively. FVJ consumers had higher quality diets than did non-consumers, after adjusting for covariates. The respective NRF9.3 values were 486.4 ± 4.3 vs. 428.7 ± 7.5 for children and 460.7 ± 4.4 vs. 435.4 ± 4.4 for adults. FVJ consumers had similar or higher intakes of fruits and vegetables than did non-consumers. The socioeconomic gradient for FVJ consumption was much weaker (p < 0.046) than for whole fruit (p < 0.01). CONCLUSIONS: In a nationally representative sample of French children and adults, fruit and vegetable consumption fell short of recommended values. Higher FVJ consumption was associated with higher-quality diets and better compliance with the French National Plan for Nutrition and Health (PNNS).

Effects of chewing on appetite, food intake and gut hormones: A systematic review and meta-analysis.

OBJECTIVES: To seek insights into the relationship between chewing, appetite, food intake and gut hormones, and to consider potentially useful recommendations to promote benefits of chewing for weight management. MATERIALS AND METHODS: Papers were obtained from two electronic databases (Medline and Cochrane), from searches of reference lists, and from raw data collected from the figures in the articles. A total of 15 papers were identified that detailed 17 trials. All 15 papers were included in the systematic review; however, a further five studies were excluded from the meta-analysis because appropriate information on hunger ratings was not available. The meta-analysis was conducted on a total of 10 papers that detailed 13 trials. RESULTS: Five of 16 experiments found a significant effect of chewing on satiation or satiety using self-report measures (visual analogue scales, VASs). Ten of 16 experiments found that chewing reduced food intake. Three of five studies showed that increasing the number of chews per bite increased relevant gut hormones and two linked this to subjective satiety. The meta-analysis found evidence of both publication bias and between study heterogeneity (IA(2) = 93.4%, tau(2) = 6.52, p < 0.001) which decreased, but remained, when covariates were considered. Analysis of the heterogeneity found a substantial effect of the fasting period where the duration of fasting influenced the decrease in hunger due to chewing. Prolonged mastication significantly reduces self-reported hunger levels (hunger: − 2.31 VAS point, 95% CI [− 4.67, − 1.38], p < 0.001). CONCLUSIONS: Evidence currently suggests that chewing may decrease self-reported hunger and food intake, possibly through alterations in gut hormone responses related to satiety. Although preliminary, the results identify a need for additional research in the area. Focused, uniform, experimental designs are required to clearly understand the relationships that exist between mastication, appetite, satiety, food intake and, ultimately, body weight.

Systematic Review and Meta-Analysis of Human Studies to Support a Quantitative Recommendation for Whole Grain Intake in Relation to Type 2 Diabetes.

BACKGROUND: Due to the increasing evidence of their health benefits, whole grains are recommended for consumption worldwide. Such recommendations are, however, rarely quantitative. Our aim was to perform a quantitative evaluation of the relationship between whole grain consumption and the occurrence of type 2 diabetes (T2D) to support a recommendation on the daily consumption of whole grains. METHODS AND FINDINGS: We conducted a systematic review by searching three bibliographic databases. We included human studies addressing the relationship between whole grain consumption and T2D occurrence, and providing quantitative information on daily intake of whole grains. A dose-response meta-regression analysis between whole grain intake and T2D occurrence was performed, using a hierarchical mixed least square linear regression model. Eight observational studies were included (all but one prospective), with a total of 15,573 cases of T2D among 316,051 participants. Quantitative meta-regression demonstrated a significant linear inverse relationship between whole grain intake and T2D occurrence (P<0.0001), with an overall absolute reduction of 0.3% in the T2D rate for each additional 10 g of whole grain ingredient consumed daily. The association persisted when adjusted on sex, age, country, study design, follow up duration, and mode of report of whole grain intakes (as foods or ingredients). CONCLUSIONS: The meta-regression model made it possible to estimate the decrease in T2D risk corresponding to various changes in whole grain intakes, and the results contribute to setting up quantitative recommendations. For instance, consuming three servings of whole grain foods (45 g of whole grain ingredients) daily would induce a 20% relative reduction in the T2D risk as compared to consuming a half serving (7.5 g of whole grain ingredients). These results should be considered for future recommendations, by considering the actual whole grain intake of the concerned populations. The systematic review protocol was published on the PROSPERO register (CRD42013006925).

A proposed framework for an appropriate evaluation scheme for microorganisms as novel foods with a health claim in Europe.

This paper concerns the procedure and the scientific approach to obtain market authorization for a microorganism to be recognized as a novel food with a health claim. Microorganisms that have not been traditionally used during food production in Europe prior to 1997 are considered as novel foods, which should undergo an in-depth characterization and safety assessment before being authorized on the European market. If a novel food bacterium is claimed to provide a beneficial effect on health, these claims must also be investigated before they can be authorized. Some requirements to obtain novel food certification are shared with those required to obtain a health claim. Although regulation exists that deals with these issues for foods in general, bacteria in food raise a specific set of questions that are only minimally addressed in official documentation. We propose a framework and suggest a list of criteria that should be assessed to obtain marketing authorization and health claim for a bacterium in accordance with European health policy.

Do the lactotripeptides isoleucine-proline-proline and valine-proline-proline reduce systolic blood pressure in European subjects? A meta-analysis of randomized controlled trials.

BACKGROUND: The milk-derived peptides isoleucine-proline-proline (IPP) and valine-proline- proline (VPP) have been shown to reduce systolic blood pressure (SBP). This decrease is convincingly shown in subjects of Asian origin, but less consistent results have been obtained in European populations. METHODS: A meta-analysis was conducted in accord with the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) requirements, to assess the effect of IPP and VPP on SBP in Europeans, and to explore some determinants of this effect. RESULTS: Ninety-one publications on the effect of IPP and VPP on SBP in Europeans were identified, and 14 trials with 15 sets of data (n = 1,306) met the inclusion criteria for the meta-analysis. A random-effects model (using the restricted maximum likelihood (REML) estimator) was used for the analysis. Although not all individual trials showed a statistically significant effect of IPP or VPP in reducing SBP, the combination of all data for the two peptides yielded a statistically significantly greater effect for IPP/VPP than for placebo. The decrease in SBP with IPP/VPP was 1.28mm Hg (95% CI, -2.09 to -0.48, P = 0.0017) and the decrease in diastolic BP (DBP) was 0.59mm Hg (95% CI, -1.18 to -0.01, P = 0.047). There was no evidence in the meta-analysis of any publication bias or of heterogeneity (P = 0.13). Among other features, a significant effect was seen for age, with each additional year of age reducing the effect on SBP by 0.09mm Hg. This might be related to isolated systolic hypertension, a condition often encountered in the elderly, who may be poorly responsive to first-line treatments for hypertension. CONCLUSION: The peptides IPP and VPP are effective in moderately reducing SBP in European subjects, as is known for Asian populations. These two peptides could therefore have a role in controlling blood pressure (BP), a prospect that merits their further study.

Inhibition of bone turnover by milk intake in postmenopausal women.

Increased postmenopausal bone turnover leads to bone loss and fragility fracture risk. In the absence of osteoporosis, risk preventive measures, particularly those modifying nutritional lifestyle, are appropriate. We tested the hypothesis that milk supplementation affects bone turnover related to biochemical markers in a direction that, in the long term, may be expected to reduce postmenopausal bone loss. Thirty healthy postmenopausal women aged 59.3 (SD 3.3) years were enrolled in a prospective crossover trial of 16 weeks. After a 4-week period of adaptation with diet providing 600 mg calcium plus 300 mg ingested as 250 ml semi-skimmed milk, participants were maintained during 6 weeks under the same 600 mg calcium diet and randomized to receive either 500 ml semi-skimmed milk, thus providing a total of 1200 mg calcium, or no milk supplement. In the next 6 weeks they were switched to the alternative regimen. At the end of the each period, i.e. after 4, 10 and 16 weeks, blood and urinary samples were collected. The changes in blood variables between the periods of 6 weeks without and with milk supplementation were: for parathyroid hormone, -3.2 pg/ml (P=0.0054); for crosslinked telopeptide of type I collagen, -624 pg/ml (P<0.0001); for propeptide of type I procollagen, -5.5 ng/ml (P=0.0092); for osteocalcin, -2.8 ng/ml (P=0.0014). In conclusion, a 6-week period of milk supplementation induced a decrease in several biochemical variables compatible with diminished bone turnover mediated by reduction in parathyroid hormone secretion. This nutritional approach to postmenopausal alteration in bone metabolism may be a valuable measure in the primary prevention of osteoporosis.

Food matrix and isoflavones bioavailability in early post menopausal women: a European clinical study.

The estrogenic effects of soy isoflavones (IF) on symptoms of menopause are of particular interest. The aim of the present study was to improve compliance of IF in two IF-enriched foods providing the same IF circulating levels in postmenopausal women. Forty-two healthy postmenopausal women (mean age: 53.28 years) were recruited for a randomized, crossover, multicenter trial conducted in the Netherlands, Italy and France. Over 18 days, volunteers were assigned to two groups and supplemented with two different IF-enriched foods (100 mg IF aglycones/two servings). The first group had to eat two biscuits daily for three days. After a wash-out period (11 d), they received cereal bars for three days. The second group started with the cereal bars and finished with biscuits. After IF intake, plasma and urinary levels of genistein, daidzein, O desmethyl angolensin and equol significantly increased and returned to baseline level after the washout period. There was no difference between biscuits and cereals bars intake, as shown by group values at each end of experimental period (day 4 or day 18). Both matrixes are comparable in terms of IF-circulating levels and could be used independently.

Uptake and esterification of vitamin A by RCS rat retinal pigment epithelial cells in primary culture.

We investigated the capacity of Royal College of Surgeons (RCS) rat retinal pigment epithelial (RPE) cells to take up all-trans-retinol (ROL) (vitamin A) and to metabolize it into retinyl esters (RE). Cultures of RPE cells were established from RCS and control newborn rats. All-trans-ROL was delivered to the apical surface of the RPE monolayer. Retinoids were analyzed by high-performance liquid chromatography. The cellular retinol-binding protein type I (CRBP-I) was assessed by Western blotting. Before supplementation with ROL, RE were lower in RCS rats. After ROL supplementation, esters increased and reached values that were similar in the two strains, but the increase, expressed relative to the initial value, was higher in RCS rats. The uptake of ROL and the level of CRBP-I were greater in RCS rats. Our results provide evidence of a functional retinol esterifying enzyme in cultured RCS RPE cells and suggest that CRBP-I could play a role in the uptake and esterification of ROL in the RPE cells.

The intestine and its microflora are partners for the protection of the host: report on the Danone Symposium "The Intelligent Intestine," held in Paris, June 14, 2002.

The intestine is an extremely complex living system that participates in the protection of the host through a strong defense against aggressions from the external environment. This defensive task is based on 3 constituents that are in permanent contact and dialog with each other: the microflora, mucosal barrier, and local immune system. We review herein current knowledge about these important functions. The gut microflora play a major role against exogenous bacteria through colonization resistance, but the mechanism of action is not yet established, although it is linked to the bacteria colonizing the gut. This colonization involves bacteria-bacteria dialog, bacteria-mucins interactions, and bacteria-colonocytes cross-talk associated with environmental factors. The intestinal mucosa is a cellular barrier and the main site of interaction with foreign substances and exogenous microorganisms. It is a complex physicochemical structure consisting of a mucous layer linked to cellular and stromal components that participate in the defense of the host through mucosal blood flow, mucosal secretions, epithelial cell functionals, surface hydrophobicity, and defensin production. The intestine is the primary immune organ of the body represented by the gut-associated lymphoid tissue through innate and acquired immunity. This immune system can tolerate dietary antigens and the gut-colonizing bacteria and recognizes and rejects enteropathogenic microorganisms that may challenge the body's defenses. In cooperation with these endogenous barriers, some in-transit bacteria, such as probiotics, can act as partners of the defense system of the intestine.

PAV-1, a new rat hepatic stellate cell line converts retinol into retinoic acid, a process altered by ethanol.

During liver fibrogenesis or long term culture, hepatic stellate cells (HSCs) evolved from "quiescent" to activated phenotype called "myofibroblast-like", a transition prevented by retinoic acid (RA). Little is known about RA generation by HSCs. Our study aimed to check the ability of these cells to produce RA from retinol (Rol) and the alterations of this metabolic step by ethanol. To study this metabolic pathway, primary cultures of HSCs represent the most physiological model but technically suffer several drawbacks. To circumvent these problems, an immortalized rat HSC line (named PAV-1) has been established. We validated PAV-1 cell line as a convenient model to study retinoids metabolism by HSCs. Then, we showed that PAV-1 cells express Rol-binding proteins (RBPs), enzymes and nuclear receptors involved in RA signaling pathway. We also demonstrated in situ generation of functional all-trans-RA (ATRA), using transient transfections with a RA-sensitive reporter gene, in situ modulation of tissue transglutaminase (tTG) activity and HPLC experiments. This production was Rol dose-dependent; 4-methylpyrazole, citral, and ethanol-inhibited which argues in favor of an enzymatic process.In conclusion, we first demonstrate in situ RA generation from Rol in a newly immortalized rat HSC line, named PAV-1. Inhibition of RA production by ethanol in PAV-1 and recent data, suggesting fundamental role of RA to prevent fibrosis development in the liver, allow us to hypothesize that Rol metabolism could be a primary target for ethanol during development of hepatic fibrosis.