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Research has shown that vegetarian diets have a low environmental impact, but few studies have examined the environmental impacts and nutritional adequacy of these diets together, even though vegetarian diets can lead to nutritional issues.Our objective was to optimize and compare 6 types of diets with varying degrees of plant foods (lacto-, ovolacto-, and pescovegetarian diets and diets with low, medium, and high meat content) under nutritional constraints.Consumption data in 30,000 participants were derived from the French NutriNet-Santé cohort using an FFQ. Diets were optimized by a nonlinear algorithm minimizing the diet deviation while meeting multiple constraints at both the individual and population levels: nonincrease of the cost and environmental impacts (as partial ReCiPe accounting for greenhouse gas emissions, cumulative energy demand, and land occupation, distinguishing production methods: organic and conventional), under epidemiologic, nutritional (based on nutrient reference values), and acceptability (according to the diet type) constraints.Optimized diets were successfully identified for each diet type, except that it was impossible to meet the EPA (20:5n-3) + DHA (22:6n-3) requirements in lacto- and ovolactovegetarians. In all cases, meat consumption was redistributed or reduced and the consumption of legumes (including soy-based products), whole grains, and vegetables were increased, whereas some food groups, such as potatoes, fruit juices, and alcoholic beverages, were entirely removed from the diets. The lower environmental impacts (as well as individual indicators) observed for vegetarians could be attained even when nutritional references were reached except for long-chain n-3 (omega-3) fatty acids.A low-meat diet could be considered as a target for the general population in the context of sustainable transitions, although all diets tested can be overall nutritionally adequate (except for n-3 fatty acids) when planned appropriately.This trial was registered at clinicaltrials.gov as NCT03335644.

International audience; Purpose. While consumer demand for meat substitutes is growing, their varied composition raises questions regarding their nutritional value. We aimed to identify and characterize the optimal composition of a meat substitute that would best improve diet quality after complete meat replacement.Methods. From an average individual representing the dietary intake of French adults (INCA3, n=1125), meat was replaced with an equivalent amount of a mostly pulse-based substitute, whose composition was based on a list of 159 possible plant ingredients and optimized non-linearly to maximize diet quality assessed with the PANDiet score (considering adequacy for 32 nutrients), while taking account of technological constraints and applying nutritional constraints to limit the risk of overt deficiency in 12 key nutrients.Results. The optimized meat substitute contained 13 minimally processed ingredients. When used to substitute meat, the PANDiet score increased by 5.7 points above its initial value before substitution (versus -3.1 to +1.5 points when using other substitutes on the market), mainly because of higher intakes of nutrients that are currently insufficiently consumed (e.g. alpha-linolenic acid, fiber, linoleic acid) and a lower SFA intake. The meat substitute also mostly compensated for the lower provision of some indispensable nutrients to which meat greatly contributed (e.g. vitamin B6, potassium, bioavailable iron), but it could not compensate for bioavailable zinc and vitamin B12. Conclusion. Choosing the correct ingredients can result in a nutritionally highly effective meat substitute that could compensate for reductions in many nutrients supplied by meat while providing key nutrients that are currently insufficiently consumed.

International audience; The dietary shift from animal protein (AP) to plant protein (PP) sources is encouraged for both environmental and health reasons. For instance, PPs are associated with lower cardiovascular and diabetes risks compared with APs, although the underlying mechanisms mostly remain unknown. Metabolomics is a valuable tool for globally and mechanistically characterizing the impact of AP and PP intake, given its unique ability to provide integrated signatures and specific biomarkers of metabolic effects through a comprehensive snapshot of metabolic status. This scoping review is aimed at gathering and analyzing the available metabolomics data associated with PP- and AP-rich diets, and discusses the metabolic effects underlying these metabolomics signatures and their potential implication for cardiometabolic health. We selected 24 human studies comparing the urine, plasma, or serum metabolomes associated with diets with contrasted AP and PP intakes. Among the 439 metabolites reported in those studies as able to discriminate AP- and PP-rich diets, 46 were considered to provide a robust level of evidence, according to a scoring system, especially amino acids (AAs) and AA-related products. Branched-chain amino acids, aromatic amino acids (AAAs), glutamate, short-chain acylcarnitines, and trimethylamine-N-oxide, which are known to be related to an increased cardiometabolic risk, were associated with AP-rich diets, whereas glycine (rather related to a reduced risk) was associated with PP-rich diets. Tricarboxylic acid (TCA) cycle intermediates and products from gut microbiota AAA degradation were also often reported, but the direction of their associations differed across studies. Overall, AP- and PP-rich diets result in different metabolomics signatures, with several metabolites being plausible candidates to explain some of their differential associations with cardiometabolic risk. Additional studies specifically focusing on protein type, with rigorous intake control, are needed to better characterize the associated metabolic phenotypes and understand how they could mediate differential AP and PP effects on cardiometabolic risk.

Background Plant-based substitutes are designed to have the same use as animal-based foods in the diet and could therefore assist the transition toward more plant-based diets. However, their nutritional impact has not been characterized. Objectives We assessed and compared the effects of plant-based substitutes on the nutritional quality of the diet. Methods We simulated separately the substitution of meat, milk, and dairy desserts with 96 plant-based substitutes in the diets of 2121 adults (18-79 y old) from the cross-sectional French Third Individual and National Study on Food Consumption Survey (INCA3; 2014-2015). The quality of initial individual diets and the 203,616 substituted diets was evaluated using the Probability of Adequate Nutrient Intake (PANDiet) scoring system, which assesses the probability of adequate (sufficient and not excessive) nutrient intake; also, nutrient security was evaluated using the SecDiet scoring system, which assesses the risk of overt deficiency. Results Impacts on PANDiet depended on both the food substituted and the types of substitutes. Soy-based substitutes provided a slight improvement in diet quality (0.8% increase of the PANDiet score when substituting meat), whereas cereal-based substitutes resulted in a 1.1% decrease. Globally, substitutions led to better adequacies for fiber, linoleic acid, α-linolenic acid, vitamin E, folate, and SFAs, but lower adequacies regarding vitamin B-12 and riboflavin, as well as bioavailable zinc and iron when substituting meat, and calcium and iodine when substituting milk/dairy desserts. When they substituted dairy products, calcium-fortified substitutes allowed maintenance of calcium adequacy but there was a higher risk of iodine deficiency when substituting dairy, which may warrant iodine fortification. Substitutions modified the energy share of ultra-processed foods from 29% to 27%-40%, depending on the food substituted and the substitute used. Conclusions Plant-based substitutes had a small effect on overall diet quality and heterogeneous impacts on nutrient adequacy and security. Plant-based substitutes that include legumes appear more nutritionally adequate to substitute animal products than do other substitutes.

Although micronutrient deficiencies affect 2 billion people worldwide, no index focuses on measuring the risk of overt nutrient deficiency. We aimed to develop an index that could capture the nutrient dimension of nutritional security, a nutrient security index (named SecDiet), and evaluate its apparent validity. The SecDiet (range: 0–1) is based on the square-weighted average of the probabilities that the intake of twelve critical nutrients exceeds the threshold value associated with a risk of overt deficiency. Using adult populations from a French representative survey (INCA3, n 1774) and a large cohort (NutriNet-Santé, n 104 382), the content and construct validity of the SecDiet was evaluated by estimating associations of the SecDiet with its components and with relevant socio-demographic characteristics. The SecDiet was high in the overall population (0·93 (SD 0·09) in INCA3) and markedly skewed towards 1 (i.e. lower risk of insufficient intake). It correlated positively with its twelve components (r 0·17–0·78, all P < 0·001). The SecDiet was associated with monthly income (P = 0·002), perception of financial situation, professional situation, food insufficiency and security statuses (all P < 0·001) in the INCA3 population and with monthly income, professional situation and level of education (all P < 0·001) in the NutriNet-Santé population. Unlike a broader nutrient-based quality index taken as comparison, the SecDiet mean decreased and the tail of its distribution notably extended downwards in at-risk sub-populations, thus revealing its specific sensitivity. The SecDiet could be used to screen sub-groups or study the determinants of nutrient insecurity in large population surveys.

International audience; Background: Plant proteins (PP) have been associated with better cardiovascular health than animal proteins (AP) in epidemiological studies. However, the underlying metabolic mechanisms remain mostly unknown. Objective: Using a combination of cutting-edge isotopic methods, we aimed at better characterizing the differences in protein and energy metabolisms induced by dietary protein sources (PP vs AP), in a prudent or western dietary context.Methods: Male Wistar rats (n=44, 8 weeks old) were fed for 4.5 months with isoproteic diets differing in their protein isolate sources, either AP (100% milk) or PP (50%:50% pea: wheat), and being normal (NSF) or high (HFS) in sucrose (6 or 15%kcal, respectively) and saturated fat (7 or 20%kcal, respectively). We measured body weight and composition, hepatic enzyme activities and lipid content, and plasma metabolites. In the intestine, liver, adipose tissues and skeletal muscles, we concomitantly assessed the extent of amino acid (AA) trafficking using a 15N natural abundance method, the rates of macronutrient routing to dispensable AA using a 13C natural abundance method, and the metabolic fluxes of protein synthesis (PS) and de novo lipogenesis (DNL) using a 2H labelling method. Data were analyzed using ANOVA and mixed models.Results: At the whole-body level, PP limited HFS-induced insulin resistance (-27% in HOMA-IR between HFS groups, P

Visioconférence; International audience; Objectives: A dietary shift in favor of plant protein (PP) sources over animal protein (AP) sources has been advocated for both sustainability and health reasons, this dietary transition being noticeably associated to decreased cardiovascular and diabetes risks. The differences in amino acid composition between PP and AP may have several effects on the metabolic pathways, and in turn health impacts, which are still poorly characterized. This project aims at characterizing, with a combination of “omics” approaches, the metabolic reorientations induced by a dietary shift from AP to PP sources and understanding their health effects in a population at cardiometabolic risk. Methods: We will conduct a cross-over randomized feeding trial (NCT04236518) in 20 healthy overweight males (BMI 25–35), aged 25–55, with an enlarged waist circumference (> 94cm) and high plasma triglycerides (>1.5g/L). Participants will be assigned for 1 month each to 2 diets containing predominantly either AP (65% AP:35% PP) or PP (35% AP:65% PP) in a randomized order, separated by a 2-week wash-out period. Lunch and diner will be directly provided while dietary guidelines will be given for breakfast and snacks. Blood, urine and stool samples will be collected at the fasted state every 2 weeks. At the end of each dietary intervention, blood and urine will be collected following a high fat meal, which challenges metabolism and vascular homeostasis. Plasma and urine non-targeted metabolomics analyses (LC-MS) will be combined with Peripheral Blood Mononuclear Cell (PBMC) transcriptomics and fluxomics analyses (D2O tracer) to get a comprehensive overview of the metabolic phenotype associated with AP or PP intake. Flow-Mediated Dilatation (FMD) and Flow Laser Doppler (FLD) will be used to measure respectively macrovascular endothelial function and microvascular skin blood flow at the fasted state and after the high-fat meal. We will also measure anthropometric parameters and analyze biochemistry and inflammatory markers. Results: Not applicable (protocols abstract). Conclusions: We expect the multi-omics fingerprinting to reveal subtle metabolic differences associated to AP or PP intake, with a positive effect of PP intake. Improved inflammatory status and endothelial function are also expected to be associated to PP intake. Funding Sources INRAE and Roquette Frères.

International audience; Abstract Objectives While consumers’ demand is growing, meat substitutes have much varied composition, raising questions about their nutritional interest. We aimed to identify the composition of a meat substitute that would best improve diet quality, and analyze the impact on nutrient adequacy. Methods We aimed at maximizing the overall diet quality of an average individual representing the nutrient intake of the French adult population (INCA3, n = 1125) by modeling the composition of a meat substitute intended to replace meat, using non-linear optimization (using SAS, proc optmodel). The diet quality was assessed using the PANDiet scoring system, which assesses the probability of adequate nutrient intake. Nutritional constraints were applied in order to not increase the risk of overt deficiency for 12 nutrients. A list of 159 ingredients was used to compose the meat replacer and technological constraints were defined so as to take into account the feasibility of the formulation. The impacts on diet quality of the modelled meat substitute were analyzed and compared with those of 43 meat substitutes on the market. Results The optimized meat substitute was composed of 13 ingredients (such as coco bean, yellow sweet pepper, rapeseed oil, dried shiitake mushroom, wheat bran and thyme) and this formulation proved to be relatively robust to variations in the model constraints, as shown by a sensitivity analysis. Meat substitution with this optimized meat substitute largely increased the PANDiet, by 5.5 points above its initial value before substitution (73.7/100). In particular, it led to better adequacies for nutrients that are currently insufficiently consumed (e.g., alpha-linolenic acid, fiber, linoleic acid). It also allowed to compensate for loss of some nutrients partly provided by meat (e.g., vitamin B6, potassium and, to a certain extent, bioavailable iron), but was not sufficient to compensate for bioavailable zinc and vitamin B12. The optimized meat substitute proved to be dramatically more nutritionally efficient than the available meat substitutes, whose individual impact on the PANDiet ranged from −3.1 to +1.5 points. Conclusions We proved that it is possible to select appropriate ingredients resulting in a meat substitute that could be a fairly good nutritional lever when substituting meat. Funding Sources Partly funded by a PhD fellowship from Terres Univia.

International audience; Abstract Objectives We aimed to characterize the effects of a low dose of a sustained-release L-arginine (L-ARG) supplementation on plasma metabolome in healthy overweight adults with cardiometabolic risk factors, and study if its effect could improve the capacity to handle a high fat-high sugar meal, that deeply and acutely challenge metabolic capacities. Methods In a randomized, double-blind, controlled trial, 33 healthy overweight adults (BMI > 25kg/m²) with cardiometabolic risk (plasma triglycerides > 150 mg/dL; waist circumference > 94 cm (men) or > 80 cm (women)) were treated with 1.5 g L-ARG 3 times/d (4.5 g/d) or placebo for 4 weeks. On the last day of treatment, the volunteers consumed a high fat, high sugar meal challenge (900 kcal). Plasma was collected at fasting and 2, 4 and 6 h after the meal. Metabolites were analyzed by high-resolution mass spectrometry hyphenated to liquid chromatography, using reversed and normal phase columns, and operated in both positive and negative ionization modes. Annotation was performed using an in-house database referencing more than 1300 metabolites. Metabolic profiles were analyzed using Linear Mixed Models-PCA (LiMM-PCA), which enables to analyze repeated multivariate data. LiMM-PCA combines linear mixed models and PCA to assess the effects of both fixed factors (Treatment, Time before and after meal, interaction Treatment x Time, Order of treatment administration and Period of the study) and random factors (Individual). Results 521 metabolic features were identified in the plasma. Time accounted for most part of the variance in dataset (30.0%, P 0.10). The analysis of the metabolites contributing the most to these effects is under progress. Conclusions L-ARG supplementation has a significant effect on the metabolome in a situation where the metabolome is heavily impacted by a large allostatic load, and these two effects are independent of each other. Funding Sources Supported by a grant from Pierre Fabre Research Institute.

International audience; Objectives We aimed to study if, and to what extent, the current nutrient reference values for bioavailable iron and zinc limit the identification of healthier dietary patterns. Methods Using observed diets from a representative French survey (INCA3) and multi-criteria optimization, we identified diets that comply with all nutrient reference values and maximize a health criteria based on food-based dietary guidelines while minimally departing from the observed diet. Nutrient reference values included absorbed iron and zinc. This non-linear diet optimization problem was solved in men and women with higher (Fe−) and lower (Fe+) iron requirements separately, either strictly (Non Flexible model, NF) or by allowing some tolerance on absorbed iron and zinc using goal programming to minimize their decreases below reference values (Flexible Model, F). Using a comparative risk assessment framework and a probabilistic approach, we estimated changes in risks of cardiovascular diseases, diabetes and colorectal cancer, and changes in estimates of the prevalence of iron-deficiency anemia for the diets optimized using each model. Results With the NF model, the reference values for absorbed iron and zinc were the most binding constraints (over 34 constraints). Compared to the observed diets, the NF-optimized diets showed large redistributions within cereals and meats, with total meat consumption remaining similar in men and Fe- women and doubling in Fe + women. In contrast, the F-optimized diets had higher value for the health criteria objective, being systematically lower in meat, especially red meat, and higher in whole grain products. We estimated that the reduction in mortality risk would be 17.7% wih the NF-optimized diets and 21.5% with the F-optimized diets. However, the later diets would increase the prevalence of iron-deficiency anemia from 2.1% currently to 5.6%. Conclusions We evidenced that the reference values for iron and zinc with regard to their bioavailability are critical factors when modelling healthy eating patterns. Considering lower references for iron and zinc leads to identify diets with an apparent higher benefit for the population health with regards long-term health. Funding Sources None.

International audience; Background: Healthier dietary patterns involve more plant-based foods than current Western diets rich in animal products containing high levels of bioavailable iron and zinc. Little consideration is given to the bioavailability of iron and zinc when studying healthy eating patterns.Objectives Our aim was to determine whether currently estimated requirements for bioavailable iron and zinc limit the identification of healthier dietary patterns.Methods Using dietary data from a representative French survey and multi-criteria non-linear optimization, we identified diets that maximize health criteria based on Food-Based Dietary Guidelines and concomitantly depart only minimally from the observed diet, while complying with all nutrient reference values either strictly (non-flexible optimization) or by allowing bioavailable iron and zinc below the current reference values, but to a limited extent (flexible optimization). Using a comparative risk assessment model, we estimated the resulting impact on cardiometabolic and colorectal cancer mortality/morbidity, and changes to iron-deficiency anemia.Results Under non-flexible optimization, reference values for bioavailable iron and zinc were the most binding of the 35 nutrient constraints and modeled diets displayed considerable redistributions within grains and meat. With flexible optimization, modeled diets were healthier as they contained less red meat and more whole-grain products, but would increase iron-deficiency anemia to 5.0% (95% CI: 3.9%, 6.4%). Globally, in terms of Disability Adjusted Life Years (DALYs), as the loss due to anemia would represent

Background There is a current trend in Western countries toward increasing the intake of plant protein. A higher plant-protein intake has been associated with nutritional and health benefits, but these may depend on the pattern of plant-protein sources. Objective We hypothesized that the diversity of plant foods could be important to nutrient adequacy when increasing plant-protein intake in the diet. Methods Using data on 1341 adults (aged 18–64 y) from a representative French national dietary survey conducted in 2014–2015 (the third Individual and National Study on Food Consumption Survey—INCA3), we studied the links between plant-protein intake, dietary diversity (using various dimensions), and nutrient adequacy [assessed using the PANDiet (Probability of Adequate Nutrient Intake) scoring system, comprising adequacy (AS) and moderation (MS) subscores]. We simulated substituting plant-protein foods for animal-protein foods using different models of plant-protein diversity. Results We found that overall diet quality was weakly associated with total and protein diversity and more strongly with plant-protein diversity. Plant-protein intake was inversely associated with animal-protein intake, and positively with the PANDiet and MS, but not with the AS. Plant-protein intake displayed little diversity, mostly taking the form of grains (61% of plant-protein intake), and this diversity was even less marked under a higher plant-protein intake. Finally, modeled substitutions showed that reducing animal-protein intake increased the MS (by 32%) in a similar manner whichever plant protein was used for substitution, whereas it decreased the AS (by 20%) unless using a highly diversified plant-protein mix. These simulated improvements in overall adequacy included marked decreases in adequacy regarding certain nutrients that are typically of animal origin. Conclusions We conclude that in French adults the current pattern of plant-protein intake is hindering the nutritional benefits of a transition toward more plant protein, indicating that the consumption of plant-protein-based foods other than refined grains should be encouraged.

Visio conférence; International audience; Objectives: The dietary shift from animal protein (AP) sources to plant protein (PP) sources is promoted for both environmental and health reasons. Indeed, PP are associated to lower cardiovascular and diabetes risks compared to AP, but the underlying mechanisms remain mostly unknown. Metabolomics, which has a unique ability to provide an integrative snapshot of the metabolic status of an individual, is a valuable tool to investigate the different metabolic pathways activated by AP or PP intake and to provide biomarkers of their metabolic effects. This scoping review aimed at gathering and analyzing the available data on the metabolomics signatures associated to PP or AP intake, for discussing the metabolic effects underlying these signatures and their potential implication for cardiometabolic health. Methods: We selected a total of 23 human studies comparing the urine, plasma or serum metabolomes associated to diets with contrasted AP and PP intakes, such as vegetarian and omnivore diets, and collected all discriminant metabolites across diets. Results: Out of the 447 discriminant metabolites, 44 were repeatedly reported across studies, amino acids (AA) and AA-related products accounting for a high proportion. Branch-chained amino acids (BCAA), aromatic amino acids (AAA), glutamate, short-chained acylcarnitines and Trimethylamine-N-Oxide (TMAO) were associated to AP while glycine was associated to PP intake. TCA cycle intermediates and products from AAA gut microbiota degradation were also often reported, but the direction of their associations with AP or PP remained unclear. As regard to their implication for cardiometabolic health, BCAA, AAA, glutamate, short-chained acylcarnitines and TMAO are known to be associated to increased risk while glycine is rather associated with a decreased risk.Conclusions: AP or PP intakes result in different metabolomics signatures, several metabolites being plausible candidates to at least partially explain their differential associations with cardiometabolic risk. Additional studies with a specific focus on protein type, deep dietary data and tight intake control are needed to better characterize the associated metabolic phenotype and understand how it could mediate AP or PP effects on cardiometabolic risk. Funding Sources INRAE

Background: Oral L-arginine supplements can have a beneficial effect on nitric oxide (NO)-related functions when subjects have cardiovascular disease risk factors. Objective: The study was designed to determine the utilization for NO synthesis of oral L-arginine as a function of the cardiometabolic risk and the speed of absorption by comparing immediate-release arginine (IR-Arg), as in supplements, and sustained-release arginine (SR-Arg), which mimics the slow release of dietary arginine. Methods: In a randomized, single-blind, 2-period crossover, controlled trial (1 wk of treatment, >2 wk of washout), using[N-15-(15)-N(guanidino)]-arginine for the first morning dose, we compared the bioavailability (secondary outcome) and utilization for NO synthesis (primary outcome) of 1.5 g IR- and SR-Arg 3 times/d in 12 healthy overweight [body mass index (BMI; in kg/m(2)): 25-30] adults with the hypertriglyceridemic waist phenotype [HTW; plasma triglycerides (TGs): >150 mg/dL; waist circumference: >94 cm (men) or >80 cm (women)] and 15 healthy control adults (CON; BMI: 18.5-25; no elevated TGs and waist circumference). Results: Plasma oral arginine areas under the curve were lower after supplementation with SR-Arg than with IR-Arg (112 +/- 52.3 and 142 +/- 50.8 mu mol . h/L; P < 0.01). The utilization of oral arginine for NO synthesis was 58% higher in HTW subjects than in CON subjects and higher with SR-Arg than with IR-Arg (P < 0.05 both), particularly in HTW subjects (group-by-treatment interaction, P < 0.05). In HTW subjects administered the SR form, utilization for NO synthesis was 32% higher than with the IR form and 87% higher than in CON subjects who were administered the SR form. Conclusion: In overweight adults with the HTW phenotype, a slow- compared with a fast-release form of oral arginine markedly favors the utilization of arginine for NO synthesis. The utilization of low-dose, slow-release arginine for NO synthesis is higher in overweight adults with the HTW phenotype than in healthy controls, suggesting that the sensitivity of NO synthesis to the dietary arginine supply increases with cardiometabolic risk. The trial was registered at clinicaltrials.gov as NCT02352740.

International audience; Background : Patterns of protein food intake are undergoing a transition in Western countries, but little is known about how dietary changes to protein intake affect nutrient adequacy of the diet.Objectives : Our objective was to identify simple modifications to protein food intake that can gradually increase overall nutrient adequacy.Methods : We identified patterns of dietary protein intake in 1678 adults from a representative French national dietary survey. For each individual, we identified the increase in portion size of 1 protein food paired with a decrease in the portion size of another protein food that would best increase nutrient adequacy (using PANDiet probabilistic scoring). Then, such an optimum simple dual change was iterated 20 times for each individual according to 2 scenarios, either by manipulating the intake of foods already consumed [scenario 1 (S1)] or by enabling the introduction of foods consumed by >10% of individuals with the same protein pattern [scenario 2 (S2)]. Results : The optimum stepwise changes to protein intake primarily consisted of reducing portions of deli meats (both scenarios), sandwiches, and cheese (S2), while increasing portions of fatty fish and lean poultry (both scenarios) and legumes (S2). However, these changes differed depending on the initial dietary protein pattern of the individual. For example, in S2, legume intake increased among “poultry” and “fish” eaters only and low-fat meat among “take-away eaters” and “milk drinkers” only. The improvements in overall nutrient adequacy were similar among the different initial dietary patterns, but this was the result of changes to the adequacy of different specific nutrients. Conclusion : Beyond generic changes to protein intake in the entire French adult population, the initial dietary protein pattern is key to identifying the food groups most likely to improve overall nutrient adequacy and the profile of nutrients whose adequacy can easily be increased.

International audience; Background: The postprandial retention of dietary protein decreases when the prevailing protein intake increases. Objective: We investigated the influence of the prevailing protein intake on the regional utilization and anabolic use of wheat protein during the postprandial non-steady state in humans. Design: Healthy adults (n = 8) were adapted for 7 d, first to a normal-protein diet (NP: 1 g .kg -1 .d-1) and then to a high-protein diet (HP: 2 g .kg-1 .d-1). After each adaptation period, the subjects received the same single, solid mixed meal containing (15N)-labeled wheat protein. The postprandial kinetics of dietary nitrogen were then measured for 8 h in blood and urine. These data were further analyzed by using a multicompartmental model to predict the postprandial kinetics of dietary nitrogen in unsampled pools. Results: The postprandial whole-body retention of wheat protein nitrogen, measured 8 h after meal ingestion, decreased by 10% when the subjects switched from the NP diet to the HP diet. According to modeling results, this resulted from an increased splanchnic utilization of dietary nitrogen for urea production, whereas its incorporation into splanchnic proteins was unchanged, leading to a 20-30% decrease in peripheral availability and anabolic use in HP- adapted compared with NP-adapted subjects having ingested the same protein load. Conclusions: By combining clinical experimentation with compartmental modeling, we provide a global overview of postprandial dietary protein metabolism. Increasing prior protein intake was shown to reduce the postprandial retention of wheat protein nitrogen, mainly by diminishing the efficiency of its peripheral availability and anabolic use

International audience; AbstractBACKGROUND:Vascular endothelial dysfunction, the hallmark of early atherosclerosis, is induced transiently by a high-fat meal. High doses of free l-arginine supplements reduce fasting endothelial dysfunction.OBJECTIVE:We sought to determine the effects of a low dose of a sustained-release (SR) l-arginine supplement on postprandial endothelial function in healthy overweight adults with cardiometabolic risk factors and to investigate whether this effect may vary by baseline arginine status.METHODS:In a randomized, double-blind, 2-period crossover, placebo-controlled trial (4-wk treatment, 4-wk washout), we compared the effects of 1.5 g SR-l-arginine 3 times/d (4.5 g/d) with placebo in 33 healthy overweight adults [body mass index (BMI, in kg/m(2)): 25 to >30] with the hypertriglyceridemic waist (HTW) phenotype [plasma triglycerides > 150 mg/dL; waist circumference > 94 cm (men) or > 80 cm (women)]. The main outcome variable tested was postprandial endothelial function after a high-fat meal (900 kcal), as evaluated by use of flow-mediated dilation (FMD) and Framingham reactive hyperemia index (fRHI), after each treatment. By use of subgroup analysis, we determined whether the effect was related to the baseline plasma arginine concentration.RESULTS:In the total population, the effects of SR-arginine supplementation on postprandial endothelial function were mixed and largely varied with baseline fasting arginine concentration (P-interaction < 0.05). In the lower half of the population (below the median of 78.2 μmol arginine/L plasma), but not the upper half, SR-arginine supplementation attenuated the postprandial decrease in both FMD (29% decrease with SR-arginine compared with 50% decrease with placebo) and fRHI (5% increase with SR-arginine compared with 49% decrease with placebo), resulting in significantly higher mean ± SEM values with SR-arginine (FMD: 4.0% ± 0.40%; fRHI: 0.41 ± 0.069) than placebo (FMD: 2.9% ± 0.31%; fRHI: 0.21 ± 0.060) at the end of the postprandial period (P < 0.05).CONCLUSIONS:Supplementation with low-dose SR-arginine alleviates postprandial endothelial dysfunction in healthy HTW adults when the baseline plasma arginine concentration is relatively low. The benefits of arginine supplementation may be linked to a lower ability to mobilize endogenous arginine for nitric oxide synthesis during a postprandial challenge. This trial was registered at clinicaltrials.gov as NCT02354794

Background: Postprandial lipemia is a risk factor for cardiovascular disease. The potential impacts of the type/nature of dietary protein on postprandial lipemia and associated dysregulations have been insufficiently investigated. Objective: We investigated the postprandial effect of including in a high-fat meal some milk protein fractions that markedly differ in their physicochemical properties and composition [either casein (CAS), whey protein (WHE), or a-lactalbumin-enriched whey protein (LAC)]. Methods: The protein fractions were incorporated as 15% energy in a high-fatmeal in a W3-period, crossover postprandial study of 10 healthy overweight men with an elevated waist circumference (>94 cm). We measured postprandial changes in plasma lipids, amino acids, glucose, and oxidative stress markers, vascular function (using pulse contour analysis), and low-grade inflammation (using plasma markers). We also characterized in vitro the meal structures, including the size of the fat globule, and possible changes during digestion. Results: The type of protein did not affect postprandial plasma glucose, amino acids, insulin, or nonesterified fatty acids, but, compared with WHE and LAC, which did not differ, CAS markedly reduced postprandial triglycerides (TGs), achieving a 22 +/- 10% reduction in the 6-h area under the curve (P < 0.05). Similar trends were shown for plasma chylomicrons [apolipoprotein (apo) B-48; P < 0.05]. However, there were no significant differences between the meals regarding postprandial oxidative stress (plasma hydroperoxides and malondialdehyde), endothelial dysfunction (salbutamol-induced changes in pulse contour analysis), or low-grade inflammation. In vitro studies showed that when the pH of the meal decreased to stomach pH values, the reduction in the solubility of casein resulted in a phase separation between fat and protein, whereas the proteins in the other meals remained suspended with fat globules. Conclusion: In healthy overweight men, casein has specific physical interactions with fat that affect postprandial TGs, leading to the formation of fewer chylomicrons or an increase in chylomicron clearance. This trial was registered at clinicaltrials. gov as NCT00931151.

The natural abundance of15N in animal proteins (δ15Nanimal) is greater than that in the diet consumed by the animals (δ15Ndiet), with a discrimination factor (Δ15N = δ15Nanimal− δ15Ndiet) that is known to vary according to nutritional conditions. The objectives of the present study were to test the hypothesis that Δ15N variations depend on the efficiency of nitrogen utilisation (ENU) in growing beef cattle, and to identify some of the physiological mechanisms responsible for this N isotopic fractionation in ruminants. Thus, we performed the regression of the Δ15N of plasma proteins obtained from thirty-five finishing beef cattle fed standard and non-conventional diets against different feed efficiency indices, including ENU. We also performed the regression of the Δ15N of different ruminant N pools (plasma and milk proteins, urine and faeces) against different splanchnic N fluxes obtained from multi-catheterised lactating dairy cows. The Δ15N of plasma proteins was negatively correlated with feed efficiency indices in beef cattle, especially ENU (body protein gain/N intake) and efficiency of metabolisable protein (MP) utilisation (body protein gain/MP intake). Although Δ15N obtained from different N pools in dairy cows were all negatively correlated with ENU, the highest correlation was found when Δ15N was calculated from plasma proteins. Δ15N showed no correlation with urea-N recycling or rumen NH3absorption, but exhibited a strong correlation with liver urea synthesis and splanchnic amino acid metabolism, which points to a dominant role of splanchnic tissues in the present N isotopic fractionation study.

The investigation of protein metabolism under various nutritional and physiological conditions has been made possible by the use of indirect, principally tracer-based methods. Most studies were conducted at the whole-body level, mainly using steady-state isotopic techniques and equations based on simple two-pool models, in which amino acids are either free or protein bound. Because whole-body methods disregard regional contributions to protein metabolism, some regional approaches have tried to distinguish the distribution of protein kinetics in the different tissues. The organ-balance tracer technique, involving the arteriovenous catheterization of regions or organs with concomitant isotopic tracer infusion, distinguishes between amino acid uptake and release in the net amino acid balance and measures protein synthesis and degradation under steady-state conditions. Last, the importance has become clear of the difference in dietary and endogenous amino acids recycled from proteolysis for anabolic and catabolic pathways. In humans, the dual tracer technique, which consists of the simultaneous oral/enteral administration and intravenous infusion of different tracers of the same amino acid, allows an estimate of the splanchnic uptake of amino acids administered. Furthermore, the whole-body retention of labeled dietary nitrogen after the ingestion of a single protein meal has enabled a clearer understanding of the metabolic fate of dietary amino acids. Based on such data, a newly developed compartmental model provides a simulation of the regional distribution and metabolism of ingested nitrogen in the fed state by determining its dynamic fate through free and protein-bound amino acids in both the splanchnic and peripheral areas in humans.

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Background: The systemic availability of oral/dietary arginine and its utilization for nitric oxide (NO) synthesis remains unknown and may be related to a competitive hydrolysis of arginine into urea in the splanchnic area and systemic circulation. Objectives: We investigated the kinetics and dose-dependency of dietary arginine utilization for NO compared with urea synthesis and studied the characteristics of the arginine-NO metabolic system in healthy humans. Design: We traced the metabolic fate and analyzed the utilization dynamics of dietary arginine after its ingestion at 2 nutritional amounts in healthy humans (n = 9) in a crossover design by using [N-15-N-15-(guanido)]-arginine, isotope ratio mass spectrometry techniques, and data analysis with a compartmental modeling approach. Results: Whatever the amount of dietary arginine, 60 +/- 3% (+/-SEM) was converted to urea, with kinetics indicative of a firstpass splanchnic phenomenon. Despite this dramatic extraction, intact dietary arginine made a major contribution to the postprandial increase in plasma arginine. However, the model identified that the plasma compartment was a very minor (similar to 2%) precursor for the conversion of dietary arginine into NO, which, in any case, was small (

Background Rapeseed is an emerging and promising source of dietary protein for human nutrition and health. We previously found that rapeseed protein displayed atypical nutritional properties in humans, characterized by low bioavailability and a high postprandial biological value. The objective of the present study was to investigate the metabolic fate of rapeseed protein isolate (RPI) and its effect on protein fractional synthesis rates (FSR) in various tissues when compared to a milk protein isolate (MPI). Methods Rats (n = 48) were given a RPI or MPI meal, either for the first time or after 2-week adaptation to a MPI or RPI-based diet. They were divided in two groups for measuring the fed-state tissue FSR 2 h after the meal (using a flooding dose of 13C-valine) and the dietary N postprandial distribution at 5 h (using 15N-labeled meals). Results RPI and MPI led to similar FSR and dietary nitrogen (N) losses (ileal and deamination losses of 4% and 12% of the meal, respectively). By contrast, the dietary N incorporation was significantly higher in the intestinal mucosa and liver (+36% and +16%, respectively) and lower in skin (-24%) after RPI than MPI. Conclusions Although RPI and MPI led to the same overall level of postprandial dietary N retention in rats (in line with our findings in humans), this global response conceals marked qualitative differences at the tissue level regarding dietary N accretion. The fact that FSR did not however differed between groups suggest a differential modulation of proteolysis after RPI or MPI ingestion, or other mechanisms that warrant further study.

Background Compared with slow proteins, fast proteins are more completely extracted in the splanchnic bed but contribute less to peripheral protein accretion; however, the independent influence of absorption kinetics and the amino acid (AA) pattern of dietary protein on AA anabolism in individual tissues remains unknown. Objective We aimed to compare the postprandial regional utilization of proteins with similar AA profiles but different absorption kinetics by coupling clinical experiments with compartmental modeling. Design Experimental data pertaining to the intestine, blood, and urine for dietary nitrogen kinetics after a 15N-labeled intact (IC) or hydrolyzed (HC) casein meal were obtained in parallel groups of healthy adults (n = 21) and were analyzed by using a 13-compartment model to predict the cascade of dietary nitrogen absorption and regional metabolism. Results IC and HC elicited a similar whole-body postprandial retention of dietary nitrogen, but HC was associated with a faster rate of absorption than was IC, resulting in earlier and stronger hyperaminoacidemia and hyperinsulinemia. An enhancement of both catabolic (26%) and anabolic (37%) utilization of dietary nitrogen occurred in the splanchnic bed at the expense of its further peripheral availability, which reached 18% and 11% of ingested nitrogen 8 h after the IC and HC meals, respectively. Conclusions The form of delivery of dietary AAs constituted an independent factor of modulation of their postprandial regional metabolism, with a fast supply favoring the splanchnic dietary nitrogen uptake over its peripheral anabolic use. These results question a possible effect of ingestion of protein hydrolysates on tissue nitrogen metabolism and accretion. This trial was registered at clinicaltrials.gov as NCT00873951.

Background: The in vivo quality of milk protein fractions has seldom been studied in humans. Objective: Our objective was to compare the postprandial utilization of dietary nitrogen from 3 [15N]-labeled milk products: micellar caseins (MC), milk soluble protein isolate (MSPI), and total milk protein (TMP). Design: The macronutrient intakes of 23 healthy volunteers were standardized for 1 wk, after which time the subjects ingested a meal containing MC (n = 8), MSPI (n = 7), or TMP (n = 8). [15N] was measured for an 8-h period in plasma amino acids, proteins, and urea and in urinary urea. Results: The transfer of dietary nitrogen to urea occurred earlier after MSPI ingestion than after MC and TMP ingestion, and concentrations remained high for 8 h, concomitantly with higher but transient hyperaminoacidemia and a higher incorporation of dietary nitrogen into plasma amino acids. In contrast, deamination, postprandial hyperaminoacidemia, and the incorporation of dietary nitrogen into plasma amino acids were lower in the MC and TMP groups. Finally, total postprandial deamination values were 18.5 ± 2.9%, 21.1 ± 2.8%, and 28.2 ± 2.9% of ingested nitrogen in the TMP, MC, and MSPI groups, respectively. Conclusions: Our results confirm the major role of kinetics in dietary nitrogen postprandial utilization and highlight the paradox of MSPI, which, despite its high Protein Digestibility Corrected Amino Acid Score, ensures a rate of amino acid delivery that is too rapid to sustain the anabolic requirement during the postprandial period. Milk proteins had the best nutritional quality, which suggested a synergistic effect between soluble proteins and caseins

We used a previously developed compartmental model to assess the postprandial distribution and metabolism of dietary nitrogen (N) in the splanchnic and peripheral areas after the ingestion of a single mixed meal containing either (15)N-labeled milk or soy purified protein. Although the lower whole-body retention of dietary N from soy protein was measured experimentally, the splanchnic retention of dietary N was predicted by the model not to be affected by the protein source, and its incorporation into splanchnic proteins was predicted to reach approximately 35% of ingested N at 8 h after both meals. However, dietary N intestinal absorption and its appearance in splanchnic free amino acids were predicted to be more rapid from soy protein and were associated with a higher deamination, concomitant with a higher efficiency of incorporation of dietary N into proteins in the splanchnic bed. In contrast, soy protein was predicted to cause a reduction in peripheral dietary N uptake, as a consequence of both similar splanchnic retention and increased oxidation compared with milk protein. In addition, protein synthesis efficiency was reduced in the peripheral area after soy protein intake, leading to dietary N incorporation in peripheral proteins that fell from 26 to 19% of ingested N 8 h after milk and soy protein ingestion, respectively. Such a model thus enables a description of the processes involved in the differential metabolic utilization of dietary proteins and constitutes a valuable tool for further definition of the notion of protein quality during the period of protein gain.

The aim of this study was to follow the fate of dietary nitrogen to assess the postprandial utilization of purified milk protein and to determine the acute influence of energy nutrients. For this purpose, a [15N]-labeling dietary protein approach was used. Twenty-five subjects swallowed an ileal tube and ingested [15 N]-milk protein alone or supplemented with either milk fat or sucrose. The absorption and postprandial deamination of dietary protein was monitored for 8 h. Sucrose delayed the absorption of protein longer than fat, but the ileal digestibility did not differ among groups (94.5-94.8%). Sucrose, but not fat, significantly reduced the postprandial transfer of [15N]-milk nitrogen to urea. Consequently, the net postprandial protein utilization (NPPU) of milk protein calculated 8 h after meal ingestion was 80% when ingested either alone or supplemented with fat and was significantly greater with sucrose (NPPU = 85%). This study shows that energy nutrients do not affect the nitrogen absorption but modify the metabolic utilization of dietary protein in the phase of nitrogen gain. Our method provides information concerning the deamination kinetics of dietary amino acids and further allows the detection of differences of dietary protein utilization in acute conditions. The diet composition should be carefully considered, and protein quality must be determined under optimal conditions of utilization.

The quality of cereal protein has been little studied in humans despite its quantitative importance in the diet, particularly in developing countries.The objective of this study was to determine the nutritional value of wheat protein in humans as assessed by the measurement of their real ileal digestibility and postprandial retention.Healthy young adults (n = 14) were fitted with an intestinal tube to allow the collection of intestinal fluid in the duodenum or terminal ileum. Subjects received a mixed meal of 136 g wheat toast that contained 24.6 g uniformly and intrinsically [(15)N]-labeled wheat protein. Intestinal fluid, blood, and urine were collected for 8 h postprandially.The real ileal digestibility of dietary wheat nitrogen amounted to 90.3 +/- 4.3%. The cumulative amount of dietary nitrogen transferred to the deamination pools reached a plateau at 8 h of 24.7 +/- 6.8% of the amount ingested. The urinary excretion of dietary nitrogen in ammonia was high (0.8 +/- 0.3% of ingested dose). The incorporation of dietary nitrogen into serum protein reached 7.0 +/- 1.9% of the meal. Postprandial wheat protein retention was 66.1 +/- 5.8%.Our results show that wheat proteins had the same true ileal digestibility as did most of the plant proteins already studied in humans, but also that they had a lower postprandial nitrogen retention value. However, this low value was higher than that predicted from the calculation of indispensable amino acid scores, ie, 89% rather than 30-40% of the nutritional value of milk proteins.

Background: The influence of protein source on postprandial urea kinetics is poorly understood, despite its nutritional significance with respect to nitrogen homeostasis. Furthermore, traditional tracer infusion studies underestimate acute postprandial change in urea kinetics. Objective: We investigated postprandial, non-steady state urea kinetics and their modulation by qualitative and quantitative factors of protein intake by the combined use of robust clinical data on nitrogen postprandial distribution and mathematical modeling. Design: In healthy subjects standardized to a normal protein intake for 7 d, dietary and total nitrogen kinetics were measured for 8 h in plasma proteins, body, and urinary urea after the ingestion of a 15 N-labeled milk (n = 8), soy (n = 8), or wheat (n = 8) protein meal. In subjects who received the soy protein meal, these postprandial measurements were repeated after a further 7-d adaptation to a high protein intake. A 4-compartment model was developed to calculate from these data the postprandial kinetics of production, urinary excretion, and intestinal hydrolysis of urea nitrogen from both dietary and endogenous sources. Results: Urinary urea excretion was not influenced by the protein source in the meal but was influenced by the protein level in the diet. By contrast, urea production and hydrolysis were higher when ingesting plant versus animal protein, together with a higher efficiency of urea hydrolysis (50-60% versus 25% of the urea produced being hydrolyzed, respectively). Conclusions: We conclude that urea hydrolysis is an acute nitrogen-sparing mechanism that can counterbalance a postprandial higher urea production, and the efficiency of this recycling is higher when the usual protein intake is lower.