In Healthy Pathways of Dietary Changes, a Very Rapid Reduction of Red Meat Is Possible, but Specific Diet Changes Are Required for Full Reduction-A Graph-Based Analysis.

BACKGROUND: Although reducing meat consumption is becoming increasingly popular in Western countries, such a transition to a sustainable diet may pose some nutritional risks. OBJECTIVES: We aim to analyze the pathways for reaching a low-meat healthy diet and the changes in other food categories needed to rapidly decrease total red meat consumption. METHODS: We used a recently developed method based on graph theory to represent all possible pathways of stepwise changes that avoid nutritional deficiencies toward a target healthy diet. Initial and target diets were defined as the daily consumption of 33 food groups. For each sex, 3 initial diets were taken from the French representative survey third individual and national study on food consumption survey as the mean observed diet and low (first quintile) and high (fifth quintile) meat consumption. Target diets were identified using multicriteria optimization to minimize the long-term health risk (HR) of chronic diseases while ensuring nutritional adequacy. The Dijkstra algorithm was used to identify the optimal pathways between the initial and target diets, with the aim of reducing meat consumption as quickly as possible and thus minimizing long-term HRs. RESULTS: Unprocessed red meat was easily minimized in the first steps of the pathways regardless of sex and initial level of meat consumption. However, processed meat could only be decreased later and required prior changes such as increases in fruit, vegetables, and oily fish. During total red meat minimization in females, securing adequate intakes of bioavailable iron had the most substantial impact on the other dietary changes needed. CONCLUSIONS: Immediate reduction of red meat consumption is possible on the pathway to a healthy diet that avoids any nutrient deficiency. However, early increases in fruit, vegetables, and fish are required before minimizing total red meat early in the diet.

Identifying the most Efficient Detailed Trajectories toward Healthy Diets-A Graph-Based Analysis.

BACKGROUND: Much effort has been devoted to defining healthy diets, which could lower the burden of disease and provide targets for populations. However, these target diets are far removed from current diets, so at best, the population is expected to move slowly along a trajectory. OBJECTIVE: Our aim was to characterize the different possible trajectories toward a target diet and identify the most efficient one for health to point out the first dietary changes being the most urgent to implement. METHODS: Using graph theory, we have developed a new method to represent in a graph all stepwise change trajectories toward a target healthy diet, with trajectories all avoiding risk of nutrient deficiency. Then, we have identified and characterized the trajectory with the highest value for long-term health. Observed male and female average diets are from the French representative survey INCA3, and target diets were set using multicriteria optimization. The best trajectories were found using the Dijkstra algorithm with the Health risk criteria based on epidemiological data. RESULTS: Within ∼2.6M diets in the graphs, we found optimal trajectories that were rather similar for males and females regarding the most efficient changes in the first phase of the pathways. In particular, we found that a 1-step increase in the consumption of whole/semirefined bread (60 g) was the first step in all healthiest trajectories. In males, the subsequent decrease in red meat was immediately preceded by increases in legumes. CONCLUSIONS: We show simple practical dietary changes that can be prioritized along an integral pathway that is the most efficient overall for health when transiting toward a distant healthy diet. We put forward a new method to analyze dietary strategy for public health transition and highlight the first critical steps to prioritize.

Compared with Milk Protein, a Wheat and Pea Protein Blend Reduces High-Fat, High-Sucrose Induced Metabolic Dysregulations while Similarly Supporting Tissue Protein Anabolism in Rats.

BACKGROUND: Plant proteins (PPs) have been associated with better cardiovascular health than animal proteins (APs) in epidemiological studies. However, the underlying metabolic mechanisms remain mostly unknown. OBJECTIVES: Using a combination of cutting-edge isotopic methods, we aimed to better characterize the differences in protein and energy metabolisms induced by dietary protein sources (PP compared with AP) in a prudent or western dietary context. METHODS: Male Wistar rats (n = 44, 8 wk old) were fed for 4.5 mo with isoproteic diets differing in their protein isolate sources, either AP (100% milk) or PP (50%:50% pea: wheat) and being normal (NFS) or high (HFS) in sucrose (6% or 15% kcal) 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 using a 2H labeling 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 < 0.05). In the liver, PP induced lower lipid content (-17%, P < 0.01) and de novo lipogenesis (-24%, P < 0.05). In the different tissues studied, PP induced higher AA transamination accompanied by higher routings of dietary carbohydrates and lipids toward dispensable AA synthesis by glycolysis and ß-oxidation, resulting in similar tissue PS and protein mass. CONCLUSIONS: In growing rats, compared with AP, a balanced blend of PP similarly supports protein anabolism while better limiting whole-body and tissue metabolic dysregulations through mechanisms related to their less optimal AA profile for direct channeling to PS.

Plant-based meat substitutes are useful for healthier dietary patterns when adequately formulated - an optimization study in French adults (INCA3).

PURPOSE: We studied to what extent plant-based meat substitutes could improve the nutritional adequacy and healthiness of dietary patterns, depending on their nutrient composition. METHODS: From diets observed in French adults (INCA3, n = 1125), modeled diets were identified by allowing various dietary changes, between and within food categories, when two plant-based meat substitutes were made available: an average substitute (from 43 market substitutes) and a theoretical nutritionally designed substitute, fortified or not with zinc and iron at 30% or 50% of Nutrient Reference Values. Under each scenario, healthier but acceptable modeled diets were identified using multi-criteria optimization, by maximizing a health criteria related to Dietary Guidelines while minimizing deviation from the observed diets, under constraints for nutrient adequacy. RESULTS: Without fortification, the average substitute was hardly introduced into modeled diets, whereas the optimized substitute was preferentially introduced, in large amounts, yet together with a moderate reduction of red meat (- 20%). The comparative advantages of the optimized substitute were its higher contribution to vitamins B6 and C, fiber and α-linolenic acid (ALA) intakes, and its lower contribution to sodium intake. When fortified with iron and zinc, substitutes were introduced in larger amounts into modeled diets, with much higher red meat reductions (down to - 90%). The optimized substitute continued to be preferred, leading to healthier modeled diets that deviated less from the observed. CONCLUSION: Plant-based meat substitutes can be levers for healthy diets only when well nutritionally designed with enough zinc and iron for a substantial red meat reduction.

The potential effects of meat substitution on diet quality could be high if meat substitutes are optimized for nutritional composition-a modeling study in French adults (INCA3).

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.

Substituting Meat or Dairy Products with Plant-Based Substitutes Has Small and Heterogeneous Effects on Diet Quality and Nutrient Security: A Simulation Study in French Adults (INCA3).

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.

Development and evaluation of a new dietary index assessing nutrient security by aggregating probabilistic estimates of the risk of nutrient deficiency in two French adult populations.

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.

Plant-Protein Diversity Is Critical to Ensuring the Nutritional Adequacy of Diets When Replacing Animal With Plant Protein: Observed and Modeled Diets of French Adults (INCA3).

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.

The Initial Dietary Pattern Should Be Considered when Changing Protein Food Portion Sizes to Increase Nutrient Adequacy in French Adults.

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.

Self-declared attitudes and beliefs regarding protein sources are a good prediction of the degree of transition to a low-meat diet in France.

Meat consumption in Western countries is declining and, while the proportion of strict vegetarians remains low, intermediate diets such as flexitarianism have been developing in recent years. Our objectives were to identify the different levels of transition towards low-meat diets, characterize how these diets differ in terms of food intake, and identify whether attitudes and beliefs can explain these degrees of transition. In a representative survey of the French adult population conducted in 2018 (n = 2055), participants declared whether they followed a particular diet and completed a food frequency questionnaire on 29 food sources of protein and a questionnaire on their attitudes and beliefs regarding protein sources. We identified four dietary types based on these declarative data: vegetarians, flexitarians, pro-flexitarians and omnivores. The theory of planned behavior was used to predict meat intake and intentions to reduce meat intake. The sample contained 2.5% vegetarians, 6.3% flexitarians, 18.2% pro-flexitarians and 72.9% omnivores. The diet groups displayed specific dietary profiles and attitudinal scores. Compared with omnivores, pro-flexitarians consumed less red meat, more vegetables and legumes and were much more in agreement about the environmental impacts of meat. Compared with pro-flexitarians, flexitarians consumed less red meat and processed meat, and agreed much more about the health impacts of meat. Finally, versus flexitarians, vegetarians consumed almost no meat but far more legumes, nuts and seeds, and were much more sensitive to animal welfare issues. Attitudes, social norms and perceived behavioral control (PBC) predicted intentions to reduce meat consumption but attitude was the most important predictor. Intentions and PBC were both predictive of meat consumption. The dietary type related to the level of meat intake could be predicted by self-declared attitudes and beliefs regarding protein sources.

Metabolomics Reveals that the Type of Protein in a High-Fat Meal Modulates Postprandial Mitochondrial Overload and Incomplete Substrate Oxidation in Healthy Overweight Men.

Background: A meal rich in saturated fatty acids induces a postprandial metabolic challenge. The type of dietary protein may modulate postprandial metabolism. Objective: We studied the effect of dietary protein type on postprandial changes in the metabolome after a high-fat meal. Methods: In a 3-period, crossover, postprandial study, 10 healthy overweight men with an elevated waist circumference (>94 cm) ingested high-fat meals made up of cream fat (70% of energy), sucrose (15% energy), and protein (15% energy) from either casein (CAS), whey protein (WHE), or α-lactalbumin-enriched whey protein (LAC). Urine collected immediately before and 2, 4, and 6 h after the meal was analyzed for metabolomics, a secondary outcome of the clinical study. We used mixed-effect models, partial least-square regression, and pathway enrichment analysis. Results: At 4 and 6 h after the meal, the postprandial metabolome was found to be fully discriminated according to protein type. We identified 17 metabolites that significantly explained the effect of protein type on postprandial metabolomic changes (protein-time interaction). Among this signature, acylcarnitines and other acylated metabolites related to fatty acid or amino acid oxidation were the main discriminant features. The difference in metabolic profiles was mainly explained by urinary acylcarnitines and some other acylated products (protein type, Ps < 0.0001), with a dramatically greater increase (100- to 1000-fold) after WHE, and to a lesser extent after LAC, as compared with CAS. Pathway enrichment analysis confirmed that the type of protein had modified fatty acid oxidation (P < 0.05). Conclusion: Taken together, our results indicate that, in healthy overweight men, the type of protein in a high-fat meal interplays with fatty acid oxidation with a differential accumulation of incomplete oxidation products. A high-fat meal containing WHE, but not CAS, resulted in this outpacing of the tricarboxylic acid cycle. This study was registered at clinicaltrials.gov as NCT00931151.

Early changes in tissue amino acid metabolism and nutrient routing in rats fed a high-fat diet: evidence from natural isotope abundances of nitrogen and carbon in tissue proteins.

Little is known about how diet-induced obesity and insulin resistance affect protein and amino acid (AA) metabolism in tissues. The natural relative abundances of the heavy stable isotopes of C (δ 13C) and N (δ 15N) in tissue proteins offer novel and promising biomarkers of AA metabolism. They, respectively, reflect the use of dietary macronutrients for tissue AA synthesis and the relative metabolic use of tissue AA for oxidation v. protein synthesis. In this study, δ 13C and δ 15N were measured in the proteins of various tissues in young adult rats exposed perinatally and/or fed after weaning with a normal- or a high-fat (HF) diet, the aim being to characterise HF-induced tissue-specific changes in AA metabolism. HF feeding was shown to increase the routing of dietary fat to all tissue proteins via non-indispensable AA synthesis, but did not affect AA allocation between catabolic and anabolic processes in most tissues. However, the proportion of AA directed towards oxidation rather than protein synthesis was increased in the small intestine and decreased in the tibialis anterior muscle and adipose tissue. In adipose tissue, the AA reallocation was observed in the case of perinatal or post-weaning exposure to HF, whereas in the small intestine and tibialis anterior muscle the AA reallocation was only observed after HF exposure that covered both the perinatal and post-weaning periods. In conclusion, HF exposure induced an early reorganisation of AA metabolism involving tissue-specific effects, and in particular a decrease in the relative allocation of AA to oxidation in several peripheral tissues.

A Slow- Compared with a Fast-Release Form of Oral Arginine Increases Its Utilization for Nitric Oxide Synthesis in Overweight Adults with Cardiometabolic Risk Factors in a Randomized Controlled Study.

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 [(15)N-(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 µmol ⋅ 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.

l-Arginine Supplementation Alleviates Postprandial Endothelial Dysfunction When Baseline Fasting Plasma Arginine Concentration Is Low: A Randomized Controlled Trial in Healthy Overweight Adults with Cardiometabolic Risk Factors.

BACKGROUND: 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.

Casein Compared with Whey Proteins Affects the Organization of Dietary Fat during Digestion and Attenuates the Postprandial Triglyceride Response to a Mixed High-Fat Meal in Healthy, Overweight Men.

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 α-lactalbumin-enriched whey protein (LAC)]. METHODS: The protein fractions were incorporated as 15% energy in a high-fat meal in a 3-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.

Natural isotopic signatures of variations in body nitrogen fluxes: a compartmental model analysis.

Body tissues are generally 15N-enriched over the diet, with a discrimination factor (Δ15N) that varies among tissues and individuals as a function of their nutritional and physiopathological condition. However, both 15N bioaccumulation and intra- and inter-individual Δ15N variations are still poorly understood, so that theoretical models are required to understand their underlying mechanisms. Using experimental Δ15N measurements in rats, we developed a multi-compartmental model that provides the first detailed representation of the complex functioning of the body's Δ15N system, by explicitly linking the sizes and Δ15N values of 21 nitrogen pools to the rates and isotope effects of 49 nitrogen metabolic fluxes. We have shown that (i) besides urea production, several metabolic pathways (e.g., protein synthesis, amino acid intracellular metabolism, urea recycling and intestinal absorption or secretion) are most probably associated with isotope fractionation and together contribute to 15N accumulation in tissues, (ii) the Δ15N of a tissue at steady-state is not affected by variations of its P turnover rate, but can vary according to the relative orientation of tissue free amino acids towards oxidation vs. protein synthesis, (iii) at the whole-body level, Δ15N variations result from variations in the body partitioning of nitrogen fluxes (e.g., urea production, urea recycling and amino acid exchanges), with or without changes in nitrogen balance, (iv) any deviation from the optimal amino acid intake, in terms of both quality and quantity, causes a global rise in tissue Δ15N, and (v) Δ15N variations differ between tissues depending on the metabolic changes involved, which can therefore be identified using simultaneous multi-tissue Δ15N measurements. This work provides proof of concept that Δ15N measurements constitute a new promising tool to investigate how metabolic fluxes are nutritionally or physiopathologically reorganized or altered. The existence of such natural and interpretable isotopic biomarkers promises interesting applications in nutrition and health.

Isotopic and modeling investigation of long-term protein turnover in rat tissues.

Fractional synthesis rates (FSR) of tissue proteins (P) are usually measured using labeled amino acid (AA) tracer methods over short periods of time under acute, particular conditions. By combining the long-term and non-steady-state (15)N labeling of AA and P tissue fractions with compartmental modeling, we have developed a new isotopic approach to investigate the degree of compartmentation of P turnover in tissues and to estimate long-term FSR values under sustained and averaged nutritional and physiological conditions. We measured the rise-to-plateau kinetics of nitrogen isotopic enrichments (δ(15)N) in the AA and P fractions of various tissues in rats for 2 mo following a slight increase in diet δ(15)N. Using these δ(15)N kinetics and a numerical method based on a two-compartment model, we determined reliable FSR estimates for tissues in which P turnover is adequately represented by such a simple precursor-product model. This was the case for kidney, liver, plasma, and muscle, where FSR estimates were 103, 101, 58, and 11%/day, respectively. Conversely, we identified tissues, namely, skin and small intestine, where P turnover proved to be too complex to be represented by a simple two-compartment model, evidencing the higher level of subcompartmentation of the P and/or AA metabolism in these tissues. The present results support the value of this new approach in gaining cognitive and practical insights into tissue P turnover and propose new and integrated FSR values over all individual precursor AA and all diurnal variations in P kinetics.

Plant to animal protein ratio in the diet: nutrient adequacy, long-term health and environmental pressure.

Background: Animal and plant protein sources have contrasting relationships with nutrient adequacy and long-term health, and their adequate ratio is highly debated. Objective: We aimed to explore how the percentage of plant protein in the diet (%PP) relates to nutrient adequacy and long-term health but also to environmental pressures, to determine the adequate and potentially optimal %PP values. Methods: Observed diets were extracted from the dietary intakes of French adults (INCA3, n = 1,125). Using reference values for nutrients and disease burden risks for foods, we modeled diets with graded %PP values that simultaneously ensure nutrient adequacy, minimize long-term health risks and preserve at best dietary habits. This multi-criteria diet optimization was conducted in a hierarchical manner, giving priority to long-term health over diet proximity, under the constraints of ensuring nutrient adequacy and food cultural acceptability. We explored the tensions between objectives and identified the most critical nutrients and influential constraints by sensitivity analysis. Finally, environmental pressures related to the modeled diets were estimated using the AGRIBALYSE database. Results: We find that nutrient-adequate diets must fall within the ~15-80% %PP range, a slightly wider range being nevertheless identifiable by waiving the food acceptability constraints. Fully healthy diets, also achieving the minimum-risk exposure levels for both unhealthy and healthy foods, must fall within the 25-70% %PP range. All of these healthy diets were very distant from current typical diet. Those with higher %PP had lower environmental impacts, notably on climate change and land use, while being as far from current diet. Conclusion: There is no single optimal %PP value when considering only nutrition and health, but high %PP diets are more sustainable. For %PP > 80%, nutrient fortification/supplementation and/or new foods are required.

Plasma Metabolome Analysis Suggests That L-Arginine Supplementation Affects Microbial Activity Resulting in a Decrease in Trimethylamine N-oxide-A Randomized Controlled Trial in Healthy Overweight Adults with Cardiometabolic Risk Factors.

Background: The effects of supplementation with L-arginine (L-arg), the precursor of nitric oxide (NO), on vascular and cardiometabolic health have largely been explored. Whether other mechanisms of the action of L-arg exist remains unknown, as arginine metabolism is complicated. Objective: We aimed to characterize the effect of low dose L-arg supplementation on overall human metabolism both in a fasting state and in response to an allostatic stress. Methods: In a randomized, double-blind, crossover study, 32 healthy overweight adults (mean age 45 y) with cardiometabolic risk (fasting plasma triglycerides >150 mg/dL; waist circumference >94 cm [male] or >80 cm [female]) were treated with 1.5 g sustained-release L-arg 3 times/d (4.5 g/d) or placebo for 4 wk. On the last day of treatment, volunteers consumed a high-fat meal challenge (900 kcal, 80% as fat, 13% as carbohydrate, and 7% as protein). Plasma was collected at fasting, 2, 4, and 6 h after the challenge, and the metabolome was analyzed by high-resolution liquid chromatography-mass spectrometry. Metabolic profiles were analyzed using linear mixed models-principal component analysis. Results: The challenge meal explained most of the changes in the metabolome. The overall effect of L-arg supplementation significantly explained 0.5% of the total variance, irrespective of the response to the challenge meal (P < 0.05). Among the metabolites that explain most of the L-arg effect, we found many amino acids, including branched-chain amino acids, that were decreased by L-arg supplementation. L-arg also decreased trimethylamine N-oxide (TMAO). Other changes suggest that L-arg increased methyl demand. Conclusions: Analysis of the effect of 4 wk of L-arg supplementation on the metabolome reveals important effects on methyl balance and gut microbiota activity, such as a decrease in TMAO. Further studies are needed to investigate those mechanisms and the implications of these changes for long-term health.This trial was registered at clinicaltrials.gov as NCT02354794.