Alignment between greenhouse gas emissions reduction and adherence the EAT-Lancet diet: A modeling study based on the NutriNet-Santé cohort.

The potential of the EAT-Lancet reference diet, which promotes a healthy diet within planetary limits, to reduce greenhouse gas emissions (GHGe) remains understudied. This study examines the role of nutritional and acceptability constraints in reducing GHGe through diet optimization, and tests the alignment between GHGe reduction and the EAT-Lancet score. The study used data from 29,413 NutriNet-Santé participants to model French diets and evaluate their environmental, nutritional, economic, and health impact. The Organic Food Frequency Questionnaire was used to assess organic and conventional food consumed, and the Dialecte database was used to estimate the diet environmental impacts. Quality of diets were also evaluated based using the PNNS-GS2 (Programme National Nutrition-Santé 2 guidelines score). When testing minimizing GHGe under strict nutritional and acceptability constraints, it was possible to reduce GHGe up to 67 % (from 4.34 in the observed diet to GHGe = 1.45 kgeqCO2/d) while improving the EAT score by 103 % with 91 % of the food as organic. Greater reductions required relaxation of some constraints. When testing maximizing EAT score under gradual reduction in GHGe, the adherence to the EAT-Lancet diet was not significantly affected by the gradual reduction in GHGe. To maximize EAT score with 75 % reduction in GHGe (1.09 kgeqCO2/d), less strict constraints on the bioavailability of iron and zinc are necessary. The EAT score improved by 141 %, while land occupation decreased by 57 %, compared to the observed value. The diet contained 94 % of organic foods. There was some alignment between the degree of adherence to the EAT-Lancet diet and the reduction in GHGe, but other diets may also lead to a strong reduction in GHGe. Thus, GHGe can be greatly reduced by dietary choices, but require profound reshaping of diets which must be coupled with changes in other areas of the food chain.

Perspective: Plant-Based Meat Alternatives Can Help Facilitate and Maintain a Lower Animal to Plant Protein Intake Ratio.

The health and environmental advantages of plant-predominant diets will likely lead to increasing numbers of consumers reducing their reliance on animal products. Consequently, health organizations and professionals will need to provide guidance on how best to make this change. In many developed countries, nearly twice as much protein is derived from animal versus plant sources. Potential benefits could result from consuming a higher share of plant protein. Advice to consume equal amounts from each source is more likely to be embraced than advice to eschew all or most animal products. However, much of the plant protein currently consumed comes from refined grains, which is unlikely to provide the benefits associated with plant-predominant diets. In contrast, legumes provide ample amounts of protein as well other components such as fiber, resistant starch, and polyphenolics, which are collectively thought to exert health benefits. But despite their many accolades and endorsement by the nutrition community, legumes make a negligible contribution to global protein intake, especially in developed countries. Furthermore, evidence suggests the consumption of cooked legumes will not substantially increase over the next several decades. We argue here that plant-based meat alternatives (PBMAs) made from legumes are a viable alternative, or a complement, to consuming legumes in the traditional manner. These products may be accepted by meat eaters because they can emulate the orosensory properties and functionality of the foods they are intended to replace. PBMAs can be both transition foods and maintenance foods in that they can facilitate the transition to a plant-predominant diet and make it easier to maintain. PBMAs also have a distinct advantage of being able to be fortified with shortfall nutrients in plant-predominant diets. Whether existing PBMAs provide similar health benefits as whole legumes, or can be formulated to do so, remains to be established.

Plant Protein Can Be as Efficient as Milk Protein to Maintain Fat Free Mass in Old Rats, Even When Fat and Sugar Intakes Are High.

BACKGROUND: Alternative, sustainable, and adequate sources of protein must be found to meet global demand. OBJECTIVES: Our aim was to assess the effect of a plant protein blend with a good balance of indispensable amino acids and high contents of leucine, arginine, and cysteine on the maintenance of muscle protein mass and function during aging in comparison to milk proteins and to determine if this effect varied according to the quality of the background diet. METHODS: Old male Wistar rats (n = 96, 18 mo old) were randomly allocated for 4 mo to 1 of 4 diets, differing according to protein source (milk or plant protein blend) and energy content (standard, 3.6 kcal/g, with starch, or high, 4.9 kcal/g, with saturated fat and sucrose). We measured: every 2 mo, body composition and plasma biochemistry; before and after 4 mo, muscle functionality; after 4 mo, in vivo muscle protein synthesis (flooding dose of L-[1-13C]-valine) and muscle, liver, and heart weights. Two-factor ANOVA and repeated measures 2-factor ANOVA were conducted. RESULTS: There was no difference between protein type on the maintenance during aging of lean body mass, muscle mass, and muscle functionality. The high-energy diet significantly increased body fat (+47%) and heart weight (+8%) compared to the standard energy diet but had no effect on fasting plasma glucose and insulin. Muscle protein synthesis was significantly stimulated by feeding to the same extent in all groups (+13%). CONCLUSIONS: Since high-energy diets had little impact on insulin sensitivity and related metabolism, we could not test the hypothesis that in situations of higher insulin resistance, our plant protein blend may be better than milk protein. However, this rat study offers significant proof of concept from the nutritional standpoint that appropriately blended plant proteins can have high nutritional value even in demanding situations such as aging protein metabolism.

Plant and Animal Protein Intakes Largely Explain the Nutritional Quality and Health Value of Diets Higher in Plants: A Path Analysis in French Adults.

Diets higher in plants are associated with lower risks of chronic diseases. However, animal foods, which are rich in protein, are also rich in some important minerals and vitamins. Using data from a representative survey in France (INCA3, n = 1,125), we used path analyses as a mediation-like approach to decipher the importance of plant and animal proteins in the relationship between the plant-based diet index (PDI) and diet quality. We used three types of diet quality scores, namely, nutrient security, positive nutrient adequacy, and long-term mortality risk of four diet-related diseases (i.e., coronary heart disease, stroke, type 2 diabetes, and colorectal cancer). We identified positive and negative mediations, i.e., changes in plant/animal protein intake that are associated with changes in PDI, and favor or limit the association with the diet quality score. The PDI was positively associated with the risk of long-term mortality but not significantly with nutrient adequacy or nutrient security. A positive mediation by plant protein was found for all diet quality scores (specific indirect effects (SIEs) ranging from 0.04 to 0.10 SD). Conversely, the association between PDI and nutrient adequacy (but not nutrient security) was negatively mediated by animal protein intake (SIE: -0.06 SD). In further detailed models, the association between PDI and diet quality was mainly positively mediated by protein foods from the fruit-vegetables-legumes group (0.01 SD for the nutrient security and 0.02 SD for the nutrient adequacy) and whole grains (0.02 SD for the nutrient adequacy). Our data suggest that the positive impact of plant-based diets on diet quality is largely driven by higher intakes of plant protein foods, especially from fruits-vegetables-legumes and whole grains. Conversely, lower animal protein intake tends to limit the positive impact of plant-based diets on overall positive nutrient adequacy but not security. Protein sources appear critical to healthy plant-based diets.

Modeled healthy eating patterns are largely constrained by currently estimated requirements for bioavailable iron and zinc-a diet optimization study in French adults.

BACKGROUND: Healthier dietary patterns involve more plant-based foods than current Western diets rich in animal products containing high amounts 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 multicriteria nonlinear 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 (nonflexible 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 nonflexible 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 <30% of the gain otherwise made on chronic diseases, adding flexibility in the iron and zinc reference values would result in a further 18% decrease in the disease burden from 84,768 [95% uncertainty interval (UI): 81,066, 88,470] to 99,689 (95% UI: 95,787, 103,591) DALYs averted. CONCLUSIONS: Currently estimated requirements for bioavailable iron and zinc proved to be critical factors when modeling healthy eating patterns. Considering lower reference values enables the identification of diets that are apparently healthier overall.

Halving food-related greenhouse gas emissions can be achieved by redistributing meat consumption: Progressive optimization results of the NutriNet-Santé cohort.

BACKGROUND: Diet-related greenhouse gas emissions (GHGe) mainly comes from animal-sourced foods. As progressive changes are more acceptable for a sustainable food transition, we aimed to identify nutritionally adequate and culturally acceptable optimized diets ensuring a gradual reduction in GHGe, using observed diet from a large sample of French adults, while considering the mode of food production (organic vs conventional farming) and the co-production link between milk and beef. MATERIAL AND METHOD: Based on the consumption of 257 organic and conventional foods among 29,413 participants (75% women, age: 53.5 ± 14.0y) of the NutriNet-Santé study, we modelled optimal diets according to GHGe reduction scenarios in 5% steps, from 0 to 50% with nutritional, acceptability, and coproduct constraints, for men, premenopausal and menopausal women separately. RESULTS: Gradual GHGe decrease under these constraints led to optimal diets with an overall decrease in animal foods, with marked reductions in dairy products (up to -83%), together with a stable but largely redistributed meat consumption in favor of poultry (up to +182%) and pork (up to +46%) and at the expense of ruminant meat (down to -92%). Amounts of legumes increases dramatically (up to +238%). The greater the reduction in diet-related GHGe, the lower the cumulative energy demand (about -25%) and land use (about -43%). The proportion of organic food increased from ~30% in the observed diets to ~70% in the optimized diets. CONCLUSION: Our results suggest that meeting both nutrient reference value and environmental objectives of up to 50% GHGe reduction requires the reduction of animal foods together with important substitutions between animal food groups, which result in drastic reductions in beef and dairy products. Further research is required to explore alignment with long-term health value and conflict with acceptability, in particular for even greater GHGe reductions.

The Postprandial Appearance of Features of Cardiometabolic Risk: Acute Induction and Prevention by Nutrients and Other Dietary Substances.

The purpose of this review is to provide an overview of diets, food, and food components that affect postprandial inflammation, endothelial function, and oxidative stress, which are related to cardiometabolic risk. A high-energy meal, rich in saturated fat and sugars, induces the transient appearance of a series of metabolic, signaling and physiological dysregulations or dysfunctions, including oxidative stress, low-grade inflammation, and endothelial dysfunction, which are directly related to the amplitude of postprandial plasma triglycerides and glucose. Low-grade inflammation and endothelial dysfunction are also known to cluster together with insulin resistance, a third risk factor for cardiovascular diseases (CVD) and type-II diabetes, thus making a considerable contribution to cardiometabolic risk. Because of the marked relevance of the postprandial model to nutritional pathophysiology, many studies have investigated whether adding various nutrients and other substances to such a challenge meal might mitigate the onset of these adverse effects. Some foods (e.g., nuts, berries, and citrus), nutrients (e.g., l-arginine), and other substances (various polyphenols) have been widely studied. Reports of favorable effects in the postprandial state have concerned plasma markers for systemic or vascular pro-inflammatory conditions, the activation of inflammatory pathways in plasma monocytes, vascular endothelial function (mostly assessed using physiological criteria), and postprandial oxidative stress. Although the literature is fragmented, this topic warrants further study using multiple endpoints and markers to investigate whether the interesting candidates identified might prevent or limit the postprandial appearance of critical features of cardiometabolic risk.

Asymmetric and Symmetric Protein Arginine Dimethylation: Concept and Postprandial Effects of High-Fat Protein Meals in Healthy Overweight Men.

Asymmetric and symmetric dimethylarginine (ADMA and SDMA, respectively) are risk factors for the cardiovascular and renal systems. There is a paucity of data in humans regarding variations of protein L-arginine (Arg) methylation leading to ADMA and SDMA. In this study, we introduced and used Arg dimethylation indices based on the creatinine-corrected urinary excretion of SDMA and ADMA, and its major metabolite dimethylamine (DMA). The main objective of the present study was to assess whether, and to which extent, a high-fat protein meal (HFM), a classical allostatic load eliciting various adverse effects, may contribute to Arg dimethylation in proteins in humans. Reliable gas chromatography-mass spectrometry methods were used to measure the concentration of ADMA, DMA, SDMA, and creatinine in spot urine samples collected before (0 h), and after (2, 4, 6 h) three HFM sessions in 10 healthy overweight individuals. At baseline, urinary ADMA, DMA, and SDMA excretion correlated positively with circulating TNF-α and IL-6. Arg dimethylation indices did not change postprandially. Our study shows that three HFMs do not contribute to Arg dimethylation in proteins. The proposed indices should be useful to determine extent and status of the whole-body Arg dimethylation in proteins in humans under various conditions.

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.

Plant Protein Intake and Dietary Diversity Are Independently Associated with Nutrient Adequacy in French Adults.

BACKGROUND: Plant protein intake, which is favorably associated with the intake of many nutrients, is a marker of a healthy diet. However, the higher nutrient adequacy of diets rich in plant protein may also originate from overarching factors associated with more healthful dietary behaviors, such as a greater dietary diversity. OBJECTIVE: Our main objective was to determine whether the relation between plant protein intake and nutrient adequacy could be explained, at least in part, by an association with overall dietary diversity. METHODS: We used data from 1330 adults participating in the French Nutrition and Health Survey [Etude Nationale Nutrition Santé (ENNS); 2006-2007]. With the use of global, integrative approaches, we assessed nutrient adequacy [by using the probabilistic PANDiet (Probability of Adequate Nutrient Intake) scoring system] and overall dietary diversity (by using a 100-point score that accounts for the relative number of subgroups consumed in 7 food groups). Linear multivariate modeling was used for the analysis. RESULTS: We found a positive association between plant protein (but not total or animal protein) intake and dietary diversity (ß = 0.08) and a strong positive association between dietary diversity and nutrient adequacy (ß = 0.33). However, the association between plant protein intake and nutrient adequacy was not explained by dietary diversity (r = 0.38 and partial r = 0.36, P < 0.0001). In multivariate analysis, nutrient adequacy was positively associated with dietary diversity (ß = 0.44) and plant (ß = 0.37) and animal (ß = 0.15) protein intakes. Associations persisted after adjustment for potential confounders (total energy, energy density, sex, body mass index, income, occupational status, educational level, region, season, and smoking status). CONCLUSIONS: Overall dietary diversity is greater in French adults who consume more plant protein. Both plant protein intake and dietary diversity are associated with the nutrient adequacy of the diet. But the plant protein-nutrient adequacy association was not related to the relative overall diversity of the diet.

The Dietary Inflammatory Index Is Associated with Prostate Cancer Risk in French Middle-Aged Adults in a Prospective Study.

BACKGROUND: Chronic inflammation is one of the mechanisms involved in carcinogenesis. Diet is a major source of pro- and anti-inflammatory compounds. The Dietary Inflammatory Index (DII) was designed to estimate its overall inflammatory potential. OBJECTIVE: Our objective was to investigate the associations between the DII and overall, breast, and prostate cancer risks. METHODS: This prospective study included 6542 participants [3771 women and 2771 men with a mean ± SD age of 49.2 ± 6.4 y and a BMI (in kg/m2) of 24.0 ± 3.6 at baseline] from the Supplémentation en VItamines et Minéraux AntioXydants (SU.VI.MAX) cohort who completed at least six 24-h dietary records during the first 2 y of follow-up. The DII was based on 36 food variables. Higher scores corresponded to more proinflammatory diets. A total of 559 incident cancers were diagnosed (median follow-up, 12.6 y), including 158 female breast and 123 prostate cancers (the 2 main cancer sites in this cohort). Associations were characterized by multivariable Cox proportional hazards models. Stratified analyses were performed according to the median of usual daily alcohol intake. RESULTS: Sex-specific quartiles of the DII were positively associated with prostate cancer risk [quartile (Q) 4 compared with Q1, HR: 2.08; 95% CI: 1.06, 4.09] but not with overall or breast cancer risks. There was an interaction between the DII and alcohol intake (grams per day) on overall cancer risk (P-interaction = 0.02): the DII was positively associated with overall cancer risk in low-to-moderate alcohol drinkers (Q4 compared with Q1 HR: 1.75; 95% CI: 1.15, 2.68; P-trend = 0.02), whereas no association was detected in higher consumers of alcohol (P-trend = 0.8). This interaction was also observed for breast cancer (P-interaction = 0.001). CONCLUSION: Consistent with mechanistic data, findings from this study indicated that proinflammatory diets are associated with increased prostate cancer risk and, in low-to-moderate alcohol drinkers, with increased overall and breast cancer risk. The SU.VI.MAX trial was registered at clinicaltrials.gov as NCT00272428.

Prospective association between the Dietary Inflammatory Index and mortality: modulation by antioxidant supplementation in the SU.VI.MAX randomized controlled trial.

BACKGROUND: Chronic inflammation is a central mechanism involved in cardiovascular diseases, cancer, diabetes, and chronic respiratory diseases, 4 leading causes of mortality. Diet is a major source of pro- and anti-inflammatory bioactive compounds. The Dietary Inflammatory Index (DII) was designed to estimate the overall inflammatory potential of the diet. OBJECTIVE: Our aim was to study the prospective association between the DII and mortality, as well as assess whether antioxidant supplementation could modulate this association. DESIGN: The Supplémentation en Vitamines et Minéraux Antioxydants study was a randomized, double-blind, placebo-controlled trial in which participants received low-dose antioxidants or a placebo from 1994 to 2002. In this observational prospective analysis, 8089 participants (mean ± SD age at baseline: 49.0 ± 6.3 y) were followed between 1994 and 2007 (median: 12.4 y). The DII was calculated from repeated 24-h dietary records; higher scores correspond to more proinflammatory diets. A total of 207 deaths occurred during follow-up, including 123 due to cancer and 41 due to cardiovascular events. Multivariate Cox proportional hazards models were computed. RESULTS: Sex-specific tertiles of the DII were positively associated with cardiovascular + cancer mortality (HR for tertile 3 compared with tertile 1 = 1.53; 95% CI: 1.01, 2.32; P-trend = 0.05) and specific cancer mortality (HR for tertile 3 compared with tertile 1 = 1.83; 95% CI: 1.12, 2.99; P-trend = 0.02). The corresponding P value was 0.07 for all-cause mortality. The DII was statistically significantly associated with increased all-cause mortality in the placebo group (HR for tertile 3 compared with tertile 1 = 2.10; 95% CI: 1.15, 3.84; P-trend = 0.02) but not in the antioxidant-supplemented group (P-trend = 0.8; P-interaction = 0.098). CONCLUSION: These results suggest that a proinflammatory diet is associated with increased all-cause and cancer mortality and antioxidants may counteract some of the proinflammatory effects of the diet. This trial was registered at clinicaltrials.gov as NCT00272428.

Biosynthesis of homoarginine (hArg) and asymmetric dimethylarginine (ADMA) from acutely and chronically administered free L-arginine in humans.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthesis, whereas L-arginine (Arg) and L-homoarginine (hArg) serve as substrates for NO synthesis. ADMA and other methylated arginines are generally believed to exclusively derive from guanidine (N (G))-methylated arginine residues in proteins by protein arginine methyltransferases (PRMTs) that use S-adenosylmethionine (SAM) as the methyl donor. L-Lysine is known for decades as a precursor for hArg, but only recent studies indicate that arginine:glycine amidinotransferase (AGAT) is responsible for the synthesis of hArg. AGAT catalyzes the formation of guanidinoacetate (GAA) that is methylated to creatine by guanidinoacetate methyltransferase (GAMT) which also uses SAM. The aim of the present study was to learn more about the mechanisms of ADMA and hArg formation in humans. Especially, we hypothesized that ADMA is produced by N (G)-methylation of free Arg in addition to the known PRMTs-involving mechanism. In knockout mouse models of AGAT- and GAMT-deficiency, we investigated the contribution of these enzymes to hArg synthesis. Arg infusion (0.5 g/kg, 30 min) in children (n = 11) and ingestion of high-fat protein meals by overweight men (n = 10) were used to study acute effects on ADMA and hArg synthesis. Daily Arg ingestion (10 g) or placebo for 3 or 6 months by patients suffering from peripheral arterial occlusive disease (PAOD, n = 20) or coronary artery disease (CAD, n = 30) was used to study chronic effects of Arg on ADMA synthesis. Mass spectrometric methods were used to measure all biochemical parameters in plasma and urine samples. In mice, AGAT but not GAMT was found to contribute to plasma hArg, while ADMA synthesis was independent of AGAT and GAMT. Arg infusion acutely increased plasma Arg, hArg and ADMA concentrations, but decreased the plasma hArg/ADMA ratio. High-fat protein meals acutely increased plasma Arg, hArg, ADMA concentrations, as well as the plasma hArg/ADMA ratio. In the PAOD and CAD studies, plasma Arg concentration increased in the verum compared to the placebo groups. Plasma ADMA concentration increased only in the PAOD patients who received Arg. Our study suggests that in humans a minor fraction of free Arg is rapidly metabolized to ADMA and hArg. In mice, GAMT and N (G)-methyltransferases contribute to ADMA and hArg synthesis from Arg, whereas AGAT is involved in the synthesis of hArg but not of ADMA. The underlying biochemical mechanisms remain still elusive.

Plasma asymmetric and symmetric dimethylarginine in a rat model of endothelial dysfunction induced by acute hyperhomocysteinemia.

Hyperhomocysteinemia induces vascular endothelial dysfunction, an early hallmark of atherogenesis. While higher levels of circulating asymmetric dimethylarginine (ADMA) and symmetric dimethyl arginine (SDMA), endogenous inhibitors of nitric oxide synthesis, have been associated with increased cardiovascular risk, the role that ADMA and SDMA play in the initiation of hyperhomocysteinemia-induced endothelial dysfunction remains still controversial. In the present study, we studied the changes of circulating ADMA and SDMA in a rat model of acutely hyperhomocysteinemia-induced endothelial dysfunction. In healthy rats, endothelium-related vascular reactivity (measured as acetylcholine-induced transient decrease in mean arterial blood pressure), plasma ADMA and SDMA, total plasma homocysteine (tHcy), cysteine and glutathione were measured before and 2, 4 and 6 h after methionine loading or vehicle. mRNA expression of hepatic dimethylarginine dimethylaminohydrolase-1 (DDAH1), a key protein responsible for ADMA metabolism, was measured 6 h after the methionine loading or the vehicle. Expectedly, methionine load induced a sustained increase in tHcy (up to 54.9 ± 1.9 µM) and a 30 % decrease in vascular reactivity compared to the baseline values. Plasma ADMA and SDMA decreased transiently after the methionine load. Hepatic mRNA expression of DDAH1, cathepsin D, and ubiquitin were significantly lower 6 h after the methionine load than after the vehicle. The absence of an elevation of circulating ADMA and SDMA in this model suggests that endothelial dysfunction induced by acute hyperhomocysteinemia cannot be explained by an up-regulation of protein arginine methyltransferases or a down-regulation of DDAH1. In experimental endothelial dysfunction induced by acute hyperhomocysteinemia, down-regulation of the proteasome is likely to dampen the release of ADMA and SDMA in the circulation.

Slight chronic elevation of C-reactive protein is associated with lower aerobic fitness but does not impair meal-induced stimulation of muscle protein metabolism in healthy old men.

Ageing impairs the muscle anabolic effect of food intake, which may explain muscle loss and an increased risk of sarcopenia. Ageing is also associated with low grade inflammation (LGI), which has been negatively correlated with muscle mass and strength. In rodents, the muscle anabolic resistance observed during ageing and sarcopenia has been ascribed to the development of the LGI. We aimed to investigate this relationship in humans. We studied protein metabolism and physical fitness in healthy elderly volunteers with slight chronic C-reactive protein. Two groups of healthy elderly volunteers were selected on the presence (or not) of a chronic, slight, elevation of CRP (Control: <1; CRP+: >2 mg l(-1) and <10 mg l(-1) , for 2 months). Body composition, short performance battery test, aerobic fitness and muscle strength were assessed. Whole body and muscle protein metabolism and the splanchnic extraction of amino acids were assessed using [(13) C]leucine and [(2) H]leucine infusion. The anabolic effect of food intake was measured by studying the volunteers both at the post-absorptive and post-prandial states. Slight chronic CRP elevation resulted in neither an alteration of whole body, nor skeletal muscle protein metabolism at both the post-absorptive and the post-prandial states. However, CRP+ presented a reduction of physical fitness, increased abdominal fat mass and post-prandial insulin resistance. Plasma cytokines (interleukin-1, interleukin-6, tumour necrosis factor α) and markers of endothelial inflammation (intercellular adhesion molecule, vascular cell adhesion molecule, selectins) were similar between groups. An isolated elevated CRP in healthy older population does not indicate an impaired skeletal muscle anabolism after food intake, nor an increased risk of skeletal muscle wasting. We propose that a broader picture of LGI (notably with elevated pro-inflammatory cytokines) is required to impact muscle metabolism and mass. However, an isolated chronic CRP elevation could predict a decrease in aerobic fitness and insulin resistance installation in elderly individuals.

Evaluation of a diet quality index based on the probability of adequate nutrient intake (PANDiet) using national French and US dietary surveys.

BACKGROUND: Existing diet quality indices often show theoretical and methodological limitations, especially with regard to validation. OBJECTIVE: To develop a diet quality index based on the probability of adequate nutrient intake (PANDiet) and evaluate its validity using data from French and US populations. MATERIAL AND METHODS: The PANDiet is composed of adequacy probabilities for 24 nutrients grouped into two sub-scores. The relationship between the PANDiet score and energy intake were investigated. We evaluated the construct validity of the index by comparing scores for population sub-groups with 'a priori' differences in diet quality, according to smoking status, energy density, food intakes, plasma folate and carotenoid concentrations. French and US implementations of the PANDiet were developed and evaluated using national nutritional recommendations and dietary surveys. RESULTS: The PANDiet was not correlated with energy for the French implementation (r = -0.02, P>0.05) and correlated at a low level for the US implementation (r = -0.11, P<0.0001). In both implementations, a higher PANDiet score (i.e. a better diet quality) was associated with not smoking, having a lower-energy-dense diet, consuming higher amounts of fruits, vegetables, fish, milk and other dairy products and lower amounts of cheese, pizza, eggs, meat and processed meat, and having higher plasma folate and carotenoid concentrations after controlling for appropriate factors (all P<0.05, carotenoid data for US not available). CONCLUSIONS: The PANDiet provides a single score that measures the adequacy of nutrient intake and reflects diet quality. This index is adaptable for use in different countries and relevant at the individual and population levels.

Postprandial effects of a lipid-rich meal in the rat are modulated by the degree of unsaturation of 18C fatty acids.

The fatty acid composition of high-fat diets is known to influence the magnitude of postprandial events that increase the risk of metabolic syndrome. These variations in magnitude may be directly ascribed to differences in the channeling of lipids toward oxidation or storage. A study was designed to compare the effects of 4 dietary fats on postprandial energy expenditure and on some risk factors of the metabolic syndrome. To avoid usual confounding factors due to simultaneous variations in chain length and double-bounds number of fatty acids, dietary fats were chosen to provide mainly 18-carbon fatty acids with 0 (stearic acid [SA]), 1 (oleic acid [OA]), 2 (linoleic acid [LA]), or 3 (alpha-linolenic acid [ALA]) double bounds. They were given as single high-fat test meals to 4 different groups of male rats. The resting metabolic rate and the lipid and carbohydrate oxidation were measured from oxygen consumption and carbon dioxide production using indirect calorimetry 2 hours before and 6.5 hours after the test meal. Plasma glucose, triglyceride, and chylomicron concentrations were determined at 0, 1.5, and 4 hours after the test meal. Postprandial concentration of glucose and triglyceride did not vary with the nature of the test meals, whereas that of chylomicrons was the highest after the LA test meal and the lowest after the SA test meal. Postprandial increase in resting metabolic rate was the highest after the LA and OA test meals, and the lowest after the SA and ALA test meals. Compared with the 3 other diets, the ALA test meal enhanced lipid oxidation and decreased glucose oxidation during the early postprandial period (0.25-3.25 hours). This suggests that stearic acid may not induce all the adverse effects classically described for other saturated fatty acids and that alpha-linolenic acid may beneficially influence energy partitioning, especially during the early postprandial state.

Early postprandial low-grade inflammation after high-fat meal in healthy rats: possible involvement of visceral adipose tissue.

In the postprandial period, low-grade inflammation may contribute to vascular endothelial dysfunction, a hallmark of atherogenesis. Little is known about the involvement of the adipose tissue in the initiation of the postprandial inflammatory response such as obtained after a high-saturated fat meal (HFM). In the present study, we first studied the time course of appearance of systemic inflammation after a HFM in healthy rats, and then we investigated whether a HFM activates the inflammatory signaling in the visceral adipose tissue, with a focus on the key component, nuclear factor-kappaB (NF-kappaB). Two hours after the HFM, plasma IL-6 and PAI-1, but not plasma C-reactive protein and soluble intracellular adhesion molecule-1, showed a marked, transient increase. These changes were specific to the postprandial state as not observed after a control water load. Neutrophils count and activation markers CD11B and CD62L, assessed by flow cytometry, also rose significantly 2 h after the HFM, while remaining steady after the control. At the same time, the HFM decreased significantly B-cell count and expression of the activation marker CD62L. Interestingly, at the same early time after the HFM, in the visceral adipose tissue, there was a 2.2-fold increase in the activation of NF-kappaB (p65) in nuclear extract and an increase in IL-6 mRNA. As far as we know, this is the first study evidencing an acute, postprandial activation of inflammation in visceral adipose tissue. This early activation of NF-kappaB pathway after a HFM may play a triggering role in the initiation of the complex postprandial proatherogenic phenotype.

Rapeseed protein in a high-fat mixed meal alleviates postprandial systemic and vascular oxidative stress and prevents vascular endothelial dysfunction in healthy rats.

High-saturated fat and high-sucrose meals induce vascular endothelial dysfunction, the early hallmark of atherogenesis. The impact of dietary protein on vascular homeostasis remains misunderstood. In this study, we investigated whether rapeseed protein, an emergent arginine- and cysteine-rich protein, can acutely modulate the onset of adverse effects induced by a high-saturated fat meal (HFM). In a series of crossover experiments, healthy rats received 3 HFM (saturated fat: 60%; sucrose: 20%; protein: 20% energy) with the protein source being either total milk protein (MP; control), rapeseed protein (RP), or MP supplemented with cysteine and arginine to the same level as in RP (MP+AA). Endothelium-related vascular reactivity, measured as an acetylcholine-induced transient decrease in blood pressure, and plasma triglycerides, hydroperoxides, cyclic GMP (cGMP), and free 3-nitrotyrosine were measured before and 2, 4, and 6 h after meals. Superoxide anion production, expressed as ethidine fluorescence, was measured in the aorta 6 h after meals. Whereas plasma triglycerides rose similarly in all meals, the decrease in vascular reactivity after MP was attenuated after MP+AA and entirely prevented after RP. The type of meal had no consistent effect on plasma cGMP and free 3-nitrotyrosine over the postprandial period. The postprandial increase in plasma hydroperoxides differed according to the meal, and concentrations were 43% lower 6 h after MP+AA and RP than after MP. Aortic superoxide anion production was 36% lower 6 h after RP than MP. These results show that substituting rapeseed protein for milk protein markedly reduces vascular and oxidative disturbances induced by an HFM and this may be mediated in part by cysteine and arginine.

Rapeseed protein inhibits the initiation of insulin resistance by a high-saturated fat, high-sucrose diet in rats.

In contrast to the quality of carbohydrates and lipids, little is known on the influence of the type of dietary protein on the development of the metabolic or insulin resistance syndrome. Cysteine intake has been recently documented to impact insulin sensitivity. The aim of this study was to determine whether rapeseed protein, an emergent cysteine-rich protein, could inhibit the onset of the metabolic syndrome. For 9 weeks, rats were fed a diet rich in saturated fats and sucrose, which also included 20 % protein either as milk protein ('Induction' diet I) or rapeseed protein (diet R). A third, control group received an isoenergetic diet containing milk protein but polyunsaturated fats and starch ('Prudent' diet P). Plasma glucose, insulin, TAG and cholesterol, and blood pressure were monitored during the study, glucose tolerance was tested at week 7 and body composition determined at week 9. Plasma glucose, insulin and TAG increased during the experiment and, at week 9, plasma insulin was significantly 34 % lower in the R group and 56 % lower in P group as compared with the I group. The insulin peak after the glucose load was significantly 28-30 % lower in R and P than in I and the insulin sensitivity index was significantly higher in R than in I. Unexpectedly, peripheral fat deposition was slightly higher in R than in I. In this model, substituting rapeseed protein for milk protein had preventive effects on the early onset of insulin resistance, similar to those achieved by manipulating the types of dietary fat and carbohydrates.