The relations between dietary features and human health are varied and complex. Health-related variables are many and they have intricate relations at different and interrelated nutritional levels: nutrients, food groups, and the complex overall pattern. Food-based dietary guidelines (FBDGs) are principally designed to synthesize this information to make it available to the public. Here, we describe the method used to establish healthy eating patterns (HEPs) for the latest French FBDGs, which consists of in-depth food pattern modeling using an enhanced optimization method that gathered all aspects of HEPs. We present the novelty of this food modeling approach for FBDGs, which aims to gather information related to nutrients, food contaminants, and epidemiological relations with long-term health, and to be combined with the objective of realistic dietary patterns that deviate minimally from the prevailing diet. We draw lessons from stepwise implementation of the method and discuss its strengths, limitations, and perspectives. In light of the modeled HEPs, we discuss the importance of food grouping; of accounting for dietary habits while not precluding modeled diets that can be realistic/acceptable; and of taking into account the exposure to food contaminants. We discuss the tolerance and flexibility to be applied to certain dietary reference values for nutrients and health-based guidance values for contaminants so that HEPs can ultimately be identified, and how account can be taken of varied health-related outcomes applied to food groups. Although the approach involves all the peculiar uncertainties of numerous optimization model parameters and input data, its merit is that it offers a rationalized approach to establishing HEPs with multiple constraints and competing objectives. It is also versatile because it is possible to operationalize further dimensions of dietary patterns to favor human and planetary health.

Phytosterols and phytostanols (PAP) compete with cholesterol absorption in the intestine, resulting in a 5-15%-reduction in plasma total and LDL cholesterol. An important issue is the PAP potential to reduce the plasma concentrations of fat-soluble vitamins and provitamin A carotenoids. Here, an update of the scientific evidence is reviewed to evaluate plant PAP-enriched foods impact on plasma fat-soluble vitamins and carotenoid levels, and to discuss potential implications in terms of cardiovascular risk. Based on 49 human interventional and 3 bioavailability studies, results showed that regular consumption, particularly over the long term, of foods fortified with PAP as recommended in labeling does not significantly impact plasma vitamins A, D, and K concentration. A 10% significant median reduction was observed for alpha-tocopherol. Concerning carotenoids, while 13 studies did not demonstrate statistically significant plasma beta-carotene reduction, 20 studies showed significant reductions, with median effect size of -24%. This decline can be mitigated or offset by increased fruits and vegetables consumption. Furthermore, higher cardiovascular risk was observed for differences in plasma beta-carotene concentration of the same magnitude as the estimated average decrease by PAP consumption. These results are supported by the only study of beta-carotene bioavailability showing decrease in absorption by phytosterols daily intake.

Les sources de vitamines et mineraux antioxydants se multiplient en France avec le developpement des complements alimentaires (CA). Mais qu'en est-il des niveaux d'apports en antioxydants ? Atteignent-ils le besoin nutritionnel moyen (BNM) ? Depassent-ils les limites de securite ? Les donnees de l'etude INCA2 apportent des elements de reponse. L'alimentation courante permet de couvrir le BNM uniquement dans 40 % de la population pour le cuivre et la vitamine C et dans 50 % pour le manganese. Les limites de securite europeennes pour ces nutriments ne sont pas atteintes par l'alimentation courante, meme par les plus forts consommateurs. Si l'on considere les apports totaux (alimentation courante + CA) des seuls consommateurs de CA riches en chacun des antioxydants, les niveaux d'apports depassent parfois les limites de securite, c'est notamment le cas de la vitamine C et du zinc. Ainsi, selon la population consideree, des risques d'insuffisance d'apport ou de depassement de limite de securite peuvent etre observes. Ce constat renforce l'idee selon laquelle l'orientation des comportements alimentaires necessite une approche individuelle.

In human beings, women are at lower risk of cardiovascular diseases, and respond differently from men to dietary fatty acids.

Gender and dietary fatty acids are involved in the regulation of lipid metabolism, disturbances of which can lead to pathologies such as metabolic syndrome or CVD. Possible interactions between these factors were investigated in male and female hamsters fed diets rich in either saturated fatty acids ( "butter" diet) or in alpha-linolenic acid ( "linseed oil" diet). Gender effect predominated over the diet effect on cholesterol (CH) metabolism; compared to males, females exhibited lower concentrations of plasma total CH (-20 %, P<0.001), LDL-CH (-40 %, P<0.001) and HDL-CH (-16 %, P<0.001), together with higher LDL receptor (+40 %) and lower HDL receptor (-60 %) hepatic content. Triacylglycerol (TG) metabolism was affected by diet above all: compared to animals fed the "butter" diet, those fed the "linseed oil" diet exhibited lower plasma (-23 %, P=0.046) and liver TG (-20 %, P=0.026) concentration which may result from both an increased beta-oxidation (P<0.001), without any change in PPARalpha mRNA, and a decreased hepatic lipogenesis (P=0.023), without increased sterol response element binding protein 1c (SREBP1c) mRNA. The response to diet was much more pronounced in males than in females, without gender effect on the transcription level of PPARalpha and SREBP1c. Finally, the "linseed oil" diet decreased the insulin resistance index (-80 %, P<0.001) with a more marked effect in males, in relation to their higher hepatic PPARgamma expression (+90 %, P=0.012). In conclusion, in our model, the response of either TG or CH to dietary fatty acids is modulated differently by gender. The possible relevance of these interactions to dietary practice should be taken into account in man.

In order to meet dietary requirements, the consumption of alpha-linolenic acid (ALA, 18:3 n-3) must be promoted. However, its effects on triglyceride (TG) and cholesterol metabolism are still controversial, and may be dose-dependent. The effects of increasing dietary ALA intakes (1%, 10%, 20% and 40% of total FA) were investigated in male hamsters. ALA replaced oleic acid while linoleic and saturated FA were kept constant. Triglyceridemia decreased by 45% in response to 10% dietary ALA and was not affected by higher intakes. It was associated with lower hepatic total activities of acetyl-CoA-carboxylase (up to -29%) and malic enzyme (up to -42%), which were negatively correlated to ALA intake (r(2) = 0.33 and r(2) = 0.38, respectively). Adipose tissue lipogenesis was 2-6 fold lower than in the liver and was not affected by dietary treatment. Substitution of 10% ALA for oleic acid increased cholesterolemia by 15% but, as in TG, higher ALA intakes did not amplify the response. The highest ALA intake (40%) dramatically modified the hepatobiliary metabolism of sterols: cholesterol content fell by 45% in the liver and increased by 28% in the faeces. Besides, faecal bile acids decreased by 61%, and contained more hydrophobic and less secondary bile acids. Thus, replacing 10% oleic acid by ALA is sufficient to exert a beneficial hypotriglyceridemic effect, which may be counteracted by the slight increase in cholesterolemia. Higher intakes did not modify these parameters, but a very high dose resulted in adverse effects on sterol metabolism.

The purpose of our study was to investigate the effects of high doses of ALA provided by linseed oil (containing 50% ALA) on its own bioavailability and that of its derivatives as well as on lipid metabolism. We investigated in male hamsters the dose/response effects of ALA over a broad range of supply as linseed oil (1, 10, 20 and 41% of total fatty acids, FA, or 0.4, 3.6, 6.7 and 14.6 % of total energy intake). ALA was substituted for oleic acid in order to keep constant linoleic acid (LA) and saturated fatty acids which could interfere with the metabolism of n-3 PUFA and lipids, respectively. The capacity of ALA absorption, transport, storage and conversion into EPA had no limitation over the chosen range of dietary intake. However, dietary ALA failed to increase DHA content in plasma phospholipids. In parallel to the increase in EPA, arachidonic acid content decreased, resulting in an improved balance of 20 carbons FA. Moreover, in our atherogenic conditions, triglyceridemia decreased by 45% in response to 10 % dietary ALA and was not affected by higher intakes. It was associated with lower hepatic activities of acetyl-CoA-carboxylase (up to -29%) and malic enzyme (up to -42%), which were negatively correlated to ALA intake (r(2) = 0.33 and r(2) = 0.38, respectively). Substitution of 10 % ALA for oleic acid increased cholesterolemia by 15 % but, as in TG, higher ALA intakes did not amplify the response. The highest ALA intake (40 %) modified dramatically hepatobiliary metabolism of sterols. Thus, replacing 10 % oleic acid by ALA is sufficient to improve its bioavailability and that of EPA, and to exert a beneficial hypotriglyceridemic effect, that may be counteracted by the slight increase in cholesterolemia. Higher intakes did not modify these parameters, but a very high dose resulted in adverse effects on sterol metabolism and does not seem appropriate for humans.

The purpose of our study was to investigate the effects of high doses of ALA provided by linseed oil (containing 50% ALA) on its own bioavailability and that of its derivatives as well as on lipid metabolism. We investigated in male hamsters the dose/response effects of ALA over a broad range of supply as linseed oil (1, 10, 20 and 41% of total fatty acids, FA, or 0.4, 3.6, 6.7 and 14.6% of total energy intake). ALA was substituted for oleic acid in order to keep constant linoleic acid (LA) and saturated fatty acids which could interfere with the metabolism of n-3 PUFA and lipids, respectively. The capacity of ALA absorption, transport, storage and conversion into EPA had no limitation over the chosen range of dietary intake. However, dietary ALA failed to increase DHA content in plasma phospholipids. In parallel to the increase in EPA, arachidonic acid content decreased, resulting in an improved balance of 20 carbons FA. Moreover, in our atherogenic conditions, triglyceridemia decreased by 45% in response to 10% dietary ALA and was not affected by higher intakes. It was associated with lower hepatic activities of acetyl-CoA-carboxylase (up to – 29%) and malic enzyme (up to – 42%), which were negatively correlated to ALA intake (r2 = 0.33 and r2 = 0.38, respectively). Substitution of 10% ALA for oleic acid increased cholesterolemia by 15% but, as in TG, higher ALA intakes did not amplify the response. The highest ALA intake (40%) modified dramatically hepatobiliary metabolism of sterols. Thus, replacing 10% oleic acid by ALA is sufficient to improve its bioavailability and that of EPA, and to exert a beneficial hypotriglyceridemic effect, that may be counteracted by the slight increase in cholesterolemia. Higher intakes did not modify these parameters, but a very high dose resulted in adverse effects on sterol metabolism and does not seem appropriate for humans.

Dietary intake of whole linseeds exerts a beneficial effect on lipid metabolism and risk factors of cardiovascular diseases, due in particular to the abundance of a-linolenic acid (ALA). The effect of the form of ALA providing, either as whole extruded seeds, or as linseed oil combined with linseed meal was investigated on parameters of lipid metabolism in the male hamster, and compared to that of a diet of same gross composition, but rich in saturated fatty acids (SFA). Replacing SFA by ALA (as oil or seeds) decreased significantly plasma cholesterol concentration (-28%), the effect being more pronounced on LDL (-49%) than on HDL (-17%). There was no difference between the two forms of ALA providing on cholesterol intestinal absorption (82-85%) and plasma transport. By contrast, providing ALA as whole seeds resulted in a lesser hepatic cholesterol accumulation (-24%), and in a greater biliary acid concentration in bile (+ 20%), possibly indicative of a better cholesterol elimination. The synergy between the effect of fibres and that of ALA on hepatobiliary metabolism of cholesterol would therefore be enhanced when both components are provided as whole linseed, rather than separately.

N-3 polyunsaturated fatty acids and estrogens are recognized as protective factors of atherosclerosis, however their interactions on cholesterol metabolism remain unclear. Male and female hamsters were fed for 9 weeks diets containing 12.5% lipids and rich in either alpha-linolenic acid ("linseed" diet) or saturated fatty acids ("butter" diet). Hamsters fed the "linseed" diet exhibited lower plasma concentrations of cholesterol (-29%), total LDL (-35%) and HDL (-17%), glucose (-20%), insulin (-40%) and of the LDL-cholesterol/HDL-cholesterol ratio (-27%) than those fed the "butter" diet. In the liver, cholesterol content was 2.7-fold lower in response to the "linseed" diet, whereas the concentration of HDL receptor (SR-BI) and the activities of HMGCoA reductase and cholesterol 7alpha-hydroxylase were 30 to 50% higher than with the "butter" diet. By contrast, the LDL receptor concentration did not vary with the diet. Females exhibited higher concentration of LDL (+24%), lower concentration of plasma triglycerides (-34%), total VLDL (-46%) and VLDL-cholesterol (-37%) and of biliary phospholipids (-19%). Besides, there was also an interaction between gender and diet: in males fed the "butter" diet, plasma triglycerides and VLDL concentration, were 2 to 4 fold higher than in the other groups. These data suggest that gene and/or metabolic regulations by fatty acids could interact with that of sex hormones and explain why males are more sensitive to dietary fatty acids.

If an increased consumption of alpha-linolenic acid (ALA) is to be promoted in parallel with that of n-3 long-chain-rich food, it is necessary to consider to what extent dietary ALA can be absorbed, transported, stored, and converted into long-chain derivatives. We investigated these processes in male hamsters, over a broad range of supply as linseed oil (0.37, 3.5, 6.9, and 14.6% energy). Linoleic acid (LA) was kept constant (8.5% energy), and the LA/ALA ratio was varied from 22.5 to 0.6. The apparent absorption of individual FA was very high (>96%), and that of ALA remained almost maximum even at the largest supply (99.5%). The capacity for ALA transport and storage had no limitation over the chosen range of dietary intake. Indeed, ALA intake was significantly correlated with ALA level not only in cholesteryl esters (from 0.3 to 9.7% of total FA) but also in plasma phospholipids and red blood cells (RBC), which makes blood components extremely reliable as biomarkers of ALA consumption. Similarly, ALA storage in adipose tissue increased from 0.85 to 14% of total FA and was highly correlated with ALA intake. As for bioconversion, dietary ALA failed to increase 22:6n-3, decreased 20:4n-6, and efficiently increased 20:5n-3 (EPA) in RBC and cardiomyocytes. EPA accumulation did not tend to plateau, in accordance with identical activities of delta5- and delta6-desaturases in all groups. Dietary supply of ALA was therefore a very efficient means of improving the 20:4n-6 to 20:5n-3 balance.