Influence of phytosterol and phytostanol food supplementation on plasma liposoluble vitamins and provitamin A carotenoid levels in humans: An updated review of the evidence.

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 α-tocopherol. Concerning carotenoids, while 13 studies did not demonstrate statistically significant plasma ß-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 ß-carotene concentration of the same magnitude as the estimated average decrease by PAP consumption. These results are supported by the only study of ß-carotene bioavailability showing decrease in absorption by phytosterols daily intake.

The protein level of isoenergetic formulae does not modulate postprandial insulin secretion in piglets and has no consequences on later glucose tolerance.

Early postnatal nutrition is involved in metabolic programming, an excess of protein being suspected to enhance early growth and the propensity to later develop insulin resistance and type 2 diabetes mellitus. The aim of the present study was to test the hypothesis that excessive protein intake during the suckling period would overstimulate the endocrine pancreas in the short term and alter durably its maturation, contributing to the later disruption of glucose homeostasis. Normal-birth-weight and low-birth-weight piglets were fed isoenergetic formulae providing an adequate-protein (AP, equivalent to sow milk) or a high-protein (HP, +48 %) supply between 7 and 28 d of age and were fed a standard diet until 70 d of age. During the formula-feeding period, the HP formula did not modify postprandial insulin secretion but transiently increased fasting insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR, P < 0·05). Fasting insulin and HOMA-IR were restored to AP piglets' values 1 month after weaning. The structure of the endocrine pancreas was not affected by the protein content of the formula. The weight at birth had no major effect on the studied parameters. We concluded that a high-protein supply during the suckling period does not interfere with insulin secretion and endocrine pancreas maturation in the short term. It has no consequences either on glucose tolerance 1 month after weaning. The present study demonstrated that up-regulation of postprandial insulin secretion is not involved in higher growth observed in piglets fed a HP formula.

Effect of milk formula protein content on intestinal barrier function in a porcine model of LBW neonates.

Our study aimed at investigating the impact of the level of protein in milk formula on intestinal structure, barrier function, and its nervous regulation in normal and LBW neonates using a porcine model. Normal birth weight (NBW) or LBW piglets were fed from d7 to d28 of age either with a high protein (HP) or with an adequate protein (AP) formula or stayed with their mother [mother fed (MF)]. The proximal jejunum and distal ileum were sampled at d28 for morphometry analysis and ex vivo permeability measurement in Ussing chambers. Formula feeding induced a trophic effect on the jejunum and ileum of both NBW and LBW piglets, which exhibited longer villi than MF animals, irrespective of the type of formula. In NBW piglets, intestinal permeability was not altered by formula feeding. On the contrary, LBW piglets fed with HP formula, but not AP, exhibited a greater ileal permeability than MF piglets. Feeding the HP formula also disturbed jejunal and ileal regulation of permeability by acetylcholine and vasoactive intestinal peptide (VIP) in LBW compared with MF LBW piglets. In conclusion, the level of protein in formulas did not modify intestinal structure and function in NBW individuals but dramatically modified intestinal barrier function physiology in LBW individuals.

Growth, body composition and hormonal status of growing pigs exhibiting a normal or small weight at birth and exposed to a neonatal diet enriched in proteins.

Small birth weight and excess of early protein intake are suspected to enhance later obesity risk. The present study was undertaken to determine the impact of neonatal diets differing in protein content on growth, body composition and hormonal status of 70-d-old pigs born with normal weight (NW) or small weight (SW). At 7 d of age, male and female suckled piglets were assigned to the NW (approximately 1·4 kg at birth) or SW (approximately 0·99 kg at birth) groups. They were fed milk replacers formulated to provide an adequate protein (AP) or a high protein (HP) supply for 3 weeks. From weaning to 70 d of age, all animals received ad libitum the same standard diet. Growth rates were higher (P < 0·05) in HP piglets than in AP piglets during formula feeding and remained higher (P < 0·05) only in HP male pigs thereafter. No difference in feed consumption was detected between groups during the periods examined. Carcass lipid content and the relative weight of perirenal adipose tissue did not differ between the AP and HP pigs. Whereas plasma leptin concentration was higher (P < 0·05) in HP pigs than in AP pigs with a marked difference in SW pigs, plasma insulin-like growth factor (IGF)-I concentration and expression of IGF system genes were not affected by the diets. In summary, a HP intake during the suckling period induced an increase in growth rate that persisted only in male pigs during the post-weaning period. This response was not associated with any difference in adiposity parameters in this period.

Perspective: Modeling Healthy Eating Patterns for Food-Based Dietary Guidelines-Scientific Concepts, Methodological Processes, Limitations, and Lessons.

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.

Impact of intrauterine growth retardation and early protein intake on growth, adipose tissue, and the insulin-like growth factor system in piglets.

Small birth weight and excess of early protein intake are suspected to enhance later adiposity. The present study was undertaken to determine the impact of diets differing in protein content on short-term growth, adipose tissue development, and the insulin-like growth factor (IGF) system in piglets. Normal (NW) and small (SW) birth weight piglets were fed milk-replacers formulated to provide an adequate (AP) or a high protein (HP) supply between 7 and 28 d of age. The fractional growth rate was higher (p < 0.01) in SW than in NW piglets. At 7 d of age, the lower (p < 0.05) weight of perirenal adipose tissue relative to body mass in SW than in NW piglets did not involve significant changes in plasma IGF-I, leptin, or insulin-like growth factor binding protein levels, but involved differences (p < 0.05) in the expression of IGF-I and leptin in adipose tissue. Growth rates did not differ between AP and HP piglets. At 28 d of age, HP piglets had lower (p < 0.001) relative perirenal adipose tissue weight but did not differ clearly from AP piglets with regard to the IGF system. It remains to be determined whether piglets fed such a high protein intake will stay subsequently with a low adiposity.

Hepatic lipid metabolism response to dietary fatty acids is differently modulated by PPARalpha in male and female mice.

BACKGROUND: In human beings, women are at lower risk of cardiovascular diseases, and respond differently from men to dietary fatty acids. AIM: The aim of the present study was to investigate (i) the influence of gender on the response of lipid metabolism to dietary n-3 PUFA, and (ii) the contribution of PPARalpha to this response. METHODS: Male and female mice, wild-type (WT) and PPARalpha-null (KO), were fed on diets rich in either saturated FA (SFA) or 18:3 n-3 (ALA). Lipid composition, mRNA levels and certain activities of key enzymes and major transcription factors were determined in the liver. WT mice were slightly affected by dietary FA. However, in WT female mice, but not in males, mRNA levels of PPARalpha-dependent genes (L-FABP, ACO) were higher in the mice fed on the ALA-rich diet. When compared to WT mice, KO female mice exhibited a decreased lipogenesis capacity (40% lower FAS, ACC, and SREBP-1c mRNA level), whereas KO males showed a decrease in peroxisomal beta-oxidation (activity and expression of ACO reduced by 20 and 40%, respectively). When compared to SFA-fed KO mice, steatosis was twice lower in KO mice fed on ALA, despite the absence of dietary effect on plasma TG, CPT1 and ACO activities, or ACC and FAS expression. Besides, in mice on the SFA diet, steatosis was alleviated in females, and CPT1 expression was up-regulated to a higher extent in females than in males (2.7- and 3.6-fold, respectively, as compared to the corresponding WT groups). CONCLUSIONS: Our data suggests estrogen to modulate the regulation of hepatic lipid metabolic pathway by dietary fatty acids. Besides, PPARalpha invalidation resulted in unexpected regulations by ALA of its known targets and was compensated partly in females, which was therefore less sensitive to the detrimental effects of a SFA-rich diet.

Effects of dietary alpha linolenic acid on cholesterol metabolism in male and female hamsters of the LPN strain.

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.

Dose effect of alpha-linolenic acid on PUFA conversion, bioavailability, and storage in the hamster.

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.

Gender-related response of lipid metabolism to dietary fatty acids in the hamster.

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.

Dose effect of alpha-linolenic acid on lipid metabolism in the hamster.

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.