Jean-Michel Lecerf

Xylo-oligosaccharide (XOS) in combination with inulin modulates both the intestinal environment and immune status in healthy subjects, while XOS alone only shows prebiotic properties

The purpose of the present study was to establish the prebiotic effect of a new xylo-oligosaccharide (XOS) and of an inulin-and-XOS mixture (INU-XOS) and to determine their effect on endotoxaemia (lipopolysaccharides (LPS)) and immune parameters. In this randomised, parallel, placebo-controlled, double-blind study, sixty healthy volunteers were randomly assigned to three groups, receiving either 5 g XOS, INU-XOS (3 g inulin +1 g XOS) or an equivalent weight of wheat maltodextrin (placebo) during 4 weeks. Faecal samples were collected to assess the effects of these products on microbiota, as well as SCFA composition, enzymatic activities and secretory IgA production. Circulating LPS was measured in plasma samples, and whole blood was incubated with LPS to measure cytokine expression. Consumption of XOS alone increased the faecal concentrations of Bifidobacterium and butyrate and activities of α-glucosidase and β-glucuronidase, while decreasing the concentrations of acetate and p-cresol. Consumption of XOS in combination with inulin did not decrease the concentrations of acetate and p-cresol, but increased in addition the faecal concentrations of total SCFA and propionate. Furthermore, consumption of XOS in combination with inulin decreased LPS concentrations in blood and attenuated LPS-induced increases in gene expression in IL-1β and LPS-induced decreases in gene expression in IL-13 in blood. In conclusion, consumption of XOS alone or in combination with inulin results in beneficial albeit different changes in the intestinal microbiome on a high-fat diet. In addition, consumption of XOS in combination with inulin attenuates the proinflammatory effects of a high-fat diet in the blood of healthy subjects.

Dietary cholesterol: from physiology to cardiovascular risk

Dietary cholesterol comes exclusively from animal sources, thus it is naturally present in our diet and tissues. It is an important component of cell membranes and a precursor of bile acids, steroid hormones and vitamin D. Contrary to phytosterols (originated from plants), cholesterol is synthesised in the human body in order to maintain a stable pool when dietary intake is low. Given the necessity for cholesterol, very effective intestinal uptake mechanisms and enterohepatic bile acid and cholesterol reabsorption cycles exist; conversely, phytosterols are poorly absorbed and, indeed, rapidly excreted. Dietary cholesterol content does not significantly influence plasma cholesterol values, which are regulated by different genetic and nutritional factors that influence cholesterol absorption or synthesis. Some subjects are hyper-absorbers and others are hyper-responders, which implies new therapeutic issues. Epidemiological data do not support a link between dietary cholesterol and CVD. Recent biological data concerning the effect of dietary cholesterol on LDL receptor-related protein may explain the complexity of the effect of cholesterol on CVD risk.

Description of a large family with autosomal dominant hypercholesterolemia associated with the APOE p.Leu167del mutation

Apolipoprotein (apo) E mutants are associated with type III hyperlipoproteinemia characterized by high cholesterol and triglycerides levels. Autosomal dominant hypercholesterolemia (ADH), due to the mutations in the LDLR, APOB, or PCSK9 genes, is characterized by an isolated elevation of cholesterol due to the high levels of low‐density lipoproteins (LDLs). We now report an exceptionally large family including 14 members with ADH. Through genome‐wide mapping, analysis of regional/functional candidate genes, and whole exome sequencing, we identified a mutation in the APOE gene, c.500_502delTCC/p.Leu167del, previously reported associated with sea‐blue histiocytosis and familial combined hyperlipidemia. We confirmed the involvement of the APOE p.Leu167del in ADH, with (1) a predicted destabilization of an alpha‐helix in the binding domain, (2) a decreased apo E level in LDLs, and (3) a decreased catabolism of LDLs. Our results show that mutations in the APOE gene can be associated with bona fide ADH.

French Society of Cardiology guidelines for cardiac rehabilitation in adults

text isan extract from thereference ‘‘Good Practice for Cardiac Rehabilitation inAdults 2011’’, which available onwebsite of GERS (Groupe Exercice Readaptation Sport of the French Society of Cardiology [Societe franc¸aise de cardiologie];http://www.sfcardio.fr/groupes/groupes/exercice-readaptation-sport) and contains the complete bibliography, replacing the FrenchSociety of Cardiology text of 2002, version 2, establishing recommendations for cardiac rehabilitation in adults.

Comparison between fat intake assessed by a 3-day food record and phospholipid fatty acid composition of red blood cells: Results from the monitoring of cardiovascular disease-Lille study

We investigated the relationship between assessment of fatty acid intake by a 3-day food record and by capillary gas chromatography of erythrocyte phospholipid fatty acid. The study was performed in a sample of 244 men aged 45 to 66 years from the general population who were participating in the Monitoring of Cardiovascular Disease (MONICA)-Lille survey. The relationship between each nutrient and food item and erythrocyte phospholipid fatty acid was investigated by a regression model on proportion including each food item and nutrient as a dependent variable and percentage of fatty acid and covariables (nonalcoholic energy intake, age, alcohol intake, and smoking) as independent variables. Polyunsaturated fat and linoleic acid intake were positively correlated with linoleic acid content of erythrocytes (beta = 0.641 and 0.604, respectively, P < .001). Monounsaturated and saturated fat intake were correlated with oleic acid (beta = 0.375 and 0.373, respectively, P < .01). Fish intake correlated positively with docosahexaenoic acid (DHA) (beta = 0.383, P < .001) and negatively with arachidonic acid (beta = -0.509, P < .01). These data confirm, on a group level, a good relationship between assessment of polyunsaturated fat intake by a 3-day record and linoleic acid content of erythrocyte membranes. These data suggest that erythrocyte oleic acid content is a marker of both saturated and monounsaturated fat intake.

Strategy for the Study of the Health Impact of Dietary Maillard Products in Clinical Studies

The study of the health impact of dietary Maillard products (MPs) in realistic clinical studies requires the design of nutritionally equivalent diets with high and low levels of MPs. This difficult challenge may be achieved by setting the high‐MP diet at the regular daily level, where the common use of grilling, frying, and roasting processes allows significant amounts of carboxymethyllysine, hydroxymethylfurfural and acrylamide to be formed. In such conditions, we show that major lipid degradation does not occur, nor does degradation of vitamin E or thiamine. Based on this finding, the low‐MP diet; must be constructed accordingly, by replacing all high‐temperature techniques with steam cooking or the absence of cooking. The cooking fat must be replaced with similar raw fat as seasoning in the low‐MP diet, the high caloric density resulting from water loss in the high‐MP diet must be compensated by higher food quantities offered in the low‐MP diet, and the vitamin loss in fruit and vegetables resulting from high temperatures in the high‐MP diet can be circumvented by increasing the corresponding portion size. In the ICARE study, equilibrated diets were proposed, fulfilling all nutritional needs, but with a 3‐ to 45‐fold difference in MP concentrations. Individual quantification of nutritional and MP intakes will ensure the nutritional equivalence of the two diets and allow for quantification of the specific impact of ingested MPs.

The relationship between the phospholipid fatty acid composition of red blood cells, plasma lipids, and apolipoproteins

This study examined the relationship between the fatty acid composition of red blood cell phospholipids and lipid markers of atherosclerotic risk in an urban male population aged 45 to 66 years. There was a surprisingly significant positive association between the docosahexaenoic acid ([DHA] 22:6n-3) content of erythrocyte phospholipids and the following risk markers: plasma cholesterol (P < .01), low-density lipoprotein (LDL) cholesterol (P < .01), apolipoprotein (apo) B (P < .05), and apo B-containing lipoprotein particles (P < .05) recognized by a monoclonal antibody (LpBL3). On the other hand, phospholipid alpha-linolenate was positively correlated with apo A-I and high-density lipoprotein (HDL) cholesterol levels (P < .05), while arachidonate showed an inverse relationship with plasma cholesterol (P < .05). There was a negative association between palmitoleic acid and apo B (P < .01) and LpBL3 (P < .001); the latter showed a negative association with stearic acid (P < .001). These interesting findings emphasize the beneficial effect on atherosclerotic risk markers of dietary n-6 polyunsaturated and monounsaturated fatty acids, and suggest that long-chain n-3 polyunsaturated fatty acids (DHA) could have an adverse effect on some of the lipid risk markers.

Determination of the LDL receptor binding capacity of human lymphocytes by immunocytofluorimetric assay

The determination of the LDL receptor binding capacity of human blood lymphocytes was assessed by indirect immunocytofluorimetric assay. To produce the maximal synthesis of the LDL receptor, the cholesterol efflux was enhanced by incubation of lymphocytes with HDL3 subfractions. The binding capacity of the LDL receptor was measured by incubation at 4 degrees C either with LDL and rabbit anti-LDL immunoglobulins or with peptide receptor antibody (ARP-Ig) raised against the NH2-terminal sequence of the LDL receptor. Thereafter complexes were incubated with fluorescein-labelled anti-rabbit immunoglobulin (FITC-Ig). Fluorescence flow cytometry was used to quantify the number of fluorescent lymphocytes and results were expressed as the percentage of lymphocytes with a fluorescent intensity above the threshold. Using preimmune rabbit immunoglobulin and then FITC-Ig, only 5-10% of cells were fluorescent. Neither LDL nor ARP-Ig could bind to homozygous familial hypercholesterolemia (FH) lymphocytes. Normal lymphocytes preincubated with HDL3 could bind LDL or ARP-Ig, the number of fluorescent cells being 59 and 39.2% respectively. Subjects with confirmed or suspected heterozygous FH demonstrated cell fluorescence at about half the normal level.

Realistic approach of pesticide residues and French consumer exposure within fruit & vegetable intake

The increase of fruit and vegetable (F&V) intake contributes to the prevention of chronic diseases, but could also significantly increase pesticide exposure and may thus be of health concern. Following a previous pesticide exposure assessment study, the present study was carried out to determine actual levels of pesticides within 400 g of F&V intake and to evaluate consumer risk. Forty-three Active Substances (AS) exceeding 10 % of the Acceptable Daily Intake (ADI) in balanced menus established for our previous theoretical study were considered. Fifty-six pooled food samples were analyzed: 28 fruit samples and 28 vegetable samples. Pesticide values were compared to Maximum Residue Levels (MRL) and to the “toxicological credit” derived from ADI. It was observed that 23 out of the 43 retained AS were never detected, 5 were detected both in F&V samples, 12 only in fruits and 3 only in vegetables. The most frequently detected AS were carbendazim, iprodione and dithiocarbamates. When detected, AS were more frequently found in fruit samples (74 %) than in vegetable samples (26 %). A maximum of 3 AS were detected at once in a given sample. Overall, we observed 8 and 14 overruns of the MRL in 1204 measures in pooled vegetable and fruit samples, respectively (0.7 % and 1.2 % of cases, respectively). Chronic exposure for adults was the highest for dithiocarbamates but did not exceed 23.7 % of the ADI in F&V. It was concluded that raising both F&V consumption up to 400 g/day (∼5 F&V/day) according to recommendations of the national health and nutrition plan, does not induce pesticide overexposure and should not represent a risk for the consumer.

Poisson, acides gras oméga 3 et risque cardiovasculaire : données épidémiologiques

Resume Bang et Dyerberg mettaient pour la premiere fois en evidence, il y a 30 ans, une association entre une tres faible prevalence des maladies coronariennes et une consommation elevee de produits marins riches en acides gras omega 3 a tres longue chaine chez les eskimos. Depuis, les donnees epidemiologiques, ecologiques transculturelles, les etudes cas temoins, et les etudes prospectives ont presque toutes retrouve le benefice sur le plan cardiovasculaire d’une faible consommation de poisson, gras surtout, 1 ou 2 fois par jour sans benefice supplementaire d’une consommation plus elevee. Cet effet disparait dans certaines conditions, par exemple en cas d’apport excessif simultane de mercure. Les etudes epidemiologiques confirment aussi un effet favorable sur les parametres lipidiques (cholesterol HDL, triglycerides). Les etudes d’intervention en prevention secondaire ont confirme l’hypothese d’une relation causale entre apport en omega 3 (et en poisson) et la reduction rapide de la mortalite cardiovasculaire, notamment de la mort subite. Ceci suggere que le mecanisme en cause passerait surtout par une diminution du risque de thrombose, du fait d’une modulation des prostaglandines et d’un effet sur l’agregation plaquettaire, et par une diminution des troubles de rythme grâce a l’incorporation des acides gras omega 3 dans les phospholipides membranaires du tissu cardiaque.