European Journal of Nutrition (v.56, #4)

A systematic review of the effect of yogurt consumption on chronic diseases risk markers in adults by Audrée-Anne Dumas; Annie Lapointe; Marilyn Dugrenier; Véronique Provencher; Benoît Lamarche; Sophie Desroches (1375-1392).
We reviewed randomised controlled trials (RCTs) that have assessed the effects of yogurt containing Lactobacillus bulgaricus and Streptococcus thermophilus (LBST) on metabolic risk markers of chronic diseases in adults.We performed a systematic search in July 2016 in the scientific databases PubMed, EMBASE and The Cochrane Library. Included studies were RCTs that assessed the impact of consuming yogurt containing LBST as a treatment, and that evaluated at least one metabolic risk marker for chronic diseases compared with a control diet or a diet supplemented in another food/ingredient in healthy or chronically ill adults.Seven RCTs involving 278 participants were included in the review. Studies were conducted in the USA, France, Spain, Iran and Canada. Five studies were undertaken in healthy adults, and two were conducted among lactose malabsorbers. All studies investigated changes in blood lipids and glucose homoeostasis, with different doses of yogurt, durations of the supplementation and risks markers assessed. Consumption of LBST yogurt significantly reduced total cholesterol concentrations, ratio of total cholesterol to HDL-C and plasma glucose compared to a control yogurt-free diet or diet supplemented in another food/ingredient in two out of the seven studies. The majority of included RCTs presented high to unclear methodological risks of bias, which raises questions about the validity of their findings.Data from this systematic review indicate that the consumption of LBST yogurt shows either favourable or neutral effects on metabolic risk markers when compared with a control treatment in controlled research settings. RCTs investigating the effect of LBST yogurt consumption on metabolic risk markers of chronic diseases are scarce and presented considerable variation in methodologies making comparison between studies difficult. Further large-scale, well-designed studies assessing the impact of LBST yogurt, in particular in comparison with a control yogurt-free diet, are warranted to effectively evaluate the effect of yogurt consumption per se on risk markers of chronic diseases.
Keywords: Yogurt; Dairy products; Chronic diseases risk markers; Systematic review

Worldwide (poly)phenol intake: assessment methods and identified gaps by Paula Pinto; Cláudia N. Santos (1393-1408).
(Poly)phenols (PPs) are plant secondary metabolites widely distributed in dietary sources, and several evidences show that consumption of PP has a positive impact in human health. However, the correct estimation of food intake and the estimation of PP content of foods are essential to associate PPs intake with health effects. This review aimed to gather information from several studies on PP intake in different countries, compare methods used for both assessment of food intake and PP quantification and highlight existing gaps and future directions.Twenty-four studies of PP intake from thirteen countries were selected for analysis. The selected studies included assessment of all plant food groups contributing to PP intake, total PP content and/or content of major classes (flavonoids or phenolic acids), a large study population and both genders. Most studies presented daily intakes of extractable (poly)phenols. Very few studies have determined intake of non-extractable (poly)phenols, which is a very important fraction of PPs contributing to total PP intake. High heterogeneity was observed among countries regarding the intake of total PP intake and the two main PP classes. This may reflect not only different diet patterns, but also different methods used for collecting food consumption data and estimation of PP content. Thus, criteria of harmonization are suggested regarding assessment of food intake, determination of PP content in foods and validation with biomarkers.
Keywords: Non-extractable polyphenols; Flavonoids; Phenolic acids; Food intake; Diet; Biomarkers

Dietary polyphenols are inversely associated with metabolic syndrome in Polish adults of the HAPIEE study by Giuseppe Grosso; Urszula Stepaniak; Agnieszka Micek; Denes Stefler; Martin Bobak; Andrzej Pająk (1409-1420).
The aim of this study was to evaluate the association between total and individual classes and subclasses of dietary polyphenol intake and prevalence of metabolic syndrome (MetS) in the Polish arm of the Health, Alcohol and Psychosocial factors In Eastern Europe cohort study.A cross-sectional population-based survey including 8821 adults (51.4 % female) was conducted in Kraków, Poland. Dietary polyphenol intake was evaluated using food frequency questionnaires and matching food consumption data with the Phenol-Explorer database. MetS was defined according to the International Diabetes Federation definition. Linear and logistic regression models were performed to estimate odds ratios (ORs) and confidence intervals (CIs).Significant differences in age and energy intake among different categories of total dietary polyphenol intake were found. Body mass index (BMI), waist circumference (WC), blood pressure, and triglycerides were significantly lower among individuals in the higher quartiles of polyphenol intake, but a linear association was found only for BMI and WC. After adjusting for potential confounding factors, individuals in the highest quartile of polyphenol intake were less likely to have MetS (OR 0.80; 95 % CI 0.64, 0.98 and OR 0.70; 95 % CI 0.56, 0.86 for both men and women, respectively). High total polyphenol intake was negatively associated with WC, blood pressure, high lipoprotein cholesterol, and triglycerides in women, and fasting plasma glucose in both genders. Among individual classes of polyphenols, phenolic acids and stilbenes were significantly associated with MetS; lignans and stilbenes with WC; phenolic acids with blood pressure and triglycerides; and flavonoids with fasting plasma glucose. Among specific subclasses of polyphenols, hydroxycinnamic acids, flavanols, and dihydrochalcones had the most relevant role.Total and individual classes and subclasses of dietary polyphenols were inversely associated with MetS and some of its components.
Keywords: Dietary polyphenols; Flavonoids; Phenolic acids; Stilbenes; Lignans; Metabolic syndrome; Blood pressure; Waist circumference; Dyslipidemia; Hyperglycemia

Impact of phenolic-rich olive leaf extract on blood pressure, plasma lipids and inflammatory markers: a randomised controlled trial by Stacey Lockyer; Ian Rowland; Jeremy Paul Edward Spencer; Parveen Yaqoob; Welma Stonehouse (1421-1432).
Dietary polyphenols have been demonstrated to favourably modify a number of cardiovascular risk markers such as blood pressure (BP), endothelial function and plasma lipids. We conducted a randomised, double-blind, controlled, crossover trial to investigate the effects of a phenolic-rich olive leaf extract (OLE) on BP and a number of associated vascular and metabolic measures. A total of 60 pre-hypertensive [systolic blood pressure (SBP): 121–140 mmHg; diastolic blood pressure (DBP): 81–90 mmHg] males [mean age 45 (±SD 12.7 years, BMI 26.7 (±3.21) kg/m2] consumed either OLE (136 mg oleuropein; 6 mg hydroxytyrosol) or a polyphenol-free control daily for 6 weeks before switching to the alternate arm after a 4-week washout.Daytime [−3.95 (±SD 11.48) mmHg, p = 0.027] and 24-h SBP [−3.33 (±SD 10.81) mmHg, p = 0.045] and daytime and 24-h DBP [−3.00 (±SD 8.54) mmHg, p = 0.025; −2.42 (±SD 7.61) mmHg, p = 0.039] were all significantly lower following OLE intake, relative to the control. Reductions in plasma total cholesterol [−0.32 (±SD 0.70) mmol/L, p = 0.002], LDL cholesterol [−0.19 (±SD 0.56) mmol/L, p = 0.017] and triglycerides [−0.18 (±SD 0.48), p = 0.008] were also induced by OLE compared to control, whilst a reduction in interleukin-8 [−0.63 (±SD 1.13) pg/ml; p = 0.026] was also detected. Other markers of inflammation, vascular function and glucose metabolism were not affected.Our data support previous research, suggesting that OLE intake engenders hypotensive and lipid-lowering effects in vivo.
Keywords: Olive leaf; Polyphenols; Cardiovascular disease; Blood pressure; Plasma lipids; Oleuropein

Aspartate attenuates intestinal injury and inhibits TLR4 and NODs/NF-κB and p38 signaling in weaned pigs after LPS challenge by Haibo Wang; Yulan Liu; Haifeng Shi; Xiuying Wang; Huiling Zhu; Dingan Pi; Weibo Leng; Shuang Li (1433-1443).
This study was conducted to investigate whether aspartate (Asp) could alleviate Escherichia coli lipopolysaccharide (LPS)-induced intestinal injury by modulating intestine inflammatory response.Twenty-four weaned piglets were divided into four treatments: (1) non-challenged control; (2) LPS-challenged control; (3) LPS + 0.5 % Asp; and (4) LPS + 1.0 % Asp. After feeding with control, 0.5 or 1.0 % Asp-supplemented diets for 21 days, pigs were injected intraperitoneally with saline or LPS. At 4 h postinjection, blood and intestine samples were obtained.Asp supplementation to LPS-challenged pigs improved intestinal morphology, indicated by higher jejunal and ileal villus height/crypt depth ratio and lower ileal crypt depth linearly or quadratically. Asp also improved intestinal barrier function, indicated by increased jejunal and ileal diamine oxidase activities as well as enhanced protein expression of jejunal claudin-1 linearly or quadratically. In addition, Asp decreased plasma, jejunal and ileal tumor necrosis factor-α concentration and ileal caspase-3 protein expression linearly and quadratically. Moreover, Asp down-regulated the mRNA expression of toll-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain protein (NOD) signaling-related genes, nuclear factor-κB (NF-κB) p65 and p38, decreased phosphorylation of jejunal p38, and increased phosphorylation of ileal extracellular signal-related kinase 1/2 linearly or quadratically. Finally, Asp increased mRNA expressions of TLR4 and NOD signaling negative regulators including radioprotective 105, suppressor of cytokine signaling 1, toll-interacting protein, Erbb2 interacting protein and centaurin β1 linearly or quadratically.These results indicate that Asp supplementation is associated with inhibition of TLR4 and NODs/NF-κB and p38 signaling pathways and concomitant improvement of intestinal integrity under an inflammatory condition.
Keywords: Aspartate; Weaned piglets; Intestine injury; Lipopolysaccharide; Inflammatory response

Cr-enriched yeast: beyond fibers for the management of postprandial glycemic response to bread by Amalia E. Yanni; Nikoleta Stamataki; Maria Stoupaki; Panagiotis Konstantopoulos; Irene Pateras; Nikolaos Tentolouris; Despoina Perrea; Vaios T. Karathanos (1445-1453).
Efforts regarding the amelioration of postprandial glycemic response to bread are mainly focused in the addition of soluble dietary fibers. The current study presents another approach which is based on the supplementation of flour with Cr-enriched yeast. Cr is known for its beneficial effects on improvement of glucose tolerance and enhancement of insulin sensitivity. Twelve normoglycemic subjects were provided with white bread (WB, reference food) or whole wheat bread with Cr-enriched yeast (WWCrB, rich in insoluble fibers) or white wheat bread with Cr-enriched yeast (WCrB, poor in fibers) or whole wheat-rye-barley bread enriched with oat beta glucans (BGB, rich in soluble fibers) with 1-week intervals in amounts that yielded 50 g of available carbohydrates. Postprandial glucose, insulin and ghrelin responses as well as glycemic index (GI) were evaluated.Ingestion of WWCrB, WCrB and BGB elicited lower incremental area under the curve (iAUC) for 120-min glycemic response compared to WB (1033.02 ± 282.32, 701.69 ± 330.86 and 748.95 ± 185.42 vs 2070.87 ± 518.44 mg/dL min, respectively, P < 0.05 for WCrB and BGB). The GI was calculated as 62.35 ± 11.78 for WWCrB, 34.22 ± 11.93 for WCrB and 37.90 ± 5.00 for BGB (P < 0.05 vs WB, GI = 100). iAUC for 120-min insulin response to BGB was significantly lower than WB (2780.04 ± 303.26 vs 3915.53 ± 490.57 μU/mL min, P < 0.05), while ghrelin remained suppressed for almost 120 min after the consumption of WWCrB and BGB.Supplementation of flour with Cr-enriched yeast induces milder postprandial glycemic response to bread without the necessity of high fiber amounts, providing with another strategy for the management of glycemic control.
Keywords: Bread; Glycemic index; Chromium-enriched yeast; Beta glucans; Glucose response; Insulin response; Ghrelin response

Dietary patterns and weight change: 15-year longitudinal study in Australian adults by Simin Arabshahi; Torukiri I. Ibiebele; Maria Celia B. Hughes; Petra H. Lahmann; Gail M. Williams; Jolieke C. van der Pols (1455-1465).
Dietary intake is one of the most modifiable risk factors associated with obesity. However, data on the relationship between dietary patterns and long-term weight change are limited. We therefore investigated the association between dietary patterns and 15-year weight change in a sample of 1186 Australian adults (1992–2007).We measured body weight and collected data on socio-demographic and lifestyle characteristics in 1992 and 2007. Applying principal component analysis to 38 food groups from a food frequency questionnaire collected at baseline, we identified two dietary patterns: ‘meat-and-fat’ and ‘fruit-and-vegetable.’ Using generalized estimating equations, multivariable regression models, stratified by sex, were adjusted for concurrent changes in socio-demographic and lifestyle variables. The average increase in body weight of men in the highest tertile of the meat-and-fat pattern was more than twice that of men in the lowest tertile; mean weight change (95 % CI): 4.8 (−0.1, 9.7) kg versus 2.3 (−2.6, 7.1) kg, P-for-trend = 0.02. In contrast, average weight gain of men in the highest tertile of the fruit-and-vegetable pattern was only about half that of men in the lowest tertile; mean weight change (95 % CI): 2.9 (−2.0, 7.8) kg versus 5.4 (−1.5, 10.4) kg, P-for-trend = 0.02. Among women, dietary patterns were not related to weight change.These dietary patterns predict change in body weight in men, but not in women. In this cohort, a dietary pattern high in fruit and vegetables was related to less weight gain in men than a dietary pattern high in meat and fat.
Keywords: Dietary pattern; Longitudinal study; Weight change; Generalized estimating equations analysis

Beneficial effects of a red wine polyphenol extract on high-fat diet-induced metabolic syndrome in rats by Nathalie Auberval; Stéphanie Dal; Elisa Maillard; William Bietiger; Claude Peronet; Michel Pinget; Valérie Schini-Kerth; Séverine Sigrist (1467-1475).
Individuals with metabolic syndrome (MS) show several metabolic abnormalities including insulin resistance, dyslipidaemia, and oxidative stress (OS). Diet is one of the factors influencing the development of MS, and current nutritional advice emphasises the benefits of fruit and vegetable consumption. Here, we assessed the effects of naturally occurring antioxidants, red wine polyphenols (RWPs), on MS and OS.Wistar rats (n = 20) weighing 200–220 g received a high-fat diet (HFD) for 2 months before they were divided into two groups that received either HFD only or HFD plus 50 mg/kg RWPs in their drinking water for an additional 2 months. A control group (n = 10) received a normal diet (ND) for 4 months.Rats receiving HFD increased body weight over 20 % throughout the duration of the study. They also showed increased blood levels of C-peptide, glucose, lipid peroxides, and oxidised proteins. In addition, the HFD increased OS in hepatic, pancreatic, and vascular tissues, as well as induced pancreatic islet cell hyperplasia and hepatic steatosis. Addition of RWPs to the HFD attenuated these effects on plasma and tissue OS and on islet cell hyperplasia. However, RWPs had no effect on blood glucose levels or hepatic steatosis.RWPs showed an antioxidant mechanism of action against MS. This result will inform future animal studies exploring the metabolic effects of RWPs in more detail. In addition, these findings support the use of antioxidants as adjunctive nutritional treatments for patients with diabetes.
Keywords: Metabolic syndrome; Oxidative stress; High-fat-diet rats; Red wine polyphenols

Meta-analysis of genome-wide association studies identifies three novel loci for saturated fatty acids in East Asians by Jingwen Zhu; Ani Manichaikul; Yao Hu; Yii-Der I. Chen; Shuang Liang; Lyn M. Steffen; Stephen S. Rich; Michael Tsai; David S. Siscovick; Rozenn N. Lemaitre; Huaixing Li; Xu Lin (1477-1484).
We aimed to characterize common genetic variants that influence saturated fatty acid concentrations in East Asians.Meta-analysis of genome-wide association studies for circulating SFAs was conducted in two population-based cohorts comprising 3521 participants of Chinese ancestry.We identified two novel 14:0-associated loci at LMX1A (LIM homeobox transcription factor 1) and AMPD3 (AMP deaminase 3) (P = 5.08 × 10−9 and P = 4.33 × 10−8, respectively), and a novel 20:0-associated locus at CERS4 (ceramide synthase 4) (P = 1.76 × 10−10). We also confirmed the previously reported association of FADS1/2-rs102275 with 18:0 (P = 1.12 × 10−5). In addition, the A alleles of rs11042834 in AMPD3 and rs17159388 in CERS4 also exhibited evidence of associations with high-density lipoprotein cholesterol (P = 0.0162 and P = 0.0161, respectively).To our knowledge, this is the first GWAS analysis to examine SFA concentrations in East Asian populations. Our findings provide novel evidence that genetic variations of several genes from multiple pathways are associated with SFA concentrations in human body.
Keywords: Myristic acid; Arachidic acid; Genome-wide association study; Chinese; Lipids

Wine consumption reduced postprandial platelet sensitivity against platelet activating factor in healthy men by Marianna N. Xanthopoulou; Konstantia Kalathara; Sophia Melachroinou; Kalliopi Arampatzi-Menenakou; Smaragdi Antonopoulou; Mary Yannakoulia; Elizabeth Fragopoulou (1485-1492).
Platelet activating factor (PAF) is a potent inflammatory and thrombotic mediator that participates in the initiation and prolongation of atherosclerosis. The aim of the present study was to evaluate the potential effect of wine consumption on platelet aggregation against PAF.The study had cross-over design. Ten healthy men participated in four daily trials on separate days: They consumed a standardized meal along with white wine, Robola variety (trial R), or red wine, Cabernet Sauvignon variety (trial CS), or an ethanol solution (trial E), or water (trial W). Blood samples were collected before and after meal consumption and at several time points during the next 6 h. Platelet aggregation against PAF (EC50 values) and several blood biomarkers were measured, and incremental areas under the curve (iAUC) were calculated.A significant trial effect was found in platelet sensitivity against PAF (p trial = 0.01). Moreover, the iAUC–PAF EC50 of CS trial was higher compared to both iAUC–PAF EC50 of E and W trials (P = 0.04, P = 0.02). Plasminogen activator inhibitor-1 iAUC was higher in all alcoholic beverages compare with the one of W trial (P E  = 0.05, P R  = 0.01, P CS = 0.01). Triacylglycerol iAUC increased significantly only in E compared to W trial (P = 0.04) and were significantly lower at 60–120 min in wine trials compared to the one of E (P < 0.05).Wine consumption improved platelet sensitivity independently of alcohol, kept triacylglycerols at lower levels during their postprandial elevation, and did not affect plasminogen activator inhibitor-1 levels more adversely than ethanol per se.
Keywords: Thrombosis; Inflammation; Microconstituents; Phenolic compounds; Alcohol; Postprandial

Dietary fatty acids specifically modulate phospholipid pattern in colon cells with distinct differentiation capacities by Jiřina Hofmanová; Josef Slavík; Petra Ovesná; Zuzana Tylichová; Jan Vondráček; Nicol Straková; Alena Hyršlová Vaculová; Miroslav Ciganek; Alois Kozubík; Lucie Knopfová; Jan Šmarda; Miroslav Machala (1493-1508).
Although beneficial effects of the dietary n-3 docosahexaenoic acid (DHA) or butyrate in colon carcinogenesis have been implicated, the mechanisms of their action are not fully clear. Here, we investigated modulations of composition of individual phospholipid (PL) classes, with a particular emphasis on cardiolipins (CLs), in colon cells treated with DHA, sodium butyrate (NaBt), or their combination (DHA/NaBt), and we evaluated possible associations between lipid changes and cell fate after fatty acid treatment.In two distinct human colon cell models, foetal colon (FHC) and adenocarcinoma (HCT-116) cells, we compared patterns and composition of individual PL classes following the fatty acid treatment by HPLC-MS/MS. In parallel, we measured the parameters reflecting cell proliferation, differentiation and death.In FHC cells, NaBt induced primarily differentiation, while co-treatment with DHA shifted their response towards cell death. In contrast, NaBt induced apoptosis in HCT-116 cells, which was not further affected by DHA. DHA was incorporated in all main PL types, increasing their unsaturation, while NaBt did not additionally modulate these effects in either cell model. Nevertheless, we identified an unusually wide range of CL species to be highly increased by NaBt and particularly by DHA/NaBt, and these effects were more pronounced in HCT-116 cells. DHA and DHA/NaBt enhanced levels of high molecular weight and more unsaturated CL species, containing DHA, which was specific for either differentiation or apoptotic responses.We identified a wide range of CL species in the colon cells which composition was significantly modified after DHA and NaBt treatment. These specific CL modulations might contribute to distinct cellular differentiation or apoptotic responses.
Keywords: Colon cancer; Butyrate; Docosahexaenoic acid; Phospholipids; Cardiolipins; Apoptosis

A meta-analysis of efficacy of Morus alba Linn. to improve blood glucose and lipid profile by Wiraphol Phimarn; Kittisak Wichaiyo; Khuntawan Silpsavikul; Bunleu Sungthong; Kritsanee Saramunee (1509-1521).
The previous studies have reported the Morus alba may improve blood glucose and lipid profile. The evidence from these studies is not consistent. This meta-analysis was to evaluate efficacy of products derived from M. alba on blood glucose and lipid levels.Literature was reviewed via international database (PubMed, PubMed Central, ScienceDirect, and SciSearch) and Thai databases. Thirteen RCTs with high quality, assessed by Jadad score, were included. M. alba expressed a significant reduction in postprandial glucose (PPG) at 30 min (MD −1.04, 95 % CI −1.36, −0.73), 60 min (MD −0.87, 95 % CI −1.27, −0.48) and 90 min (MD −0.55, 95 % CI −0.87, −0.22). The difference was not found in the levels of other glycaemic (FBS, HbA1C, or HOMA-IR) and lipidaemic (TC, TG, LDL, or HDL) markers. Serious adverse effects were found neither in the control nor in the group received M. alba.Products derived from M. alba can effectively contribute to the reduction in PPG levels, but large-scale RCTs would be informative.
Keywords: Mulberry (Morus alba); Diabetes mellitus; Dyslipidaemia; Blood glucose; Blood lipid

The aim of the present study was to evaluate the relative contribution of the most commonly consumed plant foods in Brazil to the total antioxidant capacity (AC) of Brazilian’s diet. The importance of regional consuming habits and income for dietary AC was also approached.The annual per capita consumption database from the Brazilian Institute of Geography and Statistics (IBGE) was used for identification of the most consumed plant foods in Brazil. Out of 124 key plant foods, 42 top AC contributing candidates were selected for AC determination based on both the frequency of consumption, and AC results reported in the literature, and in our preliminary assays. The selected food products were prepared according to the Brazilian Food Guide, and their AC was measured by TEAC and FRAP assays. Dietary AC was determined by combining these AC results with IBGE consumption data, and the relative contribution of each plant food was calculated. Among all evaluated food products, coffee and green maté tea presented the highest AC, followed by toasted maté tea, red wine, açaí—a native Amazonian fruit—and beans. Associating AC with the annual consumption database from IBGE, coffee alone contributed, on average, to 66 % of dietary AC; other beverages, including maté and wine, contributed altogether to 13 % of dietary AC; beans contributed to 9 %, cereals and derivatives contributed to 4 %; and in natura fruits and vegetables contributed to only 3 and 2 %, respectively. In the North region, fruits were important contributors to AC—mostly because of high açaí consumption, while in the South maté and wine also gained importance, with wine contribution being specially associated with high household income.Coffee is the main contributor to the total dietary AC in Brazil, regardless of household income. Maté tea, açaí and beans are other major dietary AC contributors.
Keywords: Antioxidant capacity; Coffee; Maté; Açaí; Brazilian’s diet

Evidence of a possible connection between gut microbiota and several physiological processes linked to type 2 diabetes is increasing. However, the effect of multi-strain probiotics in people with type 2 diabetes remains unclear. This study investigated the effect of multi-strain microbial cell preparation—also refers to multi-strain probiotics—on glycemic control and other diabetes-related outcomes in people with type 2 diabetes.A randomized, double-blind, parallel-group, controlled clinical trial.Diabetes clinic of a teaching hospital in Kuala Lumpur, Malaysia.A total of 136 participants with type 2 diabetes, aged 30–70 years, were recruited and randomly assigned to receive either probiotics (n = 68) or placebo (n = 68) for 12 weeks.Primary outcomes were glycemic control-related parameters, and secondary outcomes were anthropomorphic variables, lipid profile, blood pressure and high-sensitivity C-reactive protein. The Lactobacillus and Bifidobacterium quantities were measured before and after intervention as an indicator of successful passage of the supplement through gastrointestinal tract.Intention-to-treat (ITT) analysis was performed on all participants, while per-protocol (PP) analysis was performed on those participants who had successfully completed the trial with good compliance rate.With respect to primary outcomes, glycated hemoglobin decreased by 0.14 % in the probiotics and increased by 0.02 % in the placebo group in PP analysis (p < 0.05, small effect size of 0.050), while these changes were not significant in ITT analysis. Fasting insulin increased by 1.8 µU/mL in placebo group and decreased by 2.9 µU/mL in probiotics group in PP analysis. These changes were significant between groups at both analyses (p < 0.05, medium effect size of 0.062 in PP analysis and small effect size of 0.033 in ITT analysis). Secondary outcomes did not change significantly. Probiotics successfully passed through the gastrointestinal tract.Probiotics modestly improved HbA1c and fasting insulin in people with type 2 diabetes.
Keywords: Glycated hemoglobin; Glycemic control; High-sensitivity C-reactive protein; Homeostasis model assessment-estimated insulin resistance; Probiotics; Type 2 diabetes mellitus; Blood pressure; Lipid profile

Iron bioavailability from fresh cheese fortified with iron-enriched yeast by Magalie Sabatier; Ines Egli; Richard Hurrell; Mathias Hoppler; Christof Gysler; Sandrine Georgeon; Rajat Mukherje; Pierre-Alain Richon; Mario Vigo; Jasmin Tajeri Foman; Christophe Zeder; Christelle Schaffer-Lequart (1551-1560).
An iron-enriched yeast able to lyse at body temperature was developed for iron fortification of chilled dairy products. The aim was to evaluate iron (Fe) absorption from iron-enriched yeast or ferrous sulfate added to fresh cheese.Two stable isotope studies with a crossover design were conducted in 32 young women. Fe absorption from fresh cheese fortified with iron-enriched yeast (2.5 mg 58Fe) was compared to that from ferrous sulfate (2.5 mg 57Fe) when ingested with fresh cheese alone or with fresh cheese consumed with bread and butter. Iron absorption was determined based on erythrocyte incorporation of isotopic labels 14 days after consumption of the last test meal.Geometric mean fractional iron absorption from fresh cheese fortified with iron-enriched yeast consumed alone was significantly lower than from the cheese fortified with FeSO4 (20.5 vs. 28.7 %; p = 0.0007). When the fresh cheese was consumed with bread and butter, iron absorption from both fortificants decreased to 6.9 % from the iron-enriched yeast compared to 8.4 % from ferrous sulfate. The relative bioavailability of the iron-enriched yeast compared to ferrous sulfate was 0.72 for the cheese consumed alone and 0.82 for cheese consumed with bread and butter (p = 0.157).Iron from iron-enriched yeast was 72–82 % as well absorbed as ferrous sulfate indicating that the yeast lysed during digestion and released its iron.
Keywords: Iron-enriched yeast; Human; Stable isotope; Bioavailability; Fresh cheese

Non-enzymatic antioxidant capacity (NEAC) estimated by two different dietary assessment methods and its relationship with NEAC plasma levels by Cayetano Javier Carrión-García; Eduardo J. Guerra-Hernández; Belén García-Villanova; Esther Molina-Montes (1561-1576).
We aimed to quantify and compare dietary non-enzymatic antioxidant capacity (NEAC), estimated using two dietary assessment methods, and to explore its relationship with plasma NEAC.Fifty healthy subjects volunteer to participate in this study. Two dietary assessment methods [a food frequency questionnaire (FFQ) and a 24-hour recall (24-HR)] were used to collect dietary information. Dietary NEAC, including oxygen radical absorbance capacity (ORAC), total polyphenols, ferric-reducing antioxidant power (FRAP) and trolox equivalent antioxidant capacity, was estimated using several data sources of NEAC content in food. NEAC status was measured in fasting blood samples using the same assays. We performed nonparametric Spearman’s correlation analysis between pairs of dietary NEAC (FFQ and 24-HR) and diet-plasma NEAC, with and without the contribution of coffee’s NEAC. Partial correlation analysis was used to estimate correlations regardless of variables potentially influencing these relationships.FFQ-based NEAC and 24-HR-based NEAC were moderately correlated, with correlation coefficients ranging from 0.54 to 0.71, after controlling for energy intake, age and sex. Statistically significant positive correlations were found for dietary FRAP, either derived from the FFQ or the 24-HR, with plasma FRAP (r ~ 0.30). This weak, albeit statistically significant, correlation for FRAP was mostly present in the fruits and vegetables food groups. Plasma ORAC without proteins and 24-HR-based total ORAC were also positively correlated (r = 0.35).The relationship between dietary NEAC and plasma FRAP and ORAC suggests the dietary NEAC may reflect antioxidant status despite its weak in vivo potential, supporting further its use in oxidative stress-related disease epidemiology.
Keywords: Non-enzymatic antioxidant capacity; Dietary antioxidants; Oxidative stress; Dietary assessment

Vitamin D3 supplementation using an oral spray solution resolves deficiency but has no effect on VO2 max in Gaelic footballers: results from a randomised, double-blind, placebo-controlled trial by Joshua J. Todd; Emeir M. McSorley; L. Kirsty Pourshahidi; Sharon M. Madigan; Eamon Laird; Martin Healy; Pamela J. Magee (1577-1587).
Vitamin D inadequacy is a global health concern in athletes as well as the general population. Whilst the role of vitamin D in skeletal health is well defined, there remains uncertainty over whether vitamin D supplementation has an added benefit beyond bone health.This randomised placebo-controlled trial in healthy male and female Gaelic footballers (n = 42) investigated the effect of vitamin D3 supplementation [3000 IU (75 µg) daily for 12 weeks, via an oral spray solution] on VO2 max which was the primary outcome measure. Secondary outcomes included skeletal muscle and lung function.Supplementation significantly increased total 25-hydroxyvitamin D concentrations compared to the placebo group (mean ± SD change from baseline, 36.31 ± 32.34 vs. 6.11 ± 23.93 nmol/L, respectively; P = 0.006). At baseline, 50 and 22 % of footballers presented with vitamin D insufficiency (31–49 nmol/L) and deficiency (<30 nmol/L), respectively. Total 25-hydroxyvitamin D concentration did not significantly correlate with any measure of physical performance. Analysis of covariance (ANCOVA) models demonstrated that vitamin D supplementation over 12 weeks had no significant effect on VO2 max (P = 0.375), vertical jump height (P = 0.797), left and right handgrip strength (P = 0.146 and P = 0.266, respectively), forced vital capacity (P = 0.573) or forced expiratory volume at 1 s (P = 0.665), after adjusting for confounders. The high prevalence of vitamin D inadequacy observed in this cohort of collegiate Gaelic footballers supports the need for vitamin D supplementation during wintertime to avoid being at risk of poor bone health.Twelve-week daily supplementation with 3000 IU (75 µg) vitamin D3 successfully resolved deficiency but did not have any significant effect on VO2 max, skeletal muscle or lung function.
Keywords: Vitamin D; VO2 max; Athletes; Randomised controlled trial; Football

There is controversy about the effect of the rs1799983 nitric oxide synthase (NOS3) genetic variant on hypertension and blood pressure (BP) levels. The aims of the current study were to examine whether rs1799983 affects BP levels and to identify potential interactions between this polymorphism and other non-genetic risk factors.A total of 705 subjects were examined for anthropometric and body composition measurements, BP, dietary habits and physical activity. Oral epithelial cells were collected for the identification of rs1799983 using Luminex® 100/200TM System.After adjusted for covariates, TT genotype showed a 2.30-fold higher predisposition of hypertension than GG genotype subjects. According to BP levels, for each risk allele diastolic blood pressure (DBP) increased in 1.99 mmHg. Significant interactions between rs1799983 and saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) were found. Moreover, an interaction with body weight status was observed. Among overweight individuals, T allele carriers showed higher DBP than GG genotype.The present study evidenced that rs1799983 NOS3 polymorphism could be associated with hypertension and DBP among Southern Europeans, being this association influenced by dietary fat (SFA and MUFA) and body mass index.
Keywords: Hypertension; Blood pressure; NOS3 ; Saturated fatty acids; Monounsaturated fatty acids; Obesity

Frying oils with high natural or added antioxidants content, which protect against postprandial oxidative stress, also protect against DNA oxidation damage by Oriol A. Rangel-Zuñiga; Carmen Haro; Carmen Tormos; Pablo Perez-Martinez; Javier Delgado-Lista; Carmen Marin; Gracia M. Quintana-Navarro; Concha Cerdá; Guillermo T. Sáez; Fernando Lopez-Segura; Jose Lopez-Miranda; Francisco Perez-Jimenez; Antonio Camargo (1597-1607).
Using sunflower oil as frying oil increases postprandial oxidative stress, which is considered the main endogenous source of DNA oxidative damage. We aimed to test whether the protective effect of virgin olive oil and oil models with added antioxidants against postprandial oxidative stress may also protect against DNA oxidative damage.Twenty obese people received four breakfasts following a randomized crossover design consisting of different oils [virgin olive oil (VOO), sunflower oil (SFO), and a mixed seed oil (SFO/canola oil) with added dimethylpolysiloxane (SOX) or natural antioxidants from olives (SOP)], which were subjected to 20 heating cycles.We observed the postprandial increase in the mRNA levels of p53, OGG1, POLB, and GADD45b after the intake of the breakfast prepared with SFO and SOX, and an increase in the expression of MDM2, APEX1, and XPC after the intake of the breakfast prepared with SFO, whereas no significant changes at the postprandial state were observed after the intake of the other breakfasts (all p values <0.05). We observed lower 8-OHdG postprandial levels after the intake of the breakfast prepared with VOO and SOP than after the intake of the breakfast prepared with SFO and SOX (all p values <0.05).Our results support the beneficial effect on DNA oxidation damage of virgin olive oil and the oil models with added antioxidants, as compared to the detrimental use of sunflower oil, which induces p53-dependent DNA repair pathway activation.
Keywords: Frying oils; Virgin olive oil; Oxidative stress; DNA oxidation damage; Phenolic compounds

Citrus peel polymethoxyflavones nobiletin and tangeretin suppress LPS- and IgE-mediated activation of human intestinal mast cells by Yvonne Hagenlocher; Katharina Feilhauer; Michael Schäffer; Stephan C. Bischoff; Axel Lorentz (1609-1620).
Allergic diseases with mast cells (MC) as main effector cells show an increased prevalence. MC also play an essential role in other inflammatory conditions. Therapeutical use of anti-inflammatory nutraceuticals directly targeting MC activation could be of interest for afflicted patients. Nobiletin and tangeretin are citrus peel polymethoxyflavones, a group of citrus flavonoids, possessing anticancer, antimetastatic, and anti-inflammatory activities. Here, we analyzed the effects of nobiletin/tangeretin on LPS- and IgE-mediated stimulation of human intestinal mast cells (hiMC).MC isolated from human intestinal tissue were treated with different concentrations of nobiletin or tangeretin prior to stimulation via LPS/sCD14 or IgE-dependently. Degranulation, pro-inflammatory cytokine expression and phosphorylation of ERK1/2 were examined.Expression of CXCL8, CCL3, CCL4 and IL-1β in response to LPS-mediated stimulation was inhibited by nobiletin/tangeretin. hiMC activated IgE-dependently showed a reduced release of β-hexosaminidase and cysteinyl LTC4 in response to nobiletin, but not in response to tangeretin. Expression of CXCL8, CCL2, CCL3, CCL4 and TNF in IgE-dependently activated hiMC was decreased in a dose-dependent manner following treatment with nobiletin/tangeretin. IL-1β expression was only reduced by tangeretin. Compared to treatment with NF-κB inhibitor BMS345541 or MEK-inhibitor PD98059, nobiletin and tangeretin showed similar effects on mediator production. Phosphorylation of ERK1/2 upon IgE-mediated antigen stimulation was significantly suppressed by nobiletin and tangeretin.Nobiletin and, to a lesser extent, tangeretin could be considered as anti-inflammatory nutraceuticals by reducing release and production of proinflammatory mediators in MC.
Keywords: Mast cells; Allergy; Nutraceuticals; Flavonoids; Citrus fruits

Dietary fat may modulate adipose tissue homeostasis through the processes of autophagy and apoptosis by A. Camargo; O. A. Rangel-Zúñiga; J. Alcalá-Díaz; F. Gomez-Delgado; J. Delgado-Lista; S. García-Carpintero; C. Marín; Y. Almadén; E. M. Yubero-Serrano; J. López-Moreno; F. J. Tinahones; P. Pérez-Martínez; H. M. Roche; J. López-Miranda (1621-1628).
Obesity increases the risk of cardiovascular disease, type 2 diabetes mellitus and cancer development. Autophagy and apoptosis are critical processes for development and homeostasis in multicellular organisms and have been linked to a variety of disorders. We aimed to investigate whether the quantity and quality of dietary fat can influence these processes in the adipose tissue of obese people.A randomized, controlled trial within the LIPGENE study assigned 39 obese people with metabolic syndrome to 1 of 4 diets: (a) a high-saturated fatty acid diet, (b) a high-monounsaturated fatty acid (HMUFA) diet, and (c, d) two low-fat, high-complex carbohydrate diets supplemented with long-chain n-3 polyunsaturated fatty acids (LFHCC n-3) or placebo (LFHCC), for 12 weeks each.We found an increase in the expression of autophagy-related BECN1 and ATG7 genes after the long-term consumption of the HMUFA diet (p = 0.001 and p = 0.004, respectively) and an increase in the expression of the apoptosis-related CASP3 gene after the long-term consumption of the LFHCC and LFHCC n-3 diets (p = 0.001 and p = 0.029, respectively). CASP3 and CASP7 gene expression changes correlated with HOMA index.Our results suggest that the processes of autophagy and apoptosis in adipose tissue may be modified by diet and that the consumption of a diet rich in monounsaturated fat may contribute to adipose tissue homeostasis by increasing autophagy. They also reinforce the notion that apoptosis in adipose tissue is linked to insulin resistance.ClinicalTrials.gov NCT00429195.
Keywords: Obesity; Autophagy; Apoptosis; Insulin resistance; Dietary fat

A specific dose of grape seed-derived proanthocyanidins to inhibit body weight gain limits food intake and increases energy expenditure in rats by Joan Serrano; Àngela Casanova-Martí; Andreu Gual; Anna Maria Pérez-Vendrell; M. Teresa Blay; Ximena Terra; Anna Ardévol; Montserrat Pinent (1629-1636).
Several studies have suggested that flavanols may have antiobesity effects; however, those effects clearly depend on the experimental conditions. In a previous study, we found that a single acute dose of grape seed proanthocyanidin extract (GSPE) has satiating effects. We therefore hypothesise that satiating doses of GSPE could be used to reduce body weight gain, and our present objective was to define the most effective dose.We assayed two GSPE doses in aged male Wistar rats. First we performed a subchronic (8-day) treatment by intragastric administration, which was repeated after a washout period. We measured body weight, energy intake and faeces composition; we performed indirect calorimetry; and we analysed the mRNA expression of genes involved in lipid metabolism to determine the target tissue for the GSPE.We observed that 0.5 g GSPE/kg BW significantly reduced food intake and thus the amount of energy absorbed. This dosage also increased lipid oxidation in subcutaneous adipose tissue, thus causing a higher total energy expenditure. These combined effects caused a decrease in body weight. Conversely, 1 g GSPE/kg BW, which also reduced energy absorption after the first treatment, had a rebound effect on body weight gain which resulted in a lower response to the proanthocyanidin extract. That is, after the second treatment, the GSPE did not reduce the energy absorbed or modify energy expenditure and body weight.GSPE at a dose of 0.5 g/kg can reduce body weight by limiting food intake and activating energy expenditure in subcutaneous adipose tissue.
Keywords: Proanthocyanidin; Obesity; Food intake; Energy expenditure; Subcutaneous adipose tissue

Dietary mineral intake and lung cancer risk: the Rotterdam Study by Taulant Muka; Bledar Kraja; Rikje Ruiter; Lies Lahousse; Catherine E. de Keyser; Albert Hofman; Oscar H. Franco; Guy Brusselle; Bruno H. Stricker; Jessica C. Kiefte-de Jong (1637-1646).
Limited data are available on the role of mineral intake in the development of lung cancer (LC). We investigated whether dietary calcium, copper, iron, magnesium, selenium and zinc intake were associated with LC risk.We analyzed data from 5435 participants of the Rotterdam Study, a prospective population-based cohort study among subjects aged 55 years and older. At baseline (1990–1993), diet was measured by a validated food frequency questionnaire. LC events were diagnosed on the basis of pathology data and medical records. Hazard ratios (HRs) on LC for energy-adjusted mineral intake were calculated using Cox regression models while adjusting for potential confounders.During a follow-up period of 22 years, we identified 211 incident cases of LC. A higher zinc intake was associated with 42 % reduction in risk of LC (top tertile vs. first tertile: HR 0.58, 95 % CI 0.35; 0.94, P-for trend = 0.039). Similarly, high intake of iron was associated with reduced risk of LC (top tertile vs. first tertile: HR 0.58, 95 % CI 0.37; 0.92, P-for trend = 0.021). There was no association between dietary intake of calcium, copper, magnesium and selenium and LC risk.Our results suggest that dietary zinc and iron intake are associated with reduced risk of LC. No evidence was found for an association between calcium, copper, magnesium and selenium intake and LC risk.
Keywords: Zinc; Iron; Calcium; Copper; Magnesium; Selenium; Lung cancer

Long-term association between the dietary inflammatory index and cognitive functioning: findings from the SU.VI.MAX study by Emmanuelle Kesse-Guyot; Karen E. Assmann; Valentina A. Andreeva; Mathilde Touvier; Lola Neufcourt; Nitin Shivappa; James R. Hébert; Michael D. Wirth; Serge Hercberg; Pilar Galan; Chantal Julia (1647-1655).
Inflammation is a ubiquitous underlying mechanism of the links between diet and cognitive functioning. No study has yet evaluated the overall inflammatory potential of the diet, using the dietary inflammatory index (DII), in relation to cognitive functioning. In a French cohort of middle-aged adults, we evaluated the association between the DII, assessed in midlife, and cognitive performance evaluated 13 years later.The DII is a literature-derived dietary index developed to determine the inflammatory potential of diet. The DII was estimated at baseline (1994–1996) among 3080 subjects of the SU.VI.MAX (supplementation with antioxidant vitamins and minerals) cohort. Cognitive performance was assessed in 2007–2009 via a battery of standardized neuropsychological tests. Principal component analysis was performed to extract a summary score of cognitive performance. Multivariable-adjusted linear regression analyses were performed to provide regression coefficients and 95 % confidence intervals (95 % CI).In a multivariate model, a strong inverse association was observed between a higher DII (reflecting a more inflammatory diet) and overall cognitive functioning (mean difference Q4 vs. Q1 = −1.76; 95 % CI = −2.81, −0.72, P for trend =0.002). With regard to specific cognitive domains, similar associations were observed with scores reflecting verbal memory, but not executive functioning.This study suggests that a pro-inflammatory diet at midlife might be associated with subsequent lower cognitive functioning. A diet exhibiting anti-inflammatory properties may help to maintain cognitive health during aging.Clinicaltrials.gov (number NCT00272428).
Keywords: Cognition; Memory; Inflammation; Diet; Dietary inflammatory index

A combination of scGOS/lcFOS with Bifidobacterium breve M-16V protects suckling rats from rotavirus gastroenteritis by M. Rigo-Adrover; S. Saldaña-Ruíz; K. van Limpt; K. Knipping; J. Garssen; J. Knol; A. Franch; M. Castell; F. J. Pérez-Cano (1657-1670).
Rotavirus (RV) is the leading cause of severe diarrhoea among infants and young children, and although more standardized studies are needed, there is evidence that probiotics can help to fight against RV and other infectious and intestinal pathologies. On the other hand, the effects of prebiotics have not been properly addressed in the context of an RV infection. The aim of this study was to demonstrate a protective role for a specific scGOS/lcFOS 9:1 prebiotic mixture (PRE) separately, the probiotic Bifidobacterium breve M-16V (PRO) separately and the combination of the prebiotic mixture and the probiotic (synbiotic, SYN) in a suckling rat RV infection model.The animals received the intervention from the 3rd to the 21st day of life by oral gavage. On day 7, RV was orally administered. Clinical parameters and immune response were evaluated.The intervention with the PRO reduced the incidence, severity and duration of the diarrhoea (p < 0.05). The PRE and SYN products improved clinical parameters as well, but a change in stool consistency induced by the PRE intervention hindered the observation of this effect. Both the PRE and the SYN, but not the PRO, significantly reduced viral shedding. All interventions modulated the specific antibody response in serum and intestinal washes at day 14 and 21 of life.A daily supplement of a scGOS/lcFOS 9:1 prebiotic mixture, Bifidobacterium breve M-16V or a combination of both is highly effective in modulating RV-induced diarrhoea in this preclinical model.
Keywords: Prebiotic; Probiotic; Synbiotic; Rotavirus; FOS; GOS; Bifidobacterium breve

Beneficial effects of white mulberry against diabetes mellitus have been reported. However, the molecular mechanisms of how white mulberry can attenuate diabetic retinopathy remain poorly understood. Here, the mechanism underlying the protective effect of Morus alba leaves ethanolic extract on oxidative stress, inflammation, apoptosis, and angiogenesis in diabetic retinopathy was investigated.Diabetes was induced by injection of streptozotocin. One week after, M. alba (100 mg/kg) was administrated to the rats daily for 16 weeks. Morus alba extract showed high content of polyphenolics and free radical scavenging activity. Oral M. alba administration significantly attenuated hyperglycemia and weight loss, and decreased sorbitol, fructose, protein kinase C, pro-inflammatory cytokines, and oxidative stress markers in retinas of the diabetic rats. Moreover, M. alba produced marked down-regulation of caspase-3 and Bax, with concomitant up-regulation of Bcl-2 in the diabetic retinas. M. alba also reduced the expression of VEGF in the retina.These results indicate that M. alba has protective effect on diabetic retinopathy with possible mechanisms of inhibiting hyperglycemia-induced oxidative stress, apoptosis, inflammation, polyol pathway activation, and VEGF expression in the retina.
Keywords: Mulberry; Retina; Diabetes; Oxidative stress; Apoptosis

In order to collect information on food intake, lifestyle and health status of the Italian population, a random cohort of about 2000 adults was selected in collaboration with the Italian society of general practitioners’ network (SIMG).Cohort subjects underwent a full clinical evaluation, by their family doctor, who also collected anthropometric data and information on the prevalence of cardiovascular disease risk factors; they were also administered diary forms developed to assess dietary use of simple sugars, of sugar-containing food and of selected food items.Data obtained indicate that the consumption of simple sugars (either added or as natural part of food) by the Italian adult population is, on average, not high (65 and 67 g/day, among women and men, respectively) and mostly derived from food items such as fruit, milk and yogurt. In addition, no correlations were found, in this low-sugar-consuming cohort, between sugar intake and weight, body mass index and waist circumference.Intakes of simple sugars in the LIZ cohort are not associated with weight, BMI and waist circumference. Prospective data, from cohorts like the LIZ one, might shed further light on the contribution of simple sugar intake to health in countries like Italy.
Keywords: Sugar intake; Fructose; Lactose; Diet; Cardiometabolic risk factors; Public health

The nutritional changes that have accompanied the modernization of Japanese dietary patterns have led to significant increases in the number of people who are overweight or obese. This study aimed to clarify the effects of these nutritional changes on postprandial energy expenditure and the release of metabolism-regulating hormones.The total daily energy content (20 % breakfast, 40 % lunch, and 40 % dinner) and macronutrient composition (carbohydrate/fat/protein) was 8807.3 kJ and 364.3:30.1:66.4 (g) for the traditional test diet and 9217.6 kJ and 331.7:66.1:76.9 (g) for the modern test diet. In experiment 1, nine healthy Japanese men participated in a crossover study during which they ingested a test diet comprising three meals; postprandial blood parameters were measured after each meal. In experiment 2, another ten men participated in a crossover study during which they ingested 2 meals, after which metabolic responses and blood variables were evaluated.The modern diet induced greater blood levels of glucose-dependent insulinotropic polypeptide (GIP) and ghrelin than did the traditional diet. The expected increase in postprandial energy expenditure (∆REE) tended to be dampened after the modern compared with the traditional diet. GIP was inversely correlated with ∆REE after lunch, and ghrelin was positively associated with ∆REE.Both GIP and ghrelin are robust indicators of postprandial energy expenditure. The nutritional changes accompanying the modernization of Japanese dietary patterns may increase the levels of the anabolic intestinal hormone GIP, which is associated with ∆REE, in the Japanese population. The contribution of an increased ghrelin concentration to the decreased ∆REE after the modern diet warrants further investigation.
Keywords: Gastrointestinal hormones; Ghrelin; Glucose-dependent insulinotropic polypeptide; Japanese meal; Postprandial energy expenditure

Agaricus brasiliensis (sun mushroom) affects the expression of genes related to cholesterol homeostasis by Aline Mayrink de Miranda; Joamyr Victor Rossoni Júnior; Lorena Souza e Silva; Rinaldo Cardoso dos Santos; Marcelo Eustáquio Silva; Maria Lúcia Pedrosa (1707-1717).
The sun mushroom (Agaricus brasiliensis) is considered a major source of bioactive compounds with potential health benefits. Mushrooms typically act as lipid-lowering agents; however, little is known about the mechanisms of action of A. brasiliensis in biological systems. This study aimed to determine the underlying mechanism involved in the cholesterol-lowering effect of A. brasiliensis through the assessment of fecal and serum lipid profiles in addition to gene expression analysis of specific transcription factors, enzymes, and transporters involved in cholesterol homeostasis.Twenty-four albino Fischer rats approximately 90 days old, with an average weight of 205 g, were divided into four groups of 6 each and fed a standard AIN-93 M diet (C), hypercholesterolemic diet (H), hypercholesterolemic diet +1 % A. brasiliensis (HAb), or hypercholesterolemic diet +0.008 % simvastatin (HS) for 6 weeks. Simvastatin was used as a positive control, as it is a typical drug prescribed for lipid disorders. Subsequently, blood, liver, and feces samples were collected for lipid profile and quantitative real-time polymerase chain reaction gene expression analyses.Diet supplementation with A. brasiliensis significantly improved serum lipid profiles, comparable to the effect observed for simvastatin. In addition, A. brasiliensis dietary supplementation markedly promoted fecal cholesterol excretion. Increased expression of 7α-hydroxylase (CYP7A1), ATP-binding cassette subfamily G-transporters (ABCG5/G8), and low-density lipoprotein receptor (LDLR) was observed following A. brasiliensis administration.Our results suggest that consumption of A. brasiliensis improves the serum lipid profile in hypercholesterolemic rats by modulating the expression of key genes involved in hepatic cholesterol metabolism.
Keywords: Agaricus brasiliensis ; Edible mushroom; Statin; Hypercholesterolemia; Rats; Cholesterol homeostasis

Trans-fatty acid levels in erythrocytes in Europe by Clemens von Schacky; Adrian Passow; Rosemarie Kiefl (1719-1723).
High, but not low levels of trans-fatty acids (TFA) in erythrocytes are associated with increased mortality. Current erythrocyte TFA levels in Europe are not known. TFA levels in samples submitted by physicians for erythrocyte omega-3 fatty acid analyses are reported, as analysed with a method (HS-Omega-3 Index®) previously used in pertinent prospective epidemiologic studies. From Germany, 6754 samples were included from 2008 through 2015, and 496 samples from 10 other European countries.In Germany, mean levels of C16:1n-7t, a marker for dairy and meat intake, decreased, as did mean levels of industrially produced (IP)-TFA, as did the percentage of individuals with IP-TFA > 1.04 %. Mean levels of IP-TFA in Austria and Switzerland were low before and after measures were taken to reduce them. Average levels of C16:1n-7t were low, and at levels associated with increased risk of death in previous studies. A limitation of our study is that samples were not obtained in a specific or representative manner.Levels of IP-TFA appear to be decreasing, as are those of ruminant-derived C16:1n-7t, a marker for dairy and meat intake. Few individuals had high levels of IP-TFA above a safe range, while many had low levels of C16:1n-7t. Our data argue against further action against TFA in the countries studied. More systematic biomarker-based studies are needed.
Keywords: Trans-fatty acidss; Cardiovascular disease; Fatty acid composition; Erythrocyte fatty acids

Appetite-regulating hormones in early life and relationships with type of feeding and body composition in healthy term infants by Laura M. Breij; Monique T. Mulder; Leonie C. van Vark-van der Zee; Anita C. S. Hokken-Koelega (1725-1732).
Body composition in early life influences development of obesity during childhood and beyond. Appetite-regulating hormones (ARH) play a role in regulation of food intake and might thus influence body composition in later life. Studies on associations between ARH and body composition in early life are limited.In 197 healthy term infants, we measured serum fasting levels of ghrelin, leptin, insulin, glucose-dependent insulinotropic peptide (GIP), pancreatic polypeptide (PP) and peptide YY (PYY) at 3 months and in 41 infants also at 6 months and their associations with type of feeding and longitudinal fat mass percentage (FM%) measured by air displacement plethysmography at 1, 3 and 6 months and abdominal visceral and subcutaneous fat, measured by ultrasound, at 3 and 6 months.Infants with formula feeding for 3 months had significantly higher serum levels of ghrelin, leptin, insulin, GIP and PP (p = 0.026, p = 0.018, p = 0.002, p < 0.001, resp.) and lower serum levels of PYY (p = 0.002) at 3 months than breastfed infants. Leptin and ghrelin correlated positively with FM% at 3 months and insulin with change in FM% between 1 and 3 months (r = 0.40, p < 0.001, r = 0.23, p < 0.05, r = 0.22, p < 0.01, resp.). Leptin at 3 months correlated with subcutaneous fat at 3 months (r = 0.23, p < 0.001), but not with visceral fat. Other ARH did not correlate with body composition.Formula-fed infants had a different profile of ARH than breastfed infants, suggesting that lower levels of ghrelin, leptin and insulin in breastfed infants contribute to the protective role of breastfeeding against obesity development. Leptin, ghrelin and insulin were associated with fat mass percentage or its changes.
Keywords: Appetite-regulating hormones; Early life; Formula fed; Breastfed; Body composition

Choline and polyunsaturated fatty acids in preterm infants’ maternal milk by Christoph Maas; Axel R. Franz; Anna Shunova; Michaela Mathes; Christine Bleeker; Christian F. Poets; Erwin Schleicher; Wolfgang Bernhard (1733-1742).
Choline, docosahexaenoic acid (DHA), and arachidonic acid (ARA) are essential to fetal development, particularly of the brain. These components are actively enriched in the fetus. Deprivation from placental supply may therefore result in impaired accretion in preterm infants.To determine choline, choline metabolites, DHA, and ARA in human breast milk (BM) of preterm infants compared to BM of term born infants.We collected expressed BM samples from 34 mothers (N = 353; postnatal day 6–85), who had delivered 35 preterm infants undergoing neonatal intensive care (postmenstrual age 30 weeks, range 25.4–32.0), and from mothers after term delivery (N = 9; postnatal day 6–118). Target metabolites were analyzed using tandem mass spectrometry and gas chromatography and reported as medians and 25th/75th percentiles.In BM, choline was mainly present in the form of phosphocholine and glycerophosphocholine, followed by free choline, phosphatidylcholine, sphingomyelin, and lyso-phosphatidylcholine. In preterm infants’ BM total choline ranged from 61 to 360 mg/L (median: 158 mg/L) and was decreased compared to term infants’ BM (range 142–343 mg/L; median: 258 mg/L; p < 0.01). ARA and DHA comprised 0.81 (range: 0.46–1.60) and 0.43 (0.15–2.42) % of total preterm BM lipids, whereas term BM values were 0.68 (0.52–0.88) and 0.35 (0.18–0.75) %, respectively. Concentrations of all target parameters decreased after birth, and frequently 150 ml/kg/d BM did not meet the estimated fetal accretion rates.Following preterm delivery, BM choline concentrations are lower, whereas ARA and DHA levels are comparable versus term delivery. Based on these findings we suggest a combined supplementation of preterm infants’ BM with choline, ARA and DHA combined to improve the nutritional status of preterm infants.This study was registered at www.clinicaltrials.gov. Identifier: NCT01773902.
Keywords: Choline deficiency; Neonate; Neurological development; Mothers’ milk; Polyunsaturated fatty acids; Preterm infants

The pro-/anti-inflammatory effects of different fatty acids on visceral adipocytes are partially mediated by GPR120 by Francisca Rodriguez-Pacheco; Carolina Gutierrez-Repiso; Sara Garcia-Serrano; Miguel A. Alaminos-Castillo; Ailec Ho-Plagaro; Sergio Valdes; Juan Garcia-Arnes; Montserrat Gonzalo; Raul J. Andrade; Francisco J. Moreno-Ruiz; Alberto Rodriguez-Cañete; Abelardo Martinez-Ferriz; Eduardo Garcia-Fuentes (1743-1752).
This study examines whether G-protein coupled receptor 120 (GPR120) is involved in the pro-/anti-inflammatory effects of different types of fatty acids (FAs) in human visceral adipocytes, and whether these effects may be altered in obesity, a state with a chronic inflammation.Pro-/anti-inflammatory effects of palmitic, oleic, linoleic and docosahexaenoic acids on human visceral adipocytes were tested in mature adipocytes from non-obese and morbidly obese (MO) subjects. Also, the effects of these FAs were tested when the GPR120 gene was silenced.In adipocytes from non-obese subjects, palmitic and linoleic acids increased TNF-α and IL-6 mRNA expression (p < 0.05), and decreased IL-10 and adiponectin expression (p < 0.05). However, oleic and docosahexaenoic acids (DHA) produced the opposite effect (p < 0.05). In adipocytes from MO subjects, all FAs used increased TNF-α and IL-6 expression (p < 0.05). Palmitic and linoleic acids decreased IL-10 and adiponectin expression (p < 0.05), but oleic acid and DHA did not have significant effects. Only oleic acid increased adiponectin expression (p < 0.05). The effects of FAs on TNF-α, IL-6, IL-10 and adiponectin expression in non-obese and MO subjects were significantly annulled when the GPR120 gene was silenced in visceral adipocytes differentiated from human mesenchymal stem cells.FAs are capable of directly acting on visceral adipocytes to modulate differently TNF-α, IL-6, IL-10 and adiponectin expression, with a different and greater effect in MO subjects. These effects are largely annulled when GPR120 expression was silenced, which suggests that they could be mediated by GPR120.
Keywords: Fatty acids; GPR120; Visceral adipocytes; Inflammation; Obesity

Effects of intrauterine growth retardation and Bacillus subtilis PB6 supplementation on growth performance, intestinal development and immune function of piglets during the suckling period by Liang Hu; Xie Peng; Hong Chen; Chuan Yan; Yan Liu; Qin Xu; Zhengfeng Fang; Yan Lin; Shengyu Xu; Bin Feng; Jian Li; De Wu; Lianqiang Che (1753-1765).
The aim of this study was to investigate the effects of intrauterine growth retardation (IUGR) and Bacillus subtilis PB6 supplementation in formula milk (FORM) on growth performance, intestinal development and immune function of neonates using a porcine model.Fourteen pairs of normal birth weight and IUGR piglets (7 days old) were randomly assigned to receive FORM or FORM supplemented with B. subtilis PB6 (FORM-BsPB6) for a period of 21 days. Blood samples, intestinal tissues and digesta were collected at necropsy and analysed for morphology, digestive enzyme activities, immune cell abundance, expression of genes associated with innate immunity and barrier function and microbial populations.Regardless of diet, IUGR significantly decreased average daily dry matter intake and average daily weight gain (P < 0.05). Moreover, IUGR significantly decreased plasma concentrations of immunoglobulin A, interleukin 1β, count and percentage of blood lymphocytes (P < 0.05). Meanwhile, IUGR markedly decreased villous height and maltase activity, as well as mRNA abundance of Toll-like receptor 9 and Toll-interacting protein in the ileum (P < 0.05). Regardless of body weight, FORM-BsPB6 markedly decreased the feed conversion ratio (P < 0.05), due to better intestinal development, as indicated by increased villous height (P < 0.05), activities of maltase and sucrase in the intestine (P < 0.10). Moreover, both mRNA and protein abundances of zonula occludens-1 and claudin-1 in the ileum as well as the copy number of Bacillus in colonic digesta were increased (P < 0.05) in piglets fed FORM-BsPB6 relative to FORM.The results of this study indicate that IUGR delayed growth, intestinal development and immune function of piglets, while FORM-BsPB6 improved digestive capability and intestinal barrier function.
Keywords: Birth weight; Probiotics; Intestine; Barrier function; Immunity

Foods contributing to vitamin B6, folate, and vitamin B12 intakes and biomarkers status in European adolescents: The HELENA study by Iris Iglesia; Theodora Mouratidou; Marcela González-Gross; Inge Huybrechts; Christina Breidenassel; Javier Santabárbara; Ligia-Esperanza Díaz; Lena Hällström; Stefaan De Henauw; Frédéric Gottrand; Anthony Kafatos; Kurt Widhalm; Yannis Manios; Denes Molnar; Peter Stehle; Luis A. Moreno; Luis A. Moreno; Jesús Fleta; José A. Casajús; Gerardo Rodríguez; Concepción Tomás; María I. Mesana; Germán Vicente-Rodríguez; Adoración Villarroya; Carlos M. Gil; Ignacio Ara; Juan Fernández Alvira; Gloria Bueno; Aurora Lázaro; Olga Bueno; Juan F. León; Jesús Mª Garagorri; Manuel Bueno; Idoia Labayen; Iris Iglesia; Silvia Bel; Luis A. Gracia Marco; Theodora Mouratidou; Alba Santaliestra-Pasías; Iris Iglesia; Esther González-Gil; Pilar De Miguel-Etayo; Cristina Julián Almárcegui; Mary Miguel-Berges; Isabel Iguacel; Ascensión Marcos; Julia Wärnberg; Esther Nova; Sonia Gómez; Ligia Esperanza Díaz; Javier Romeo; Ana Veses; Belén Zapatera; Tamara Pozo; David Martínez; Laurent Beghin; Christian Libersa; Frédéric Gottrand; Catalina Iliescu; Juliana Von Berlepsch; Mathilde Kersting; Wolfgang Sichert-Hellert; Ellen Koeppen; Dénes Molnar; Eva Erhardt; Katalin Csernus; Katalin Török; Szilvia Bokor; Mrs. Angster; Enikö Nagy; Orsolya Kovács; Judit Répasi; Anthony Kafatos; Caroline Codrington; María Plada; Angeliki Papadaki; Katerina Sarri; Anna Viskadourou; Christos Hatzis; Michael Kiriakakis; George Tsibinos; Constantine Vardavas; Manolis Sbokos; Eva Protoyeraki; Maria Fasoulaki; Peter Stehle; Klaus Pietrzik; Marcela González-Gross; Christina Breidenassel; Andre Spinneker; Jasmin Al-Tahan; Miriam Segoviano; Anke Berchtold; Christine Bierschbach; Erika Blatzheim; Adelheid Schuch; Petra Pickert; Manuel J. Castillo; Ángel Gutiérrez; Francisco B. Ortega; Jonatan R. Ruiz; Enrique G. Artero; Vanesa España; David Jiménez-Pavón; Palma Chillón; Cristóbal Sánchez-Muñoz; Magdalena Cuenca; Davide Arcella; Elena Azzini; Emma Barrison; Noemi Bevilacqua; Pasquale Buonocore; Giovina Catasta; Laura Censi; Donatella Ciarapica; Paola D’Acapito; Marika Ferrari; Myriam Galfo; Cinzia Le Donne; Catherine Leclercq; Giuseppe Maiani; Beatrice Mauro; Lorenza Mistura; Antonella Pasquali; Raffaela Piccinelli; Angela Polito; Romana Roccaldo; Raffaella Spada; Stefania Sette; Maria Zaccaria; Luca Scalfi; Paola Vitaglione; Concetta Montagnese lyName>; Ilse De Bourdeaudhuij; Stefaan De Henauw; Tineke De Vriendt; Lea Maes; Christophe Matthys; Carine Vereecken; Mieke de Maeyer; Charlene Ottevaere; Inge Huybrechts; Kurt Widhalm; Katharina Phillipp; Sabine Dietrich; Birgit Kubelka; Marion Boriss-Riedl; Yannis Manios; Eva Grammatikaki; Zoi Bouloubasi; Tina Louisa Cook; Sofia Eleutheriou; Orsalia Consta; George Moschonis; Ioanna Katsaroli; George Kraniou; Stalo Papoutsou; Despoina Keke; Ioanna Petraki; Elena Bellou; Sofia Tanagra; Kostalenia Kallianoti; Dionysia Argyropoulou; Stamatoula Tsikrika; Christos Karaiskos; Jean Dallongeville; Aline Meirhaeghe; Michael Sjöstrom; Jonatan R. Ruiz; Francisco B. Ortega; María Hagströmer; Anita Hurtig Wennlöf; Lena Hallström; Emma Patterson; Lydia Kwak; Julia Wärnberg; Nico Rizzo; Jackie Sánchez-Molero; Sara Castelló; Elena Picó; Maite Navarro; Blanca Viadel; José Enrique Carreres; Gema Merino; Rosa Sanjuán; María Lorente; María José Sánchez; Chantal Gilbert; Sarah Thomas; Elaine Allchurch; Peter Burgess; Gunnar Hall; Annika Astrom; Anna Sverkén; Agneta Broberg; Annick Masson; Claire Lehoux; Pascal Brabant; Philippe Pate; Laurence Fontaine; Andras Sebok; Tunde Kuti; Adrienn Hegyi; Cristina Maldonado; Ana Llorente; Emilio García; Holger von Fircks; Marianne Lilja Hallberg; Maria Messerer; Mats Larsson; Helena Fredriksson; Viola Adamsson; Ingmar Börjesson; Laura Fernández; Laura Smillie; Josephine Wills; Marcela González-Gross; Raquel Pedrero-Chamizo; Agustín Meléndez; Jara Valtueña; David Jiménez-Pavón; Ulrike Albers; Pedro J. Benito; Juan José Gómez Lorente; David Cañada; Alejandro Urzanqui; Rosa María Torres; Paloma Navarro (1767-1782).
To examine the association between food groups consumption and vitamin B6, folate and B12 intakes and biomarkers in adolescents.In total 2189 individuals participating in the cross-sectional Healthy Lifestyle in Europe by Nutrition in Adolescence study met the eligibility criteria for analysis of dietary intakes (46 % males) and 632 for biomarker analysis (47 % males). Food intakes were assessed by two non-consecutive 24-h recalls. Biomarkers were measured by chromatography and immunoassay. Food groups which best discriminated participants in the extreme tertiles of the distribution of vitamins were identified by discriminant analyses. Food groups with standardised canonical coefficients higher or equal to 0.3 were selected as valid discriminators of vitamins intake and biomarkers extreme tertiles. Linear mixed model elucidated the association between food groups and vitamins intakes and biomarkers.Vitamin B6 intakes and biomarkers were best discriminated by meat (males and females), margarine and mixed origin lipids only in males and breakfast cereals (females). Breakfast cereals (males), and fruits, margarine and mixed origin lipids, vegetables excluding potatoes, breakfast cereals, and soups/bouillon (females) determined the most folate intakes and biomarkers. Considering vitamin B12 intakes and biomarkers, meat, and white and butter milk (males and females), snacks (males), and dairy products (females) best discriminated individual in the extremes of the distribution. Fewer associations were obtained with mixed model for biomarkers than for vitamins intakes with food groups.Whereas B-vitamin intakes were associated with their food sources, biomarkers did with overall food consumption. Low-nutrient-density foods may compromise adolescents’ vitamin status.
Keywords: Foods contributors; B-vitamins; Adolescents

Erratum to: Foods contributing to vitamin B6, folate, and vitamin B12 intakes and biomarkers status in European adolescents: The HELENA study by Iris Iglesia; Theodora Mouratidou; Marcela González-Gross; Inge Huybrechts; Christina Breidenassel; Javier Santabárbara; Ligia-Esperanza Díaz; Lena Hällström; Stefaan De Henauw; Frédéric Gottrand; Anthony Kafatos; Kurt Widhalm; Yannis Manios; Denes Molnar; Peter Stehle; Luis A. Moreno; Luis A. Moreno; Jesús Fleta; José A. Casajús; Gerardo Rodríguez; Concepción Tomás; María I. Mesana; Germán Vicente-Rodríguez; Adoración Villarroya; Carlos M. Gil; Ignacio Ara; Juan Fernández Alvira; Gloria Bueno; Aurora Lázaro; Olga Bueno; Juan F. León; Jesús Mª Garagorri; Manuel Bueno; Idoia Labayen; Iris Iglesia; Silvia Bel; Luis A. Gracia Marco; Theodora Mouratidou; Alba Santaliestra-Pasías; Iris Iglesia; Esther González-Gil; Pilar De Miguel-Etayo; Cristina Julián Almárcegui; Mary Miguel-Berges; Isabel Iguacel; Ascensión Marcos; Julia Wärnberg; Esther Nova; Sonia Gómez; Ligia Esperanza Díaz; Javier Romeo; Ana Veses; Belén Zapatera; Tamara Pozo; David Martínez; Laurent Beghin; Christian Libersa; Frédéric Gottrand; Catalina Iliescu; Juliana Von Berlepsch; Mathilde Kersting; Wolfgang Sichert-Hellert; Ellen Koeppen; Dénes Molnar; Eva Erhardt; Katalin Csernus; Katalin Török; Szilvia Bokor; Mrs. Angster; Enikö Nagy; Orsolya Kovács; Judit Répasi; Anthony Kafatos; Caroline Codrington; María Plada; Angeliki Papadaki; Katerina Sarri; Anna Viskadourou; Christos Hatzis; Michael Kiriakakis; George Tsibinos; Constantine Vardavas; Manolis Sbokos; Eva Protoyeraki; Maria Fasoulaki; Peter Stehle; Klaus Pietrzik; Marcela González-Gross; Christina Breidenassel; Andre Spinneker; Jasmin Al-Tahan; Miriam Segoviano; Anke Berchtold; Christine Bierschbach; Erika Blatzheim; Adelheid Schuch; Petra Pickert; Manuel J. Castillo; Ángel Gutiérrez; Francisco B. Ortega; Jonatan R. Ruiz; Enrique G. Artero; Vanesa España; David Jiménez-Pavón; Palma Chillón; Cristóbal Sánchez-Muñoz; Magdalena Cuenca; Davide Arcella; Elena Azzini; Emma Barrison; Noemi Bevilacqua; Pasquale Buonocore; Giovina Catasta; Laura Censi; Donatella Ciarapica; Paola D’Acapito; Marika Ferrari; Myriam Galfo; Cinzia Le Donne; Catherine Leclercq; Giuseppe Maiani; Beatrice Mauro; Lorenza Mistura; Antonella Pasquali; Raffaela Piccinelli; Angela Polito; Romana Roccaldo; Raffaella Spada; Stefania Sette; Maria Zaccaria; Luca Scalfi; Paola Vitaglione; Concetta Montagnese lyName>; Ilse De Bourdeaudhuij; Stefaan De Henauw; Tineke De Vriendt; Lea Maes; Christophe Matthys; Carine Vereecken; Mieke de Maeyer; Charlene Ottevaere; Inge Huybrechts; Kurt Widhalm; Katharina Phillipp; Sabine Dietrich; Birgit Kubelka; Marion Boriss-Riedl; Yannis Manios; Eva Grammatikaki; Zoi Bouloubasi; Tina Louisa Cook; Sofia Eleutheriou; Orsalia Consta; George Moschonis; Ioanna Katsaroli; George Kraniou; Stalo Papoutsou; Despoina Keke; Ioanna Petraki; Elena Bellou; Sofia Tanagra; Kostalenia Kallianoti; Dionysia Argyropoulou; Stamatoula Tsikrika; Christos Karaiskos; Jean Dallongeville; Aline Meirhaeghe; Michael Sjöstrom; Jonatan R. Ruiz; Francisco B. Ortega; María Hagströmer; Anita Hurtig Wennlöf; Lena Hallström; Emma Patterson; Lydia Kwak; Julia Wärnberg; Nico Rizzo; Jackie Sánchez-Molero; Sara Castelló; Elena Picó; Maite Navarro; Blanca Viadel; José Enrique Carreres; Gema Merino; Rosa Sanjuán; María Lorente; María José Sánchez; Chantal Gilbert; Sarah Thomas; Elaine Allchurch; Peter Burgess; Gunnar Hall; Annika Astrom; Anna Sverkén; Agneta Broberg; Annick Masson; Claire Lehoux; Pascal Brabant; Philippe Pate; Laurence Fontaine; Andras Sebok; Tunde Kuti; Adrienn Hegyi; Cristina Maldonado; Ana Llorente; Emilio García; Holger von Fircks; Marianne Lilja Hallberg; Maria Messerer; Mats Larsson; Helena Fredriksson; Viola Adamsson; Ingmar Börjesson; Laura Fernández; Laura Smillie; Josephine Wills; Marcela González-Gross; Raquel Pedrero-Chamizo; Agustín Meléndez; Jara Valtueña; David Jiménez-Pavón; Ulrike Albers; Pedro J. Benito; Juan José Gómez Lorente; David Cañada; Alejandro Urzanqui; Rosa María Torres; Paloma Navarro (1783-1783).

Letter to the Editor by Yoshihiro Miyake; Keiko Tanaka; Hitomi Okubo; Satoshi Sasaki; Shinya Furukawa; Masashi Arakawa (1787-1787).