European Journal of Nutrition (v.55, #4)

Coffee consumption and the risk of cutaneous melanoma: a meta-analysis by Jia Wang; Xutong Li; Dongfeng Zhang (1317-1329).
Results from epidemiologic studies on coffee consumption and the risk of cutaneous melanoma are inconsistent. We conducted a meta-analysis to assess the associations between the consumption of total coffee, caffeinated coffee and decaffeinated coffee and the risk of cutaneous melanoma, respectively.A literature search was performed in PubMed, Web of Science and EMBASE for relevant articles published up to August 2015. Pooled relative risks (RRs) with 95 % confidence intervals (CIs) were calculated with a random-effects model. Dose–response relationship was assessed by restricted cubic spline.Twelve studies involving 832,956 participants for total coffee consumption, 5 studies involving 717,151 participants for caffeinated coffee consumption and 6 studies involving 718,231 participants for decaffeinated coffee consumption were included in this meta-analysis. Compared with the lowest level of consumption, the pooled RRs were 0.80 (95 % CI 0.69–0.93, I 2 = 53.5 %), 0.85 (95 % CI 0.71–1.01, I 2 = 65.0 %) and 0.92 (95 % CI 0.81–1.05, I 2 = 0.0 %) for the consumption of total coffee, caffeinated coffee and decaffeinated coffee, respectively. In subgroup analysis by study design, the pooled RRs in cohort studies and case–control studies were 0.83 (95 % CI 0.72–0.97) and 0.74 (95 % CI 0.51–1.07) for total coffee consumption, respectively. Dose–response analysis suggested cutaneous melanoma risk decreased by 3 % [0.97 (0.93–1.00)] and 4 % [0.96 (0.92–1.01)] for 1 cup/day increment of total coffee and caffeinated coffee consumption, respectively.This meta-analysis suggests that coffee consumption may reduce the risk of cutaneous melanoma.
Keywords: Coffee; Caffeinated coffee; Cutaneous melanoma; Meta-analysis

Caffeine and cardiovascular diseases: critical review of current research by Anthony Zulli; Renee M. Smith; Peter Kubatka; Jan Novak; Yoshio Uehara; Hayley Loftus; Tawar Qaradakhi; Miroslav Pohanka; Nazarii Kobyliak; Angela Zagatina; Jan Klimas; Alan Hayes; Giampiero La Rocca; Miroslav Soucek; Peter Kruzliak (1331-1343).
Caffeine is a most widely consumed physiological stimulant worldwide, which is consumed via natural sources, such as coffee and tea, and now marketed sources such as energy drinks and other dietary supplements. This wide use has led to concerns regarding the safety of caffeine and its proposed beneficial role in alertness, performance and energy expenditure and side effects in the cardiovascular system. The question remains “Which dose is safe?”, as the population does not appear to adhere to the strict guidelines listed on caffeine consumption. Studies in humans and animal models yield controversial results, which can be explained by population, type and dose of caffeine and low statistical power. This review will focus on comprehensive and critical review of the current literature and provide an avenue for further study.
Keywords: Cardiovascular diseases; Caffeine; Cardioprotective effects; Pathogenesis; Clinical studies; Experimental studies

Coffee consumption, obesity and type 2 diabetes: a mini-review by Roseane Maria Maia Santos; Darcy Roberto Andrade Lima (1345-1358).
The effects of regular coffee intake on weight gain and development of diabetes are reviewed. The pathophysiology of obesity and type 2 diabetes as well as the necessity of preventive options based on the increasing prevalence of these two disorders worldwide is briefly discussed. The relationship between weight gain and development of diabetes is also presented. The two major constituents in the brewed coffee, chlorogenic acids and caffeine, are responsible for many of the beneficial effects suggested by numerous epidemiological studies of coffee consumption and the development of diabetes.A wide search of various databases, such as PubMed and Google Scholar, preceded the writing of this manuscript, focusing on key words that are part of the title. It was selected mainly review papers from in vivo, ex vivo, in vitro experimental studies in animals and human tissues as well as wide population-based epidemiological studies in the last 10 years.As of today, there are mounting evidences of the reduced risk of developing type 2 diabetes by regular coffee drinkers of 3–4 cups a day. The effects are likely due to the presence of chlorogenic acids and caffeine, the two constituents of coffee in higher concentration after the roasting process.
Keywords: Coffee; Obesity; Diabetes; Chlorogenic acid; Caffeine

Dietary polyphenol intake in Europe: the European Prospective Investigation into Cancer and Nutrition (EPIC) study by Raul Zamora-Ros; Viktoria Knaze; Joseph A. Rothwell; Bertrand Hémon; Aurelie Moskal; Kim Overvad; Anne Tjønneland; Cecilie Kyrø; Guy Fagherazzi; Marie-Christine Boutron-Ruault; Marina Touillaud; Verena Katzke; Tilman Kühn; Heiner Boeing; Jana Förster; Antonia Trichopoulou; Elissavet Valanou; Eleni Peppa; Domenico Palli; Claudia Agnoli; Fulvio Ricceri; Rosario Tumino; Maria Santucci de Magistris; Petra H. M. Peeters; H. Bas Bueno-de-Mesquita; Dagrun Engeset; Guri Skeie; Anette Hjartåker; Virginia Menéndez; Antonio Agudo; Esther Molina-Montes; José María Huerta; Aurelio Barricarte; Pilar Amiano; Emily Sonestedt; Lena Maria Nilsson; Rikard Landberg; Timothy J. Key; Kay-Thee Khaw; Nicholas J. Wareham; Yunxia Lu; Nadia Slimani; Isabelle Romieu; Elio Riboli; Augustin Scalbert (1359-1375).
Polyphenols are plant secondary metabolites with a large variability in their chemical structure and dietary occurrence that have been associated with some protective effects against several chronic diseases. To date, limited data exist on intake of polyphenols in populations. The current cross-sectional analysis aimed at estimating dietary intakes of all currently known individual polyphenols and total intake per class and subclass, and to identify their main food sources in the European Prospective Investigation into Cancer and Nutrition cohort.Dietary data at baseline were collected using a standardized 24-h dietary recall software administered to 36,037 adult subjects. Dietary data were linked with Phenol-Explorer, a database with data on 502 individual polyphenols in 452 foods and data on polyphenol losses due to cooking and food processing. Mean total polyphenol intake was the highest in Aarhus—Denmark (1786 mg/day in men and 1626 mg/day in women) and the lowest in Greece (744 mg/day in men and 584 mg/day in women). When dividing the subjects into three regions, the highest intake of total polyphenols was observed in the UK health-conscious group, followed by non-Mediterranean (non-MED) and MED countries. The main polyphenol contributors were phenolic acids (52.5–56.9 %), except in men from MED countries and in the UK health-conscious group where they were flavonoids (49.1–61.7 %). Coffee, tea, and fruits were the most important food sources of total polyphenols. A total of 437 different individual polyphenols were consumed, including 94 consumed at a level >1 mg/day. The most abundant ones were the caffeoylquinic acids and the proanthocyanidin oligomers and polymers.This study describes the large number of dietary individual polyphenols consumed and the high variability of their intakes between European populations, particularly between MED and non-MED countries.
Keywords: Polyphenols; Dietary intake; Food sources; EPIC

Combining vitamin C and carotenoid biomarkers better predicts fruit and vegetable intake than individual biomarkers in dietary intervention studies by Alanna J. McGrath; Lesley L. Hamill; Chris R. Cardwell; Claire R. Draffin; Charlotte E. Neville; Katherine M. Appleton; Jane McEneny; Michelle C. McKinley; Ian S. Young; Jayne V. Woodside (1377-1388).
The aim of this study was to determine whether combining potential biomarkers of fruit and vegetables is better at predicting FV intake within FV intervention studies than single biomarkers. Data from a tightly controlled randomised FV intervention study (BIOFAV; all food provided and two meals/day on weekdays consumed under supervision) were used. A total of 30 participants were randomised to either 2, 5 or 8 portions FV/day for 4 weeks, and blood samples were collected at baseline and 4 weeks for plasma vitamin C and serum carotenoid analysis. The combined biomarker approach was also tested in three further FV intervention studies conducted by the same research team, with less strict dietary control (FV provided and no supervised meals).The combined model containing all carotenoids and vitamin C was a better fit than either the vitamin C only (P < 0.001) model or the lutein only (P = 0.006) model in the BIOFAV study. The C-statistic was slightly lower in the lutein only model (0.85) and in the model based upon factor analysis (0.88), and much lower in the vitamin C model (0.68) compared with the full model (0.95). Results for the other studies were similar, although the differences between the models were less marked.Although there was some variation between studies, which may relate to the level of dietary control or participant characteristics, a combined biomarker approach to assess overall FV consumption may more accurately predict FV intake within intervention studies than the use of a single biomarker. The generalisability of these findings to other populations and study designs remains to be tested.Clinical trial Registration Number NCT01591057 ( www.clinicaltrials.gov ).
Keywords: Fruit; Vegetables; Dietary intake; Biomarkers; Methodology

Effects of low-fat milk consumption at breakfast on satiety and short-term energy intake in 10- to 12-year-old obese boys by Sanaz Mehrabani; Seyyed Morteza Safavi; Sepideh Mehrabani; Mehdi Asemi; Awat Feizi; Nick Bellissimo; Amin Salehi-Abargouei (1389-1396).
Although controversy exists, some researchers have proposed that dairy products increase the sense of satiety and decrease energy intake; however, data about these effects are lacking in children. Our objective was to assess the effect of low-fat milk compared with iso-volumic and iso-volumic/iso-energetic controls on satiety and energy intake at lunch in obese boys using a randomized three-way crossover controlled clinical trial.Thirty-four obese boys aged 10–12 years were randomized to consume a fixed content breakfast with low-fat milk (LFM), apple juice (AJ) or water (W) for two consecutive days. Subjective appetite, hunger, fullness, desire to eat and prospective food consumption were measured using a visual analogue scale every 1 h after breakfast followed by an ad libitum buffet lunch at 5 h.All participants completed the study. Energy intake was significantly lower after intake of LFM compared with AJ and W (adjusted mean ± standard error of energy intake: LFM = 1010 ± 14 kcal, AJ = 1059 ± 16 kcal, W = 1236 ± 20 kcal; P < 0.001). The total appetite score and its components were significantly affected by time for all intervention beverages (P < 0.05). Obese children reported higher satiety score after drinking LFM with breakfast compared with W and AJ (P < 0.05).Low-fat milk consumption might have favorable short-term effects on satiety and energy intake in obese boys. Future studies with more participants from both genders and longer follow-up periods are merited.The study protocol was registered with the Iranian Registry of Clinical Trials (Registration No: IRCT2013022312571N1).
Keywords: Milk; Appetite; Energy intake; Child; Obesity

Diets high in corn oil or extra-virgin olive oil differentially modify the gene expression profile of the mammary gland and influence experimental breast cancer susceptibility by Raquel Moral; Raquel Escrich; Montserrat Solanas; Elena Vela; M. Carme Ruiz de Villa; Eduard Escrich (1397-1409).
Nutritional factors, especially dietary lipids, may have a role in the etiology of breast cancer. We aimed to analyze the effects of high-fat diets on the susceptibility of the mammary gland to experimental malignant transformation.Female Sprague–Dawley rats were fed a low-fat, high-corn-oil, or high-extra-virgin olive oil (EVOO) diet from weaning or from induction. Animals were induced with 7,12-dimethylbenz[a]anthracene at 53 days and euthanized at 36, 51, 100 and 246 days. Gene expression profiles of mammary glands were determined by microarrays. Further molecular analyses were performed by real-time PCR, TUNEL and immunohistochemistry. Carcinogenesis parameters were determined at 105 and 246 days.High-corn-oil diet increased body weight and mass when administered from weaning. The EVOO diet did not modify these parameters and increased the hepatic expression of UCP2, suggesting a decrease in intake/expenditure balance. Both diets differentially modified the gene expression profile of the mammary gland, especially after short dietary intervention. Corn oil down-regulated the expression of genes related to immune system and apoptosis, whereas EVOO modified the expression of metabolism genes. Further analysis suggested an increase in proliferation and lower apoptosis in the mammary glands by effect of the high-corn-oil diet, which may be one of the mechanisms of its clear stimulating effect on carcinogenesis.The high-corn-oil diet strongly stimulates mammary tumorigenesis in association with modifications in the expression profile and an increased proliferation/apoptosis balance of the mammary gland.
Keywords: Extra-virgin olive oil; Corn oil; Dietary lipids; Mammary gland; Experimental tumors; Gene expression profile

Folic acid supplementation, dietary folate intake and risk of preterm birth in China by Xiaohui Liu; Ling Lv; Hanru Zhang; Nan Zhao; Jie Qiu; Xiaochun He; Min Zhou; Xiaoying Xu; Hongmei Cui; Sufen Liu; Catherine Lerro; Xiaojuan Lin; Chong Zhang; Honghong Zhang; Ruifeng Xu; Daling Zhu; Yun Dang; Xudong Han; Haiya Bai; Ya Chen; Zhongfeng Tang; Ru Lin; Tingting Yao; Jie Su; Wendi Wang; Yueyuan Wang; Bin Ma; Huang Huang; Jiaxin Liang; Weitao Qiu; Qing Liu; Yawei Zhang (1411-1422).
Folic acid supplementation has been suggested to reduce the risk of preterm birth. However, results from previous epidemiologic studies have been inconclusive. We investigated the hypothesis that folic acid supplementation and dietary folate intake during pre- and post-conception reduces the risk of preterm birth.We analyzed data from a birth cohort study conducted between 2010 and 2012 in Lanzhou, China, including 10,179 pregnant women with live singleton births.Compared to non-users, folic acid supplement users with >12-week duration had a reduced risk of preterm birth (OR 0.67, 95 % CI 0.55–0.83) with a significant dose–response relationship (P for trend = 0.01). A similar pattern was observed for spontaneous preterm birth. Stronger associations were seen for ever use of folic acid supplement and very preterm birth (OR 0.50, 95 % CI 0.36–0.69) and spontaneous very preterm birth (OR 0.42, 95 % CI 0.29–0.63). Dietary folate intake during preconception and pregnancy were also associated with reduced risk of preterm birth (OR 0.68, 95 % CI 0.56–0.83, OR 0.57, 95 % CI 0.47–0.70 for the highest quartiles, respectively), particularly for spontaneous very preterm (OR 0.41, 95 % CI 0.24–0.72, OR 0.26, 95 % CI 0.15–0.47 for the highest quartiles, respectively). There were also decreased risks of preterm birth observed per 10-µg increase in dietary folate intake, and similar associations were found after stratification by folic acid supplementation status.Our results suggest that folic acid supplementation and higher dietary folate intake during preconception and pregnancy reduces the risk of preterm birth, and the protective effect varies by preterm subtypes.
Keywords: Dietary folate; Epidemiology; Folic acid supplements; Preterm birth

Protein-energy malnutrition at mid-adulthood does not imprint long-term metabolic consequences in male rats by Ananda Malta; Egberto Gaspar de Moura; Tatiane Aparecida Ribeiro; Laize Peron Tófolo; Latifa Abdennebi-Najar; Didier Vieau; Luiz Felipe Barella; Paulo Cezar de Freitas Mathias; Patrícia Cristina Lisboa; Júlio Cezar de Oliveira (1423-1433).
The long-term effects of the development of chronic metabolic diseases such as type 2 diabetes and obesity have been associated with nutritional insults in critical life stages. In this study, we evaluated the effect of a low-protein diet on metabolism in mid-adulthood male rats.At 90 days of age, Wistar male rats were fed a low-protein diet (4.0 %, LP group) for 30 days, whereas control rats were fed a normal-protein diet (20.5 %, NP group) throughout their lifetimes. To allow for dietary rehabilitation, from 120 to 180 days of age, the LP rats were fed a normal-protein diet. Then, we measured body composition, fat stores, glucose-insulin homeostasis and pancreatic islet function.At 120 days of age, just after low-protein diet treatment, the LP rats displayed a strong lean phenotype, hypoinsulinemia, as assessed under fasting and glucose tolerance test conditions, as well as weak pancreatic islet insulinotropic response to glucose and acetylcholine (p < 0.01). At 180 days of age, after poor-protein diet rehabilitation, the LP rats displayed a slight lean phenotype (p < 0.05), which was associated with a high body weight gain (p < 0.001). Additionally, fat pad accumulation, glycemia and insulinemia, as well as the pancreatic islet insulinotropic response, were not significantly different between the LP and NP rats (p > 0.05).Taken together, the present data suggest that the effects of dietary restriction as a stressor in adulthood are reversible with dietary rehabilitation, indicating that adulthood is not a sensitive or critical time window for metabolic programming.
Keywords: Low-protein diet; Insulin secretion; Thrifty phenotype hypothesis; Metabolic programming

Baccaurea angulata fruit inhibits lipid peroxidation and induces the increase in antioxidant enzyme activities by Maryam Abimbola Mikail; Idris Adewale Ahmed; Muhammad Ibrahim; Norazlanshah Hazali; Mohammad Syaiful Bahari Abdul Rasad; Radiah Abdul Ghani; Ridzwan Hashim; Ridhwan Abdul Wahab; Solachuddin Jahuari Arief; Muhammad Lokman Md Isa; Samsul Draman; Mohammad Noor Adros Yahya (1435-1444).
The consequence of the increased demand due to the population expansion has put tremendous pressure on the natural supply of fruits. Hence, there is an unprecedented growing interest in the exploration of the potentials of underutilized fruits as alternatives to the commercially available fruits. Baccaurea angulata is an underutilized fruit widely distributed in Borneo Island of Malaysia. The present study was conducted to investigate the effects of B. angulata whole fruit (WF), skin (SK) and pulp (PL) juices on malondialdehyde (MDA) levels and antioxidant enzymes in rabbits fed high-cholesterol diet. Thirty-six male rabbits of New Zealand strain were randomly assigned to six groups. Rabbits were fed either a standard pellet (group NC) or a high-cholesterol diet (groups HC, PC, WF, SK and PL). Groups WF, SK and PL were also given 1 ml/kg/day B. angulata WF, SK and PL juices, respectively. Baccaurea angulata had high antioxidant activities. The administration of the various juices significantly reduced (p < 0.05) the concentration of induced plasma MDA. The decrease in the SOD, GPx, CAT and TAC levels caused by cholesterol feeding was also ameliorated with B. angulata.Our results show that B. angulata fruit is beneficial in positively influencing and managing oxidative damage.
Keywords: Antioxidant enzymes; Baccaurea angulata ; Malondialdehyde; Underutilized fruit

Fructooligosaccharides exert intestinal anti-inflammatory activity in the CD4+ CD62L+ T cell transfer model of colitis in C57BL/6J mice by Fermín Capitán-Cañadas; Borja Ocón; Carlos José Aranda; Andrea Anzola; María Dolores Suárez; Antonio Zarzuelo; Fermín Sánchez de Medina; Olga Martínez-Augustin (1445-1454).
Fructooligosaccharides (FOS) are used as functional foods due to their prebiotic effects. Intestinal anti-inflammatory activity has been established in most, but not all, studies in animal models of colitis, using mainly chemically induced inflammation. Our goal was to test the effect of FOS (degree of polymerization 2–8) in the chronic, lymphocyte-driven CD4+ CD62L+ T cell transfer model of colitis.Colitis was induced by transfer of CD4+ CD62L+ T cells to C57BL/6J Rag1−/− mice. FOS (75 mg day−1) was administered by gavage as a post-treatment. Three groups were established: non-colitic (NC), colitic control (C, CD4+ CD62L+ transferred mice treated with vehicle) and colitic+FOS (C+FOS, similar but treated with FOS). Mice were killed after 13 days.Treatment of mice with FOS ameliorated colitis, as evidenced by an increase in body weight, a lesser myeloperoxidase and alkaline phosphatase activities, a lower secretion of proinflammatory cytokines by mesenteric lymph node cells ex vivo (IFN-γ, IL-17, and TNF-α), and a higher colonic expression of occludin (C+FOS vs. C, p < 0.05). Increased relative abundance of lactic acid bacteria was observed in FOS-treated mice (p < 0.05).FOS exert intestinal anti-inflammatory activity in T lymphocyte-dependent colitis, suggesting it may be useful in the management of inflammatory bowel disease in appropriate conditions.
Keywords: Fructooligosaccharides; Prebiotic; Colitis; CD4+ CD62L+ T cell; Alkaline phosphatase; Inflammatory bowel disease

Grape skin extract-derived polyphenols modify programming-induced renal endowment in prenatal protein-restricted male mouse offspring by Mariana Ribeiro Costa; Karla Maria Pereira Pires; Mariane Nogueira Nalbones-Barbosa; Samuel dos Santos Valença; Ângela Castro Resende; Roberto Soares de Moura (1455-1464).
Protein-restricted diet during pregnancy is related to oxidative stress and, as a consequence, damage to nephrogenesis. We investigated the effects of vinifera grape skin extract (ACH09)-derived polyphenols on preserving renal morphology of maternal protein-restricted 1-day-old offspring.Female C57/Bl-6 mice were fed two different isocaloric diets: control diet (19.3 % protein) and low-protein diet (6 % protein) with access to water or to the extract dissolved in drinking water (19.3 % protein plus ACH09 200 mg kg−1 day−1 and 6 % protein plus ACH09 200 mg kg−1 day−1) throughout gestation. Renal morphology—glomerular number N[glom]; renal maturity—vascular glomeruli and avascular glomeruli ratio (v–N[glom]/a-N[glom]); medullar and cortical volumes, as well as mean glomerular volume, were analyzed in male offspring. Hepatic superoxide dismutase and catalase (CAT) activities were evaluated, and renal lipid peroxidation levels were measured.Maternal protein restriction affected birth weight and naso-anal length in low-protein offspring compared to control and ACH09 restored both parameters. Protein restriction increased lipid peroxidation in kidney and liver and reduced CAT activity in low-protein group compared to control. Supplementation with ACH09 reduced the kidney oxidative damage and restored the antioxidant activity of CAT. ACH09 prevented glomerular loss and renal immaturity in the offspring.The treatment of low-protein-fed dams during pregnancy with ACH09 provides protection from early-life deleterious renal morphological changes. The protective effect of ACH09 may involve antioxidant action and vasodilator effect of the extract.
Keywords: Protein restriction; Pregnancy; Oxidative stress; Renal morphology; Grape skin extract

We aim to examine whether honey ameliorates hepatic injury in non-alcoholic steatohepatitis (NASH) animal and cell line steatosis models.NASH was induced in female Sprague–Dawley rat by 8-week feeding with a high-fat diet. During the experiment, 5 g/kg honey was intragastrically fed daily. Rat normal hepatocyte BRL-3A cell was treated with sodium palmitate (SP) to induce steatosis in the absence or presence of honey pre-treatment or specific siRNA/overexpress plasmid of thioredoxin-interacting protein (TXNIP) or antagonist/agonist of Nod-like receptor protein 3 (NLRP3).Honey significantly improved the high-fat-diet-induced hepatic injury, steatosis, fibrosis, oxidative stress, and inflammation in rats. Honey also inhibited the overexpression of TXNIP and the activation of NLRP3 inflammasome. These effects were replicated in BRL-3A cell line which showed that the down-regulation of TXNIP or inhibition of NLRP3 contributed to the suppression of NLRP3 inflammasome activation, inflammation, and re-balanced lipid metabolism. In contrast, overexpression of TXNIP or agonism of NLRP3 exacerbated the cellular damage induced by SP.Suppression of the TXNIP–NLRP3 inflammasome pathway may partly contribute to the amelioration of hepatic injury during the progression of NASH by honey. Targeting hepatic TXNIP–NLRP3 inflammasome pathway is a potential therapeutic way for the prevention and treatment of NASH.
Keywords: Honey; NASH; TXNIP; NLRP3 inflammasome; Inflammation

Effects of high doses of vitamin D3 on mucosa-associated gut microbiome vary between regions of the human gastrointestinal tract by Mina Bashir; Barbara Prietl; Martin Tauschmann; Selma I. Mautner; Patrizia K. Kump; Gerlies Treiber; Philipp Wurm; Gregor Gorkiewicz; Christoph Högenauer; Thomas R. Pieber (1479-1489).
Vitamin D is well known for its effects on bone mineralisation but has also been attributed immunomodulatory properties. It positively influences human health, but in vivo data describing vitamin D effects on the human gut microbiome are missing. We aimed to investigate the effects of oral vitamin D3 supplementation on the human mucosa-associated and stool microbiome as well as CD8+ T cells in healthy volunteers.This was an interventional, open-label, pilot study. Sixteen healthy volunteers (7 females, 9 males) were endoscopically examined to access a total of 7 sites. We sampled stomach, small bowel, colon, and stools before and after 8 weeks of vitamin D3 supplementation. Bacterial composition was assessed by pyrosequencing the 16S rRNA gene (V1–2), and CD8+ T cell counts were determined by flow cytometry.Vitamin D3 supplementation changed the gut microbiome in the upper GI tract (gastric corpus, antrum, and duodenum). We found a decreased relative abundance of Gammaproteobacteria including Pseudomonas spp. and Escherichia/Shigella spp. and increased bacterial richness. No major changes occurred in the terminal ileum, appendiceal orifice, ascending colon, and sigmoid colon or in stools, but the CD8+ T cell fraction was significantly increased in the terminal ileum.Vitamin D3 modulates the gut microbiome of the upper GI tract which might explain its positive influence on gastrointestinal diseases, such as inflammatory bowel disease or bacterial infections. The local effects of vitamin D demonstrate pronounced regional differences in the response of the GI microbiome to external factors, which should be considered in future studies investigating the human microbiome.
Keywords: Vitamin D; Human gut microbiome; IBD; Inflammation; Gammaproteobacteria

Association between inflammatory potential of diet and mortality in the Iowa Women’s Health study by Nitin Shivappa; Cindy K. Blair; Anna E. Prizment; David R. Jacobs Jr.; Susan E. Steck; James R. Hébert (1491-1502).
Chronic diseases such as cancer and cardiovascular disease (CVD) are well-established causes of disability and premature deaths. Dietary components that are known to affect chronic inflammation have been implicated in the etiology and prognosis of these chronic diseases. We examined the ability of the dietary inflammatory index (DII) to predict overall, cancer and CVD mortality in the Iowa Women’s Health study.The DII was computed from baseline dietary intake assessed in this cohort of 37,525 women, who were aged 55–69 years when enrolled starting in 1986. During the follow-up period, through December 31, 2010, in a total of 17,793 deaths, 5044 cancer- and 6528 CVD-related deaths were identified through mortality record linkage. Cox proportional hazards regression was used to estimate hazard ratios (HR) with DII expressed both as a continuous variable and as quartiles. Comparing subjects in DII Quartile 4 versus Quartile 1, modest positive associations were noted for all-cause mortality (HRQ4vsQ1 1.07; 95 % CI 1.01–1.13; p-trend = 0.006), digestive cancer mortality (HRQ4vsQ1 1.19; 95 % CI 1.00–1.43; p-trend = 0.05), CVD mortality (HRQ4vsQ1 1.09; 95 % CI 1.01–1.18; p-trend = 0.08), non-cancer/non-CVD/non-acute mortality (HRQ4vsQ1 1.09; 95 % CI 1.00–1.19; p-trend = 0.19), coronary heart disease (CHD) mortality (HRQ4vsQ1 1.17; 95 % CI 1.05–1.30; p-trend = 0.001) and chronic obstructive pulmonary disease (COPD) mortality (HRQ4vsQ1 1.43; 95 % CI 1.18–1.75; p-trend = 0.0006). No substantial associations were observed for mortality from stroke, Alzheimer’s disease or unspecified dementia.These results indicate that a pro-inflammatory diet, as evidenced by higher DII scores, may be associated with total mortality as well as mortality from digestive cancer, CVD, CHD and COPD.
Keywords: Diet; Inflammation; Mortality; Cohort; Women

Serum 25-hydroxyvitamin D is associated with reduced verbal episodic memory in healthy, middle-aged and older adults by Virginie Lam; Matthew A. Albrecht; Ryusuke Takechi; Prachya Prasopsang; Ya Ping Lee; Jonathan K. Foster; John C. L. Mamo (1503-1513).
There is increasing evidence supporting an association of higher serum vitamin D concentration with better cognitive performance in older individuals. However, to date, consideration of the putative association between vitamin D and cognition has been based principally on studies investigating clinical participant samples manifesting vitamin D deficiency, particularly in older people. Moreover, relationships between vitamin D and cognition are typically not considered in the context of counter-regulatory calcium-modulating hormones or calcium homeostasis. Serum vitamin D/bioactive (ionised) calcium/parathyroid hormone homeostasis was considered in the context of cognitive performance in healthy, middle-aged and older individuals.A cross-sectional sample of 179 participants between the ages of 47–84 years was recruited for this study (114 females, 65 males). Participants provided fasting blood samples for analysis of serum 25-hydroxyvitamin D levels, ionised calcium (iCa) and parathyroid hormone (PTH) and completed cognitive measures of verbal episodic learning and memory.Serum 25-hydroxyvitamin D concentrations were negatively associated (with and without covariates of age, gender, depression and NART scores, iCa, and PTH) with measures of verbal episodic learning and memory, in particular with trial 5 of the Rey Auditory Verbal Learning Test (RAVLT) and long-delay free recall on the RAVLT.Overall, the findings from this study suggest an association between higher vitamin D status and poorer performance on verbal episodic memory in middle-aged and older individuals with normal vitamin D–calcium–PTH homeostasis. Despite requiring replication in other participant samples, this is a potentially important finding as it indicates that it may not be beneficial from a cognitive perspective to provide vitamin D supplements in individuals with already adequate vitamin D status.
Keywords: Vitamin D; Serum 25-hydroxyvitamin D; Cognition; Ionised calcium; Parathyroid hormone; Verbal episodic memory

Relationship of three different types of low-carbohydrate diet to cardiometabolic risk factors in a Japanese population: the INTERMAP/INTERLIPID Study by Yasuyuki Nakamura; Hirotsugu Ueshima; Nagako Okuda; Katsuyuki Miura; Yoshikuni Kita; Naoko Miyagawa; Katsushi Yoshita; Hideaki Nakagawa; Kiyomi Sakata; Shigeyuki Saitoh; Tomonori Okamura; Akira Okayama; Sohel R. Choudhry; Beatriz Rodriguez; Kamal H. Masaki; Queenie Chan; Paul Elliott; Jeremiah Stamler (1515-1524).
Low-carbohydrate diets (LCD) are a popular dietary strategy for weight reduction. The effects of LCD on long-term outcome vary depending on type of LCD, possibly due to the fact that effects on cardiometabolic risk factors may vary with different types of LCD. Accordingly, we studied these relations.We assessed serum concentrations of high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), high-sensitivity C-reactive protein (CRP), total cholesterol, glycated hemoglobin, and uric acid, and nutrient intakes by standardized methods in men and women ages 40–59 years from four population samples of Japanese in Japan (553 men and 544 women, combined). For people consuming usual, animal-based, and plant-based LCDs, we calculated LCD scores, based on relative level of fat, protein, and carbohydrate, by modifying the methods of Halton et al. Instead of calculating scores based on animal or vegetable fat, we used saturated fatty acids (SFA) or monounsaturated fatty acids (MUFA) + polyunsaturated fatty acids (PUFA).In multivariate regression analyses with adjustment for site, age, sex, BMI, smoking, alcohol intake, physical activity, and years of education, all three LCD scores were significantly positively related to HDLc (all P < 0.001), but not to LDLc. The plant-based LCD score was significantly inversely related to log CRP (coefficient = −0.010, P = 0.018).All three LCD scores were significantly positively related to HDLc. The plant-based LCD score was significantly inversely related to CRP. Carbohydrate intake below 50 % of total energy with higher intakes of vegetable protein and MUFA + PUFA, and lower intakes of SFA may be favorable for reducing cardiometabolic risk factors.
Keywords: Low-carbohydrate diet; C-reactive protein; Cardiometabolic risk factors; High-density lipoprotein cholesterol

Low vitamin D status is associated with more depressive symptoms in Dutch older adults by E. M. Brouwer-Brolsma; R. A. M. Dhonukshe-Rutten; J. P. van Wijngaarden; N. L. van der Zwaluw; E. Sohl; P. H. In’t Veld; S. C. van Dijk; K. M. A. Swart; A. W. Enneman; A. C. Ham; N. M. van Schoor; N. van der Velde; A. G. Uitterlinden; P. Lips; E. J. M. Feskens; L. C. P. G. M. de Groot (1525-1534).
The existence of vitamin D receptors in the brain points to a possible role of vitamin D in brain function. We examined the association of vitamin D status and vitamin D-related genetic make-up with depressive symptoms amongst 2839 Dutch older adults aged ≥65 years.25-Hydroxyvitamin D (25(OH)D) was measured, and five ‘vitamin D-related genes’ were selected. Depressive symptoms were measured with the 15-point Geriatric Depression Scale. Results were expressed as the relative risk of the score of depressive symptoms by quartiles of 25(OH)D concentration or number of affected alleles, using the lowest quartile or minor allele group as reference.A clear cross-sectional and prospective association between serum 25(OH)D and depressive symptom score was observed. Fully adjusted models indicated a 22 % (RR 0.78, 95 % CI 0.68–0.89), 21 % (RR 0.79, 95 % CI 0.68–0.90), and 18 % (RR 0.82, 95 % CI 0.71–0.95) lower score of depressive symptoms in people in the second, third, and fourth 25(OH)D quartiles, when compared to people in the first quartile (P for trend <0.0001). After 2 years of daily 15 µg vitamin D supplementation, similar associations were observed. 25(OH)D concentrations did not significantly interact with the selected genes.Low serum 25(OH)D was associated with higher depressive symptom scores. No interactions between 25(OH)D concentrations and vitamin D genetic make-up were observed. In view of the probability of reverse causation, we propose that the association should be further examined in prospective studies as well as in randomized controlled trials.
Keywords: Vitamin D; Vitamin D receptor polymorphisms; Depression; Elderly; Diabetes

MnSOD and CAT polymorphisms modulate the effect of the Mediterranean diet on breast cancer risk among Greek-Cypriot women by Maria G. Kakkoura; Christiana A. Demetriou; Maria A. Loizidou; Giorgos Loucaides; Ioanna Neophytou; Simon Malas; Kyriacos Kyriacou; Andreas Hadjisavvas (1535-1544).
Oxidative stress arises due to a cellular imbalance in oxidants and antioxidants and/or due to an altered activity of antioxidant enzymes, caused by SNPs. Oxidative stress increases susceptibility to breast cancer (BC) risk, and we previously showed that the Mediterranean diet (MD), which is rich in antioxidants, reduces BC risk in Greek-Cypriot women. Here, we investigated the effect of MnSOD (p.Val16Ala, rs4880) and CAT (-262C>T, rs1001179) SNPs on the association between the MD and BC risk in the case–control study of BC MASTOS in Cyprus.Dietary intake data were obtained using a 32-item food frequency questionnaire, from which a dietary pattern was previously derived, using principal component analysis. This pattern included high loadings of vegetables, fruit, legumes and fish, a combination that closely resembles the MD and was used as our dietary variable.High vegetable intake lowered BC risk in women with at least one MnSOD Val allele (ORHigh vs. Low for Val/Val = 0.56, 95 % CI 0.35–0.88, for Val/Ala = 0.57, 95 % CI 0.39–0.82), or one CAT -262C allele (ORHigh vs. Low for -262CC = 0.66, 95 % CI 0.47–0.92, for -262CT = 0.53, 95 % CI 0.35–0.81). High fish intake conferred a decreased BC risk of CAT -262CC women (ORQ4 vs. Q1 0.66, 95 % CI 0.47–0.92) compared with the CAT -262TT women and low fish intake (ORQ2 vs. Q1 2.79, 95 % CI 1.08–7.17). Additionally, high fish intake reduced BC risk in MnSOD Val/Val women (ORQ4 vs. Q1 0.63, 95 % CI 0.40–0.98). p interaction values were, however, not statistically significant.Our results demonstrate that the antioxidative effects of the MD against BC risk may be enhanced by the wild-type alleles of the MnSOD or CAT SNPs among Greek-Cypriot women.
Keywords: Mediterranean diet; CAT; MnSOD; Oxidative stress; Breast cancer

Effects of triacylglycerol structure and solid fat content on fasting responses of mice by Xiaosan Wang; Tong Wang; Michael E. Spurlock; Xingguo Wang (1545-1553).
Fat randomization and interesterification change triacylglycerol (TAG) structure and its solid fat content profile. It has not been thoroughly investigated whether these changes affect lipid metabolism.Two experiments were conducted to investigate the effects of TAG structure and solid fat content on feed intake, body weight change, and serum metabolite concentrations in mice. An experiment used two fats rich in 1,2-dipalmitoyl-3-oleoylglycerol (PPO) and 1,3-dipalmitoyl-2-oleoylglycerol (POP) as comparative pair of fats to assess the effect of TAG structure since PPO and POP have the same fatty acid composition and solid fat content at 37 °C. Another experiment used a fat rich in 1-palmitoyl-2,3-dioleoylglycerol (POO) with solid fat content of zero at 37 °C and a mixture of fats that had the same general fatty acid composition and palmitic acid positional distribution, but with solid fat content of 22 % at 37 °C. This pair of fats was used to examine the effect of solid fat content on blood lipid profile.After 6-week feeding, the pair of fats with different solid fat contents did not significantly affect the concentrations of total serum cholesterol, HDL cholesterol, TAG, non-esterified fatty acid (NEFA), or blood glucose. However, the PPO fat significantly reduced feed intake, body weight, and serum glucose concentration as compared to POP.These results suggest that the presence of solid fat at the level examined does not affect lipid metabolism and lipemia, but PPO diet significantly affects NEFA and glucose concentrations. Palmitic acid at the sn-2 position of the TAG may have significant effect on appetite, which may be mediated via the gut receptors.
Keywords: Fatty acid positional distribution; Lipid metabolism; Triacylglycerol structure; Randomization; Solid fat content

Relationship between fruit and vegetable intake and interference control in breast cancer survivors by Krystle E. Zuniga; Michael J. Mackenzie; Sarah A. Roberts; Lauren B. Raine; Charles H. Hillman; Arthur F. Kramer; Edward McAuley (1555-1562).
Nutrition plays an important role in brain structure and function, and the effects of diet may even be greater in those at greater risk of cognitive decline, such as individuals with cancer-related cognitive impairment. However, the relation of dietary components to cognitive function in cancer survivors is unknown. The objective of this study was to determine whether breast cancer survivors (BCS) evidenced impairments in interference control, a component of cognitive control, compared to age-matched women with no prior history of cancer, and to examine the moderating role of diet on cognitive function.In this cross-sectional study, a modified flanker task was used to assess interference control in BCS (n = 31) and age-matched women with no prior history of cancer (n = 30). Diet was assessed with 3-day food records. Differences between BCS and age-matched controls were assessed using linear mixed models, and multilevel regression analyses were conducted to assess the moderating role of diet on cognitive performance.Cognitive performance was not different between groups. Fruit intake and vegetable intake were significantly associated with better performance on the incompatible condition of the flanker task (i.e., shorter reaction time and increased accuracy), independent of disease status. The association between dietary components and cognition was stronger for the incompatible incongruent condition, suggesting that fruit and vegetables may be important for the up-regulation of cognitive control when faced with higher cognitive demands.There was no difference in performance on an interference control task between BCS and age-matched controls. The data suggest that greater fruit intake and vegetable intake were positively associated with interference control in both BCS and age-matched controls.
Keywords: Cognition; Fruit; Vegetable; Cancer survivors

Adherence to WCRF/AICR lifestyle recommendations for cancer prevention and the risk of Barrett’s esophagus onset and evolution to esophageal adenocarcinoma: results from a pilot study in a high-risk population by Stefano Realdon; Alessandro Antonello; Diletta Arcidiacono; Elisa Dassie; Francesco Cavallin; Matteo Fassan; Maria Teresa Nardi; Alfredo Alberti; Massimo Rugge; Giorgio Battaglia (1563-1571).
While adherence to the World Cancer Research Fund (WCRF) guidelines on lifestyle and cancer was recently proven to be associated with an increased risk of esophageal cancer, no investigation has yet been carried out on its role on Barrett’s esophagus (BE) development and its progression to esophageal adenocarcinoma (EAC). The primary aim of this study was to evaluate the role of adherence to WCRF lifestyle recommendations in BE onset and progression. The secondary aim was to investigate the association between disease progression and specific aspects of diet and lifestyle.Established risk factors for BE and EAC development and adherence to WCRF guidelines were assessed in 107 consecutive patients undergoing an upper gastrointestinal endoscopy for symptoms suggesting gastroesophageal reflux (GERD) and a suspected diagnosis of BE/dysplasia on BE. Patients were divided according to histology: those with GERD without metaplasia, with non-dysplastic BE, with low-grade dysplasia, with high-grade dysplasia or with early EAC. The four groups were expressed as an ordered categorical variable of disease progression. An ordered logit model was estimated to identify the independent predictors of disease progression.Adherence to WCRF guidelines was identified as independent protective factor (OR 0.51, 95 % CI 0.37–0.67) of disease progression. Disease progression was associated with reduced adherence to guidelines on physical activity (from 48.2 to 5.3 %, p = 0.001), sedentary habits (from 33.3 to 0 %, p = 0.03), fruit consumption (from 37.0 to 5.6 %, p = 0.02) and processed meat consumption (from 51.9 to 10.5 %, p = 0.002).Adherence to WCRF guidelines has a protective factor in BE onset and its evolution to EAC.
Keywords: Barrett’s esophagus; Esophageal adenocarcinoma; Lifestyle; Diet

The role of digestive factors in determining glycemic response in a multiethnic Asian population by Verena Ming Hui Tan; Delicia Shu Qin Ooi; Jeevesh Kapur; Ting Wu; Yiong Huak Chan; Christiani Jeyakumar Henry; Yung Seng Lee (1573-1581).
There are wide inter-individual differences in glycemic response (GR). We aimed to examine key digestive parameters that influence inter-individual and ethnic differences in GR in healthy Asian individuals.Seventy-five healthy male subjects (25 Chinese, 25 Malays, and 25 Asian-Indians) were served equivalent available carbohydrate amounts (50 g) of jasmine rice (JR) and basmati rice (BR) on separate occasions. Postprandial blood glucose concentrations were measured at fasting (−5 and 0 min) and at 15- to 30-min interval over 180 min. Mastication parameters (number of chews per mouth and chewing time per mouthful), saliva α-amylase activity, AMY1 gene copy numbers and gastric emptying rate were measured to investigate their relationships with GR.The GR for jasmine rice was significantly higher than for basmati rice (P < 0.001). The median number of AMY1 gene copies was 6, with a range of 2–15. There was a significant positive relationship between AMY1 copy number and α-amylase activity (P = 0.002). There were no significant ethnic differences in GR. For both rice varieties, the number of chews per mouthful was positively associated with the GR (JR, P = 0.011; BR, P = 0.005), while chewing time per mouthful showed a negative association (JR, P = 0.039; BR, P = 0.016). Ethnicity, salivary α-amylase activity, particle size distribution, gastric emptying rate and AMY1 gene copy numbers were not significant contributors to GR (P > 0.05).Mastication parameters contribute significantly to GR. Eating slowly and having larger food boluses before swallowing (less chewing), both potentially modifiable, may be beneficial in glycemic control.
Keywords: Glycemic response; Mastication; Salivary amylase; AMY1 ; Gastric emptying

Carbohydrate supplementation does not blunt the prolonged exercise-induced reduction of in vivo immunity by Glen Davison; Corinna Kehaya; Bethany C. Diment; Neil P. Walsh (1583-1593).
Carbohydrate (CHO) supplementation during prolonged exercise is widely acknowledged to blunt in vitro immunoendocrine responses, but no study has investigated in vivo immunity.To determine the effect of CHO supplementation during prolonged exercise on in vivo immune induction using experimental contact hypersensitivity with the novel antigen diphenylcyclopropenone (DPCP).In a double-blind design, 32 subjects were randomly assigned to 120 min of treadmill exercise at 60 % $$dot{V}{ ext{O}}_{2} { hbox{max} }$$ V ˙ O 2 max with CHO (Ex-CHO) or placebo (Ex-PLA) supplementation. Responses were also compared to 16 resting control (CON) subjects from a previous study (for additional comparison with a resting non-exercise condition). Standardised diets (24 h pre-trial) and breakfasts (3.5 h pre-trial) were provided. Subjects received a primary DPCP exposure (sensitisation) 20 min after trial completion, and exactly 28 days later the strength of immune reactivity was quantified by magnitude of the cutaneous response (skin-fold thickness and erythema) to a low dose-series DPCP challenge. Stress hormones and leucocyte trafficking were also monitored.CHO supplementation blunted the cortisol and leucocyte trafficking responses, but there was no difference (P > 0.05) between Ex-CHO and Ex-PLA in the in vivo immune responses (e.g. both ~46 % lower than CON for skin-fold response).CHO supplementation does not influence the decrease in in vivo immunity seen after prolonged exercise. The effects with more stressful (or fasted) exercise remain to be determined. However, there appears to be no benefit under the conditions of the present study, which have practical relevance to what many athletes do in training or competition.
Keywords: Running; Immune; Contact hypersensitivity; Diphenylcyclopropenone; Glucose; Whole integrated immune response

Energy and macronutrient intakes and adherence to dietary guidelines of infants and toddlers in Belgium by Koen Huysentruyt; Dorothée Laire; Tom Van Avondt; Jean De Schepper; Yvan Vandenplas (1595-1604).
Early feeding habits may have a significant impact on later body composition and health. The knowledge on dietary habits is, however, still limited for older infants and toddlers. Therefore, we aimed to: (1) assess the average daily energy and macronutrient intakes and to identify their major foods sources; (2) compare it to the nationally and internationally recommended dietary intake (RDI). A food survey (January–February 2012) was conducted in a cohort of healthy infants and toddlers, stratified for age, gender, region, occupation and socio-economic status of the mother and week and weekend days. The national dietary software programme Nubel® was used to analyse nutritional values.We included 92 (19.8 %) 6-to 12-month-olds, 200 (43.0 %) 13- to 24-month-olds and 173 (37.2 %) 25- to 36-month-olds in the analysis. Median energy intake was 15–20 % above the RDI of 79–82 kcal/kg/day. Nearly, all children had a protein intake above the RDI, and for 156 (33.5 %), this was above the upper tolerable limit of 15 % of total energy intake. The median fat intake increased with increasing age and was slightly below the RDI. Mean water and carbohydrate intake were in accordance with the RDI. Fibre intake was below the RDI of 15 g/d for 93.1 % of the oldest and 83.5 % of the middle age group (p < 0.01). Milk is the most important source for energy en macronutrients until the age of 2 years.Energy and especially protein intakes are too high, while fat and fibre intakes are too low in Belgian infants and toddlers.
Keywords: Child; Energy intake; Food survey; Macronutrient intake; Protein intake; Recommended dietary intake

Polyunsaturated fatty acid intake and risk of cardiovascular mortality in a low fish-consuming population: a prospective cohort analysis by Alice J. Owen; Dianna J. Magliano; Kerin O’Dea; Elizabeth L. M. Barr; Jonathan E. Shaw (1605-1613).
The aim of this study was to examine the relationship between polyunsaturated fatty acids (PUFA) intake (n-6 and n-3) and mortality in a population-based sample with a low fish intake.Cox regression was used to examine the relationships between dietary PUFA intake and all-cause or CVD mortality in the Australian Diabetes, Obesity and Lifestyle Study (AusDiab) cohort, a population of 11,247 Australians aged ≥25 years recruited in 1999/2000 and followed until 2012. Demographic, lifestyle and behavioural information were collected by questionnaire and fasting blood tests undertaken. Dietary intake was collected by a 121-item food frequency questionnaire. Vital status and causes of death were collected by death registry linkage.Those in the highest quintile of n-6 PUFA intake had lower risk of CVD mortality (HR 0.57, 95 % CI 0.38–0.86) after age and sex adjustment, but this failed to retain significance after further risk factor adjustment. Consumption of ≥1 serves/week of non-fried fish was associated with reduced risk of CVD mortality (HR 0.64, 95 % CI 0.45–0.91, p = 0.013) compared to those eating less than 1 serve/month, after sex and age adjustment, but did not retain significance after further adjustment. However, long-chain n-3 intake was not associated with CVD mortality, and those in the highest quintile of n-3 intake had a higher risk of all-cause mortality.These findings do not support previous suggestions that n-6 PUFA have adverse effects on CVD risk. Greater intake of non-fried fish was associated with lower risk of CVD mortality, but those with the highest total n-3 intake were at slightly increased risk of all-cause mortality.
Keywords: Diet; Fatty acids; Mortality; Cardiovascular disease

Decreased rates of operant food self-administration are associated with reward deficits in high-fat feeding mice by Javier Íbias; Miguel Miguéns; Danila del Rio; Ismael Valladolid-Acebes; Paula Stucchi; Emilio Ambrosio; Miriam Martín; Lidia Morales; Mariano Ruiz-Gayo; Nuria Del Olmo (1615-1622).
Highly palatable foods behave as appetitive reinforcers and tend to be consumed compulsively. Nevertheless, the motivation for this kind of diets in experimental diet-induced obesity models has not been well established. Our hypothesis is that obesity caused by a regular consumption of high-fat diet (HFD) occurs concomitantly with the inhibition of food reward. The ultimate goal of our study was to further analyze the extent to which the perception of food as an appetitive reinforcer is a necessary condition for obesity.We have evaluated the influence of HFD on operant food self-administration (FSA) during a whole light–dark (12–12-h) cycle in mice that consumed HFD either during 1, 4 or 8 weeks. The study has been complemented by a two-bottle free-choice assay between tap water and sweetened drinks.These data show that both 4- and 8-week HFD treatments induced a significant decrease in operant FSA rate. Moreover, HFD impaired the sweetened-conditioned flavor preference in the two-bottle choice assay.Our results, showing a reduction in how hard an animal is willing to work for food reinforcers, provide evidence that chronic consumption of HFD negatively contributes to the incentive motivation to acquire food/drink reinforcers. We demonstrate that energy homeostasis imbalance triggered by HFD is associated with the inhibition of hedonic feeding.
Keywords: Food self-administration; High-fat diets; Reward; Two-bottle choice; Motivation; Obesity

Sensitivity to reward is associated with snack and sugar-sweetened beverage consumption in adolescents by Nathalie De Cock; Wendy Van Lippevelde; Leentje Vervoort; Jolien Vangeel; Lea Maes; Steven Eggermont; Caroline Braet; Carl Lachat; Lieven Huybregts; Lien Goossens; Kathleen Beullens; Patrick Kolsteren; John Van Camp (1623-1632).
High intake of palatable foods, such as energy-dense snacks and sugar-sweetened beverages (SSBs), is common among adolescents. An individual’s sensitivity to reward (SR) may influence these intakes. The main objective of this study was to investigate the association between SR and both snack and SSB intake among adolescents.A representative cross-sectional survey was conducted among 1104 14- to 16-year-olds (mean age = 14.7 ± 0.8 years; 50.9 % boys; 18.0 % overweight) in Flanders. Daily intakes were measured by a food frequency questionnaire. SR was assessed using the behavioral activation system (BAS) scales. Multilevel regression analyses (two level: adolescent school) were conducted using STATA version 13.BAS drive was positively associated with daily intakes of SSBs (13.79 %, p < 0.01), unhealthy snacks (5.42 %, p < 0.001), and energy and nutrients derived from SSBs (p < 0.001) and snacks (p < 0.01). BAS reward responsiveness (RR) was only positively associated with intake of unhealthy snacks (3.85 %, p < 0.05), healthy snacks (6.41 %, p < 0.05), and fat (4.05 %, p < 0.01) and Na (3.89 %, p < 0.05) from snacks. Interaction effects of gender and BAS RR (p < 0.05) were found. Significant positive associations between BAS RR and daily intakes of energy from snacks (6.48 %, p < 0.01) and fat from snacks (7.22 %, p < 0.001) were found only for girls.SR was associated with snack and SSB consumption in adolescents, especially in girls. These findings suggest that SR should be taken into account when designing interventions to improve the snack and SSB intake of adolescents.
Keywords: Sensitivity to reward; Adolescents; Snacking; sugar-sweetened beverages

Fatty acid supply with complementary foods and LC-PUFA status in healthy infants: results of a randomised controlled trial by Lars Libuda; Christina M. Mesch; Madlen Stimming; Hans Demmelmair; Berthold Koletzko; Petra Warschburger; Katharina Blanke; Eva Reischl; Hermann Kalhoff; Mathilde Kersting (1633-1644).
Introduction of complementary food usually leads to decreasing intakes of long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFA), compared to full breastfeeding. In the randomised controlled PINGU intervention trial, we tested the effects of complementary foods with different contents of alpha-linolenic acid (ALA) and docosahexaenoic acid (DHA) on term infant LC-PUFA status. Healthy infants born at term were randomised to receive from the introduction of complementary feeding at the age of 4 to 6 months until age of 10 months ready-made complementary meals either with ALA-rich rapeseed oil (intervention group (IG)-R), with salmon twice weekly to provide preformed DHA (IG-F), or with linoleic acid-rich corn oil (control group, CG). Fatty acid composition was assessed in erythrocyte (RBC) and plasma glycerophospholipids.Complete data of fatty acids in RBC (plasma) were available from 158 (155) infants. After intervention, infants assigned to IG-F showed higher RBC and plasma percentages of eicosapentaenoic acid (EPA), DHA, and total n-3 LC-PUFA than CG (each p < 0.001). In IG-R, levels of ALA and the ratio of ALA to LA in plasma and RBC (all p < 0.0001) as well as RBC–EPA (p < 0.0001) were higher than in CG, while DHA levels did not differ between IG-R and CG.Regular fish consumption during complementary feeding enhances infant EPA and DHA status. The usage of rapeseed oil in small amounts concordant with EU-law for commercial meals enhances endogenic EPA-synthesis, but does not affect DHA status. Provision of oily fish with complementary feeds is advisable to prevent a decline of DHA status. www.clinicaltrials.gov , identifier: NCT01487889, title: Polyunsaturated fatty acids in child nutrition—a German multimodal optimisation study (PINGU).
Keywords: DHA; Fish; Rapeseed oil; Complementary food; Complementary feeding; Alpha-linolenic acid; DHA status

Influence of dietary fat and carbohydrates proportions on plasma lipids, glucose control and low-grade inflammation in patients with type 2 diabetes—The TOSCA.IT Study by M. Vitale; M. Masulli; A. A. Rivellese; A. C. Babini; M. Boemi; E. Bonora; R. Buzzetti; O. Ciano; M. Cignarelli; M. Cigolini; G. Clemente; G. Citro; L. Corsi; E. Dall’Aglio; S. Del Prato; G. Di Cianni; M. A. Dolci; C. Giordano; R. Iannarelli; C. Iovine; A. Lapolla; D. Lauro; S. Leotta; C. Mazzucchelli; V. Montani; G. Perriello; G. Romano; F. Romeo; L. Santarelli; R. Schiano di Cola; S. Squatrito; L. Tonutti; R. Trevisan; A. A. Turco; C. Zamboni; G. Riccardi; O. Vaccaro (1645-1651).
The optimal macronutrient composition of the diet for the management of type 2 diabetes is debated, particularly with regard to the ideal proportion of fat and carbohydrates. The aim of the study was to explore the association of different proportions of fat and carbohydrates of the diet—within the ranges recommended by different guidelines—with metabolic risk factors. We studied 1785 people with type 2 diabetes, aged 50–75, enrolled in the TOSCA.IT Study. Dietary habits were assessed using a validated food-frequency questionnaire (EPIC). Anthropometry, fasting lipids, HbA1c and C-reactive protein (CRP) were measured.Increasing fat intake from <25 to ≥35 % is associated with a significant increase in LDL-cholesterol, triglycerides, HbA1c and CRP (p < 0.05). Increasing carbohydrates intake from <45 to ≥60 % is associated with significantly lower triglycerides, HbA1c and CRP (p < 0.05). A fiber intake ≥15 g/1000 kcal is associated with a better plasma lipids profile and lower HbA1c and CRP than lower fiber consumption. A consumption of added sugars of ≥10 % of the energy intake is associated with a more adverse plasma lipids profile and higher CRP than lower intake.In people with type 2 diabetes, variations in the proportion of fat and carbohydrates of the diet, within the relatively narrow ranges recommended by different nutritional guidelines, significantly impact on the metabolic profile and markers of low-grade inflammation. The data support the potential for reducing the intake of fat and added sugars, preferring complex, slowly absorbable, carbohydrates.
Keywords: Diet; Carbohydrates; Fat; Glucose control; HDL-cholesterol; Triglycerides; Type 2 diabetes; Nutritional guidelines

Pomegranate inhibits neuroinflammation and amyloidogenesis in IL-1β-stimulated SK-N-SH cells by Ravikanth Velagapudi; Gina Baco; Sunjeet Khela; Uchechukwu Okorji; Olumayokun Olajide (1653-1660).
Pomegranate fruit, Punica granatum L. (Punicaceae), and its constituents have been shown to inhibit inflammation. In this study, we aimed to assess the effects of freeze-dried pomegranate (PWE) on PGE2 production in IL-1β-stimulated SK-N-SH cells.An enzyme immunoassay (EIA) was used to measure prostaglandin E2 (PGE2) production from supernatants of IL-1β-stimulated SK-N-SH cells. Expression of COX-2, phospho-IκB, and phospho-IKK proteins was evaluated, while NF-κB reporter gene assay was carried out in TNFα-stimulated HEK293 cells to determine the effect of PWE on NF-κB transactivation. Levels of BACE-1 and Aβ in SK-N-SH cells stimulated with IL-1β were measured with an in cell ELISA.PWE (25–200 μg/ml) dose dependently reduced COX-2-dependent PGE2 production in SK-N-SH cells stimulated with IL-1β. Phosphorylation of IκB and IKK was significantly (p < 0.001) inhibited by PWE (50–200 μg/ml). Our studies also show that PWE (50–200 μg/ml) significantly (p < 0.01) inhibited NF-κB transactivation in TNFα-stimulated HEK293 cells. Furthermore, PWE inhibited BACE-1 and Aβ expression in SK-N-SH cells treated with IL-1β.Taken together, our study demonstrates that pomegranate inhibits inflammation, as well as amyloidogenesis in IL-1β-stimulated SK-N-SH cells. We propose that pomegranate is a potential nutritional strategy in slowing the progression of neurodegenerative disorders such as Alzheimer’s disease.
Keywords: Pomegranate; Neuroinflammation; Amyloidogenesis; Neurons; Interleukin-1β

Effects of wheat bran extract rich in arabinoxylan oligosaccharides and resistant starch on overnight glucose tolerance and markers of gut fermentation in healthy young adults by Elin V. Johansson Boll; Linda M. N. K. Ekström; Christophe M. Courtin; Jan A. Delcour; Anne C. Nilsson; Inger M. E. Björck; Elin M. Östman (1661-1670).
Specific combinations of dietary fiber (DF) have been observed to result in improved glucose tolerance at a subsequent standardized breakfast. Arabinoxylan oligosaccharides (AXOS) are considered as DF with prebiotic potential, but so far no studies have investigated their metabolic effects in humans. This randomized cross-over study evaluated the overnight impact of breads containing AXOS-rich wheat bran extract and resistant starch (RS, Hi-Maize), separately or combined, on glucose tolerance, related metabolic parameters and markers of gut fermentation in healthy subjects.Evening reference and test products were: (1) reference white wheat flour bread (WWB), WWB supplemented with (2) AXOS and RS (WWB + AXOS + RS), (3) an increased content of either AXOS (WWB + hiAXOS) or (4) RS (WWB + hiRS). At the subsequent standardized breakfast, blood was sampled for 3 h to monitor glucose, insulin, nonesterified fatty acids, glucagon-like peptide (GLP)-1 and GLP-2. Breath hydrogen (H2) and short chain fatty acids (SCFA) were measured as markers of gut fermentation, and subjective appetite was rated using visual analog scales.Dose-dependent decreases in glucose responses were observed with increased AXOS over the duration of 3 h. Insulin sensitivity index was improved in the morning after the WWB + hiAXOS evening meal. An increase in breath H2 concentration and circulating SCFA was observed in the morning after both evening meals containing AXOS.The present study indicates that AXOS have the potential of improving glucose tolerance in an overnight perspective and suggested mechanisms are improved insulin sensitivity and increased gut fermentation.
Keywords: Arabinoxylan oligosaccharides; Resistant starch; Glucose tolerance; Gut fermentation; Healthy subjects; Overnight

Individual and collective factors predicting change in diet quality over 3 years in a subset of older men and women from the NuAge cohort by Bryna Shatenstein; Lise Gauvin; Heather Keller; Lucie Richard; Pierrette Gaudreau; Francine Giroux; Mira Jabbour; José A. Morais; Hélène Payette (1671-1681).
This study examined individual and collective factors as predictors of change in global diet quality (DQ).Subjects were 373 older adults (57 % female) aged 68–82 years at recruitment (T1) into the NuAge Cohort Study, and followed for three years. Data were collected by questionnaires, physical performance tests and anthropometric measurements. Diet was assessed at T1 and T4 using three non-consecutive 24-h diet recalls (24HR) and DQ (Canadian Healthy Eating Index), and was computed on the means of the 24HR. DQ change over three years was determined as “DQT4-DQT1”. Baseline (T1) measures significantly correlated with DQ at T1 were entered into backward stepwise linear regression analyses along with selected theoretical constructs and controlled for baseline DQ to determine predictors of change in DQ over 3 years. Among men, education (p = .009) and sensations of hunger (p = .01) were positive predictors of DQ change over time, while DQ at T1 (p < .0001), cognition (p = .003) and social network (p = .019) were negative predictors (adjusted R 2 = 30.4 %). Finally, among women, diet knowledge (p = .044) was a positive predictor of DQ change, while DQ at T1 (p < .0001) and social network (p = .033) were negative predictors of DQ change over 3 years (adjusted R 2 = 24.1 %).These results can inform dietary intervention programmes targeting gender-specific determinants of diet quality in older adults.
Keywords: Diet quality; Older adults; Cohort; Determinants; Predictors; Gender differences

Diet-related inflammation and oesophageal cancer by histological type: a nationwide case–control study in Sweden by Yunxia Lu; Nitin Shivappa; Yulan Lin; Jesper Lagergren; James R. Hébert (1683-1694).
This project sought to test the role of diet-related inflammation in modulating the risk of oesophageal cancer.A nationwide population-based case–control study was conducted from 1 December 1994 through 31 December 1997 in Sweden. All newly diagnosed patients with adenocarcinoma of the oesophagus or gastroesophageal junction and a randomly selected half of patients with oesophageal squamous cell carcinoma were eligible as cases. Using the Swedish Registry of the Total Population, the control group was randomly selected from the entire Swedish population and frequency-matched on age (within 10 years) and sex. The literature-derived dietary inflammatory index (DII) was developed to describe the inflammatory potential of diet. DII scores were computed based on a food frequency questionnaire. Higher DII scores indicate more pro-inflammatory diets. Odds ratios and 95 % confidence intervals (CI) were computed to assess risk associated between DII scores and oesophageal cancer using logistic regression adjusted by potential confounders.In total, 189 oesophageal adenocarcinomas, 262 gastroesophageal junctional adenocarcinomas, 167 oesophageal squamous cell carcinomas, and 820 control subjects were recruited into the study. Significant associations with DII were observed for oesophageal squamous cell carcinoma (ORQuartile4vs1 4.35, 95 % CI 2.24, 8.43), oesophageal adenocarcinoma (ORQuartile4vs1 3.59, 95 % CI 1.87, 6.89), and gastroesophageal junctional adenocarcinoma (ORQuartile4vs1 2.04, 95 % CI 1.24, 3.36). Significant trends across quartiles of DII were observed for all subtypes of oesophageal cancer.Diet-related inflammation appears to be associated with an increased risk of oesophageal cancer, regardless of histological type.
Keywords: Diet; Inflammation; Neoplasm; Oesophagus

Phytochemical uptake following human consumption of Montmorency tart cherry (L. Prunus cerasus) and influence of phenolic acids on vascular smooth muscle cells in vitro by Karen M. Keane; Phillip G. Bell; John K. Lodge; Costas L. Constantinou; Sarah E. Jenkinson; Rosemary Bass; Glyn Howatson (1695-1705).
To investigate the phytochemical uptake following human consumption of Montmorency tart cherry (L. Prunus cerasus) and influence of selected phenolic acids on vascular smooth muscle cells in vitro.In a randomised, double-blinded, crossover design, 12 healthy males consumed either 30 or 60 mL of Montmorency tart cherry concentrate. Following analysis of the juice composition, venous blood samples were taken before and 1, 2, 3, 5 and 8 h post-consumption of the beverage. In addition to examining some aspects of the concentrate contents, plasma concentrations of protocatechuic acid (PCA), vanillic acid (VA) and chlorogenic (CHL) acid were analysed by reversed-phase high-performance liquid chromatography (HPLC) with diode array for quantitation and mass spectrometry detection (LCMS) for qualitative purposes. Vascular smooth muscle cell migration and proliferation were also assessed in vitro.Both the 30 and 60 mL doses of Montmorency cherry concentrate contained high amounts of total phenolics (71.37 ± 0.11; 142.73 ± 0.22 mg/L) and total anthocyanins (62.47 ± 0.31; 31.24 ± 0.16 mg/L), as well as large quantities of CHL (0.205 ± 0.24; 0.410 ± 0.48 mg/L) and VA (0.253 ± 0.84; 0.506 ± 1.68 mg/L). HPLC/LCMS identified two dihydroxybenzoic acids (PCA and VA) in plasma following MC concentrate consumption. Both compounds were most abundant 1–2 h post-initial ingestion with traces detectable at 8 h post-ingestion. Cell migration was significantly influenced by the combination of PCA and VA, but not in isolation. There was no effect of the compounds on cell proliferation.These data show new information that phenolic compounds thought to exert vasoactive properties are bioavailable in vivo following MC consumption and subsequently can influence cell behaviour. These data may be useful for the design and interpretation of intervention studies investigating the health effects of Montmorency cherries.
Keywords: Montmorency; Phenolic acids; Bioavailability; Cell behaviour; Recovery

Intake of fish and long-chain omega-3 polyunsaturated fatty acids and incidence of metabolic syndrome among American young adults: a 25-year follow-up study by Yong-Seok Kim; Pengcheng Xun; Carlos Iribarren; Linda Van Horn; Lyn Steffen; Martha L. Daviglus; David Siscovick; Kiang Liu; Ka He (1707-1716).
Studies suggest that long-chain ω-3 polyunsaturated fatty acid (LCω3PUFA) intake and its primary food source—fish—may have beneficial effects on the individual components of metabolic syndrome (MetS). We examined the longitudinal association between fish or LCω3PUFA intake and MetS incidence.We prospectively followed 4356 American young adults, free from MetS and diabetes at baseline, for incident MetS and its components in relation to fish and LCω3PUFA intake. MetS was defined by the National Cholesterol Education Program/Adult Treatment Panel III criteria. Cox proportional hazards model was used for analyses, controlling for socio-demographic, behavioral, and dietary factors.During the 25-year follow-up, a total of 1069 incident cases of MetS were identified. LCω3PUFA intake was inversely associated with the incidence of MetS in a dose–response manner. The multivariable adjusted hazards ratio (HR) [95 % confidence interval (CI)] of incident MetS was 0.54 (95 % CI 0.44, 0.67; P for linear trend < 0.01) as compared the highest to the lowest quintile of LCω3PUFA intake. A threshold inverse association was found between non-fried fish consumption and the incidence of MetS. The multivariable adjusted HRs (95 % CIs) from the lowest to the highest quintile were 1.00, 0.70 (0.51, 0.95), 0.68 (0.52, 0.91), 0.67 (0.53, 0.86), and 0.71 (0.56, 0.89) (P for linear trend = 0.49). The observed inverse associations were independent of the status of baseline individual components of MetS.Our findings suggest that intakes of LCω3PUFAs and non-fried fish in young adulthood are inversely associated with the incidence of MetS later in life.
Keywords: Longitudinal studies; Omega-3 fatty acids; Fish consumption; Metabolic syndrome

Methylating micronutrient supplementation during pregnancy influences foetal hepatic gene expression and IGF signalling and increases foetal weight by M. Oster; W. Nuchchanart; N. Trakooljul; E. Muráni; A. Zeyner; E. Wirthgen; A. Hoeflich; S. Ponsuksili; K. Wimmers (1717-1727).
Maternal diet during pregnancy impacts foetal growth and development. In particular, dietary levels of methylating micronutrients (methionine, folate, choline, vitamins B6, and B12) interfere with the availability and allocation of methyl groups for methylation reactions, thereby influencing normal transcription. However, the currently recommended methylating micronutrient supplementation regimen is haphazard and arbitrary at best.To investigate the effects of a methylating micronutrient-rich maternal diet, pregnant Pietrain sows were fed either a standard diet (CON) or a diet supplemented with methionine, folate, choline, B6, B12, and zinc (MET). Foetal liver and muscle (M. longissimus dorsi) tissues were collected at 35, 63, and 91 days post-conception. Transcriptional responses to diet were assessed in foetal liver. Altered insulin-like growth factor (IGF) signalling in transcriptome analyses prompted investigation of IGF-2 and insulin-like growth factor binding proteins (IGFBPs) levels in muscle and liver.Maternal diet enriched with methylating micronutrients was associated with increased foetal weight in late gestation. Hepatic transcriptional patterns also revealed differences in vitamin B6 and folate metabolism between the two diets, suggesting that supplementation was effective. Additionally, shifts in growth-supporting metabolic routes of the lipid and energy metabolism, including IGF signalling, and of cell cycle-related pathways were found to occur in liver tissue in supplemented individuals. Weight differences and modulated IGF pathways were also reflected in the muscle content of IGF-2 (increased in MET) and IGFBP-2 (decreased in MET).Maternal dietary challenges provoke stage-dependent and tissue-specific transcriptomic modulations in the liver pointing to molecular routes contributing to the organismal adaptation. Subtle effects on late foetal growth are associated with changes in the IGF signalling mainly in skeletal muscle tissue that is less resilient to dietary stimuli than liver.
Keywords: Foetal programming; IGF system; Maternal diet; Methyl donors; One-carbon cycle; Pigs

Energy and protein intakes and their association with a decline in functional capacity among diabetic older adults from the NuAge cohort by Berna Rahi; José A. Morais; Pierrette Gaudreau; Hélène Payette; Bryna Shatenstein (1729-1739).
Diabetic older adults (OA) are at greater risk of muscle strength (MS) loss and functional capacity (FC) decline than non-diabetics. Protein and energy intakes are important determinants of muscle mass and MS maintenance and indirectly affect FC. The study sought to determine whether low protein and energy intakes were associated with FC decline and whether this association was mediated by MS in diabetic OA over a 3-year follow-up, in secondary analyses of the Quebec Longitudinal Study on Nutrition and Successful Aging.In 172 diabetic OA (62 % men, mean age = 75 years), FC decline was defined as the change between SMAF (Système de Mesure de l’Autonomie Fonctionnelle) scores at baseline (T1) and 3 years later (T4). Baseline adequate protein and energy intakes were set at ≥1 g/kg BW and ≥30 kcal/kg BW, respectively. Sex-stratified linear regressions were controlled for confounding variables.Mean body weight (BW) was 85.42 ± 13.8 in men and 79.7 ± 11.5 in women (p ≤ .001). Adequate protein intake in women was associated with lesser FC decline (mean ± SE) (2.11 ± 0.81 vs. 4.91 ± 0.72; p = .029), while adequate energy intake was not associated with FC decline either in men or in women. In women, 1 g protein/kg BW helped maintain MS, hence minimizing FC decline.These results demonstrate that protein intake is important in maintaining FC in diabetic OA, albeit with sex differences. This study provides further evidence that protein requirements may be greater than the 0.8 g/kg BW currently recommended for OA. Future research in larger samples over longer follow-up is needed to confirm these results.
Keywords: Diabetic older adults; Protein intake; Energy intake; Functional capacity

Influence of cafeteria diet and fish oil in pregnancy and lactation on pups’ body weight and fatty acid profiles in rats by Clara Sánchez-Blanco; Encarnación Amusquivar; Kenia Bispo; Emilio Herrera (1741-1753).
The aim was to determine the effects of cafeteria diet (CD) and fish oil supplements given to pregnant and lactating rats on the birth weight and fatty acid profiles of their offspring.Female rats were given standard diet (STD) or CD for 22 days before pregnancy. After mating, some animals remained on STD or CD; for some CD rats, the diet was supplemented with 8.78 % fish oil (CD-FO). After 12 days, half the CD-FO group returned to CD (CD-FO12) and the others remained on CD-FO.At birth, body weights of pups of the three CD groups were lower than STD, maintained until 21 days in the CD-FO group only. At the end of lactation, dams of the CD groups had increased plasma triacylglycerols (TAG), non-esterified fatty acids, and glycerol concentrations, whereas most n-6 long-chain polyunsaturated fatty acids (LCPUFA) were decreased, the effect being greatest in the CD-FO group, where most n-3 LCPUFA were increased and indices of Δ5 and Δ6 desaturase activities decreased. The 21-day-old pups of the CD group had increased plasma TAG, not present in the CD-FO group, which had increased 3-hydroxybutyrate concentrations. In both 2- and 21-day-old CD pups, plasma concentrations of ARA were lower than STD, and even lower in the two CD-FO groups.The effect of CD and CD-FO decreasing pups body weight could be related to decreased concentrations of ARA, caused by the inhibition of the Δ5 and Δ6 desaturases in the pathway of n-6 LCPUFA biosynthesis.
Keywords: Cafeteria diet; Dietary fish oil supplement; Postnatal development; High-fat diet; Index of desaturases; Arachidonic acid

Age-related changes in basal substrate oxidation and visceral adiposity and their association with metabolic syndrome by Mario Siervo; Jose Lara; Carlos Celis-Morales; Michele Vacca; Clio Oggioni; Alberto Battezzati; Alessandro Leone; Anna Tagliabue; Angela Spadafranca; Simona Bertoli (1755-1767).
Ageing is directly associated with visceral fat (VAT) deposition and decline of metabolically active cellular mass, which may determine age-related shifts in substrate oxidation and increased cardiometabolic risk. We tested whether VAT and fasting respiratory quotient (RQ, an index of macronutrient oxidation) changed with age and if they were associated with increased risk of metabolic syndrome (MetSyn). A total of 2819 adult participants (age range: 18–81 years; men/women: 894/1925) were included; we collected history, anthropometric measures, biochemistry, smoking habits, and physical activity. The body mass index range was 18.5–60.2 kg/m2. Gas exchanges (VO2 and VCO2) were measured by indirect calorimetry in fasting conditions, and RQ was calculated. Body composition was measured by bioelectrical impedance. Abdominal subcutaneous fat and VAT were measured by ultrasonography. MetSyn was diagnosed using harmonised international criteria. Multivariate linear and logistic regression models were utilised.VAT increased with age in both men (r = 0.31, p < 0.001) and women (r = 0.37, p < 0.001). Basal RQ was not significantly associated with age (p = 0.49) and VAT (p = 0.20); in addition, basal RQ was not a significant predictor of MetSyn (OR 3.31, 0.57–19.08, p = 0.27). VAT was the primary predictor of MetSyn risk in a fully adjusted logistic model (OR 4.25, 3.01–5.99, p < 0.001).Visceral adiposity remains one of the most important risk factors for cardiometabolic risk and is a significant predictor of MetSyn. Post-absorptive substrate oxidation does not appear to play a significant role in age-related changes in body composition and cardiometabolic risk, except for a correlation with triglyceride concentration.
Keywords: Indirect calorimetry; Substrate oxidation; Ageing; Body composition; Metabolic risk

Inflammatory bowel diseases (IBD) are characterized by severe inflammation within the gastrointestinal (GI) tract. This inflammation is known to drive the catabolism of protein in the affected tissue and modulate systemic protein metabolism. Yet despite the established increase in oxidative stress and changes in protein catabolism, little is known as to the effects of IBD on metabolism of glutathione (GSH) and related metabolites. The aim of this study was to conduct a comprehensive analysis of the response of GSH and related sulfhydryl metabolites to malnutrition and GI inflammation. We hypothesized that the inflammatory stress of colitis would decrease the concentration and the synthesis of GSH in various tissues of well-nourished piglets. Additionally, the superimposition of malnutrition on colitis would further decrease glutathione status.Healthy, well-nourished piglets were compared to those receiving dextran sulphate sodium-induced, a macronutrient-restricted diet or both. The synthesis of GSH was determined by primed constant infusion of [15N,13C2]glycine and tandem mass spectrometry analysis. Additionally, the concentrations of GSH and related sulfhydryl metabolites were also determined by UHPLC–tandem mass spectrometry—a novel analytic technique.In healthy piglets, GSH synthesis was highest in the liver, along with the concentrations of both cysteine and γ-glutamylcysteine. Piglets with colitis had decreased synthesis of GSH and decreased concentrations of GSH, cysteine and γ-glutamylcysteine in the distal colon compared to healthy controls. Additionally, there was no change with superimposition of malnutrition on colitis in the distal colon.Synthesis and metabolism of GSH are uniquely regulated in each tissue. Colitis, independent of nutrition, compromises GSH status and the concentration of cysteine in the distal colon of piglets with GI inflammation. The techniques developed in this study have translational applications and can be scaled for use in clinical investigation of GI inflammation.
Keywords: Glutathione; Piglet; Malnutrition; Colitis; Stable isotopes; Paediatric

Moderately increased maternal dietary energy intake delays foetal skeletal muscle differentiation and maturity in pigs by Tiande Zou; Dongting He; Bing Yu; Jie Yu; Xiangbing Mao; Ping Zheng; Jun He; Zhiqing Huang; Yan Shu; Yue Liu; Daiwen Chen (1777-1787).
This study aimed to evaluate the effects of moderately increased maternal dietary energy intake during gestation on foetal skeletal muscle development and metabolism with pig as a model.Twelve primiparous purebred Large White sows (initial body weight 135.5 ± 1.6 kg) were allocated to one of two energy intake treatments: normal-energy-intake group (Con, 30.96 MJ DE/day) as recommended by the National Research Council (NRC; 2012) and high-energy-intake group (HE, 34.15 MJ DE/day). The nutritional treatments were introduced from mating to day 90 of gestation. On day 90 of gestation, foetuses were examined by morphological, biochemical and molecular analysis of the longissimus muscle. Umbilical vein serum hormones were measured.Sow body weight was increased in HE group compared with Con group (P < 0.05), whereas foetal myofibre density was decreased (P < 0.05). Meanwhile, protein concentration, creatine kinase and lactate dehydrogenase activities and umbilical vein serum triiodothyronine (T3) concentration were decreased in HE foetuses (P < 0.05). Maternal HE diets decreased the mRNA abundance of muscle growth-related genes, myosin heavy-chain (MYH/MyHC) genes (MYH2 and MYH1) and insulin-like growth factor 1 and insulin growth factor-binding protein 5 (P < 0.05). Furthermore, the protein expressions of myogenic differentiation factor 1, myogenin and fast-MyHC isoforms were reduced in HE foetuses (P < 0.05).Our results suggest that moderately increased maternal dietary energy intake delays the differentiation and maturation in skeletal muscle of the foetus on day 90 of gestation.
Keywords: Energy intake; Gestation; Longissimus; Foetus; Myogenesis; Pig

The effect of snacking and eating frequency on dietary quality in British adolescents by E. Llauradó; S. A. Albar; M. Giralt; R. Solà; C. E. L. Evans (1789-1797).
To describe the effects of number of eating occasions and snacks on dietary quality (DQ), defined as adherence to dietary recommendations.A sample of 884 adolescents (11–18 years) in the UK National Diet and Nutrition Survey (NDNS) were included. The Diet Quality Index for Adolescents (DQI-A) was implemented. The total number of eating occasions and snacks was frequency of food or beverages consumed over 24 h and frequency of foods or beverages consumed outside of the three mealtimes, respectively. Results were generated with and without low-energy food under 210 kJ (50 kcal). Regression models were generated with DQ score as the outcome variable and number of eating occasions and snacks as predictors. The mean (95 % CI) DQ score was 31.1 % (30.2, 32.0). The mean number of eating occasions and snacks was 7.5 (7.3, 7.7) and 2.6 (2.6, 2.7) times/day, respectively. When low-energy events were excluded, the mean number of eating occasions and snacks reduced to 6.2 (6.1, 6.4) and 2.0 (2.0, 2.1) times/day, respectively. DQ score increased by 0.74 points (0.42, 1.05; p < 0.01) and 0.55 points (−0.08, 0.69; p = 0.17) for total eating occasions and snacks, respectively. When low-energy events were excluded, DQ score increased by 0.30 points (−0.84, 0.69; p = 0.13) for each eating occasion and decreased by 1.20 points (−2.1, −0.3; p < 0.01) for each snack.Eating more frequently improves dietary quality especially if some eating occasions are low in energy. A focus on replacing high-energy snacks with low-energy alternatives rather than reducing the number of eating occasions may result in improved dietary quality in adolescents.
Keywords: Adolescents; Dietary quality; Snacking; Eating occasions; Cross-sectional data

Responses of peripheral endocannabinoids and endocannabinoid-related compounds to hedonic eating in obesity by A M Monteleone; V Di Marzo; P Monteleone; R Dalle Grave; T Aveta; M El Ghoch; F Piscitelli; U Volpe; S Calugi; M Maj (1799-1805).
Hedonic eating occurs independently from homeostatic needs prompting the ingestion of pleasurable foods that are typically rich in fat, sugar and/or salt content. In normal weight healthy subjects, we found that before hedonic eating, plasma levels of 2-arachidonoylglycerol (2-AG) were higher than before nonhedonic eating, and although they progressively decreased after food ingestion in both eating conditions, they were significantly higher in hedonic eating. Plasma levels of anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), instead, progressively decreased in both eating conditions without significant differences. In this study, we investigated the responses of AEA, 2-AG, OEA and PEA to hedonic eating in obese individuals.Peripheral levels of AEA, 2-AG, OEA and PEA were measured in 14 obese patients after eating favourite (hedonic eating) and non-favourite (nonhedonic eating) foods in conditions of no homeostatic needs.Plasma levels of 2-AG increased after eating the favourite food, whereas they decreased after eating the non-favourite food, with the production of the endocannabinoid being significantly enhanced in hedonic eating. Plasma levels of AEA decreased progressively in nonhedonic eating, whereas they showed a decrease after the exposure to the favourite food followed by a return to baseline values after eating it. No significant differences emerged in plasma OEA and PEA responses to favourite and non-favourite food.Present findings compared with those obtained in our previously studied normal weight healthy subjects suggest deranged responses of endocannabinoids to food-related reward in obesity.
Keywords: Endocannabinoids; Hedonic eating; Obesity; Reward

Erratum to: Responses of peripheral endocannabinoids and endocannabinoid‑related compounds to hedonic eating in obesity by Alessio Maria Monteleone; Vincenzo Di Marzo; Palmiero Monteleone; Riccardo Dalle Grave; Teresa Aveta; Marwan El Ghoch; Fabiana Piscitelli; Umberto Volpe; Simona Calugi; Mario Maj (1807-1807).

Erratum to: Increased dietary levels of α-linolenic acid inhibit mammary tumor growth and metastasis by Marianela Vara-Messler; Maria E. Pasqualini; Andrea Comba; Renata Silva; Carola Buccellati; Annalisa Trenti; Lucia Trevisi; Aldo R. Eynard; Angelo Sala; Chiara Bolego; Mirta A. Valentich (1809-1809).

Erratum to: Profile of European adults interested in internet-based personalised nutrition: the Food4Me study by Katherine M. Livingstone; Carlos Celis-Morales; Santiago Navas-Carretero; Rodrigo San-Cristobal; Clare B. O’Donovan; Hannah Forster; Clara Woolhead; Cyril F. M. Marsaux; Anna L. Macready; Rosalind Fallaize; Silvia Kolossa; Lydia Tsirigoti; Christina P. Lambrinou; George Moschonis; Magdalena Godlewska; Agnieszka Surwiłło; Christian A. Drevon; Yannis Manios; Iwona Traczyk; Eileen R. Gibney; Lorraine Brennan; Marianne C. Walsh; Julie A. Lovegrove; J. Alfredo Martinez; Wim H. Saris; Hannelore Daniel; Mike Gibney; John C. Mathers (1811-1812).