European Journal of Nutrition (v.56, #1)

Optimal nutrition and the ever-changing dietary landscape: a conference report by A. Shao; A. Drewnowski; D. C. Willcox; L. Krämer; C. Lausted; M. Eggersdorfer; J. Mathers; J. D. Bell; R. K. Randolph; R. Witkamp; J. C. Griffiths (1-21).
The field of nutrition has evolved rapidly over the past century. Nutrition scientists and policy makers in the developed world have shifted the focus of their efforts from dealing with diseases of overt nutrient deficiency to a new paradigm aimed at coping with conditions of excess—calories, sedentary lifestyles and stress. Advances in nutrition science, technology and manufacturing have largely eradicated nutrient deficiency diseases, while simultaneously facing the growing challenges of obesity, non-communicable diseases and aging. Nutrition research has gone through a necessary evolution, starting with a reductionist approach, driven by an ambition to understand the mechanisms responsible for the effects of individual nutrients at the cellular and molecular levels. This approach has appropriately expanded in recent years to become more holistic with the aim of understanding the role of nutrition in the broader context of dietary patterns. Ultimately, this approach will culminate in a full understanding of the dietary landscape—a web of interactions between nutritional, dietary, social, behavioral and environmental factors—and how it impacts health maintenance and promotion.
Keywords: Aging; Big data; Bioactives; Biomarkers; Dietary patterns; Dietary supplements; Longevity; Micronutrients; Obesity; Overfed; Phytonutrients; Sarcopenic obesity; Systems approaches; Undernourished; Wellness

Coffee, tea and caffeine intake and the risk of non-melanoma skin cancer: a review of the literature and meta-analysis by Saverio Caini; Sofia Cattaruzza; Benedetta Bendinelli; Giulio Tosti; Giovanna Masala; Patrizia Gnagnarella; Melania Assedi; Ignazio Stanganelli; Domenico Palli; Sara Gandini (1-12).
Laboratory studies suggested that caffeine and other nutrients contained in coffee and tea may protect against non-melanoma skin cancer (NMSC). However, epidemiological studies conducted so far have produced conflicting results.We performed a literature review and meta-analysis of observational studies published until February 2016 that investigated the association between coffee and tea intake and NMSC risk. We calculated summary relative risk (SRR) and corresponding 95 % confidence intervals (95 % CI) by using random effects with maximum likelihood estimation. Overall, 37,627 NMSC cases from 13 papers were available for analysis. Intake of caffeinated coffee was inversely associated with NMSC risk (SRR for those in the highest vs. lowest category of intake: 0.82, 95 % CI 0.75–0.89, I 2 = 48 %), as well as intake of caffeine (SRR 0.86, 95 % CI 0.80–0.91, I 2 = 48 %). In subgroup analysis, these associations were limited to the basal cell cancer (BCC) histotype. There was no association between intake of decaffeinated coffee (SRR 1.01, 95 % CI 0.85–1.21, I 2 = 0) and tea (0.88, 95 % CI 0.72–1.07, I 2 = 0 %) and NMSC risk. There was no evidence of publication bias affecting the results. The available evidence was not sufficient to draw conclusions on the association between green tea intake and NMSC risk.Coffee intake appears to exert a moderate protective effect against BCC development, probably through the biological effect of caffeine. However, the observational nature of studies included, subject to bias and confounding, suggests taking with caution these results that should be verified in randomized clinical trials.
Keywords: Coffee; Tea; Caffeine; Non-melanoma skin cancer; Meta-analysis

Acute effects of caffeine-containing energy drinks on physical performance: a systematic review and meta-analysis by Diego B. Souza; Juan Del Coso; Juliano Casonatto; Marcos D. Polito (13-27).
Caffeine-containing energy drinks (EDs) are currently used as ergogenic aids to improve physical performance in a wide variety of sport disciplines. However, the outcomes of previous investigations on this topic are inconclusive due to methodological differences, especially, in the dosage of the active ingredients and the test used to assess performance.We performed a systematic review and meta-analysis of published studies to evaluate the effects of acute ED intake on physical performance. The search for references was conducted in the databases PubMed, ISI Web of Knowledge and SPORTDiscus until December 2015.Thirty-four studies published between 1998 and 2015 were included in the analysis. Using a random-effects model, effect sizes (ES) were calculated as the standardized mean difference. Overall, ED ingestion improved physical performance in muscle strength and endurance (ES = 0.49; p < 0.001), endurance exercise tests (ES = 0.53; p < 0.001), jumping (ES = 0.29; p = 0.01) and sport-specific actions (ES = 0.51; p < 0.001), but not in sprinting (ES = 0.14; p = 0.06). The meta-regression demonstrated a significant association between taurine dosage (mg) and performance (slope = 0.0001; p = 0.04), but not between caffeine dosage (mg) and performance (slope = 0.0009; p = 0.21). ED ingestion improved performance in muscle strength and endurance, endurance exercise tests, jumping and sport-specific actions. However, the improvement in performance was associated with taurine dosage.
Keywords: Caffeine; Taurine; Performance-enhancing substances; Sports

Understanding the cholesterol metabolism-perturbing effects of docosahexaenoic acid by gas chromatography–mass spectrometry targeted metabonomic profiling by Priti Bahety; Thi Hai Van Nguyen; Yanjun Hong; Luqi Zhang; Eric Chun Yong Chan; Pui Lai Rachel Ee (29-43).
Over the past few decades, docosahexaenoic acid (DHA) has gained special attention for management of cholesterol-associated metabolic disorders and neurodegenerative diseases such as Alzheimer’s disease (AD) owing to its neuroprotective, anti-inflammatory and hypolipidemic properties. Several epidemiological studies have reported the effect of DHA in reducing the risk of developing AD by lowering cholesterol. Hypercholesterolemia is a pro-amyloidogenic factor influencing the enzymatic processing of amyloid-β precursor protein (AβPP) to toxic β-amyloid. However, the mechanism by which DHA modulates the cholesterol pathway has not been established. Thus, the objective of this study was to investigate the mechanism of regulation of cholesterol metabolism by DHA in an AβPP695 overexpressing AD cell model.A gas chromatography/mass spectrometry method was developed and validated for the targeted profiling of 11 cholesterol metabolites in DHA-treated Chinese hamster ovary wild-type (CHO-wt) and AβPP695 overexpressing (CHO-AβPP695) cells. The differential metabolite profiles between DHA- and vehicle-treated groups were further analyzed using fold change values of the ratio of concentration of metabolites in CHO-AβPP695 to CHO-wt cells. Effect of DHA on key rate-limiting enzymatic activities within the cholesterol pathway was established using biochemical assays.Our results showed that DHA reduced the levels of key cholesterol anabolites and catabolites in CHO-AβPP695 cells as compared to CHO-wt cells. Further enzymatic studies revealed that the cholesterol-lowering effect of DHA was mediated by regulating HMG-CoA reductase and squalene epoxidase enzyme activities.We demonstrate for the first time the dual effects of DHA in inhibiting HMG-CoA reductase and squalene epoxidase and modulating the sterol biosynthesis axis of the cholesterol pathway in AβPP695 overexpressing AD. Our novel findings underscore the potential of DHA as a multi-target hypocholesterolemic agent for the prophylaxis of AD and other cholesterol-associated diseases.
Keywords: Docosahexaenoic acid (DHA); Amyloid β-precursor protein (AβPP); Cholesterol; Gas chromatography; Metabonomics; HMG-CoA reductase; Squalene epoxidase

Daily intake of fermented milk with Lactobacillus casei strain Shirota reduces the incidence and duration of upper respiratory tract infections in healthy middle-aged office workers by Kan Shida; Tadashi Sato; Ryoko Iizuka; Ryotaro Hoshi; Osamu Watanabe; Tomoki Igarashi; Kouji Miyazaki; Masanobu Nanno; Fumiyasu Ishikawa (45-53).
Although several studies have demonstrated the efficacy of probiotics for preventing upper respiratory tract infections (URTIs) in at-risk populations, including children and the elderly, few studies have investigated the efficacy of probiotics in healthy adults living normal, everyday lives. Thus, we tried to evaluate the effects of Lactobacillus casei strain Shirota-fermented milk (LcS-FM) on the incidence of URTIs in healthy middle-aged office workers.In a randomized controlled trial, 96 eligible male workers aged 30–49 years consumed LcS-FM containing 1.0 × 1011 viable LcS cells or control milk (CM) once daily for 12 weeks during the winter season. URTI episodes were evaluated by a physician via a questionnaire of URTI symptoms.The incidence of URTIs during the intervention period was significantly lower in the LcS-FM group than in the CM group (22.4 vs. 53.2 %, P = 0.002). The time-to-event analysis showed that the LcS-FM group had a significantly higher URTI-free rate than the CM group over the test period (log-rank test: χ 2 11.25, P = 0.0008). The cumulative number of URTI episodes and cumulative days with URTI symptoms per person was lower in the LcS-FM group, and the duration per episode was shorter. Inhibition of both reductions in NK cell activity in peripheral blood mononuclear cells and increases in salivary cortisol levels was observed in the LcS-FM group.The results suggest that the daily intake of fermented milk with LcS may reduce the risk of URTIs in healthy middle-aged office workers, probably through modulation of the immune system.
Keywords: Probiotics; Lactobacillus casei strain Shirota; Upper respiratory tract infection; Common cold; NK cell activity; Cortisol

Associations of infant milk feed type on early postnatal growth of offspring exposed and unexposed to gestational diabetes in utero by Izzuddin M. Aris; Shu E. Soh; Mya Thway Tint; Seang Mei Saw; Victor S. Rajadurai; Keith M. Godfrey; Peter D. Gluckman; Fabian Yap; Yap Seng Chong; Yung Seng Lee (55-64).
Infants on prolonged breastfeeding are known to grow slower during the first year of life. It is still unclear if such effects are similar in offspring exposed to gestational diabetes (GDM) in utero. We examined the associations of infant milk feeding on postnatal growth from birth till 36 months of age in offspring exposed and unexposed to GDM.Pregnant mothers undertook 75 g 2-h oral glucose tolerance tests at 26–28 weeks of gestation for GDM diagnosis. Up to 9 measurements of offspring weight and length were collected from birth till 36 months, and interviewer-administered questionnaires were used to ascertain the duration of breastfeeding.There was a statistically significant interaction between GDM status and breastmilk intake by any (p interaction = 0.038) or exclusive/predominant breastfeeding (p interaction = 0.035) for the outcome of conditional weight gain. In offspring of non-GDM mothers (n = 835), greater breastmilk intake (BF ≥ 4 milk months) was associated with lower conditional gains in weight [B (95 % CI) −0.48 (−0.58, −0.28); p < 0.001] within the first year of life, as well as decreasing weight SDS velocity [−0.01 (−0.02, −0.005); p < 0.001] and BMI SDS velocity [−0.008 (0.01, −0.002); p = 0.008] across age in the first 36 months. In offspring of GDM mothers (n = 181), however, greater breastmilk intake was associated with increased conditional gains in weight [0.72 (0.23, 1.20); p = 0.029] and BMI SDS [0.49 (0.04, 0.95); p = 0.04] in the first 6 months and did not demonstrate the decreasing weight and BMI SDS velocity observed in offspring of non-GDM mothers.The reduced weight gain in the first year of life conferred by greater breastmilk intake in non-GDM children was not observed in GDM children.This study is registered under the Clinical Trials identifier NCT01174875; http://www.clinicaltrials.gov/ct2/show/NCT01174875?term=GUSTO&rank=2 .
Keywords: Gestational diabetes; Infant milk feeding; Offspring growth

Associations of maternal folic acid supplementation and folate concentrations during pregnancy with foetal and child head growth: the Generation R Study by Jolien Steenweg-de Graaff; Sabine J. Roza; Alette N. Walstra; Hanan El Marroun; Eric A. P. Steegers; Vincent W. V. Jaddoe; Albert Hofman; Frank C. Verhulst; Henning Tiemeier; Tonya White (65-75).
Folic acid supplementation during pregnancy has been associated with a reduced risk of common neurodevelopmental delays in the offspring. However, it is unclear whether low folate status has effects on the developing brain. We evaluated the associations of maternal folic acid supplementation and folate concentrations during pregnancy with repeatedly measured prenatal and postnatal head circumference in the offspring.Within a population-based prospective cohort, we measured maternal plasma folate concentrations at approximately 13 weeks of gestation (90 % range 10.5–17.2) and assessed folic acid supplementation by questionnaire (2001–2005). Up to 11 repeated measures of head circumference were obtained during foetal life (20 and 30 weeks of gestation) and childhood (between birth and age 6 years) in 5866 children (2002–2012).In unadjusted models, foetal head growth was 0.006 SD (95 % CI 0.003; 0.009, P < 0.001) faster per week per 1-SD higher maternal folate concentration. After adjustment for confounders, this association was attenuated to 0.004 SD per week (95 % CI 0.000; 0.007, P = 0.02; estimated absolute difference at birth of 2.7 mm). The association was independent of overall foetal growth. No associations were found between maternal folate concentrations and child postnatal head growth. Preconceptional start of folic acid supplementation was associated with larger prenatal head size, but not with prenatal or postnatal head growth.Our results suggest an independent, modest association between maternal folate concentrations in early pregnancy and foetal head growth. More research is needed to identify whether specific brain regions are affected and whether effects of folate on foetal head growth influence children’s long-term functioning.
Keywords: Folate; Folic acid supplementation; Pregnancy; Foetal neurodevelopment; Head growth; Head size

Impact of preloading either dairy or soy milk on postprandial glycemia, insulinemia and gastric emptying in healthy adults by Lijuan Sun; Kevin Wei Jie Tan; Cathy Mok Sook Han; Melvin Khee-Shing Leow; Christiani Jeyakumar Henry (77-87).
Milk protein ingestion reduces post-meal glycemia when consumed either before or together with carbohydrate foods. The aim of this study was to compare the effects of dairy and soy milk consumed either before (preload) or together with (co-ingestion) a carbohydrate (bread), on postprandial blood glucose, insulin and gastric emptying in healthy participants.Twelve healthy Chinese male participants were studied on five separate occasions using a randomized crossover design. White wheat bread consumed with water was used as a reference meal. Capillary and venous bloods were sampled pretest and 3.5 h post-test meal for glucose and insulin measurement. Gastric emptying was measured using real-time ultrasonography.Co-ingestion of dairy milk or soy milk with bread lowered postprandial blood glucose response and glycemic index. Co-ingesting soy milk with bread increased insulin response and insulinemic index significantly compared to co-ingestion of dairy milk and preload treatments. Preloads (30 min prior to bread) significantly lowered postprandial glycemia and insulinemia compared to co-ingestion. Gastric emptying was slower after co-ingesting dairy milk with bread than after reference meal. Preloading either soy milk or dairy milk results in greater reduction in glycemic response compared to co-ingestion alone. This dietary practice may have therapeutic advantage in communities consuming high GI diets. Optimal glucose control may have the potential for increasing the time of transition from prediabetes to type 2 diabetes in Asian communities.This trial was registered at clinicaltrials.gov as NCT 02151188.
Keywords: Glycemic index; Insulinemic index; Milk; Preload; Gastric emptying

A Mediterranean diet supplemented with extra virgin olive oil or nuts improves endothelial markers involved in blood pressure control in hypertensive women by C. E. Storniolo; R. Casillas; M. Bulló; O. Castañer; E. Ros; G. T. Sáez; E. Toledo; R. Estruch; V. Ruiz-Gutiérrez; M. Fitó; M. A. Martínez-González; J. Salas-Salvadó; M. T. Mitjavila; J. J. Moreno (89-97).
Serum nitric oxide (NO) reduction and increased endothelin-1 (ET-1) play a pivotal role in endothelial dysfunction and hypertension. Considering that traditional Mediterranean diet (TMD) reduces blood pressure (BP), the aim of this study was to analyze whether TMD induced changes on endothelial physiology elements such as NO, ET-1 and ET-1 receptors which are involved in BP control.Non-smoking women with moderate hypertension were submitted for 1 year to interventions promoting adherence to the TMD, one supplemented with extra virgin olive oil (EVOO) and the other with nuts versus a control low-fat diet (30 participants/group). BP, NO, ET-1 and related gene expression as well as oxidative stress biomarkers were measured.Serum NO and systolic BP (SBP) or diastolic BP (DBP) were negatively associated at baseline, as well as between NO and ET-1. Our findings also showed a DBP reduction with both interventions. A negative correlation was observed between changes in NO metabolites concentration and SBP or DBP after the intervention with TMD + EVOO (p = 0.033 and p = 0.044, respectively). SBP reduction was related to an impairment of serum ET-1 concentrations after the intervention with TMD + nuts (p = 0.008). We also observed changes in eNOS, caveolin 2 and ET-1 receptors gene expression which are related to NO metabolites levels and BP.The changes in NO and ET-1 as well as ET-1 receptors gene expression explain, at least partially, the effect of EVOO or nuts on lowering BP among hypertensive women.
Keywords: Endothelin-1; Hypertension; Nitric oxide; PREDIMED study; Oxidative stress

Gastrointestinal stability of urolithins: an in vitro approach by Pedro Mena; Margherita Dall’Asta; Luca Calani; Furio Brighenti; Daniele Del Rio (99-106).
Urolithins are bioactive ellagitannin-derived metabolites showing a wide phenotypic variation in their production by the gut microbiota. This work represents a first in vitro step toward the development of new strategies focused on the oral supplementation of urolithins with the aim of overcoming their selective production and making their putative health benefits available for the whole population.In order to study their gastrointestinal stability, urolithin A, urolithin B, and urolithin B-glucuronide, as well as ellagic acid, were subjected to a simulated gastrointestinal digestion model consisting of oral, gastric, and pancreatic steps followed by a 24-h fecal fermentation. The effect of the entero-hepatic recirculation on urolithin B-glucuronide, a phase II metabolite, was also investigated.Urolithin B was the molecule able to resist to a greater extent the conditions of the gastrointestinal tract, while urolithin A and ellagic acid were drastically unstable during the colonic step. Conjugation with glucuronic acid, ideally occurring in the liver, conferred to urolithin B an increased stability, which may be interesting in the framework of entero-hepatic recirculation.This set of experiments lets hypothesize that orally supplemented urolithins may come into contact with the colonic epithelium and become accessible for uptake or exert local anti-inflammatory activity, overcoming the limitations of enterotypes unable to convert ellagitannins into these putatively beneficial metabolites.
Keywords: Ellagitannin; Ellagic acid; Microbial metabolite; Gastrointestinal tract; Colonic fermentation; Bioaccessibility

Intake and sources of gluten in 20- to 75-year-old Danish adults: a national dietary survey by Camilla Hoppe; Rikke Gøbel; Mette Kristensen; Mads Vendelbo Lind; Jeppe Matthiessen; Tue Christensen; Ellen Trolle; Sisse Fagt; Mia Linda Madsen; Steffen Husby (107-117).
Celiac disease, an immunological response triggered by gluten, affects ~1 % of the Western population. Information concerning gluten intake in the general population is scarce. We determined intake of gluten from wheat, barley, rye and oat in the Danish National Survey of Diet and Physical Activity 2005–2008. The study population comprised a random cross-sectional sample of 1494 adults 20–75 years, selected from the Danish Civil Registration System. Protein content in wheat, rye, barley and oat was determined from the National Danish Food Composition Table and multiplied with the amount of cereal used in recipes. Amount of gluten was calculated as amount of cereal protein ×0.80 for wheat and oat, ×0.65 for rye and ×0.50 for barley. Dietary intake was recorded daily during seven consecutive days in pre-coded food diaries with open-answer possibilities. Mean total gluten intake was 10.4 ± 4.4 g/day (10th–90th percentiles; 5.4–16.2 g/day), in men 12.0 ± 4.6 g/day and 9.0 ± 3.4 g/day in women. It was higher among men than among women in all age groups (20–75 years; P < 0.0001); however, this difference was eliminated when adjusting for energy intake. Intake of different gluten sources tended to be higher in men than in women with the exception of gluten from barley. Total gluten intake decreased with increasing age (P < 0.0001) as did gluten intake from wheat (P < 0.0001), whereas intake of gluten from rye (P < 0.0001) and barley (P = 0.001) increased with increasing age, also when adjusted for energy intake or body weight.This study presents representative population-based data on gluten intake in Danish adults. Total gluten intake decreased with increasing age.
Keywords: Gluten; Wheat; Oats; Barley; Rye; Danish; Adults

Effect of virgin olive oil and thyme phenolic compounds on blood lipid profile: implications of human gut microbiota by Sandra Martín-Peláez; Juana Ines Mosele; Neus Pizarro; Marta Farràs; Rafael de la Torre; Isaac Subirana; Francisco José Pérez-Cano; Olga Castañer; Rosa Solà; Sara Fernandez-Castillejo; Saray Heredia; Magí Farré; María José Motilva; Montserrat Fitó (119-131).
To investigate the effect of virgin olive oil phenolic compounds (PC) alone or in combination with thyme PC on blood lipid profile from hypercholesterolemic humans, and whether the changes generated are related with changes in gut microbiota populations and activities.A randomized, controlled, double-blind, crossover human trial (n = 12) was carried out. Participants ingested 25 mL/day for 3 weeks, preceded by 2-week washout periods, three raw virgin olive oils differing in the concentration and origin of PC: (1) a virgin olive oil (OO) naturally containing 80 mg PC/kg, (VOO), (2) a PC-enriched virgin olive oil containing 500 mg PC/kg, from OO (FVOO), and (3) a PC-enriched virgin olive oil containing a mixture of 500 mg PC/kg from OO and thyme, 1:1 (FVOOT). Blood lipid values and faecal quantitative changes in microbial populations, short chain fatty acids, cholesterol microbial metabolites, bile acids, and phenolic metabolites were analysed.FVOOT decreased seric ox-LDL concentrations compared with pre-FVOOT, and increased numbers of bifidobacteria and the levels of the phenolic metabolite protocatechuic acid compared to VOO (P < 0.05). FVOO did not lead to changes in blood lipid profile nor quantitative changes in the microbial populations analysed, but increased the coprostanone compared to FVOOT (P < 0.05), and the levels of the faecal hydroxytyrosol and dihydroxyphenylacetic acids, compared with pre-intervention values and to VOO, respectively (P < 0.05).The ingestion of a PC-enriched virgin olive oil, containing a mixture of olive oil and thyme PC for 3 weeks, decreases blood ox-LDL in hypercholesterolemic humans. This cardio-protective effect could be mediated by the increases in populations of bifidobacteria together with increases in PC microbial metabolites with antioxidant activities.
Keywords: Bifidobacteria; Gut microbiota; ox-LDL; Cholesterol; Phenolic compounds; Prebiotic; Virgin olive oil

Anti-inflammatory γ- and δ-tocotrienols improve cardiovascular, liver and metabolic function in diet-induced obese rats by Weng-Yew Wong; Leigh C. Ward; Chee Wai Fong; Wei Ney Yap; Lindsay Brown (133-150).
This study tested the hypothesis that γ- and δ-tocotrienols are more effective than α-tocotrienol and α-tocopherol in attenuating the signs of diet-induced metabolic syndrome in rats.Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. Separate groups from each diet were supplemented with either α-, γ-, δ-tocotrienol or α-tocopherol (85 mg/kg/day) for the final 8 of the 16 weeks.H rats developed visceral obesity, hypertension, insulin resistance, cardiovascular remodelling and fatty liver. α-Tocopherol, α-, γ- and δ-tocotrienols reduced collagen deposition and inflammatory cell infiltration in the heart. Only γ- and δ-tocotrienols improved cardiovascular function and normalised systolic blood pressure compared to H rats. Further, δ-tocotrienol improved glucose tolerance, insulin sensitivity, lipid profile and abdominal adiposity. In the liver, these interventions reduced lipid accumulation, inflammatory infiltrates and plasma liver enzyme activities. Tocotrienols were measured in heart, liver and adipose tissue showing that chronic oral dosage delivered tocotrienols to these organs despite low or no detection of tocotrienols in plasma.In rats, δ-tocotrienol improved inflammation, heart structure and function, and liver structure and function, while γ-tocotrienol produced more modest improvements, with minimal changes with α-tocotrienol and α-tocopherol. The most important mechanism of action is likely to be reduction in organ inflammation.
Keywords: Tocotrienols; Tocopherols; Cardiovascular; Anti-inflammatory; Metabolic syndrome; Obesity

Fructose-enriched diet induces inflammation and reduces antioxidative defense in visceral adipose tissue of young female rats by Sanja Kovačević; Jelena Nestorov; Gordana Matić; Ivana Elaković (151-160).
The consumption of refined, fructose-enriched food continuously increases and has been linked to development of obesity, especially in young population. Low-grade inflammation and increased oxidative stress have been implicated in the pathogenesis of obesity-related disorders including type 2 diabetes. In this study, we examined alterations in inflammation and antioxidative defense system in the visceral adipose tissue (VAT) of fructose-fed young female rats, and related them to changes in adiposity and insulin sensitivity.We examined the effects of 9-week fructose-enriched diet applied immediately after weaning on nuclear factor κB (NF-κB) intracellular distribution, and on the expression of pro-inflammatory cytokines (IL-1β and TNFα) and key antioxidative enzymes in the VAT of female rats. Insulin signaling in the VAT was evaluated at the level of insulin receptor substrate-1 (IRS-1) protein and its inhibitory phosphorylation on Ser307.Fructose-fed rats had increased VAT mass along with increased NF-κB nuclear accumulation and elevated IL-1β, but not TNFα expression. The protein levels of antioxidative defense enzymes, mitochondrial manganese superoxide dismutase 2, and glutathione peroxidase, were reduced, while the protein content of IRS-1 and its inhibitory phosphorylation were not altered by fructose diet.The results suggest that fructose overconsumption-related alterations in pro-inflammatory markers and antioxidative capacity in the VAT of young female rats can be implicated in the development of adiposity, but do not affect inhibitory phosphorylation of IRS-1.
Keywords: Fructose diet; Inflammation; NF-κB; Visceral adipose tissue; Oxidative stress; Female rats

Association between body weight and composition and plasma 25-hydroxyvitamin D level in the Diabetes Prevention Program by Lisa Ceglia; Jason Nelson; James Ware; Konstantinos-Dionysios Alysandratos; George A. Bray; Cheryl Garganta; David M. Nathan; Frank B. Hu; Bess Dawson-Hughes; Anastassios G. Pittas (161-170).
We examined associations between body weight and plasma 25-hydroxyvitamin D concentration (25OHD) in prediabetes and sought to estimate the impact of adiposity on these associations. The study was conducted in the placebo (n = 1082) and intensive lifestyle (n = 1079) groups of the Diabetes Prevention Program (DPP), a multicenter trial to prevent type 2 diabetes in adults with prediabetes. Weight and 25OHD were measured at baseline, month 6, years 1 and 2. In a subset (n = 584), visceral (VAT) and subcutaneous (SAT) adiposity were assessed by computed tomography at baseline and year 1. In cross-sectional analyses, baseline body weight, total fat, VAT, and SAT were inversely associated with plasma 25OHD concentration after multivariable adjustment. VAT accounted for 40 % [95 % CI 11, 69] of the association of body weight with plasma 25OHD concentration. There was no significant contribution by total fat or SAT. Two-year changes in plasma 25OHD concentration varied inversely with changes in body weight (p < 0.0001). One-year changes in total fat, VAT, or SAT were not significant mediators of the association between change in plasma 25OHD concentration and body weight.Our study found an inverse association between body weight and plasma 25OHD concentration at baseline and over a 2-year period in adults with prediabetes. These findings in the DPP, a weight loss intervention study, raise the possibility that weight loss increases plasma 25OHD concentration. Whether adiposity mediates this association remains inconclusive.
Keywords: Body composition; Diabetes Prevention Program; Body weight; Obesity; Vitamin D; Adipose tissue

Estimation of salt intake assessed by urinary excretion of sodium over 24 h in Spanish subjects aged 7–11 years by A. Aparicio; E. Rodríguez-Rodríguez; E. Cuadrado-Soto; B. Navia; A. M. López-Sobaler; R. M. Ortega (171-178).
High intake of salt is associated with early development of cardiovascular risk factors (e.g., hypertension, obesity). In “developed” countries, individuals frequently exceed dietary recommendations for salt intake. Taking into account the limited data on sodium intake by 24-h excretion in urine in schoolchildren, we wished to determine baseline salt intake in Spanish subjects aged 7–11 years.The present study was an observational study involving 205 schoolchildren (109 boys and 96 girls) selected from various Spanish provinces. Sodium intake was ascertained by measuring sodium excretion in urine over 24 h. Creatinine was used to validate completeness of urine collections. The correlation between fat-free mass determined by anthropometry and that determined via urinary excretion of creatinine was calculated (r = 0.651; p < 0.001).Mean 24-h urinary excretion of sodium was 132.7 ± 51.4 mmol/24 h (salt equivalent: 7.8 ± 3.1 g/day). Hence, 84.5 % of subjects aged ≤10 years had intakes of >4 g salt/day, and 66.7 % of those aged >10 years had intakes of >5 g salt/day. Urinary excretion of sodium was correlated with systolic blood pressure and diastolic blood pressure (r = 0.1574 and r = 0.1400, respectively). Logistic regression analyses, adjusted by sex, showed that a high body mass index (odds ratio = 1.159; 95 % CI 1.041–1.290; p < 0.05) was associated with an increased likelihood of high urinary excretion of sodium.Sodium intake, as estimated by 24-h urinary excretion, was (on average) higher than recommended. Reducing the sodium content children’s diet is a sound policy to reduce cardiovascular risk.
Keywords: Urinary sodium excretion; Salt intake; Schoolchildren; Spain

Preventive rather than therapeutic treatment with high fiber diet attenuates clinical and inflammatory markers of acute and chronic DSS-induced colitis in mice by Ana Letícia Malheiros Silveira; Adaliene Versiani Matos Ferreira; Marina Chaves de Oliveira; Milene Alvarenga Rachid; Larissa Fonseca da Cunha Sousa; Flaviano dos Santos Martins; Ana Cristina Gomes-Santos; Angelica Thomaz Vieira; Mauro Martins Teixeira (179-191).
Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with important impact on global health. Prebiotic and probiotic strategies are thought to be useful in the context of experimental IBD. Here, we compared the effects of preventive versus therapeutic treatment with a high fiber diet (prebiotic) in combination or not with Bifidobacterium longum (probiotic) in a murine model of chronic colitis.Colitis was induced by adding dextran sulfate sodium (DSS) to drinking water for 6 days (acute colitis) or for 5 cycles of DSS (chronic colitis).Administration of the high fiber diet protected from acute colitis. Protection was optimal when diet was started 20 days prior to DSS. A 5-day pretreatment with acetate, a short-chain fatty acid, provided partial protection against acute colitis. In chronic colitis, pretreatment with the high fiber diet attenuated clinical and inflammatory parameters of disease. However, when the treatment with the high fiber diet started after disease had been established, overall protection was minimal. Similarly, delayed treatment with acetate or B. longum did not provide any protection even when the probiotic was associated with the high fiber diet.Preventive use of a high fiber diet or acetate clearly protects mice against acute and chronic damage induced by DSS in mice. However, protection is lost when therapies are initiated after disease has been established. These results suggest that any therapy aimed at modifying the gut environment (e.g., prebiotic or probiotic strategies) should be given early in the course of disease.
Keywords: Inflammatory bowel disease; DSS; Colitis; High fiber diet

Body mass index cut-points to identify cardiometabolic risk in black South Africans by H. Salome Kruger; Aletta E. Schutte; Corinna M. Walsh; Annamarie Kruger; Kirsten L. Rennie (193-202).
To determine optimal body mass index (BMI) cut-points for the identification of cardiometabolic risk in black South African adults.We performed a cross-sectional study of a weighted sample of healthy black South Africans aged 25–65 years (721 men, 1386 women) from the North West and Free State Provinces. Demographic, lifestyle and anthropometric measures were taken, and blood pressure, fasting serum triglycerides, high-density lipoprotein (HDL) cholesterol and blood glucose were measured. We defined elevated cardiometabolic risk as having three or more risk factors according to international metabolic syndrome criteria. Receiver operating characteristic curves were applied to identify an optimal BMI cut-point for men and women.BMI had good diagnostic performance to identify clustering of three or more risk factors, as well as individual risk factors: low HDL-cholesterol, elevated fasting glucose and triglycerides, with areas under the curve >.6, but not for high blood pressure. Optimal BMI cut-points averaged 22 kg/m2 for men and 28 kg/m2 for women, respectively, with better sensitivity in men (44.0–71.9 %), and in women (60.6–69.8 %), compared to a BMI of 30 kg/m2 (17–19.1, 53–61.4 %, respectively). Men and women with a BMI >22 and >28 kg/m2, respectively, had significantly increased probability of elevated cardiometabolic risk after adjustment for age, alcohol use and smoking.In black South African men, a BMI cut-point of 22 kg/m2 identifies those at cardiometabolic risk, whereas a BMI of 30 kg/m2 underestimates risk. In women, a cut-point of 28 kg/m2, approaching the WHO obesity cut-point, identifies those at risk.
Keywords: Body mass index; Black adults; Cardiometabolic risk; Sub-Saharan Africa

Pancreatic cancer is an aggressive cancer type, of which the most important characteristics are migration and metastasis. Anthocyanins (ACN) are discussed to be protective phytochemicals; however, up to now only scarce data are available regarding their effects on cancer prevention. In this study, we aimed to determine whether ACN and their metabolites from plasma (PAM), isolated from blood of healthy volunteers after ingestion of an ACN-rich juice, are effective in modulating cancer cell migration in vitro.PAM were isolated from blood of healthy volunteers (n = 10) after consumption of an ACN-rich berry juice. Before ingestion (PAM0min) and after 60 min (PAM60min), blood was taken and PAM were isolated from plasma by solid-phase extraction. Migration of pancreatic cancer cells PANC-1 and AsPC-1 was assayed in a Boyden chamber. The influence of PAM on cellular reactive oxygen species (ROS) or mitochondria-specific ROS was measured fluorimetrically. mRNA expression levels of matrix metalloproteinases (MMP-2 and MMP-9) and NF-κB mRNA were determined by real-time PCR.After application of PAM60min to PANC-1, we observed a reduced cell migration, which was associated with reduced levels of endogenously generated ROS concomitant with reduced NF-κB as well as MMP-2 and MMP-9 mRNA expression levels. In AsPC-1 cells, however, migration was not affected by PAM60min.It can be assumed that physiologically relevant ACN and their metabolites were able to inhibit pancreatic cancer cell migration in dependency of the phenotype of cells and may thus deserve further attention as potential bioactive phytochemicals in cancer prevention.
Keywords: Grapes and bilberries; Anthocyanins; Pancreatic cancer cells; Metalloproteinases; Migration

To date, several in vitro and in vivo studies have shown phenolic compounds occurring naturally in olives and olive oil to be beneficial to human health due to their interaction with intracellular signaling pathways. However, the bioavailability of the most important of these compounds, hydroxytyrosol (HT), and its transformation into derivatives within the organism after oral intake are still not completely understood, requiring further in vivo research. This study deals with the differential bioavailability and metabolism of oral HT and its derivatives in rats.Hydroxytyrosol (HT), hydroxytyrosol acetate (HTA), and 2,3-dihydroxyphenylacetic acid (DOPAC) were administered at doses of 1 and 5 mg/kg to Sprague–Dawley rats (n = 9 per treatment) by oral gavage. Their plasma kinetics and absorption ratio, assessed as their excretion in 24-h urine, were determined by UHPLC/MS/MS.Plasma and urine levels indicated that although the three compounds are efficiently absorbed in the gastrointestinal tract and show similar metabolism, the bioavailability is strongly dependent on the derivative considered, dosage, and gender. Inter-conversion among them has been described also, suggesting an interaction with internal routes. Microbiota metabolites derived from these phenolics were also taken into account; thereby, homovanillic alcohol and tyrosol were identified and quantified in urine samples after enzymatic de-conjugation, concluding the metabolic profile of HT.Our results suggest that different dosages of HT, HTA, and DOPAC do not provide a linear, dose-dependent plasma concentration or excretion in urine, both of which can be affected by the saturation of first-phase metabolic processes and intestinal transporters.
Keywords: Hydroxytyrosol; Hydroxytyrosol acetate; DOPAC; Oral administration; Bioavailability; Plasma; Urine

Food supplementation with rice bran enzymatic extract prevents vascular apoptosis and atherogenesis in ApoE−/− mice by C. Perez-Ternero; M. D. Herrera; U. Laufs; M. Alvarez de Sotomayor; C. Werner (225-236).
Atherosclerosis is associated with reduced mononuclear cell (MNC) telomere length, and senescent cells have been detected in atherosclerotic plaques. Rice bran is a source of γ-oryzanol, phytosterols and tocols with potential lipid-lowering, antioxidant and anti-inflammatory activities. Here, we tested the hypothesis that rice bran enzymatic extract (RBEE) impacts on apoptosis, telomere length and atherogenesis in mice. Seven-week-old male ApoE−/− mice were fed high-fat diet (HFD) or isocaloric HFD supplemented with 5 % (w/w) RBEE for 23 weeks. Wild-type mice of the same age were kept under standard diet as controls.RBEE treatment reduced total cholesterol (19.24 ± 1.63 vs 24.49 ± 1.71 mmol/L) and triglycerides (1.13 ± 0.18 vs 1.75 ± 0.22 mmol/L) and augmented HDL-cholesterol (1.86 ± 0.20 vs 1.07 ± 0.20 mmol/L). RBEE attenuated macrophage infiltration by 56.69 ± 4.65 % and plaque development (7737 ± 836 vs 12,040 ± 1001 μm2) in the aortic sinus. In the aorta, RBEE treatment reduced expression of the apoptosis pathway components p16, p53 and bax/bcl-2 ratio. RBEE prevented apoptosis of aortic endothelial cells (2.81 ± 0.71–1.14 ± 0.35 apoptotic nuclei/ring for ApoE−/− HFD and ApoE−/− HFD 5 % RBEE, respectively). In contrast, MNC of RBEE-fed mice exhibited enhanced apoptosis marker expression with increased p53 and bax/bcl-2 protein levels. Compared to WT, ApoE−/− mice on HFD were characterized by significant telomere shortening in aorta (11 ± 2 %) and MNC (73 ± 7 %), which was reduced by supplementation with RBEE (aorta: 40 ± 7 %; MNC: 105 ± 10 %). Expression of telomere repeat-binding factor 2 was increased in RBEE-fed mice.Long-term food supplementation with RBEE lowers cholesterol and prevents atherosclerotic plaque development in ApoE−/− mice. Differential regulation of vascular and MNC apoptosis and senescence were identified as potential mechanisms.
Keywords: ApoE−/−; Rice bran enzymatic extract; Atherosclerosis; Inflammation; Apoptosis; Telomeres

Deteriorated glucose metabolism with a high-protein, low-carbohydrate diet in db mice, an animal model of type 2 diabetes, might be caused by insufficient insulin secretion by Emi Arimura; Wijang Pralampita Pulong; Ancah Caesarina Novi Marchianti; Miwa Nakakuma; Masaharu Abe; Miharu Ushikai; Masahisa Horiuchi (237-246).
We previously showed the deleterious effects of increased dietary protein on renal manifestations and glucose metabolism in leptin receptor-deficient (db) mice. Here, we further examined its effects on glucose metabolism, including urinary C-peptide. We also orally administered mixtures corresponding to low- or high-protein diets to diabetic mice.In diet experiments, under pair-feeding (equivalent energy and fat) conditions using a metabolic cage, mice were fed diets with different protein content (L diet: 12 % protein, 71 % carbohydrate, 17 % fat; H diet: 24 % protein, 59 % carbohydrate, 17 % fat) for 15 days. In oral administration experiments, the respective mixtures (L mixture: 12 % proline, 71 % maltose or starch, 17 % linoleic acid; H mixture: 24 % proline, 59 % maltose or starch, 17 % linoleic acid) were supplied to mice. Biochemical parameters related to glucose metabolism were measured.The db–H diet mice showed significantly higher water intake, urinary volume, and glucose levels than db–L diet mice but similar levels of excreted urinary C-peptide. In contrast, control-H diet mice showed significantly higher C-peptide excretion than control-L diet mice. Both types of mice fed H diet excreted high levels of urinary albumin. When maltose mixtures were administered, db–L mixture mice showed significantly higher blood glucose after 30 min than db–H mixture mice. However, db mice administered starch–H mixture showed significantly higher blood glucose 120–300 min post-administration than db–L mixture mice, although both groups exhibited similar insulin levels.High-protein, low-carbohydrate diets deteriorated diabetic conditions and were associated with insufficient insulin secretion in db mice. Our findings may have implications for dietary management of diabetic symptoms in human patients.
Keywords: High-protein diet; Insulin secretion; db mice; Oral administration; Urinary C-peptide

The impact of MTHFR 677 C/T genotypes on folate status markers: a meta-analysis of folic acid intervention studies by Natalie J. Colson; Helen L. Naug; Elham Nikbakht; Ping Zhang; Joanna McCormack (247-260).
Methylenetetrahydrofolate reductase (MTHFR) is a key folate pathway enzyme with the T variant of the MTHFR gene increasing the risk of low folate status, particularly coupled with low folate intake. As genetic variability of MTHFR influences folate status, it is important to ensure an adequate intake that overrides genetic effects but minimises any adverse effects. Our aim was to assess the influence of MTHFR genotype on folate status followed by response to supplementation.We performed a meta-analysis of ten folate intervention studies to assess the degree to which MTHFR C677T genotype influenced plasma homocysteine and serum folate levels as measures of folate status. We then examined response after supplementation at intake values up to the upper tolerable limit.The MTHFR 677TT genotype was associated with higher plasma homocysteine (2.7 μmol/L, TT vs. CT/CC; 2.8 μmol/L, TT vs. CC) and lower serum folate (2.5 nmol/L, TT vs. CT/CC; 3.6 nmol/L, TT vs. CC). In two studies, the TT groups had mean plasma Hcy >15 μmol/L. Serum folate levels were >7 nmol/L for all genotype groups. After supplementation of 400 up to 1670 μg DFEs of folic acid or folic acid + fortified foods and/or natural food folates for a minimum of 4 weeks, there were no significant differences in plasma homocysteine levels; however, individuals with the TT genotype had a lower serum folate response to supplementation (7.2 nmol/L, TT vs. CT/CC; 8.7 nmol/L, TT vs. CC).This meta-analysis confirms observations from observational and intervention studies that MTHFR TT genotype is associated with increased plasma homocysteine and lowered serum folate and less response to short-term supplementation. The results can be used for modelling and guiding personalised intake recommendations for the nutrient folate.
Keywords: Folate; Folic acid; Homocysteine; MTHFR

Associations between intake of fish and n-3 long-chain polyunsaturated fatty acids and plasma metabolites related to the kynurenine pathway in patients with coronary artery disease by Therese Karlsson; Elin Strand; Jutta Dierkes; Christian A. Drevon; Jannike Øyen; Øivind Midttun; Per M. Ueland; Oddrun A. Gudbrandsen; Eva Ringdal Pedersen; Ottar Nygård (261-272).
Enhanced tryptophan degradation via the kynurenine pathway has been related to several pathological conditions. However, little is known about the effect of diet on individual metabolites of this pathway. We investigated cross-sectional associations between reported intake of fish and omega-3 (n-3) long-chain PUFA (LC-PUFA) and plasma metabolites related to the kynurenine pathway.Participants were 2324 individuals with coronary artery disease from the Western Norway B Vitamin Intervention Trial. Fish and n-3 LC-PUFA intakes were assessed using a food frequency questionnaire. Plasma concentrations of tryptophan, kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, xanthurenic acid, 3-hydroxyanthranilic acid, neopterin, and kynurenine-to-tryptophan ratio (KTR) were analyzed. Associations were investigated using partial Spearman’s rank correlations and multiple linear regressions.Median age at inclusion was 62 years (80 % males), and 84 % had stable angina pectoris. Intake of fatty fish and n-3 LC-PUFA was inversely associated with plasma 3-hydroxykynurenine. Consumption of total fish, lean fish, and n-3 LC-PUFA was inversely associated with plasma neopterin. Intake of total fish, fatty fish, and n-3 LC-PUFA was inversely associated with KTR. All these correlations were weak (ρ between −0.12 and −0.06, P < 0.01). In 306 patients with diabetes, lean fish intake was positively associated with plasma 3-hydroxyanthranilic acid (ρ = 0.22, P < 0.001, P for interaction = 0.01), and total fish intake was inversely associated with KTR (ρ = −0.17, P < 0.01, P for interaction = 0.02).Fish intake was not an important determinant of individual metabolites in the kynurenine pathway. However, some correlations were stronger in patients with diabetes. The inverse associations of fish or n-3 LC-PUFA with neopterin and KTR may suggest a slightly lower IFN-γ-mediated immune activation with a higher intake.
Keywords: Fish intake; Omega-3 polyunsaturated fatty acid; Neopterin; Kynurenine pathway

Prospective study on the association between diet quality and depression in mid-aged women over 9 years by Jun S. Lai; Alexis J. Hure; Christopher Oldmeadow; Mark McEvoy; Julie Byles; John Attia (273-281).
To examine the longitudinal association between diet quality and depression using prospective data from the Australian Longitudinal Study on Women’s Health.Women born in 1946–1951 (n = 7877) were followed over 9 years starting from 2001. Dietary intake was assessed using the Dietary Questionnaire for Epidemiological Studies (version 2) in 2001 and a shortened form in 2007 and 2010. Diet quality was summarised using the Australian Recommended Food Score. Depression was measured using the 10-item Centre for Epidemiologic Depression Scale and self-reported physician diagnosis. Pooled logistic regression models including time-varying covariates were used to examine associations between diet quality tertiles and depression. Women were also categorised based on changes in diet quality during 2001–2007. Analyses were adjusted for potential confounders.The highest tertile of diet quality was associated marginally with lower odds of depression (OR 0.94; 95 % CI 0.83, 1.00; P = 0.049) although no significant linear trend was observed across tertiles (OR 1.00; 95 % CI 0.94, 1.10; P = 0.48). Women who maintained a moderate or high score over 6 years had a 6–14 % reduced odds of depression compared with women who maintained a low score (moderate vs low score—OR 0.94; 95 % CI 0.80, 0.99; P = 0.045; high vs low score—OR 0.86; 95 % CI 0.77, 0.96; P = 0.01). Similar results were observed in analyses excluding women with prior history of depression.Long-term maintenance of good diet quality may be associated with reduced odds of depression. Randomised controlled trials are needed to eliminate the possibility of residual confounding.
Keywords: Diet; Depression; Prospective study; Women

Micronutrient status and intake in omnivores, vegetarians and vegans in Switzerland by R. Schüpbach; R. Wegmüller; C. Berguerand; M. Bui; I. Herter-Aeberli (283-293).
Vegetarian and vegan diets have gained popularity in Switzerland. The nutritional status of individuals who have adopted such diets, however, has not been investigated. The aim of this study was to assess the intake and status of selected vitamins and minerals among vegetarian and vegan adults living in Switzerland.Healthy adults [omnivores (OVs), n OV = 100; vegetarians (VGs), n VG = 53; vegans (VNs), n VN = 53] aged 18–50 years were recruited, and their weight and height were measured. Plasma concentrations of the vitamins A, C, E, B1, B2, B6, B12, folic acid, pantothenic acid, niacin, biotin and β-carotene and of the minerals Fe, Mg and Zn and urinary iodine concentration were determined. Dietary intake was assessed using a three-day weighed food record, and questionnaires were issued in order to assess the physical activity and lifestyle of the subjects.Omnivores had the lowest intake of Mg, vitamin C, vitamin E, niacin and folic acid. Vegans reported low intakes of Ca and a marginal consumption of the vitamins D and B12. The highest prevalence for vitamin and mineral deficiencies in each group was as follows: in the omnivorous group, for folic acid (58 %); in the vegetarian group, for vitamin B6 and niacin (58 and 34 %, respectively); and in the vegan group, for Zn (47 %). Despite negligible dietary vitamin B12 intake in the vegan group, deficiency of this particular vitamin was low in all groups thanks to widespread use of supplements. Prevalence of Fe deficiency was comparable across all diet groups.Despite substantial differences in intake and deficiency between groups, our results indicate that by consuming a well-balanced diet including supplements or fortified products, all three types of diet can potentially fulfill requirements for vitamin and mineral consumption.
Keywords: Vegetarian; Vegan; Vitamins; Minerals; Dietary intake; Micronutrient status

No association between blood telomere length and longitudinally assessed diet or adiposity in a young adult Filipino population by Hilary J. Bethancourt; Mario Kratz; Shirley A. A. Beresford; M. Geoffrey Hayes; Christopher W. Kuzawa; Paulita L. Duazo; Judith B. Borja; Daniel T. A. Eisenberg (295-308).
Telomeres, DNA–protein structures that cap and protect chromosomes, are thought to shorten more rapidly when exposed to chronic inflammation and oxidative stress. Diet and nutritional status may be a source of inflammation and oxidative stress. However, relationships between telomere length (TL) and diet or adiposity have primarily been studied cross-sectionally among older, overweight/obese populations and yielded inconsistent results. Little is known about the relationship between diet or body composition and TL among younger, low- to normal-weight populations. It also remains unclear how cumulative exposure to a specific diet or body composition during the years of growth and development, when telomere attrition is most rapid, may be related to TL in adulthood.In a sample of 1459 young adult Filipinos, we assessed the relationship between blood TL at ages 20.8–22.5 and measures of BMI z-score, waist circumference, and diet collected between the ages of 8.5 and 22.5. TL was measured using monochrome multiplex quantitative PCR, and diet was measured using multiple 24-h recalls.We found no associations between blood TL and any of the measures of adiposity or between blood TL and the seven dietary factors examined: processed meats, fried/grilled meats and fish, non-fried fish, coconut oil, fruits and vegetables, bread and bread products, and sugar-sweetened beverages.Considering the inconsistencies in the literature and our null results, small differences in body composition and consumption of any single pro- or anti-inflammatory dietary component may not by themselves have a meaningful impact on telomere integrity, or the impact may differ across distinct ecological circumstances.
Keywords: Telomere length; Diet; Nutrition; Adiposity; Nutrition transition

Adherence to the DASH diet in relation to psychological profile of Iranian adults by Ghazaleh Valipour; Ahmad Esmaillzadeh; Leila Azadbakht; Hamid Afshar; Ammar Hassanzadeh; Peyman Adibi (309-320).
Although empirically derived dietary patterns have been examined in relation to depression, limited data are available linking theory-based dietary patterns and psychological health.We aimed to investigate the association between adherence to DASH-style diet and psychological health among Iranian adults.This cross-sectional study was done among 3846 general public adults in Isfahan, Iran. Dietary assessment was conducted using a validated 106-item dish-based semiquantitative food frequency questionnaire. To investigate participants’ adherence to DASH-style diet, we created DASH score based on earlier publications focusing on eight components (fruits, vegetables, nuts and legumes, dairy products, grains, sweetened beverages and sweets, sodium, and red and processed meats). Participants were classified into three categories based on their DASH score [low (≤40), moderate (41–50), and high adherence (≥51)]. This categorization, instead of distribution-based classification, was used due to low adherence to the DASH dietary pattern in the study population. Psychological health was examined by means of validated Hospital Anxiety and Depression Scale and General Health Questionnaire. Depression, anxiety, and psychological distress were defined based on standard criteria.We found that moderate adherence to DASH-style diet was associated with lower odds of depression (OR 0.73; 95 % CI 0.59–0.90, P trend = 0.63) compared with those with the lowest adherence. In our stratified analyses, these associations remained significant for women (0.70; 0.54–0.91) and for normal-weight participants (0.70; 0.52–0.92). Moreover, after controlling for potential confounders, an inverse association was observed between high adherence to DASH-style diet and anxiety in normal-weight participants (0.61; 0.37–0.98). Such associations were also seen between moderate adherence to DASH-eating style and anxiety in overweight or obese individuals (0.63; 0.42–0.95). We failed to find any significant association between consumption of DASH-style diet and psychological distress.We found an inverse association between moderate adherence to DASH dietary pattern and depression. Further prospective studies are required to confirm these findings.
Keywords: Diet; Healthy eating; Psychological health; Depression; Anxiety; Mood

Vitamin B2, vitamin B12 and total homocysteine status in children and their associations with dietary intake of B-vitamins from different food groups: the Healthy Growth Study by Yannis Manios; George Moschonis; Renske Dekkers; Christina Mavrogianni; Eva Grammatikaki; Ellen van den Heuvel (321-331).
To examine the associations between the dietary intakes of certain B-vitamins from different food sources with the relevant plasma status indices in children.A representative subsample of 600 children aged 9–13 years from the Healthy Growth Study was selected. Dietary intakes of vitamins B2, B12, B6 and folate derived from different food sources were estimated. Plasma levels of vitamin B2 (or riboflavin), methylmalonic acid (MMA) and total homocysteine (tHcy) were also measured.Plasma concentrations of vitamin B2 below 3 μg/L were found in 22.8 % of the children. Children in the lower quartile of dietary vitamin B2 intake were found to have the lowest plasma vitamin B2 levels compared to children in the upper three quartiles (5.06 ± 7.63 vs. 6.48 ± 7.88, 6.34 ± 7.63 and 6.05 ± 4.94 μg/L respectively; P = 0.003). Regarding vitamin B12 children in the lower quartile of dietary intake had higher mean plasma tHcy levels compared to children in the upper two quartiles, respectively (6.00 ± 1.79 vs. 5.41 ± 1.43 and 5.46 ± 1.64 μmol/L; P = 0.012). Positive linear associations were observed between plasma vitamin B2 levels and dietary vitamin B2 derived from milk and fruits (β = 0.133; P = 0.001 and β = 0.086; P = 0.037). Additionally, nonlinear associations were also observed between plasma vitamin B2 levels and vitamin B2 derived from red meat, as well as between tHcy levels and vitamins B12 and B6 derived from milk; vitamins B12, B6 and folate derived from cereal products and folate derived from fruits.A considerably high prevalence of poor plasma vitamin B2 status was observed in children. The intake of milk, fruits and cereals was associated with more favorable tHcy levels, while the intake of milk and fruits with more favorable plasma B2 levels. However, these findings need to be further confirmed from controlled dietary intervention studies examining the modulation of biomarkers of B-vitamins.
Keywords: Vitamin B2 ; Vitamin B12 ; Homocysteine; Diet; Status; Children

Consumption of anthocyanin-rich cherry juice for 12 weeks improves memory and cognition in older adults with mild-to-moderate dementia by Katherine Kent; Karen Charlton; Steven Roodenrys; Marijka Batterham; Jan Potter; Victoria Traynor; Hayley Gilbert; Olivia Morgan; Rachelle Richards (333-341).
Dietary flavonoids, including anthocyanins, may positively influence cognition and may be beneficial for the prevention and treatment of dementia. We aimed to assess whether daily consumption of anthocyanin-rich cherry juice changed cognitive function in older adults with dementia. Blood pressure and anti-inflammatory effects were examined as secondary outcomes. A 12-week randomised controlled trial assessed cognitive outcomes in older adults (+70 year) with mild-to-moderate dementia (n = 49) after consumption of 200 ml/day of either a cherry juice or a control juice with negligible anthocyanin content. Blood pressure and inflammatory markers (CRP and IL-6) were measured at 6 and 12 weeks. ANCOVA controlling for baseline and RMANOVA assessed change in cognition and blood pressure.Improvements in verbal fluency (p = 0.014), short-term memory (p = 0.014) and long-term memory (p ≤ 0.001) were found in the cherry juice group. A significant reduction in systolic (p = 0.038) blood pressure and a trend for diastolic (p = 0.160) blood pressure reduction was evident in the intervention group. Markers of inflammation (CRP and IL-6) were not altered. Inclusion of an anthocyanin-rich beverage may be a practical and feasible way to improve total anthocyanin consumption in older adults with mild-to-moderate dementia, with potential to improve specific cognitive outcomes.
Keywords: Cherry; Cognition; Anthocyanin; Dementia

Higher plasma quercetin levels following oral administration of an onion skin extract compared with pure quercetin dihydrate in humans by Constanze Burak; Verena Brüll; Peter Langguth; Benno F. Zimmermann; Birgit Stoffel-Wagner; Udo Sausen; Peter Stehle; Siegfried Wolffram; Sarah Egert (343-353).
To investigate the plasma kinetics of quercetin derived from hard capsules filled with onion skin extract powder or quercetin dihydrate in humans.In a randomized, single-blind, diet-controlled crossover study, 12 healthy subjects (six men and six women) aged 21–33 years were administered a single oral supra-nutritional dose of approximately 163 mg quercetin derived from onion skin extract powder (containing 95.3 % of total flavonoids as quercetin aglycone) or quercetin dihydrate (134 mg quercetin aglycone equivalent). Blood samples were collected before and during a 24-h period after quercetin administration. The concentrations of quercetin and its two monomethylated derivatives, isorhamnetin (3′-O-methyl quercetin), and tamarixetin (4′-O-methyl quercetin), were measured using HPLC with fluorescence detection after plasma enzymatic treatment.The systemic availability, determined by comparing the plasma concentration–time curves of quercetin, was 4.8 times higher, and the maximum plasma concentration (C max) was 5.4 times higher after ingestion of the onion skin extract than after ingestion of pure quercetin dihydrate. By contrast, t max did not differ significantly between the two formulations. The C max values for isorhamnetin and tamarixetin were 3.8 and 4.4 times higher, respectively, after administration of onion skin extract than after pure quercetin dihydrate. The plasma kinetics of quercetin were not significantly different in men and women.Quercetin aglycone derived from onion skin extract powder is significantly more bioavailable than that from quercetin dihydrate powder filled hard capsules.
Keywords: Quercetin; Bioavailability; Onion; Human study

Urine color as an indicator of urine concentration in pregnant and lactating women by Amy L. McKenzie; Colleen X. Muñoz; Lindsay A. Ellis; Erica T. Perrier; Isabelle Guelinckx; Alexis Klein; Stavros A. Kavouras; Lawrence E. Armstrong (355-362).
Urine concentration measured via osmolality (U OSM) and specific gravity (U SG) reflects the adequacy of daily fluid intake, which has important relationships to health in pregnant (PREG) and lactating (LACT) women. Urine color (U COL) may be a practical, surrogate marker for whole-body hydration status. To determine whether U COL was a valid measure of urine concentration in PREG and LACT, and pair-matched non-pregnant, non-lactating control women (CON).Eighteen PREG/LACT (age 31 ± 1 years, pre-pregnancy BMI 24.3 ± 5.9 kg m−2) and eighteen CON (age 29 ± 4 years, BMI 24.1 ± 3.7 kg m−2) collected 24-h and single-urine samples on specified daily voids at five time points (15 ± 2, 26 ± 1, and 37 ± 1 weeks gestation, 3 ± 1 and 9 ± 1 weeks postpartum during lactation; CON visits were separated by similar time intervals) for measurement of 24-h U OSM, U SG, and U COL and single-sample U OSM and U COL.Twenty-four-hour U COL was significantly correlated with 24-h U OSM (r = 0.6085–0.8390, P < 0.0001) and 24-h U SG (r = 0.6213–0.8985, P < 0.0001) in all groups. A 24-h U COL ≥ 4 (AUC = 0.6848–0.9513, P < 0.05) and single-sample U COL ≥ 4 (AUC = 0.9094–0.9216, P < 0.0001) indicated 24-h U OSM ≥ 500 mOsm kg−1 (representing inadequate fluid intake) in PREG, LACT, and CON.Urine color was a valid marker of urine concentration in all groups. Thus, PREG, LACT, and CON can utilize U COL to monitor their daily fluid balance. Women who present with a U COL ≥ 4 likely have a U OSM ≥ 500 mOsm kg−1 and should increase fluid consumption to improve overall hydration status.
Keywords: Fluid intake; Hydration status; Biomarker; Urine color; Pregnant women; Lactating women

Effects of chronic sugar consumption on lipid accumulation and autophagy in the skeletal muscle by Daniela De Stefanis; Raffaella Mastrocola; Debora Nigro; Paola Costelli; Manuela Aragno (363-373).
In recent years, the increasing consumption of soft drinks containing high-fructose corn syrup or sucrose has caused a rise in fructose intake, which has been related to the epidemic of metabolic diseases. As fructose and glucose intake varies in parallel, it is still unclear what the effects of the increased consumption of the two single sugars are. In the present study, the impact of chronic consumption of glucose or fructose on skeletal muscle of healthy mice was investigated.C57BL/6J male mice received water (C), 15 % fructose (ChF) or 15 % glucose (ChG) to drink for up to 7 months. Lipid metabolism and markers of inflammation and autophagy were assessed in gastrocnemius muscle.Increased body weight and gastrocnemius muscle mass, as well as circulating glucose, insulin, and lipid plasma levels were observed in sugar-drinking mice. Although triglycerides increased in the gastrocnemius muscle of both ChF and ChG mice (+32 and +26 %, vs C, respectively), intramyocellular lipids accumulated to a significantly greater extent in ChF than in ChG animals (ChF +10 % vs ChG). Such perturbations were associated with increased muscle interleukin-6 levels (threefold of C) and with the activation of autophagy, as demonstrated by the overexpression of LC3B-II (ChF, threefold and ChG, twofold of C) and beclin-1 (ChF, sevenfold and ChG, tenfold of C).The present results suggest that intramyocellular lipids and the pro-inflammatory signaling could contribute to the onset of insulin resistance and lead to the induction of autophagy, which could be an adaptive response to lipotoxicity.
Keywords: Fructose; Glucose; Autophagy; Intramyocellular lipids

Adipose tissue metabolic and inflammatory responses to a mixed meal in lean, overweight and obese men by Rebecca L. Travers; Alexandre C. Motta; James A. Betts; Dylan Thompson (375-385).
Most of what we know about adipose tissue is restricted to observations derived after an overnight fast. However, humans spend the majority of waking hours in a postprandial (fed) state, and it is unclear whether increasing adiposity impacts adipose tissue responses to feeding. The aim of this research was to investigate postprandial responses in adipose tissue across varying degrees of adiposity.Thirty males aged 35–55 years with waist circumference 81–118 cm were divided equally into groups categorized as either lean, overweight or obese. Participants consumed a meal and insulinaemic, glycaemic and lipidaemic responses were monitored over 6 h. Subcutaneous adipose tissue samples were obtained at baseline and after 6 h to examine changes in gene expression and adipose tissue secretion of various adipokines.Following consumption of the meal, insulin and glucose responses were higher with increased adiposity (total AUC effects of group; p = 0.058 and p = 0.027, respectively). At 6 h, significant time effects reflected increases in IL-6 (F = 14.7, p = 0.001) and MCP-1 (F = 10.7, p = 0.003) and reduction in IRS2 adipose tissue gene expression (F = 24.6, p < 0.001), all independent of adiposity. Ex vivo adipokine secretion from adipose tissue explants remained largely unchanged after feeding.Increased systemic measures of postprandial metabolism with greater adiposity do not translate into increased inflammatory responses within adipose tissue. Instead, postprandial adipose tissue changes may represent a normal response to feeding or a (relatively) normalized response with increased adiposity due to either similar net exposure (i.e. per g of adipose) or reduced adipose tissue responsiveness.
Keywords: Adipose tissue; Metabolism; Inflammation; Postprandial; Human

Benzoxazinoids (BXs) are a group of wholegrain phytochemicals with potential pharmacological properties; however, limited information exists on their absorption, metabolism, and excretion in humans. The aim of this study was to investigate the dose-dependent uptake and excretion of dietary BXs in a healthy population.Blood and urine were collected from 19 healthy participants from a crossover study after a washout, a LOW BX diet or HIGH BX diet, and analysed for 12 BXs and 4 phenoxazinone derivatives.We found that the plasma BX level peaked approximately 3 h after food intake, whereas BXs in urine were present even at 36 h after consuming a meal. No phenoxazinone derivatives could be detected in either plasma or urine. The dominant BX metabolite in both plasma and urine was 2-β-d-glucopyranosyloxy-1,4-benzoxazin-3-one (HBOA-Glc), even though 2-β-d-glucopyranosyloxy-4-hydroxy-1,4-benzoxazin-3-one (DIBOA-Glc) was the major component in the diet. The dietary BX treatment correlated well with the plasma and urine levels, illustrating strong dose-dependent BX absorption, which also had a rapid washout, especially from the plasma compartment.
Keywords: Benzoxazinoids; Rye bread; Wholegrain; Metabolism; Weight loss

A Western dietary pattern is associated with higher blood pressure in Iranian adolescents by Abdollah Hojhabrimanesh; Masoumeh Akhlaghi; Elham Rahmani; Sasan Amanat; Masoumeh Atefi; Maryam Najafi; Maral Hashemzadeh; Saedeh Salehi; Shiva Faghih (399-408).
The dietary determinants of adolescent blood pressure (BP) are not well understood. We determined the association between major dietary patterns and BP in a sample of Iranian adolescents. This cross-sectional study was conducted among a representative sample (n = 557) of Shirazi adolescents aged 12–19 years. Participants’ systolic and diastolic BP was measured using a validated oscillometric BP monitor. Usual dietary intakes during the past 12 months were assessed using a valid and reproducible 168-item semiquantitative food frequency questionnaire through face-to-face interviews. Principal component factor analysis was used to identify major dietary patterns based on a set of 25 predefined food groups.Overall, three major dietary patterns were identified, among which only the Western pattern (abundant in soft drinks, sweets and desserts, salt, mayonnaise, tea and coffee, salty snacks, high-fat dairy products, French fries, and red or processed meats) had a significant association with BP. After adjusting for potential confounders in the analysis of covariance models, multivariable adjusted means of the systolic and mean BP of subjects in the highest tertile of the Western pattern score were significantly higher than those in the lowest tertile (for systolic BP: mean difference 6.9 mmHg, P = 0.001; and for mean BP: mean difference 4.2 mmHg, P = 0.003). A similar but statistically insignificant difference was observed in terms of diastolic BP.The findings suggest that a Western dietary pattern is associated with higher BP in Iranian adolescents. However, additional large-scale prospective studies with adequate methodological quality are required to confirm these findings.
Keywords: Diet; Factor analysis; Blood pressure; Adolescent; Iran

Fish oil diet in pregnancy and lactation reduces pup weight and modifies newborn hepatic metabolic adaptations in rats by Maria J. Jiménez; Carlos Bocos; Maribel Panadero; Emilio Herrera (409-420).
To determine the effects of a diet containing fish oil (FD) during pregnancy and lactation in rats on the metabolic adaptations made by the offspring during early extrauterine life and to compare it to an olive oil diet (OD).Rats were mated and randomly allocated to OD or FD containing 10 % of the corresponding oil. During lactation, litters were adjusted to eight pups per dam. Fetuses of 20 days and pups of 0, 1, 10, 20 and 30 days of age were studied. Body weight and length were lower in pups of the FD group from birth. The diet, milk, pups’ plasma and liver of FD group had higher proportions of n-3 LCPUFA, but the content of arachidonic acid (ARA) was lower. Plasma glucose was higher, but unesterified fatty acids, triacylglycerols (TAG), 3-hydroxybutyrate and liver TAG in 1-day-old pups were lower in the FD group, and differences in some of these variables were also found in pups up to 30 days old. Liver lipoprotein lipase activity and mRNA expression, and the expression of carnitine palmitoyl transferase I, acyl-CoA oxidase and 3-hydroxy 3-methyl glutaryl-CoA synthase increased more at birth in pups of the FD group, but the expression of sterol regulatory element binding protein-1c and Δ6-desaturase mRNA was lower in the FD group.Maternal intake of high n-3 LCPUFA retards postnatal development, which could be the result of impaired ARA synthesis, and affects hepatic metabolic adaptations to extrauterine life.
Keywords: Dietary fatty acids; Pregnancy; Lactation; Olive oil; Fish oil

Mediterranean diet score and total and cardiovascular mortality in Eastern Europe: the HAPIEE study by Denes Stefler; Sofia Malyutina; Ruzena Kubinova; Andrzej Pajak; Anne Peasey; Hynek Pikhart; Eric J. Brunner; Martin Bobak (421-429).
Mediterranean-type dietary pattern has been associated with lower risk of cardiovascular (CVD) and other chronic diseases, primarily in Southern European populations. We examined whether Mediterranean diet score (MDS) is associated with total, CVD, coronary heart disease (CHD) and stroke mortality in a prospective cohort study in three Eastern European populations.A total of 19,333 male and female participants of the Health Alcohol and Psychosocial factors in Eastern Europe (HAPIEE) study in the Czech Republic, Poland and the Russian Federation were included in the analysis. Diet was assessed by food frequency questionnaire, and MDS was derived from consumption of nine groups of food using absolute cut-offs. Mortality was ascertained by linkage with death registers.Over the median follow-up time of 7 years, 1314 participants died. The proportion of participants with high adherence to Mediterranean diet was low (25 %). One standard deviation (SD) increase in the MDS (equivalent to 2.2 point increase in the score) was found to be inversely associated with death from all causes (HR, 95 % CI 0.93, 0.88–0.98) and CVD (0.90, 0.81–0.99) even after multivariable adjustment. Inverse but statistically not significant link was found for CHD (0.90, 0.78–1.03) and stroke (0.87, 0.71–1.07). The MDS effects were similar in each country cohort.Higher adherence to the Mediterranean diet was associated with reduced risk of total and CVD deaths in these large Eastern European urban populations. The application of MDS with absolute cut-offs appears suitable for non-Mediterranean populations.
Keywords: Diet; Nutrition; Mortality; Prevention; Eastern Europe

A high-fat, high-saturated fat diet decreases insulin sensitivity without changing intra-abdominal fat in weight-stable overweight and obese adults by Anize D. von Frankenberg; Anna Marina; Xiaoling Song; Holly S. Callahan; Mario Kratz; Kristina M. Utzschneider (431-443).
We sought to determine the effects of dietary fat on insulin sensitivity and whether changes in insulin sensitivity were explained by changes in abdominal fat distribution or very low-density lipoprotein (VLDL) fatty acid composition. Overweight/obese adults with normal glucose tolerance consumed a control diet (35 % fat/12 % saturated fat/47 % carbohydrate) for 10 days, followed by a 4-week low-fat diet (LFD, n = 10: 20 % fat/8 % saturated fat/62 % carbohydrate) or high-fat diet (HFD, n = 10: 55 % fat/25 % saturated fat/27 % carbohydrate). All foods and their eucaloric energy content were provided. Insulin sensitivity was measured by labeled hyperinsulinemic-euglycemic clamps, abdominal fat distribution by MRI, and fasting VLDL fatty acids by gas chromatography.The rate of glucose disposal (Rd) during low- and high-dose insulin decreased on the HFD but remained unchanged on the LFD (Rd-low: LFD: 0.12 ± 0.11 vs. HFD: −0.37 ± 0.15 mmol/min, mean ± SE, p < 0.01; Rd-high: LFD: 0.11 ± 0.37 vs. HFD: −0.71 ± 0.26 mmol/min, p = 0.08). Hepatic insulin sensitivity did not change. Changes in subcutaneous fat were positively associated with changes in insulin sensitivity on the LFD (r = 0.78, p < 0.01) with a trend on the HFD (r = 0.60, p = 0.07), whereas there was no association with intra-abdominal fat. The LFD led to an increase in VLDL palmitic (16:0), stearic (18:0), and palmitoleic (16:1n7c) acids, while no changes were observed on the HFD. Changes in VLDL n-6 docosapentaenoic acid (22:5n6) were strongly associated with changes in insulin sensitivity on both diets (LFD: r = −0.77; p < 0.01; HFD: r = −0.71; p = 0.02).A diet very high in fat and saturated fat adversely affects insulin sensitivity and thereby might contribute to the development of type 2 diabetes.NCT00930371.
Keywords: Dietary fat; Saturated fat; High-fat diet; Insulin sensitivity

Are Belgian toddlers over-eating? by Ute Alexy; Annett Hilbig (445-446).

Methodological issues in food surveys by K. Huysentruyt; J. De Schepper; Y. Vandenplas (447-447).