European Journal of Nutrition (v.57, #5)

Height and body fatness and colorectal cancer risk: an update of the WCRF–AICR systematic review of published prospective studies by Leila Abar; Ana Rita Vieira; Dagfinn Aune; Jakub G. Sobiecki; Snieguole Vingeliene; Elli Polemiti; Christophe Stevens; Darren C. Greenwood; Doris S. M. Chan; Sabrina Schlesinger; Teresa Norat (1701-1720).
There is no published dose–response meta-analysis on the association between height and colorectal cancer risk (CRC) by sex and anatomical sub-site. We conducted a meta-analysis of prospective studies on the association between height and CRC risk with subgroup analysis and updated evidence on the association between body fatness and CRC risk.PubMed and several other databases were searched up to November 2016. A random effects model was used to calculate dose–response summary relative risks (RR’s).47 studies were included in the meta-analyses including 50,936 cases among 7,393,510 participants. The findings support the existing evidence regarding a positive association of height, general and abdominal body fatness and CRC risk. The summary RR were 1.04 [95% (CI)1.02–1.05, I² = 91%] per 5 cm increase in height, 1.02 [95% (CI)1.01–1.02, I² = 0%] per 5 kg increase in weight, 1.06 [95% (CI)1.04–1.07, I² = 83%] per 5 kg/m2 increase in BMI, 1.02 [95% (CI)1.02–1.03, I² = 4%] per 10 cm increase in waist circumference, 1.03 [95% (CI)1.01–1.05, I² = 16%] per 0.1 unit increase in waist to hip ratio. The significant association for height and CRC risk was similar in men and women. The significant association for BMI and CRC risk was stronger in men than in women.The positive association between height and risk of CRC suggests that life factors during childhood and early adulthood might play a role in CRC aetiology. Higher general and abdominal body fatness during adulthood are risk factors of CRC and these associations are stronger in men than in women.
Keywords: Height; BMI; Colorectal cancer; Meta-analysis; Continuous update project

The number of overweight and obese women is increasing in the obstetric population. The aim of this study was to review studies that reported results related to the efficacy of dietary interventions on gestational weight gain (GWG) or the prevention of gestational diabetes (GDM) in overweight and obese women.The search was performed using the CINAHL, PubMed, Scopus and Medic electronic databases and limited to the years between 2000 and March 2016. This systematic review includes 15 research articles of which 12 were randomized controlled trials, and three were controlled trials. Three main categories emerged as follows: (1) the types of interventions, (2) the contents of the interventions and (3) the efficacy of the intervention on GWG and the prevention of GDM. The quality of the selected studies was evaluated using the AHRQ Methods Reference Guide for Effectiveness and Comparative Effectiveness Reviews.Of the selected 15 studies, eight included a specified diet with limited amounts of nutrients or energy, and the others included a dietary component along with other components. Ten studies reported significant differences in the measured outcomes regarding GWG or the prevention of GDM between the intervention and the control groups.This review confirms the variability in the strategies used to deliver dietary interventions in studies aiming to limit GWG and prevent GDM in overweight and obese women. Inconsistency in the provider as well as the content of the dietary interventions leaves the difficulty of summarizing the components of effective dietary interventions.
Keywords: Dietary intervention; Gestational weight gain; Gestational diabetes; Systematic review

Effect of GPR84 deletion on obesity and diabetes development in mice fed long chain or medium chain fatty acid rich diets by Eugene Du Toit; Liam Browne; Helen Irving-Rodgers; Helen M. Massa; Nicolette Fozzard; Michael P. Jennings; Ian R. Peak (1737-1746).
Although there is good evidence showing that diets rich in medium chain fatty acids (MCFAs) have less marked obesogenic and diabetogenic effects than diets rich in long chain fatty acids (LCFAs), the role of the pro-inflammatory, medium chain fatty acid receptor (GPR84) in the aetiology of obesity and glucose intolerance is not well characterised. We set out to determine whether GPR84 expression influences obesity and glucose intolerance susceptibility in MCFA and LCFA rich diet fed mice.Wild type (WT) and GPR84 knockout (KO) mice were fed a control, MCFA or LCFA diet, and body mass, heart, liver and epididymal fat mass was assessed, as well as glucose tolerance and adipocyte size.LCFA diets increased body mass and decreased glucose tolerance in both WT and GPR84 KO animals while MCFA diets had no effect on these parameters. There were no differences in body weight when comparing WT and GPR84 KO mice on the respective diets. Glucose tolerance was also similar in WT and GPR84 KO mice irrespective of diet. Liver mass was increased following LCFA feeding in WT but not GPR84 KO mice. Hepatic triglyceride content was increased in GPR84 KO animals fed MCFA, and myocardial triglyceride content was increased in GPR84 KO animals fed LCFA.GPR84 deletion had no effects on body weight or glucose tolerance in mice fed either a high MCFA or LCFA diet. GPR84 may influence lipid metabolism, as GPR84 KO mice had smaller livers and increased myocardial triglyceride accumulation when fed LCFA diets, and increased liver triglyceride accumulation in responses to increased dietary MCFAs.
Keywords: Fatty acid receptor; Medium chain fatty acid; Dietary study

Associations between a Mediterranean diet pattern and inflammatory biomarkers in European adolescents by Aline Arouca; Nathalie Michels; Luis A. Moreno; Esther M. González-Gil; Ascensión Marcos; Sonia Gómez; Ligia Esperanza Díaz; Kurt Widhalm; Dénes Molnár; Yannis Manios; Frederic Gottrand; Antonio Kafatos; Mathilde Kersting; Michael Sjöström; Alejandro de la O; Marika Ferrari; Inge Huybrechts; Marcela Gonzalez-Gross; Stefaan De Henauw (1747-1760).
To test whether the Mediterranean diet score and each food-subgroup is associated with inflammatory biomarkers in European adolescents.In 464 adolescents (13–17 years) of the European HELENA study, data were available on body composition, inflammation markers, and food intake determined by two computerized 24-h recalls. The Mediterranean diet score and its food-subgroups (Vegetables, Fruits and Nuts, Pulses, Cereal and Roots, Monounsaturated/Saturated fat ratio, Dairy, Fish, Meat and Alcohol) were evaluated. A set of inflammation-related biomarkers was measured: IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, TGFβ-1, TNF-α, sVCAM-1, sICAM1, sE-selectin, white blood cells, lymphocytes, CD3, CRP, GGT, ALT, and homocysteine. Multivariate and multiple linear regression analyses were adjusted for age, sex, country, socioeconomic status, paternal and maternal education, adiposity, and smoking habits.The Mediterranean diet score was positively associated with CRP, and negatively with sVCAM-1. The subgroups showed the following positive/negative associations: Vegetables with IL-10(+), CRP(+), CD3(+), ALT(+), lymphocytes(+), sE-selectin(−); Fruits and Nuts with IL-4(−), TNF-alpha; Pulses with IL-5(+), IL-6(+), IL-2(−); Cereals and Roots with IL-6(−), IL-10(−); Monounsaturated/Saturated-fat ratio with IL-6(+), TGFβ-1(+), sVCAM-1(+boys, −girls), homocysteine(−); Dairy with IL-1(+), IL-5(+), IL-6(+), IL-10(+), TGFβ-1(+), homocysteine(−); Fish with homocysteine(−); Meat with IL-2(+), IL-10(+); Alcohol with CRP(+), lymphocytes(−). Sex differences were found.Some specific food–inflammation associations were found, suggesting that diet is to a certain extent already related to inflammation in adolescents and can be used in disease prevention. Also some counterintuitive results were found, which might be due to grouping very different foods into a single group, besides considering that the human body may respond differently depending on the interaction between diet, lifestyle, genetics, biochemical individuality, age and sex.
Keywords: Mediterranean diet; Inflammation; Adolescents; Diet–inflammation associations

Exploring the relationship between perceived barriers to healthy eating and dietary behaviours in European adults by M. G. M. Pinho; J. D. Mackenbach; H. Charreire; J.-M. Oppert; H. Bárdos; K. Glonti; H. Rutter; S. Compernolle; I. De Bourdeaudhuij; J. W. J. Beulens; J. Brug; J. Lakerveld (1761-1770).
Dietary behaviours may be influenced by perceptions of barriers to healthy eating. Using data from a large cross-European study (N = 5900), we explored associations between various perceived barriers to healthy eating and dietary behaviours among adults from urban regions in five European countries and examined whether associations differed across regions and socio-demographic backgrounds.Frequency of consumption of fruit, vegetables, fish, fast food, sugar-sweetened beverages, sweets, breakfast and home-cooked meals were split by the median into higher and lower consumption. We tested associations between barriers (irregular working hours; giving up preferred foods; busy lifestyle; lack of willpower; price of healthy food; taste preferences of family and friends; lack of healthy options and unappealing foods) and dietary variables using multilevel logistic regression models. We explored whether associations differed by age, sex, education, urban region, weight status, household composition or employment.Respondents who perceived any barrier were less likely to report higher consumption of healthier foods and more likely to report higher consumption of fast food. ‘Lack of willpower’, ‘time constraints’ and ‘taste preferences’ were most consistently associated with consumption. For example, those perceiving lack of willpower ate less fruit [odds ratio (OR) 0.57; 95% confidence interval (CI) 0.50–0.64], and those with a busy lifestyle ate less vegetables (OR 0.54; 95% CI 0.47–0.62). Many associations differed in size, but not in direction, by region, sex, age and household composition.Perceived ‘lack of willpower’, ‘time constraints’ and ‘taste preferences’ were barriers most strongly related to dietary behaviours, but the association between various barriers and lower intake of fruit and vegetables was somewhat more pronounced among younger participants and women.
Keywords: Dietary behaviours; Perceived barriers; Willpower; Price; Time; Taste preferences

Folate required to achieve desirable red blood cell (RBC) folate concentrations within 4–8 weeks pre-pregnancy is not known. We studied the effect of supplementation with 400 or 800 µg/day folate in achieving RBC-folate ≥906 nmol/L.Non-pregnant women were randomized to receive multinutrient supplements containing 400 µg/day (n = 100) or 800 µg/day (n = 101) folate [folic acid and (6S)-5-CH3-H4folate-Ca (1:1)]. The changes of folate biomarkers were studied after 4 and 8 weeks in the 198 women who returned at least for visit 2.At baseline, 12 of the 198 participants (6.1%) had RBC-folate <340 nmol/L, but 88% had levels <906 nmol/L. The RBC-folate concentrations increased significantly in the 800 µg/day (mean ± SD = 652 ± 295 at baseline; 928 ± 330 at 4 weeks; and 1218 ± 435 nmol/L at 8 weeks) compared with the 400 µg/day [632 ± 285 at baseline (p = 0.578); 805 ± 363 at 4 weeks (p < 0.001); 1021 ± 414 nmol/L at 8 weeks (p < 0.001)]. The changes of RBC-folate were greater in the 800 µg/day than in the 400 µg/day at any time (changes after 8 weeks: 566 ± 260 vs. 389 ± 229 nmol/L; p < 0.001). Significantly more women in the 800 µg group achieved desirable RBC-folate concentrations at 4 weeks (45.5 vs. 31.3%; p = 0.041) or 8 weeks (83.8 vs. 54.5%; p < 0.001) compared with the 400 µg group. RBC-folate levels below the population median (590 nmol/L) were associated with a reduced response to supplements.88% of the women had insufficient RBC-folate to prevent birth defects, while 6.1% had deficiency. Women with low RBC-folate were unlikely to achieve desirable levels within 4–8 weeks, unless they receive 800 µg/day. The current supplementation recommendations are not sufficient in countries not applying fortification.The trial was registered at The German Clinical Trials Register: DRKS-ID: DRKS00009770.
Keywords: (6S)-5-CH3-H4folate-Ca; Folic acid; RBC-folate; Homocysteine; Preconceptional; Neural tube defects; Supplementation

Interleukin (IL)-1β can activate glial cells to trigger neuroinflammation and neurodegeneration. Lower omega (n)-3 polyunsaturated fatty acids (PUFAs) and lower n-3/n-6 PUFA ratios occur in the brain of patients with Alzheimer’s disease (AD). We have previously reported that an n-3 PUFA, eicosapentaenoic acid (EPA), can improve memory and attenuate neurodegeneration-like changes in animal models of AD. However, whether and how EPA modulates glial cell activity and functions remains unclear. The aim of this study was to test the hypothesis that EPA may attenuate neuroinflammation by inhibiting microglial activation and microglia-produced proinflammatory cytokines, and by enhancing the expression of astrocytes-produced neurotrophins and their receptors.Male Long-Evans rats were fed either palm oil supplemented diet or EPA supplemented diet for 42 days. On day 36 of diet feeding, rats received an intracerebroventricular injection of IL-1β or saline for 7 days. The glial activation, the expression of amyloid precursor protein (APP), calcium-dependent phospholipase (cPL) A2, brain-derived neurotrophic factor (BDNF) and its receptor, and PUFA profile in the hippocampus were analyzed.IL-1β elevated biomarkers of microglial CD11b and astrocyte GFAP expression, increased the expression of APP, tumor-necrosis factor (TNF)-α, but reduced BDNF and its receptor (TrKB). IL-1β also lowered n-3 EPA and docosapentaenoic acid concentrations but increased n-6 PUFAs and cPLA2 activity in the hippocampus. EPA supplement normalized the n-3 and n-6 PUFA profiles and cPLA2 levels, inhibited glial activation, reduced APP and TNF-α expression, as well as up-regulated BDNF and TrKB.Supplementation with EPA appear to have potential effects on improving glial over-activation, n3/n6 imbalance and BDNF down-regulation, which contribute to anti-inflammatory and may provide beneficial effects on inflammation-associated disease such as AD.
Keywords: Eicosapentaenoic acid; IL-1β; Inflammation; Brain-derived neurotrophic factor; Proinflammatory cytokine

Polyphenolic extract attenuates fatty acid-induced steatosis and oxidative stress in hepatic and endothelial cells by Laura Vergani; Giulia Vecchione; Francesca Baldini; Elena Grasselli; Adriana Voci; Piero Portincasa; Pier Francesco Ferrari; Bahar Aliakbarian; Alessandro A. Casazza; Patrizia Perego (1793-1805).
Phenolic compounds (PC) of virgin olive oil exert several biochemical and pharmacological beneficial effects. Some dietary PC seem to prevent/improve obesity and metabolic-related disorders such as non-alcoholic fatty liver disease (NAFLD). We investigated the possible effects of PC extracted from olive pomace (PEOP) and of the main single molecules present in the extract (tyrosol, apigenin, oleuropein, p-coumaric and caffeic acid) in protecting hepatocytes and endothelial cells against triglyceride accumulation and oxidative stress.Rat hepatoma and human endothelial cells were exposed to a mixture of oleate/palmitate to mimic the condition of NAFLD and atherosclerosis, respectively. Then, cells were incubated for 24 h in the absence or in the presence of PC or PEOP. Different parameters were evaluated, such as lipid accumulation and oxidative stress-related markers.In hepatic cells, expression of peroxisome proliferator-activated receptors (PPARs) and of stearoyl-CoA desaturase 1 (SCD-1) were assessed as index of lipid metabolism. In endothelial cells, expression of intercellular adhesion molecule-1 (ICAM-1), activation of nuclear factor kappa-B (NF-kB), release of nitric oxide (NO), and wound-healing rate were assessed as index of inflammation.PEOP extract ameliorated hepatic lipid accumulation and lipid-dependent oxidative imbalance thus showing potential applications as therapeutic agent tuning down hepatosteatosis and atherosclerosis.
Keywords: Non-alcoholic fatty liver disease; Atherosclerosis; Olive pomace; Phenolic compound; Oxidative stress

Comparison of urinary iodine levels in women of childbearing age during and after pregnancy by Ane Miren Castilla; Mario Murcia; Juan José Arrizabalaga; Mercedes Espada; Jordi Julvez; Mikel Basterrechea; Mar Alvarez-Pedrerol; Marisa Estarlich; Elena Moreno; Mònica Guxens; Jesús Vioque; Marisa Rebagliato (1807-1816).
Median urinary iodine concentration (UIC) is used to describe the iodine status of a population. However, the link between UIC and iodine intake may vary during pregnancy. The aim of this study was to compare UIC during and after pregnancy, adjusting for factors that affect iodine intake.Two repeated measures of UIC and data on maternal iodine intake estimated through questionnaires were collected during pregnancy and 1–4 years after pregnancy in a subsample of women (n = 598) from a mother and child cohort study in Spain. Random-effects interval regression was used to assess the changes in UIC according to pregnancy status.Median UIC was similar during (133 μg/L) and after pregnancy (139 μg/L). After adjusting for iodised salt, iodine supplement consumption, and socio-demographic related variables, UIC was 24.0% (95% CI 11.3, 38.2) higher after than during pregnancy. This difference was maintained in a subsample of women with exhaustive information on diet (n = 291): 26.2%, 95% CI 10.3, 44.4.In an iodine sufficient area for the general population, iodine excretion was lower during than after pregnancy when factors affecting iodine intake were controlled for. Current recommendations of median UIC during pregnancy are based on the equivalence between iodine intake and UIC estimated from studies in non-pregnant populations, which might lead to overestimation of iodine deficiency during gestation. Further studies should evaluate the equivalence between iodine intake and its urinary excretion during pregnancy.
Keywords: Iodine/urine; Pregnancy; Female; Nutritional status; Reference values

Comparison of the effects of three different Baccaurea angulata whole fruit juice doses on plasma, aorta and liver MDA levels, antioxidant enzymes and total antioxidant capacity by Muhammad Ibrahim; Maryam Abimbola Mikail; Idris Adewale Ahmed; Norazlanshah Hazali; Mohammad Syaiful Bahari Abdul Rasad; Radiah Abdul Ghani; Ridzwan Hashim; Solachuddin Jahuari Arief; Muhammad Lokman Md Isa; Samsul Draman (1817-1828).
Baccaurea angulata (common names: belimbing dayak or belimbing hutan) is a Malaysian underutilized fruit. The preliminary work on B. angulata fruit juice showed that it possesses antioxidant properties. Therefore, further work is needed to confirm the efficacy and proper dosage of B. angulata as a potential natural antioxidant. The present study was thus carried out to compare the effects of three different B. angulata whole fruit (WF) juice doses administered at nutritional doses of 0.50, 1.00 and 1.50 ml/kg/day on plasma, aorta and liver malondialdehyde (MDA) levels, antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase) as well as total antioxidant capacity in rabbits fed high-cholesterol diet.Thirty-five male rabbits of New Zealand strain were randomly assigned to seven groups. For 12 weeks, group CH was fed 1% cholesterol diet only; group C1 was fed 1% cholesterol diet and 0.50 ml/kg/day B. angulata WF juice; group C2 was fed 1% cholesterol diet and 1.00 ml/kg/day B. angulata WF juice; group C3 was fed 1% cholesterol diet and 1.50 ml/kg/day B. angulata WF juice; group N was fed standard pellet only; group N1 was fed standard pellet and 0.50 ml/kg/day B. angulata WF juice; and group N2 was fed standard pellet and 1.00 ml/kg/day B. angulata WF juice.The three doses reduced the formation of MDA and enhanced the expression of endogenous antioxidant enzymes. The highest dose used (1.50 ml/kg/day) was, however, seen as the most potent.Higher doses of B. angulata juice exerted better antioxidant activity.
Keywords: Antioxidant enzymes; Baccaurea angulata ; Doses; Malondialdehyde; Underutilized fruit

Cranberry (Vaccinium macrocarpon) extract treatment improves triglyceridemia, liver cholesterol, liver steatosis, oxidative damage and corticosteronemia in rats rendered obese by high fat diet by Thamara C. Peixoto; Egberto G. Moura; Elaine de Oliveira; Patrícia N. Soares; Deysla S. Guarda; Dayse N. Bernardino; Xu Xue Ai; Vanessa da S. T. Rodrigues; Gabriela Rodrigues de Souza; Antonio Jorge Ribeiro da Silva; Mariana S. Figueiredo; Alex C. Manhães; Patrícia C. Lisboa (1829-1844).
Obese individuals have higher production of reactive oxygen species, which leads to oxidative damage. We hypothesize that cranberry extract (CE) can improve this dysfunction in HFD-induced obesity in rats since it has an important antioxidant activity. Here, we evaluated the effects of CE in food intake, adiposity, biochemical and hormonal parameters, lipogenic and adipogenic factors, hepatic morphology and oxidative balance in a HFD model.At postnatal day 120 (PN120), male Wistar rats were assigned into two groups: (1) SD (n = 36) fed with a standard diet and (2) HFD (n = 36), fed with a diet containing 44.5% (35.2% from lard) energy from fat. At PN150, 12 animals from SD and HFD groups were killed while the others were subdivided into four groups (n = 12/group): animals that received 200 mg/kg cranberry extract (SD CE, HFD CE) gavage/daily/30 days or water (SD, HFD). At PN180, animals were killed.HFD group showed higher body mass and visceral fat, hypercorticosteronemia, higher liver glucocorticoid sensitivity, cholesterol and triglyceride contents and microsteatosis. Also, HFD group had higher lipid peroxidation (plasma and tissues) and higher protein carbonylation (liver and adipose tissue) compared to SD group. HFD CE group showed lower body mass gain, hypotrygliceridemia, hypocorticosteronemia, and lower hepatic cholesterol and fatty acid synthase contents. HFD CE group displayed lower lipid peroxidation, protein carbonylation (liver and adipose tissue) and accumulation of liver fat compared to HFD group.Although adiposity was not completely reversed, cranberry extract improved the metabolic profile and reduced oxidative damage and steatosis in HFD-fed rats, which suggests that it can help manage obesity-related disorders.
Keywords: Obesity; High fat diet; Cranberry extract; Corticosterone; Lipids; Oxidative stress

High protein intake along with paternal part-time employment is associated with higher body fat mass among girls from South China by Ming-zhe Yang; Hong-mei Xue; Jay Pan; Lars Libuda; Rebecca Muckelbauer; Min Yang; Liming Quan; Guo Cheng (1845-1854).
Protein intake has been suggested to be associated with body composition among western children. Our aim was to determine whether protein intake is associated with body composition among Chinese children and to investigate whether parental socioeconomic status modifies these associations.Cross-sectional data were collected from the baseline survey of an ongoing population-based prospective open cohort study conducted in 2013. In this survey, 2039 children in South China were recruited using cluster random sampling. Information of 1704 children (47% girls), aged 7–12 years from three primary schools (42 classes), on diet and anthropometry was included finally. Their daily protein intake was obtained by 3-day 24-h dietary recalls. Skinfold thickness, body height, and weight were measured to calculate percent body fat (%BF), fat mass index (FMI), and fat-free mass index (FFMI). Parental characteristics were collected by questionnaires.Among girls, protein intake was positively associated with %BF and FMI [estimate (SE) for %BF: 0.007 (0.003), p = 0.04; for FMI: 0.092 (0.002), p = 0.03], adjusted for pubertal stage, breast-feeding, maternal overweight, carbohydrate intake, energy intake, and physical activity level. Furthermore, there was interaction between paternal occupation and the relations of dietary protein with %BF and FMI (p for interaction ≤ 0.04). None of the associations between protein intake and %BF, FMI, or FFMI was found among boys.Our data indicate that school-aged girls, but not boys, living in South China with higher dietary protein intake might have higher body fat mass, which could be modified by paternal occupation.
Keywords: Dietary protein; Body composition; Paternal occupation; Children

Effect of increasing fruit and vegetable intake by dietary intervention on nutritional biomarkers and attitudes to dietary change: a randomised trial by Susan J. Duthie; Garry G. Duthie; Wendy R. Russell; Janet A. M. Kyle; Jennie I. Macdiarmid; Vanessa Rungapamestry; Sylvia Stephen; Cristina Megias-Baeza; Joanna J. Kaniewska; Lindsey Shaw; Lesley Milne; David Bremner; Karen Ross; Philip Morrice; Lynn P. Pirie; Graham Horgan; Charles S. Bestwick (1855-1872).
Low fruit and vegetable consumption is linked with an increased risk of death from vascular disease and cancer. The benefit of eating fruits and vegetables is attributed in part to antioxidants, vitamins and phytochemicals. Whether increasing intake impacts on markers of disease remains to be established. This study investigates whether increasing daily intake of fruits, vegetables and juices from low (approx. 3 portions), to high intakes (approx. 8 portions) impacts on nutritional and clinical biomarkers. Barriers to achieving the recommended fruit and vegetable intakes are also investigated.In a randomised clinical trial, the participants [19 men and 26 women (39–58 years)] with low reported fruit, juice and vegetable intake (<3 portions/day) were randomised to consume either their usual diet or a diet supplemented with an additional 480 g of fruit and vegetables and fruit juice (300 ml) daily for 12 weeks. Nutritional biomarkers (vitamin C, carotenoids, B vitamins), antioxidant capacity and genomic stability were measured pre-intervention, at 4-, 8- and 12 weeks throughout the intervention. Samples were also taken post-intervention after a 6-week washout period. Glucose, homocysteine, lipids, blood pressure, weight and arterial stiffness were also measured. Intake of fruit, fruit juice and vegetables was reassessed 12 months after conducting the study and a questionnaire was developed to identify barriers to healthy eating.Intake increased significantly in the intervention group compared to controls, achieving 8.4 portions/day after 12 weeks. Plasma vitamin C (35%), folate (15%) and certain carotenoids [α-carotene (50%) and β-carotene (70%) and lutein/zeaxanthin (70%)] were significantly increased (P < 0.05) in the intervention group. There were no significant changes in antioxidant capacity, DNA damage and markers of vascular health. Barriers to achieving recommended intakes of fruits and vegetables measured 12 months after the intervention period were amount, inconvenience and cost.While increasing fruit, juice and vegetable consumption increases circulating level of beneficial nutrients in healthy subjects, a 12-week intervention was not associated with effects on antioxidant status or lymphocyte DNA damage.This trial was registered at; registration ISRCTN71368072.
Keywords: Fruit; Vegetables; Human intervention; Dietary change; Biomarkers; Attitudes

SEPP1 polymorphisms modulate serum glucose and lipid response to Brazil nut supplementation by Janaina L. S. Donadio; Marcelo M. Rogero; Elvira M. Guerra-Shinohara; Charles Desmarchelier; Patrick Borel; Silvia M. F. Cozzolino (1873-1882).
The consumption of Brazil nuts has been associated with benefits to lipid metabolism and reductions in total cholesterol and LDL concentrations. They are the richest natural source of selenium which has essential functions in human physiology. Genetic polymorphisms in Selenoprotein P could impair lipid and glucose metabolisms. The aim of this work was to verify the influence of polymorphisms in genes for selenoproteins on blood lipid levels after dietary supplementation with Brazil nuts in healthy adults.The study included 130 healthy volunteers selected at the University of São Paulo, Brazil. They were supplemented with one nut a day for 8 weeks, followed by 8 weeks without intervention. The following analyses were performed: anthropometric measurements, serum fasting glucose, lipid profile, C-reactive protein and plasma MDA levels. The volunteers were genotyped for SNPs rs1050450, rs3811699, rs1800699, rs713041, rs3877899, rs7579, rs34713741, and rs5845 in genes for selenoproteins.The concentrations of total cholesterol and fasting glucose levels decreased after 8 weeks of supplementation (p < 0.05). Glucose levels were modulated by rs3877899 in SEPP1, with significantly lower levels observed for individuals with the GA + AA genotype (p = 0.025). In addition, rs7579 was associated with cholesterol concentrations, which were significantly lower for individuals with the GG genotype (p = 0.053).Supplementation with one Brazil nut a day for 8 weeks reduced total cholesterol and glucose levels. Furthermore, our results suggest that rs3877899 might be associated with glucose concentrations and rs7579 with cholesterol concentrations. Therefore, the effect of genetic variations should be considered in future nutritional interventions evaluating the response to Brazil nut supplementation.
Keywords: Brazil nuts; Lipid profile; Polymorphisms; Nutrigenetics

Effect of increased water intake on plasma copeptin in healthy adults by Guillaume Lemetais; Olle Melander; Mariacristina Vecchio; Jeanne H. Bottin; Sofia Enhörning; Erica T. Perrier (1883-1890).
Inter-individual variation in median plasma copeptin is associated with incident type 2 diabetes mellitus, progression of chronic kidney disease, and cardiovascular events. In this study, we examined whether 24-h urine osmolality was associated with plasma copeptin and whether increasing daily water intake could impact circulating plasma copeptin.This trial was a prospective study conducted at a single investigating center. Eighty-two healthy adults (age 23.6 ± 2.9 years, BMI 22.2 ± 1.5 kg/m2, 50% female) were stratified based upon habitual daily fluid intake volumes: arm A (50–80% of EFSA dietary reference values), arm B (81–120%), and arm C (121–200%). Following a baseline visit, arms A and B increased their water intake to match arm C for a period of 6 consecutive weeks.At baseline, plasma copeptin was positively and significantly associated with 24-h urine osmolality (p = 0.002) and 24-h urine specific gravity (p = 0.003) but not with plasma osmolality (p = 0.18), 24-h urine creatinine (p = 0.09), and total fluid intake (p = 0.52). Over the 6-week follow-up, copeptin decreased significantly from 5.18 (3.3;7.4) to 3.90 (2.7;5.7) pmol/L (p = 0.012), while urine osmolality and urine specific gravity decreased from 591 ± 206 to 364 ± 117 mOsm/kg (p < 0.001) and from 1.016 ± 0.005 to 1.010 ± 0.004 (p < 0.001), respectively.At baseline, circulating levels of copeptin were positively associated with 24-h urine concentration in healthy young subjects with various fluid intakes. Moreover, this study shows, for the first time, that increased water intake over 6 weeks results in an attenuation of circulating copeptin. NCT02044679.
Keywords: Copeptin; Fluid intake; Hydration; Urine osmolality; Water intake

High-fat diet inhibits PGC-1α suppressive effect on NFκB signaling in hepatocytes by Wermerson Assunção Barroso; Vanessa Jacob Victorino; Isabela Casagrande Jeremias; Ricardo Costa Petroni; Suely Kunimi Kubo Ariga; Thiago A Salles; Denise Frediani Barbeiro; Thais Martins de Lima; Heraldo Possolo de Souza (1891-1900).
The peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) regulates the expression of genes implicated in fatty acid oxidation and oxidative phosphorylation. Its role in liver steatosis is well established, since mice with liver-specific deletion of PGC-1α exhibit lipid accumulation and high-fat diet reduces hepatic PGC-1α expression in mice. In this study, we investigated the role of PGC-1α in the inflammatory changes observed in steatohepatitis induced by high-fat diet.C57black/6 mice were fed a high-fat diet containing 30% fat for 10 weeks. After euthanasia, liver morphology was examined by HE staining and inflammation was determined by IL-6, TNF-α, and IL-1β quantification. Liver gene expression of PGC-1 isoforms was evaluated by real-time PCR and p65 NFκB nuclear translocation by Western blotting. HepG2 cells were treated with linoleic acid overload for 72 h to create an in vitro model of steatohepatitis. RNA interference (RNAi) was used to evaluate the involvement of PGC-1α on inflammatory mediators’ production by hepatocytes.The high-fat diet led to a state of nonalcoholic steatohepatitis, associated with increased deposits of intra-abdominal fat, hyperglycemia and hyperlipidemia. Mice liver also exhibited increased proinflammatory cytokines’ levels, decreased PGC-1α expression, and marked increase in p65 NFκB nuclear translocation. Linoleic acid treated cells also presented increased expression of proinflammatory cytokines and decreased PGC-1α expression. The knockdown of PGC-1α content caused an increase in IL-6 expression and release via enhanced IκBα phosphorylation and subsequent increase of p65 NFκB nuclear translocation.High-fat diet induces liver inflammation by inhibiting PGC-1α expression and its suppressive effect in NFκB pathway.
Keywords: PGC-1α; Steatosis; Inflammation; Hepatocytes; Interleukin-6; NF-κB

Father’s obesity programs the adipose tissue in the offspring via the local renin–angiotensin system and MAPKs pathways, especially in adult male mice by Fernanda Ornellas; Isabele Bringhenti; Brenda Akemi N. F. Mattos; Carlos Alberto Mandarim-de-Lacerda; Marcia Barbosa Aguila (1901-1912).
Studies demonstrated the influence of mother’s obesity on offspring. However, the father is also related to programming the future generation. The study aimed to evaluate the effects of father’s obesity upon white adipose tissue (WAT) remodeling, resulting in activation of signaling pathways and inflammation in male and female offspring.Male C57BL/6 mice received control diet (lean father group; 17% energy from lipids) or high-fat diet (obese father group; 49% energy from lipids) for 8 weeks before mating. The mothers received control diet throughout the experiment. Mice were mated: lean mother and lean father, and lean mother and obese father. Offspring received control diet from weaning until 3 months of age when they were studied.In the offspring, father’s obesity led to decreased QUICKI with impairment of the insulin signaling pathway in both sexes. In line with these findings, in white adipose tissue, male offspring demonstrated hypertrophied adipocytes, enhanced proinflammatory cytokines, overactivation of components of the local renin–angiotensin system (RAS) and extracellular signal-regulated kinase 1/2 (ERK1/2), and inhibition of peroxisome proliferator-activated receptors (alpha and gamma).We observed that father’s obesity influences the offspring in adult life, with an impairment in insulin homeostasis, adipocyte remodeling, and adipose tissue overexpression of IL-6 and TNF-alpha in male offspring. The activation of local RAS and ERK1/2, a concomitant PPAR diminishing, and impairment in phosphorylation of AKT and IRS-1 could explain at least in part the findings regardless of the increase in body mass in the offspring.
Keywords: Adipocyte; Genital fat pad; Programming; Inflammation; Molecular biology

Effect of a trans fatty acid-enriched diet on mitochondrial, inflammatory, and oxidative stress parameters in the cortex and hippocampus of Wistar rats by Rafael Longhi; Roberto Farina Almeida; Leticia Ferreira Pettenuzzo; Débora Guerini Souza; Letiane Machado; André Quincozes-Santos; Diogo Onofre Souza (1913-1924).
Previously showed that dietary trans fatty acids (TFAs) may cause systemic inflammation and affect the central nervous system (CNS) in Wistar rats by increased levels of cytokines in the cerebrospinal fluid (CSF) and serum (Longhi et al. Eur J Nutr 56(3):1003–1016, 1). Here, we aimed to clarifying the impact of diets with different TFA concentrations on cerebral tissue, focusing on hippocampus and cortex and behavioral performance.Wistar rats were fed either a normolipidic or a hyperlipidic diet for 90 days; diets had the same ingredients except for fat compositions, concentrations, and calories. We used lard in the cis fatty acid (CFA) group and PHSO in the TFA group. The intervention groups were as follows: (1) low lard (LL), (2) high lard (HL), (3) low partially hydrogenated soybean oil (LPHSO), and (4) high partially hydrogenated soybean oil (HPHSO). Mitochondrial parameters, tumor necrosis factor alpha (TNF-α), 2′7′-dichlorofluorescein (DCFH) levels in brain tissue, and open field task were analyzed.A worse brain tissue response was associated with oxidative stress in cortex and hippocampus as well as impaired inflammatory and mitochondrial parameters at both PHSO concentrations and there were alterations in the behavioral performance. In many analyses, there were no significant differences between the LPHSO and HPHSO diets.Partially hydrogenated soybean oil impaired cortical mitochondrial parameters and altered inflammatory and oxidative stress responses, and the hyperlipidic treatment caused locomotor and exploratory effects, but no differences on weight gain in all treatments. These findings suggest that quality is more important than the quantity of fat consumed in terms of CFA and TFA diets.
Keywords: Brain damage; Diet; Lipids; Neurodegeneration; Partially hydrogenated soybean oil

Effect of olive cultivar on bioaccessibility and antioxidant activity of phenolic fraction of virgin olive oil by Angélica Quintero-Flórez; Gema Pereira-Caro; Cristina Sánchez-Quezada; José Manuel Moreno-Rojas; José J. Gaforio; Antonio Jimenez; Gabriel Beltrán (1925-1946).
This study aims to characterize the phenolic profile and antioxidant capacity of seven monovarietal virgin olive oils (VOOs) and evaluate their in vitro gastrointestinal stability.‘Picual’, ‘Blanqueta’, ‘Sevillana’, ‘Habichuelero’, and ‘Chetoui’ olive cultivars were selected for VOO extraction. The oils were subjected to in vitro digestion. The recovery index (RI) of phenolic compounds after each digestion step and the bioaccessibility index (BI) were evaluated. In addition, the antioxidant activity of the bioaccessible fraction (BF) of VOOs was determined by DPPH, ABTS, and ORAC assays, as well as by studying the intracellular reactive oxygen species in Caco-2 cells.Differences were found in the composition of phenolic compounds in VOOs depending on cultivars. During the digestive process, important losses of phenolic compounds were observed between the buccal and duodenal steps, unlike HTy and Ty, which presented increased recovery due to the hydrolysis of secoiridoid derivatives. Differences in the bioaccessibility of phenolic compounds were found between varieties of VOOs. ‘Sevillana’ VOO had the highest total bioaccessibility (36%), followed by the ‘Picual’ (19%), ‘Chetoui’ (17%), ‘Habichuelero’ (10%), and ‘Blanqueta’ (8%) varieties. The BF of all the varieties of VOO showed similar radical ABTS scavenging capacity, ‘Chetoui’, and ‘Blanqueta’-BF having the highest radical DPPH scavenging capacity, and ‘Habichuelero’ and ‘Picual’-BF showing protective effects against the peroxyl radical measured by ORACFL assay. All VOO-BFs presented decreases in ROS levels in Caco-2 cells.Our results suggest differences in the bioaccessibility of phenolics from diverse VOO varieties, which could lead to different biological properties. Therefore, this study represents a first step toward the development of novel dietary strategies focusing on the phenolic supplementation of different VOOs to preserve human health.
Keywords: Extra virgin olive oil; Phenolic compounds; Bioaccessibility; Antioxidant capacity

Anti-gliadin antibodies in breast milk from celiac mothers on a gluten-free diet by María Roca; Sabine Lisa Vriezinga; Paula Crespo-Escobar; Renata Auricchio; David Hervás; Gemma Castillejo; Maria Carmen Mena; Isabel Polanco; Riccardo Troncone; Maria Luisa Mearin; Carmen Ribes-Koninckx (1947-1955).
To analyze the presence of total IgA and anti-gliadin antibodies (AGA) in BM from CD mothers who follow a gluten-free diet (GFD) and from mothers on a normal gluten-containing diet (ND).218 samples of mature milk were obtained at different months of lactation (1–6) from 83 mothers (2 or more samples per mother) from Italy (Naples), The Netherlands (Leiden) and Spain (Madrid, Valencia and Reus): 42 CD mothers on GFD for more than 2 years and 41 non-CD mothers on a ND. Whey samples were analyzed for AGA-IgA by an indirect homemade ELISA and for total IgA (g/L) by a commercial ELISA kit.AGA-IgA was detected in BM, both in mothers on a GFD and mothers on a ND. AGA-IgA levels in both groups of mothers, CD and non-CD, show the same trend towards decreasing slightly along the months of lactation (p = 0.91). A different trend is observed for total IgA levels, decreasing markedly in CD mothers from the first month of lactation onwards but remaining stable in non-CD mothers (p = 0.048). A statistically significant association was found between the means of total IgA and AGA-IgA (p < 0.001).AGA-IgA is present in BM from mothers on a ND as well as in BM from mothers who had been on a GFD for years. This reflects the existence of a long-lasting immunological memory independent of the mother’s diet. If the presence of these antibodies has any role in promoting the acquisition of gluten tolerance in the infant, our study shows that children of CD mothers would be on equal conditions as children of non-CD mothers.
Keywords: Gliadin antibodies; Breast milk; Celiac disease; Immunoglobulin A

Oxidative damage of mitochondrial respiratory chain in different organs of a rat model of diet-induced obesity by Hai-Tao Yu; Xiao-Yi Fu; Bing Liang; Shuang Wang; Jian-Kang Liu; Shu-Ran Wang; Zhi-Hui Feng (1957-1967).
Mitochondrial dysfunction plays an important role in the development of obesity and obesity-associated metabolic diseases.In this study, we dynamically observed the characteristics of mitochondrial damage in a rat model of diet-induced obesity (DIO). From the 2nd to the 10th week, animals were killed every 2 weeks and the heart, liver, kidney, and testicular tissues were harvested. Mitochondria were isolated and the activities of respiratory chain complexes I, II, III, and IV as well as the 8-Hydroxy-2-deoxy Guanosine content were determined. Reactive oxygen species and malondialdehyde were measured.Mitochondrial damages were observed in the heart and liver of DIO and DR rats, and the damages occurred later in DR group than that in DIO group. The mitochondrial membrane potential of heart and liver decreased in DIO and DR groups. The activity of the heart mitochondria complexes I, III, and IV (composing NADH oxidative respiratory) was higher in the early stage of DIO and lower in the end of week 10. The higher activity of the liver complexes I, III, and IV was found until the end of week 10 in DIO and DR groups, accompanied with enhanced oxidative stress. Besides, mitochondrial DNA damages were observed in all tissues.In DIO rats, the heart mitochondrial dysfunction occurred first and the liver presented the strongest compensatory ability against oxidative stress.
Keywords: Mitochondria; Respiratory chain; Complex; Oxidative stress; Obesity

The relative advantages of dietary analysis methods, particularly in identifying dietary patterns associated with bone mass, have not been investigated. We evaluated principal component analysis (PCA), partial least-squares (PLS) and reduced-rank regressions (RRR) in determining dietary patterns associated with bone mass.Data from 1182 study participants (45.9% males; aged 50 years and above) from the North West Adelaide Health Study (NWAHS) were used. Dietary data were collected using a food frequency questionnaire (FFQ). Dietary patterns were constructed using PCA, PLS and RRR and compared based on the performance to identify plausible patterns associated with bone mineral density (BMD) and content (BMC).PCA, PLS and RRR identified two, four and four dietary patterns, respectively. All methods identified similar patterns for the first two factors (factor 1, “prudent” and factor 2, “western” patterns). Three, one and none of the patterns derived by RRR, PLS and PCA were significantly associated with bone mass, respectively. The “prudent” and dairy (factor 3) patterns determined by RRR were positively and significantly associated with BMD and BMC. Vegetables and fruit pattern (factor 4) of PLS and RRR was negatively and significantly associated with BMD and BMC, respectively.RRR was found to be more appropriate in identifying more (plausible) dietary patterns that are associated with bone mass than PCA and PLS. Nevertheless, the advantage of RRR over the other two methods (PCA and PLS) should be confirmed in future studies.
Keywords: Dietary analysis methods; Principal component analysis; Partial least-squares regression; Reduced-rank regression; Bone mass; Ageing population

Early introduction of complementary foods and childhood overweight in breastfed and formula-fed infants in the Netherlands: the PIAMA birth cohort study by Linda P. M. Pluymen; Alet H. Wijga; Ulrike Gehring; Gerard H. Koppelman; Henriëtte A. Smit; L. van Rossem (1985-1993).
To investigate whether early introduction of complementary foods (CF) is associated with an increased risk of overweight during childhood, and whether this association differs between formula-fed and breastfed infants.We included 2611 participants that were born at term from a Dutch population-based birth cohort (n = 3963) designed to investigate the development of asthma and allergies. Parents kept records of their infant’s age when CF were first introduced. Weight and height were parent reported yearly from age 1 to 8 years, and at ages 11, 14 and 17 years. We used multivariate generalized estimating equations analysis to investigate the association between timing of CF introduction (before 4 months vs at or after 4 months of age) and overweight at ages 1–17 years.Children with CF introduction before 4 months had higher odds of being overweight during childhood than children with CF introduction at or after 4 months (OR 1.32, 95% CI 1.19, 1.47). This association was observed in formula-fed infants (OR 1.51, 95% CI 1.17, 1.94) and breastfed infants (OR 1.32, 95% CI 1.19, 1.47). The duration of breastfeeding modified the association between CF introduction and overweight: children breastfed for shorter than 4 months, but not children breastfed for 4 months or longer with CF introduction before 4 months had higher odds of being overweight (OR 1.37, 95% CI 1.19, 1.57 and 1.07, 95% CI 0.87, 1.32, respectively), compared to those with CF introduction at or after 4 months.In children born at term, formula-fed infants and infants who were breastfed for shorter than 4 months, but not infants who were breastfed for 4 months or longer, had a higher risk of being overweight during childhood when being introduced to CF before 4 months of age.
Keywords: Infant feeding; Solids; Overweight; Childhood