Showing papers in "Journal of Nutrition in 2013"

A Mixture of trans-Galactooligosaccharides Reduces Markers of Metabolic Syndrome and Modulates the Fecal Microbiota and Immune Function of Overweight Adults

Abstract: Metabolic syndrome is a set of disorders that increases the risk of developing cardiovascular disease. The gut microbiota is altered toward a less beneficial composition in overweight adults and this change can be accompanied by inflammation. Prebiotics such as galactooligosaccharides can positively modify the gut microbiota and immune system; some may also reduce blood lipids. We assessed the effect of a galactooligosaccharide mixture [Bi 2 muno (B-GOS)] on markers of metabolic syndrome, gut microbiota, and immune function in 45 overweight adults with $3 risk factors associated with metabolic syndrome in a double-blind, randomized, placebo (maltodextrin)-controlled, crossover study (with a 4-wk wash-out period between interventions). Whole blood, saliva, feces, and anthropometric measurements were taken at the beginning, wk 6, and end of each 12-wk intervention period. Predominant groups of fecal bacteria were quantified and full blood count, markers of inflammation and lipidmetabolism, insulin, and glucose were measured. B-GOS increased the number of fecal bifidobacteria at the expense of less desirable groups of bacteria. Increases in fecal secretory IgA and decreases in fecal calprotectin, plasma C-reactive protein, insulin, total cholesterol (TC), TG, and the TC:HDL cholesterol ratio were also observed. Administration of B-GOS to overweight adults resulted in positive effects on the composition of the gut microbiota, the immune response, and insulin, TC, and TG concentrations. B-GOS may be a useful candidate for the enhancement of gastrointestinal health, immune function, and the reduction of metabolic syndrome risk factors in overweight adults. J. Nutr. doi: 10.3945/jn.112.166132.

A diet high in resistant starch modulates microbiota composition, SCFA concentrations, and gene expression in pig intestine

Abstract: Resistant starch (RS) is highly fermentable by microbiota in the colon, resulting in the production of SCFAs. RS is thought to mediate a large proportion of its health benefits, including increased satiety, through the actions of SCFAs. The aim of this study was to investigate the effects of a diet high in RS on luminal microbiota composition, luminal SCFA concentrations, and the expression of host genes involved in SCFA uptake, SCFA signaling, and satiety regulation in mucosal tissue obtained from small intestine, cecum, and colon. Twenty adult female pigs were either assigned to a digestible starch (DS) diet or a diet high in RS (34%) for a period of 2 wk. After the intervention, luminal content and mucosal scrapings were obtained for detailed molecular analysis. RS was completely degraded in the cecum. In both the cecum and colon, differences in microbiota composition were observed between DS- and RS-fed pigs. In the colon these included the stimulation of the healthy gut-associated butyrate-producing Faecalibacterium prausnitzii, whereas potentially pathogenic members of the Gammaproteobacteria, including Escherichia coli and Pseudomonas spp., were reduced in relative abundance. Cecal and colonic SCFA concentrations were significantly greater in RS-fed pigs, and cecal gene expression of monocarboxylate transporter 1 (SLC16A1) and glucagon (GCG) was induced by RS. In conclusion, our data show that RS modulates microbiota composition, SCFA concentrations, and host gene expression in pig intestine. Combined, our data provide an enhanced understanding of the interaction between diet, microbiota, and host.

Inorganic Nitrate and Beetroot Juice Supplementation Reduces Blood Pressure in Adults: A Systematic Review and Meta-Analysis

Abstract: Diets including food products rich in inorganic nitrate are associated with lower blood pressure (BP). The evidence for the BP-lowering effects of inorganic nitrate and beetroot in randomized clinical trials has not been systematically assessed. The objective was to conduct a systematic review and meta-analysis of randomized clinical trials that examined the effects of inorganic nitrate and beetroot supplementation on BP. Medline, EMBASE, and Scopus databases were searched from inception to February 2013. The specific inclusion criteria were: 1) randomized clinical trials; 2) trials reporting effects on systolic or diastolic BP or both; and 3) trials comparing inorganic nitrate or beetroot juice supplementation with placebo control groups. Random-effects models were used to assess the pooled BP effect sizes. Sixteen trials met the eligibility criteria for the systematic review. All studies had a crossover study design. The trials were conducted between 2006 and 2012 and included a total of 254 participants with 7-30 participants/study. The duration of each intervention ranged from 2 h to 15 d. Inorganic nitrate and beetroot juice consumption were associated with greater changes in systolic BP [-4.4 mm Hg (95% CI: -5.9, -2.8); P < 0.001] than diastolic BP [-1.1 mm Hg (95% CI: -2.2, 0.1); P = 0.06]. The meta-regression showed an association between daily dose of inorganic nitrate and changes in systolic BP (P < 0.05). Inorganic nitrate and beetroot juice supplementation was associated with a significant reduction in systolic BP. These findings need to be tested in long-term trials and in individuals at greater cardiovascular risk.

Vitamin D Regulates the Gut Microbiome and Protects Mice from Dextran Sodium Sulfate-Induced Colitis

Abstract: The active form of vitamin D [1,25-dihydroxycholecalciferol, 1,25(OH)2D3] and the vitamin D receptor (VDR) regulate susceptibility to experimental colitis. The effect of the bacterial microflora on the susceptibility of C57BL/6 mice to dextran sodium sulfate-induced colitis was determined. Mice that cannot produce 1,25(OH)2D3 [Cyp27b1 (Cyp) knockout (KO)], VDR KO as well as their wild-type littermates were used. Cyp KO and VDR KO mice had more bacteria from the Bacteroidetes and Proteobacteria phyla and fewer bacteria from the Firmicutes and Deferribacteres phyla in the feces compared with wild-type. In particular, there were more beneficial bacteria, including the Lactobacillaceae and Lachnospiraceae families, in feces from Cyp KO and VDR KO mice than in feces from wild-type. Helicobacteraceae family member numbers were elevated in Cyp KO compared with wild-type mice. Depletion of the gut bacterial flora using antibiotics protected mice from colitis. 1,25(OH)2D3 treatment (1.25 μg/100 g diet) of Cyp KO mice decreased colitis severity and reduced the numbers of Helicobacteraceae in the feces compared with the numbers in the feces of untreated Cyp KO mice. The mechanisms by which the dysbiosis occurs in VDR KO and Cyp KO mice included lower expression of E-cadherin on gut epithelial and immune cells and fewer tolerogenic dendritic cells that resulted in more gut inflammation in VDR and Cyp KO mice compared with wild-type mice. Increased host inflammation has been shown to provide pathogens with substrates to out-compete more beneficial bacterial species. Our data demonstrate that vitamin D regulates the gut microbiome and that 1,25(OH)2D3 or VDR deficiency results in dysbiosis, leading to greater susceptibility to injury in the gut.

Chronic Physical and Mental Health Conditions among Adults May Increase Vulnerability to Household Food Insecurity

Abstract: Analyses of cross-sectional population survey data in Canada and the United States have indicated that household food insecurity is associated with poorer self-rated health and multiple chronic conditions. The causal inference has been that household food insecurity contributes to poorer health, but there has been little consideration of how adults' health status may relate to households' vulnerability to food insecurity. Our objectives were to examine how the presence of an adult with one or more chronic physical or mental health conditions affects the odds of a household being food insecure and how the chronic ill-health of an adult within a food-insecure household affects the severity of that household's food insecurity. Using household- and respondent-level data available for 77,053 adults aged 18-64 y from the 2007-2008 Canadian Community Health Survey, we applied logistic regression analyses, controlling for household sociodemographic characteristics, to examine the association between health and household food insecurity. Most chronic conditions increased the odds of household food insecurity independent of household sociodemographic characteristics. Compared with adults with no chronic condition, the odds of household food insecurity were 1.43 (95% CI: 1.28, 1.59), 1.86 (95% CI: 1.62, 2.14), and 3.44 (95% CI: 3.02, 3.93) for adults with 1, 2, and 3 or more chronic conditions, respectively. Among food-insecure households, adults with multiple chronic conditions had higher odds of severe household food insecurity than adults with no chronic condition. The chronic ill-health of adults may render their households more vulnerable to food insecurity. This has important practice implications for health professionals who can identify and assist those at risk, but it also suggests that appropriate chronic disease management may reduce the prevalence and severity of food insecurity.

The Challenge of Meeting Nutrient Needs of Infants and Young Children during the Period of Complementary Feeding: An Evolutionary Perspective

Abstract: Breast-fed infants and young children need complementary foods with a very high nutrient density (particularly for iron and zinc), especially at ages 6-12 mo. However, in low-income countries, their diet is usually dominated by cereal-based porridges with low nutrient density and poor mineral bioavailability. Complementary feeding diets typically fall short in iron and zinc and sometimes in other nutrients. These gaps in nutritional adequacy of infant diets have likely been a characteristic of human diets since the agricultural revolution ~10,000 y ago. Estimates of nutrient intakes before then, based on hypothetical diets of preagricultural humans, suggest that infants had much higher intakes of key nutrients than is true today and would have been able to meet their nutrient needs from the combination of breast milk and premasticated foods provided by their mothers. Strategies for achieving adequate nutrition for infants and young children in modern times must address the challenge of meeting nutrient needs from largely cereal-based diets.

The human milk metabolome reveals diverse oligosaccharide profiles.

Abstract: Breast milk delivers nutrition and protection to the developing infant. There has been considerable research on the high-molecular-weight milk components; however, low-molecular-weight metabolites have received less attention. To determine the effect of maternal phenotype and diet on the human milk metabolome, milk collected at day 90 postpartum from 52 healthy women was analyzed by using proton nuclear magnetic resonance spectroscopy. Sixty-five milk metabolites were quantified (mono-, di-, and oligosaccharides; amino acids and derivatives; energy metabolites; fatty acids and associated metabolites; vitamins, nucleotides, and derivatives; and others). The biological variation, represented as the percentage CV of each metabolite, varied widely (4-120%), with several metabolites having low variation (<20%), including lactose, urea, glutamate, myo-inositol, and creatinine. Principal components analysis identified 2 clear groups of participants who were differentiable on the basis of milk oligosaccharide concentration and who were classified as secretors or nonsecretors of fucosyltransferase 2 (FUT2) gene products according to the concentration of 2'-fucosyllactose, lactodifucotetraose, and lacto-N-fucopentaose I. Exploration of the interrelations between the milk sugars by using Spearman rank correlations revealed significant positive and negative associations, including positive correlations between fucose and products of the FUT2 gene and negative correlations between fucose and products of the fucosyltransferase 3 (FUT3) gene. The total concentration of milk oligosaccharides was conserved among participants (%CV = 18%), suggesting tight regulation of total oligosaccharide production; however, concentrations of specific oligosaccharides varied widely between participants (%CV = 30.4-84.3%). The variability in certain milk metabolites suggests possible roles in infant or infant gut microbial development. This trial was registered at clinicaltrials.gov as NCT01817127.

Gene Expression of Endoplasmic Reticulum Resident Selenoproteins Correlates with Apoptosis in Various Muscles of Se-Deficient Chicks

Abstract: Dietary selenium (Se) deficiency causes muscular dystrophy in various species, but the molecular mechanism remains unclear. Our objectives were to investigate: 1) if dietary Se deficiency induced different amounts of oxidative stress, lipid peroxidation, and cell apoptosis in 3 skeletal muscles; and 2) if the distribution and expression of 4 endoplasmic reticulum (ER) resident selenoprotein genes (Sepn1, Selk, Sels, and Selt) were related to oxidative damages in these muscles. Two groups of day-old layer chicks (n = 60/group) were fed a corn-soy basal diet (33 μg Se/kg; produced in the Se-deficient area of Heilongjiang, China) or the diet supplemented with Se (as sodium selenite) at 0.15 mg/kg for 55 d. Dietary Se deficiency resulted in accelerated (P 0.72; P < 0.05) that of Sepsecs encoding a key enzyme for biosynthesis of selenocysteine (selenocysteinyl-tRNA synthase). In conclusion, the pectoral muscle demonstrated unique expression patterns of the ER resident selenoprotein genes and GPx activity, along with elevated susceptibility to oxidative cell death, compared with the other skeletal muscles. These features might help explain why it is a primary target of Se deficiency diseases in chicks.

Short-Chain Fatty Acids Activate AMP-Activated Protein Kinase and Ameliorate Ethanol-Induced Intestinal Barrier Dysfunction in Caco-2 Cell Monolayers

Abstract: Short-chain fatty acids (SCFAs) have been shown to promote intestinal barrier function, but their protective effects against ethanol-induced intestinal injury and underlying mechanisms remain essentially unknown. The aim of the study was to analyze the influence of SCFAs on ethanol-induced barrier dysfunction and to examine the role of AMP-activated protein kinase (AMPK) as a possible mechanism using Caco-2 monolayers. The monolayers were treated apically with butyrate (2, 10, or 20 mmol/L), propionate (4, 20, or 40 mmol/L), or acetate (8, 40, or 80 mmol/L) for 1 h before ethanol (40 mmol/L) for 3 h. Barrier function was analyzed by measurement of transepithelial resistance and permeation of fluorescein isothiocyanate-labeled dextran. Distribution of the tight junction (TJ) proteins zona occludens-1, occludin, and filamentous-actin (F-actin) was examined by immunofluorescence. Metabolic stress was determined by measuring oxidative stress, mitochondrial function, and ATP using dichlorofluorescein diacetate, dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide, and bioluminescence assay, respectively. AMPK was knocked down by small interfering RNA (siRNA), and its activity was assessed by a cell-based ELISA. Exposure to ethanol significantly impaired barrier function compared with controls (P < 0.0001), disrupted TJ and F-actin cytoskeleton integrity, and induced metabolic stress. However, pretreatment with 2 mmol/L butyrate, 4 mmol/L propionate, and 8 mmol/L acetate significantly alleviated the ethanol-induced barrier dysfunction, TJ and F-actin disruption, and metabolic stress compared with ethanol-exposed monolayers (P < 0.0001). The promoting effects on barrier function were abolished by inhibiting AMPK using either compound C or siRNA. These observations indicate that SCFAs exhibit protective effects against ethanol-induced barrier disruption via AMPK activation, suggesting a potential for SCFAs as prophylactic and/or therapeutic factors against ethanol-induced gut leakiness.

Household Food Insecurity Is Associated with Higher Child Undernutrition in Bangladesh, Ethiopia, and Vietnam, but the Effect Is Not Mediated by Child Dietary Diversity

Abstract: Household food insecurity (HFI) is a recognized underlying determinant of child undernutrition, but evidence of associations between HFI and child undernutrition is mixed. The purpose of this study was to investigate if HFI is associated with undernutrition in children aged 6–59.9 mo in Bangladesh (n = 2356), Ethiopia (n = 3422), and Vietnam (n = 3075) and if child dietary diversity (DD) mediated this effect. We used baseline survey data from the Alive & Thrive project. Logisticregression,adjustingforpotentialconfoundingfactors,wasusedtodeterminethemagnitudeandsignificance of the association of HFI with stunting, underweight, and wasting. The mediating effect of child DD was tested by using a Sobel-Goodman mediation test. The prevalences of HFI were 66%, 40%, and 32% in Ethiopia, Vietnam, and Bangladesh, respectively. The prevalences of stunting, underweight, and wasting were higher in Bangladesh (47.1%, 43.7%, and 19.1%, respectively) and Ethiopia (50.7%, 27.5%, and 5.9%, respectively) than in Vietnam (20.7%, 15.8%, and 5%, respectively). In the adjusted models, the odds of being stunted or underweight were significantly higher for children in severely food-insecure households in Bangladesh (stunting OR: 1.36; 95% CI: 1.05, 1.76; underweight OR: 1.28; 95% CI: 0.99, 1.65) and Ethiopia (stunting OR: 1.48; 95% CI: 1.09, 2.00; underweight OR: 1.68; 95% CI: 1.22, 2.30) and in moderately food-insecurehouseholds in Vietnam (stunting OR: 1.39; 95% CI: 1.16, 1.65; underweight OR: 1.69; 95% CI: 1.28, 2.23). HFI was significantly associated with wasting in Bangladesh where close to 1 in 5 children demonstrated wasting. Child DD did not mediate the relation between HFI and undernutrition in any of the countries. Further research is recommended to investigate potential mediators in

Very Low Adequacy of Micronutrient Intakes by Young Children and Women in Rural Bangladesh Is Primarily Explained by Low Food Intake and Limited Diversity

Abstract: Documentation of micronutrient intake inadequacies among developing country populations is important for planning interventions to control micronutrient deficiencies. The objective of this study was to quantify micronutrient intakes by young children and their primary female caregivers in rural Bangladesh. We measured 24-h dietary intakes on 2 nonconsecutive days in a representative sample of 480 children (ages 24-48 mo) and women in 2 subdistricts of northern Bangladesh by using 12-h weighed food records and subsequent 12-h recall in homes. We calculated the probability of adequacy (PA) of usual intakes of 11 micronutrients and an overall mean PA, and evaluated dietary diversity by counting the total number of 9 food groups consumed. The overall adequacy of micronutrient intakes was compared to dietary diversity scores using correlation and multivariate regression analyses. The overall mean prevalence of adequacy of micronutrient intakes for children was 43% and for women was 26%. For children, the prevalence of adequate intakes for each of the 11 micronutrients ranged from a mean of 0 for calcium to 95% for vitamin B-6 and was <50% for iron, calcium, riboflavin, folate, and vitamin B-12. For women, mean or median adequacy was <50% for all nutrients except vitamin B-6 and niacin and was <1% for calcium, vitamin A, riboflavin, folate, and vitamin B-12. The mean PA (MPA) was correlated with energy intake and dietary diversity, and multivariate models including these variables explained 71-76% of the variance in MPA. The degree of micronutrient inadequacy among young children and women in rural Bangladesh is alarming and is primarily explained by diets low in energy and little diversity of foods.

Severity of Household Food Insecurity Is Sensitive to Change in Household Income and Employment Status among Low-Income Families

Abstract: Cross-sectional studies have established a relationship between poverty and food insecurity, but little is known about the acute changes within households that lead to changes in food insecurity. This study examined how changes in income, employment status, and receipt of welfare related to change in severity of food insecurity during 1 y among low-income families. In 2005-2007, 501 families living in market and subsidized rental housing were recruited through door-to-door sampling in high-poverty neighborhoods in Toronto. One year later, families were re-interviewed. The final longitudinal analytic sample included 331 families. Within-household change in income, employment, and welfare receipt were examined in relation to change in severity of food insecurity. Severity was denoted by the aggregate raw score on the Household Food Security Survey Module (HFSSM). Analyses were stratified by housing subsidy status owing to differences in characteristics between households. Food insecurity was a persistent problem among families; 68% were food insecure at both interviews. Severity was dynamic, however, as 73.4% answered more or fewer questions affirmatively on the HFFSM between baseline and follow-up. Among market-rent families, a $2000 gain in income during the year and gain of full-time employment were associated with a 0.29 and 1.33 decrease in raw score, respectively (P < 0.01). This study suggests that improvements in income and employment are related to improvements in families' experiences of food insecurity, highlighting the potential for income- and employment-based policy interventions to affect the severity of household food insecurity for low-income families.

Repeated exposure of infants at complementary feeding to a vegetable puree increases acceptance as effectively as flavor-flavor learning and more effectively than flavor-nutrient learning.

Abstract: Children's vegetable consumption is below the public health recommendations. This study aimed to compare learning mechanisms to increase vegetable acceptance in infants at complementary feeding, namely repeated exposure (RE), flavor-flavor learning (FFL), and flavor-nutrient learning (FNL); measure the stability of the learning effect; and examine the impact of infants' feeding history on vegetable acceptance. The study was composed of a preexposure test, an exposure period, a postexposure test, and tests at 2-wk, 3-mo, and 6-mo follow-ups. At pre- and postexposure, a basic artichoke puree and carrot puree were presented to 95 French infants (6.4 ± 0.8 mo). During the exposure period, infants were randomly split into 3 groups and were exposed 10 times to the basic (RE group; 2 kJ/g; n = 32), a sweet (FFL group; 2 kJ/g; n = 32), or an energy-dense (FNL group; 6 kJ/g; n = 31) artichoke puree 2 or 3 times/wk. To evaluate acceptance, intake (g) and liking were recorded at home by parents. Between pre- and postexposure, intake of the basic artichoke puree significantly increased in the RE (+63%) and FFL (+39%) groups but not in the FNL group; liking increased only in the RE group (+21%). After exposure, artichoke was as much consumed and as much liked as carrot only in the RE group. Learning of artichoke acceptance was stable up to 3 mo postexposure. Initial artichoke intake was significantly related to the number of vegetables offered before the study started. RE is as effective as and simpler to implement than FFL and more effective than FNL for increasing vegetable acceptance at complementary feeding.

Walnut Consumption Is Associated with Lower Risk of Type 2 Diabetes in Women

Abstract: Walnuts are rich in polyunsaturated fatty acids and have been shown to improve various cardiometabolic risk factors. We aimed to investigate the association between walnut intake and incident type 2 diabetes in 2 large cohort studies: the Nurses’ Health Study (NHS) and NHS II. We prospectively followed 58,063 women aged 52–77 y in NHS (1998–2008) and 79,893 women aged 35–52 y in NHS II (1999–2009) without diabetes, cardiovascular disease, or cancer at baseline. Consumption of walnuts and other nuts was assessed every 4 y using validated food frequency questionnaires. Selfreported type 2 diabetes was confirmed by a validated supplemental questionnaire. We documented a total of 5930 incident type 2 diabetes cases during 10 y of follow-up. In the multivariable-adjusted Cox proportional hazards model without body mass index (BMI), walnut consumption was associated with a lower risk of type 2 diabetes, and the HRs (95% CIs) for participants consuming 1–3 servings/mo (1 serving = 28 g), 1 serving/wk, and $2 servings/wk of walnuts were 0.93 (0.88–0.99), 0.81 (0.70–0.94), and 0.67 (0.54–0.82) compared with women who never/rarely consumed walnuts (P-trend < 0.001). Further adjustment for updated BMI slightly attenuated the association and the HRs (95% CIs) were 0.96 (0.90–1.02), 0.87 (0.75–1.01), and 0.76 (0.62–0.94), respectively (P-trend = 0.002). The consumption of total nuts (P-trend < 0.001) and other tree nuts (P-trend = 0.03) was also inversely associated with risk of type 2 diabetes, and the associations were largely explained by BMI. Our results suggest that higher walnut consumption is associated with a significantly lower risk of type 2 diabetes in women. J. Nutr. 143: 512–518, 2013.

Protein Blend Ingestion Following Resistance Exercise Promotes Human Muscle Protein Synthesis

Abstract: High-quality proteins such as soy, whey, and casein are all capable of promoting muscle protein synthesis postexercise by activating the mammalian target of rapamycin (mTORC1) signaling pathway. We hypothesized that a protein blend of soy and dairy proteins would capitalize on the unique properties of each individual protein and allow for optimal delivery of amino acids to prolong the fractional synthetic rate (FSR) following resistance exercise (RE). In this double-blind, randomized, clinical trial, 19 young adults were studied before and after ingestion of ∼19 g of protein blend (PB) or ∼18 g whey protein (WP) consumed 1 h after high-intensity leg RE. We examined mixed-muscle protein FSR by stable isotopic methods and mTORC1 signaling with western blotting. Muscle biopsies from the vastus lateralis were collected at rest (before RE) and at 3 postexercise time points during an early (0-2 h) and late (2-4 h) postingestion period. WP ingestion resulted in higher and earlier amplitude of blood branched-chain amino acid (BCAA) concentrations. PB ingestion created a lower initial rise in blood BCAA but sustained elevated levels of blood amino acids later into recovery (P < 0.05). Postexercise FSR increased equivalently in both groups during the early period (WP, 0.078 ± 0.009%; PB, 0.088 ± 0.007%); however, FSR remained elevated only in the PB group during the late period (WP, 0.074 ± 0.010%; PB, 0.087 ± 0.003%) (P < 0.05). mTORC1 signaling similarly increased between groups, except for no increase in S6K1 phosphorylation in the WP group at 5 h postexercise (P < 0.05). We conclude that a soy-dairy PB ingested following exercise is capable of prolonging blood aminoacidemia, mTORC1 signaling, and protein synthesis in human skeletal muscle and is an effective postexercise nutritional supplement.

Dietary Supplement Use and Folate Status during Pregnancy in the United States

Abstract: Adequate folate and iron intake during pregnancy is critical for maternal and fetal health. No previous studies to our knowledge have reported dietary supplement use and folate status among pregnant women sampled in NHANES, a nationally representative, cross-sectional survey. We analyzed data on 1296 pregnant women who participated in NHANES from 1999 to 2006 to characterize overall supplement use, iron and folic acid use, and RBC folate status. The majority of pregnant women (77%) reported use of a supplement in the previous 30 d, most frequently a multivitamin/-mineral containing folic acid (mean 817 μg/d) and iron (48 mg/d). Approximately 55-60% of women in their first trimester reported taking a folic acid- or iron-containing supplement compared with 76-78% in their second trimester and 89% in their third trimester. RBC folate was lowest in the first trimester and differed by supplement use across all trimesters. Median RBC folate was 1628 nmol/L among users and 1041 nmol/L among nonusers. Among all pregnant women, median RBC folate increased with trimester (1256 nmol/L in the first, 1527 nmol/L in the second, and 1773 nmol/L in the third). Given the role of folic acid in the prevention of neural tube defects, it is notable that supplement use and median RBC folate was lowest in the first trimester of pregnancy, with 55% of women taking a supplement containing folic acid. Future research is needed to determine the reasons for low compliance with supplement recommendations, particularly folic acid, in early pregnancy.

Maternal and Child Dietary Diversity Are Associated in Bangladesh, Vietnam, and Ethiopia

Abstract: Dietary diversity (DD) reflects micronutrient adequacy of the diet and is associated with better child growth. Emerging evidence suggests that maternal and child DD are associated. This could have measurement and programmatic implications. Data on mother-child (6-24 mo) dyads in Bangladesh, Vietnam, and Ethiopia were used to examine agreement and association between maternal and child DD and identify determinants of maternal and child DD. The DD scores were derived from a 24-h recall of intake of foods from 7 groups. Multivariable regression was used to examine for the association, adjusting for covariates at child, maternal, and household levels. There was mother/child agreement for staple foods across the 3 countries but disagreement for flesh foods, dairy, fruits, and vegetables. A strong positive association was seen between maternal and child DD; a difference of one food group in mother's consumption was associated with a difference of 0.29, 033, and 0.24 groups in child's consumption in Bangladesh, Vietnam, and Ethiopia, respectively. The odds of achieving minimum DD (≥4 groups) were higher among children whose mother consumed 4 groups compared with ≤3 food groups [Bangladesh: OR = 2.73 (95% CI: 1.76, 4.25); Vietnam: OR = 2.30 (95% CI: 1.45, 3.43); Ethiopia: OR = 5.11 (95% CI: 2.36, 11.04)]. Maternal education was associated with both maternal and child DD; food security and socioeconomic status were associated only with maternal DD. Given the disagreements in mother/child intake for nutrient-rich foods, both maternal and child DD should be measured in surveys. Behavior change communications should focus on promoting both mother and child DD and encouraging mothers to feed young children all family foods, not just a subset.

Long-Term Adherence to the Mediterranean Diet Is Associated with Overall Cognitive Status, but Not Cognitive Decline, in Women

Abstract: In this large-scale prospective epidemiological study, we examined associations of long-term adherence to the Mediterranean diet (MeDi) and subsequent cognitive function and decline. We included 16,058 women from the Nurses' Health Study, aged ≥70 y, who underwent cognitive testing by telephone 4 times during 6 y, beginning in 1995-2001, and provided repeated information on diet between 1984 and the first cognitive exam. Primary outcomes were the Telephone Interview for Cognitive Status (TICS) and composite scores of verbal memory and global cognition. MeDi adherence was based on intakes of: vegetables, fruits, legumes, whole grains, nuts, fish, red and processed meats, moderate alcohol, and the ratio of monounsaturated:saturated fat. Long-term MeDi exposure was estimated by averaging all repeated measures of diet (>13 y, on average). In primary analyses of cognitive change, the MeDi was not associated with decline in global cognition or verbal memory. In a secondary approach examining cognitive status in older age, determined by averaging all 4 repeated measures of cognition, each higher quintile of long-term MeDi score was linearly associated with better multivariable-adjusted mean cognitive scores [differences in mean Z-scores between extreme quintiles of MeDi = 0.06 (95% CI: 0.01, 0.11); = 0.05 (95% CI: 0.01, 0.08); and = 0.06 (95% CI: 0.03, 0.10) standard units; P-trends = 0.004, 0.002, and <0.001 for TICS, global cognition, and verbal memory, respectively]. These associations were similar to those observed in women 1-1.5 y apart in age. In summary, long-term MeDi adherence was related to moderately better cognition but not with cognitive change in this very large cohort of older women.

Docosahexaenoic Acid Attenuates Hepatic Inflammation, Oxidative Stress, and Fibrosis without Decreasing Hepatosteatosis in a Ldlr−/− Mouse Model of Western Diet-Induced Nonalcoholic Steatohepatitis

Abstract: The incidence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) has increased in parallel with the incidence of obesity. While both NAFLD and NASH are characterized by hepatosteatosis, NASH is characterized by hepatic damage, inflammation, oxidative stress, and fibrosis. We previously reported that feeding Ldlr(-/-) mice a high-fat, high-cholesterol diet containing menhaden oil attenuated several markers of NASH, including hepatosteatosis, inflammation, and fibrosis. Herein, we test the hypothesis that DHA [22:6 (n-3)] is more effective than EPA [20:5 (n-3)] at preventing Western diet (WD)-induced NASH in Ldlr(-/-) mice. Mice were fed the WD supplemented with either olive oil (OO), EPA, DHA, or EPA + DHA for 16 wk. WD + OO feeding induced a severe NASH phenotype, characterized by robust hepatosteatosis, inflammation, oxidative stress, and fibrosis. Whereas none of the C20-22 (n-3) fatty acid treatments prevented WD-induced hepatosteatosis, all 3 (n-3) PUFA-containing diets significantly attenuated WD-induced inflammation, fibrosis, and hepatic damage. The capacity of dietary DHA to suppress hepatic markers of inflammation (Clec4F, F4/80, Trl4, Trl9, CD14, Myd88), fibrosis (Procol1α1, Tgfβ1), and oxidative stress (NADPH oxidase subunits Nox2, p22phox, p40phox, p47phox, p67phox) was significantly greater than dietary EPA. The effects of DHA on these markers paralleled DHA-mediated suppression of hepatic Fads1 mRNA abundance and hepatic arachidonic acid content. Because DHA suppression of NASH markers does not require a reduction in hepatosteatosis, dietary DHA may be useful in combating NASH in obese humans.

Vitamin D Supplementation Affects Serum High-Sensitivity C-Reactive Protein, Insulin Resistance, and Biomarkers of Oxidative Stress in Pregnant Women

Abstract: Unfavorable metabolic profiles and oxidative stress in pregnancy are associated with several complications. This study was conducted to determine the effects of vitamin D supplementation on serum concentrations of high-sensitivity C-reactive protein (hs-CRP), metabolic profiles, and biomarkers of oxidative stress in healthy pregnant women. This randomized, double-blind, placebo-controlled clinical trial was conducted in 48 pregnant women aged 18-40 y old at 25 wk of gestation. Participants were randomly assigned to receive either 400 IU/d cholecalciferol supplements (n = 24) or placebo (n = 24) for 9 wk. Fasting blood samples were taken at study baseline and after 9 wk of intervention to quantify serum concentrations of hs-CRP, lipid concentrations, insulin, and biomarkers of oxidative stress. After 9 wk of intervention, the increases in serum 25-hydroxyvitamin D and calcium concentrations were greater in the vitamin D group (+3.7 μg/L and +0.20 mg/dL, respectively) than in the placebo group (-1.2 μg/L and -0.12 mg/dL, respectively; P < 0.001 for both). Vitamin D supplementation resulted in a significant decrease in serum hs-CRP (vitamin D vs. placebo groups: -1.41 vs. +1.50 μg/mL; P-interaction = 0.01) and insulin concentrations (vitamin D vs. placebo groups: -1.0 vs. +2.6 μIU/mL; P-interaction = 0.04) and a significant increase in the Quantitative Insulin Sensitivity Check Index score (vitamin D vs. placebo groups: +0.02 vs. -0.02; P-interaction = 0.006), plasma total antioxidant capacity (vitamin D vs. placebo groups: +152 vs. -20 mmol/L; P-interaction = 0.002), and total glutathione concentrations (vitamin D vs. placebo groups: +205 vs. -32 μmol/L; P-interaction = 0.02) compared with placebo. Intake of vitamin D supplements led to a significant decrease in fasting plasma glucose (vitamin D vs. placebo groups: -0.65 vs. -0.12 mmol/L; P-interaction = 0.01), systolic blood pressure (vitamin D vs. placebo groups: -0.2 vs. +5.5 mm Hg; P-interaction = 0.01), and diastolic blood pressure (vitamin D vs. placebo groups: -0.4 vs. +3.1 mm Hg; P-interaction = 0.01) compared with placebo. In conclusion, vitamin D supplementation for 9 wk among pregnant women has beneficial effects on metabolic status.

Supplemental naringenin prevents intestinal barrier defects and inflammation in colitic mice

Abstract: Intestinal barrier defects are involved in the pathogenesis of inflammatory bowel disease. The present study investigated the ameliorative effects of naringenin, a citrus polyphenol, on intestinal tight junction (TJ) barrier defects and inflammation in a murine model of colitis. In Expt. 1, using a 2 × 2 fractional design, the mice were administered water or 2% dextran sulfate sodium (DSS) in combination with feeding control or naringenin-containing diets for 9 d (severe disease stage). DSS administration caused severe colon damage and inflammation, as indicated by body weight loss, increased clinical sores, colon shortening, and gene expressions of inflammatory cytokines [interferon-γ, interleukin (IL)-6, macrophage inflammatory protein-2, and IL-17A). DSS administration also impaired TJ barrier integrity in the colon, as indicated by increased colon permeability and plasma LPS-binding protein levels, resulting from the impaired colonic expression of TJ proteins, occludin, junctional adhesion molecule-A, and claudin-3. Supplemental feeding with naringenin totally or partially attenuated these symptoms, suggesting that naringenin ameliorates the DSS-induced colitis at least partially through protection of the TJ barrier. In Expt. 2, analyses were performed at different disease stages (d 3, 6, and 9) to more widely examine the ameliorative role of naringenin on the initiation and development of colitis. DSS administration moderately induced colon shortening at d 3 and 6 and increased the disease activity index (DAI) and inflammatory cytokine (IL-6 and IL-17A) expression without any significant increases in colonic permeability. Feeding naringenin attenuated the increased DAI and colon shortening and tended to suppress the increased cytokine expression. These findings suggest that the presence of an additional mechanism underlying the naringenin-mediated, anticolitic effect along with barrier protection.

Normal protein intake is required for body weight loss and weight maintenance, and elevated protein intake for additional preservation of resting energy expenditure and fat free mass.

Abstract: Energy-restricted high-protein diets (HPDs) have shown favorable results for body weight (BW) management, yet studies differ in their outcomes depending on the dietary protein content. Our objective was to determine the effects of dietary protein content on BW loss-related variables during a 6-mo energy restriction with the use of diets containing protein at the level of requirement [normal-protein diet (NPD), 0.8 g . kg BW(-1) (.) d(-1)] and above (HPD, 1.2 g . kg BW(-1) (.) d(-1)). In overweight and obese participants (24 men and 48 women), BW, body composition, and metabolic responses were assessed before and after subsequent energy intakes of 100, 33, and 67% of the original individual daily energy requirements. Protein intake was consistent in the NPD (0.8 +/- 0.3 g . kg BW(-1) (.) d(-1)) and HPD (1.2 +/- 0.3 g . kg BW(-1) (.) d(-1)) groups throughout the study (P < 0.001). BMI and body fat mass similarly decreased in the NPD and HPD groups (P < 0.01). Fat free mass (FFM), resting energy expenditure (REE) compared with predicted REE, and diastolic blood pressure (DBP) changed favorably with the HPD compared with the NPD group after BW loss (P < 0.05). A NPD of 0.8 g . kg BW(-1) (.) d(-1) is sufficient for BW management, whereas a HPD of 1.2 g . kg BW(-1) (.) d(-1) is necessary for preservation of REE and a stronger initial sparing effect of FFM and lowering of DBP.

Pomegranate Polyphenols and Extract Inhibit Nuclear Factor of Activated T-Cell Activity and Microglial Activation In Vitro and in a Transgenic Mouse Model of Alzheimer Disease

Abstract: Alzheimer disease (AD) brain is characterized by extracellular plaques of amyloid β (Aβ) peptide with reactive microglia. This study aimed to determine whether a dietary intervention could attenuate microgliosis. Memory was assessed in 12-mo-old male amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice via Barnes maze testing followed by division into either a control-fed group provided free access to normal chow and water or a treatment group provided free access to normal chow and drinking water supplemented with pomegranate extract (6.25 mL/L) for 3 mo followed by repeat Barnes maze testing for both groups. Three months of pomegranate feeding decreased the path length to escape of mice compared with their initial 12-mo values (P < 0.05) and their control-fed counterparts (P < 0.05). Brains of the 3-mo study pomegranate-fed mice had lower tumor necrosis factor α (TNF-α) concentrations (P < 0.05) and lower nuclear factor of activated T-cell (NFAT) transcriptional activity (P < 0.05) compared with controls. Brains of the 3-mo pomegranate or control mice were also compared with an additional control group of 12-mo-old mice for histologic analysis. Immunocytochemistry showed that pomegranate- but not control-fed mice had attenuated microgliosis (P < 0.05) and Aβ plaque deposition (P < 0.05) compared with 12-mo-old mice. An additional behavioral study again used 12-mo-old male APP/PS1 mice tested by T-maze followed by division into a control group provided with free access to normal chow and sugar supplemented drinking water or a treatment group provided with normal chow and pomegranate extract-supplemented drinking water (6.25 mL/L) for 1 mo followed by repeat T-maze testing in both groups. One month of pomegranate feeding increased spontaneous alternations versus control-fed mice (P < 0.05). Cell culture experiments verified that 2 polyphenol components of pomegranate extract, punicalagin and ellagic acid, attenuated NFAT activity in a reporter cell line (P < 0.05) and decreased Aβ-stimulated TNF-α secretion by murine microglia (P < 0.05). These data indicate that dietary pomegranate produces brain antiinflammatory effects that may attenuate AD progression.

Postnatal overfeeding in rodents by litter size reduction induces major short- and long-term pathophysiological consequences

Abstract: Numerous studies have demonstrated that the early postnatal environment can influence body weight and energy homeostasis into adulthood. Rodents raised in small litters have been shown to be a useful experimental model to study the short- and long-term consequences of early overnutrition, which can lead to modifications not only in body weight but also of several metabolic features. Postnatal overfeeding (PNOF) induces early malprogramming of the hypothalamic system, inducing acquired persisting central leptin and insulin resistance and an increase in orexigenic signals. Visceral white adipose tissue, lipogenic activity, and inflammatory status are increased in PNOF rodents, while brown adipose tissue shows reduced thermogenic activity. Pancreatic and hepatic glucose responsiveness is persistently reduced in PNOF rodents, which also frequently present disturbances in plasma lipids. PNOF rodents present increased circulating concentrations of leptin, elevated corticosterone secretion, and significant changes in glucocorticoid sensitivity. PNOF also influences nephrogenesis and renal maturation. Increased oxidative stress is also described in circulating blood and in some tissues, such as the heart or liver. At the cardiovascular level, a moderate increase in arterial blood pressure is sometimes observed and rapid cardiac hypertrophy is observed at weaning; however, during maturation, impaired contractility and fibrosis are observed. Myocardial genome expression is rapidly modified in overfed mice. Moreover, hearts of PNOF rodents are more sensitive to ischemia-reperfusion injury. Together, these results suggest that the nutritional state in the immediate postnatal period should be taken into account, because it may have an impact on cardiometabolic risk in adulthood.

Higher Dietary Flavonol Intake Is Associated with Lower Incidence of Type 2 Diabetes

Abstract: Substantial experimental evidence suggests that several flavonoid classes are involved in glucose metabolism, but few clinical or epidemiologic studies exist that provide supporting human evidence for this relationship. The objective of this study was to determine if habitual intakes of specific flavonoid classes are related to incidence of type 2 diabetes (T2D). We followed 2915 members of the Framingham Offspring cohort who were free of T2D at baseline from 1991 to 2008. Diabetes was defined by either elevated fasting glucose (≥7.0 mmol/L) or initiation of hypoglycemic medication during follow-up. Dietary intakes of 6 flavonoid classes and total flavonoids were assessed using a validated, semiquantitative food frequency questionnaire. We observed 308 incident cases of T2D during a mean follow-up period of 11.9 y (range 2.5-16.8 y). After multivariable adjusted, time-dependent analyses, which accounted for long-term flavonoid intake during follow-up, each 2.5-fold increase in flavonol intake was associated with a 26% lower incidence of T2D [HR = 0.74 (95% CI: 0.61, 0.90); P-trend = 0.003] and each 2.5-fold increase in flavan-3-ol intake was marginally associated with an 11% lower incidence of T2D [HR = 0.89 (95% CI: 0.80, 1.00); P-trend = 0.06]. No other associations between flavonoid classes and risk of T2D were observed. Our observations support previous experimental evidence of a possible beneficial relationship between increased flavonol intake and risk of T2D.

Habitual Dietary Intake Is Associated with Stool Microbiota Composition in Monozygotic Twins

Abstract: The impact of diet on the gut microbiota has usually been assessed by subjecting people to the same controlled diet and thereafter following the shifts in the microbiota In the present study, we used habitual dietary intake, clinical data, quantitative polymerase chain reaction, and denaturing gradient gel electrophoresis (DGGE) to characterize the stool microbiota of Finnish monozygotic twins The effect of diet on the numbers of bacteria was described through a hierarchical linear mixed model that included the twin individuals, stratified by body mass index, and their families as random effects The abundance and diversity of the bacterial groups studied did not differ between normal-weight, overweight, and obese individuals with the techniques used Intakes of energy, monounsaturated fatty acids, n3 polyunsaturated fatty acids (PUFAs), n6 PUFAs, and soluble fiber had significant associations with the stool bacterial numbers (eg, increased energy intake was associated with reduced numbers of Bacteroides spp) In addition, co-twins with identical energy intake had more similar numbers and DGGE-profile diversities of Bacteroides spp than did the co-twins with different intake Moreover, the co-twins who ingested the same amounts of saturated fatty acids had very similar DGGE profiles of Bacteroides spp, whereas the co-twins with similar consumption of fiber had a very low bifidobacterial DGGE-profile similarity In conclusion, our findings confirm that the diet plays an important role in the modulation of the stool microbiota, in particular Bacteroides spp and bifidobacteria

Biofortification of Pearl Millet with Iron and Zinc in a Randomized Controlled Trial Increases Absorption of These Minerals above Physiologic Requirements in Young Children

Abstract: Millet is unusually drought resistant and consequently there is a progressive increase in the use of these grains as a human food staple, especially in large areas of India and sub-Saharan Africa. The purpose of this study was to determine the absorption of iron and zinc from pearl millet biofortified with 2 micronutrients that are typically deficient in nonfortified, plant-based diets globally. The study was undertaken in 40 children aged 2 y in Karnataka, India (n = 21 test/19 controls). Three test meals providing ∼84 ± 17 g dry pearl millet flour were fed on a single day for zinc and 2 d for iron between 0900 and 1600 h. The quantities of zinc and iron absorbed were measured with established stable isotope extrinsic labeling techniques and analyses of duplicate diets. The mean (± SD) quantities of iron absorbed from test and control groups were 0.67 ± 0.48 and 0.23 ± 0.15 mg/d, respectively (P < 0.001). The quantities of zinc absorbed were 0.95 ± 0.47 and 0.67 ± 0.24 mg/d, respectively (P = 0.03). These data did not include absorption of the modest quantities of iron and zinc contained in snacks eaten before and after the 3 test meals. In conclusion, quantities of both iron and zinc absorbed when iron and zinc biofortified pearl millet is fed to children aged 2 y as the major food staple is more than adequate to meet the physiological requirements for these micronutrients.

Urinary Excretion of Sodium, Potassium, and Chloride, but Not Iodine, Varies by Timing of Collection in a 24-Hour Calibration Study

Abstract: Because of the logistic complexity, excessive respondent burden, and high cost of conducting 24-h urine collections in a national survey, alternative strategies to monitor sodium intake at the population level need to be evaluated. We conducted a calibration study to assess the ability to characterize sodium intake from timed-spot urine samples calibrated to a 24-h urine collection. In this report, we described the overall design and basic results of the study. Adults aged 18–39 y were recruited to collect urine for a 24-h period, placing each void in a separate container. Four timed-spot specimens (morning, afternoon, evening, and overnight) and the 24-h collection were analyzed for sodium, potassium, chloride, creatinine, and iodine. Of 481 eligible persons, 407 (54% female, 48% black) completed a 24-h urine collection. A subsample (n = 133) collected a second 24-h urine 4–11 d later. Mean sodium excretion was 3.54 6 1.51 g/d for males and 3.09 6 1.26 g/d for females. Sensitivity analysis excluding those who did not meet the expected creatinine excretion criterion showed the same results. Day-to-day variability for sodium, potassium, chloride, and iodine was observed among those collecting two 24-h urine samples (CV = 16–29% for 24-h urine samples and 21–41% for timed-spot specimens). Among all race-gender groups, overnight specimens had larger volumes (P < 0.01) and lower sodium (P < 0.01 to P 5 0.26), potassium (P < 0.01), and chloride (P < 0.01) concentrations compared with other timed-spot urine samples, although the differences were not always significant. Urine creatinine and iodine concentrations did not differ by the timing of collection. The observed day-to-day and diurnal variations in sodium excretion illustrate the importance of accounting for these factors when developing calibration equations from this study. J. Nutr. 143: 1276–1282, 2013.

A Food Store–Based Environmental Intervention Is Associated with Reduced BMI and Improved Psychosocial Factors and Food-Related Behaviors on the Navajo Nation

Abstract: The prevalence of obesity is significantly higher among American Indians (AIs) and is associated with increased rates of diabetes, hypertension, and cardiovascular disease. We implemented a 14-mo intervention trial (Navajo Healthy Stores) on the Navajo Nation that sought to increase availability of healthier foods in local food stores and to promote these foods at the point of purchase and through community media. We divided the Navajo Nation into 10 store regions, half of which were randomized to intervention and half to comparison. We evaluated the program by using a pre-post sample of systematically sampled adult Navajo consumers (baseline, n = 276; postintervention, n = 145). Intervention impact was examined by analyzing pre-post differences by intervention group and by intervention exposure level. When intervention and comparison groups were compared, only body mass index (BMI) showed a trend toward impact of the intervention (P = 0.06). However, greater exposure to the intervention was associated with significantly reduced BMI (P ≤ 0.05) and improved healthy food intentions (P ≤ 0.01), healthy cooking methods (P ≤ 0.05), and healthy food getting (P ≤ 0.01). With increasing exposure, the odds of improving overweight or obese status was 5.02 (95% CI: 1.48, 16.99; P ≤ 0.01) times the odds of maintaining or worsening overweight or obese status. In summary, a food store intervention was associated with reduced overweight/obesity and improved obesity-related psychosocial and behavioral factors among those persons most exposed to the intervention on an AI reservation.

CD36 and SR-BI Are Involved in Cellular Uptake of Provitamin A Carotenoids by Caco-2 and HEK Cells, and Some of Their Genetic Variants Are Associated with Plasma Concentrations of These Micronutrients in Humans

Abstract: Scavenger receptor class B type I (SR-BI) and cluster determinant 36 (CD36) have been involved in cellular uptake of some provitamin A carotenoids. However, data are incomplete (e.g., there are no data on a-carotene), and it is not known whether genetic variants in their encoding genes can affect provitamin A carotenoid status. The objectives were 1) to assess the involvement of these scavenger receptors in cellular uptake of the main provitamin A carotenoids (i.e., b-carotene, a-carotene, and b-cryptoxanthin) as well as that of preformed vitamin A (i.e., retinol) and 2) to investigate the contribution of genetic variations in genes encoding these proteins to interindividual variations in plasma concentrations of provitamin A carotenoids. The involvement of SR-BI and CD36 in carotenoids and retinol cellular uptake was investigated in Caco-2 and human embryonic kidney (HEK) cell lines. The involvement of scavenger receptor class B type I (SCARB1 )a ndCD36 genetic variants on plasma concentrations of provitamin A carotenoids was assessed by association studies in 3 independent populations. Cell experiments suggested the involvement of both proteins in cellular uptake of provitamin A carotenoids but not in that of retinol. Association studies showed that several plasma provitamin A carotenoid concentrations were significantly different (P < 0.0083) between participants who bore different genotypes at single nucleotide polymorphisms and haplotypes in CD36 and SCARB1. In conclusion, SR-BI and CD36 are involved in cellular uptake of provitamin A carotenoids, and genetic variations in their encoding genes may modulate plasma concentrations of provitamin A carotenoids at a population level. J. Nutr. doi: 10.3945/jn.112.172734.