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1.  Isotopic estimates of sugar intake are related to chronic disease risk factors but not obesity in an Alaska Native (Yup’ik) study population 
Background
Sugar intake may be causally associated with chronic disease risk, either directly or by contributing to obesity. However, evidence from observational studies is mixed, in part due to the error and bias inherent in self-reported measures of sugar intake. Objective biomarkers may clarify the relationship between sugar intake and chronic disease risk. We have recently validated a biomarker of sugar intake in an Alaska Native (Yup’ik) study population that incorporates red blood cell carbon and nitrogen isotope ratios in a predictive model.
Objective
This study tested associations of isotopic estimates of sugar intake with BMI, waist circumference (WC), and a broad array of other physiological and biochemical measures of chronic disease risk in Yup’ik people.
Subjects/Methods
In a cross-sectional sample of 1076 Yup’ik people, multiple linear regression was used to examine associations of sugar intake with BMI, WC and other chronic disease risk factors.
Results
Isotopic estimates of sugar intake were not associated with BMI (P = 0.50) or WC (P = 0.85). They were positively associated with blood pressure, triglycerides, and leptin, and inversely associated with total-, HDL- and LDL-cholesterol and adiponectin.
Conclusions
Isotopic estimates of sugar intake were not associated with obesity, but were adversely associated with other chronic disease risk factors in this Yup’ik study population. This first use of stable isotope markers of sugar intake may influence recommendations for sugar intake by Yup’ik people; however, longitudinal studies are required to understand associations with chronic disease incidence.
doi:10.1038/ejcn.2013.230
PMCID: PMC3947290  PMID: 24219893
Isotopes; carbon; Isotopes; nitrogen; Chronic disease; Risk factors; Caloric sweeteners
2.  Vitamin D and type 2 diabetes: a systematic review 
Background/Objectives
Vitamin D may modify the risk of type 2 diabetes mellitus. The aim of this review was to examine the association between vitamin D status and incident type 2 diabetes, and the effect of vitamin D supplementation on glycemic outcomes.
Methods
We performed a systematic review of English-language studies using MEDLINE through February 2011. Longitudinal cohort studies reporting associations between vitamin D status and incident type 2 diabetes, and randomized controlled trials (RCTs) of vitamin D supplementation, were included. Study characteristics and results were extracted, and study quality was assessed.
Results
A total of 8 observational cohort studies and 11 RCTs were included. In meta-analyses of observational studies, vitamin D intake > 500 international units (IU)/day decreased the risk of type 2 diabetes by 13% compared with vitamin D intake < 200 IU/day. Individuals with the highest vitamin D status (> 25 ng/ml) had a 43% lower risk of developing type 2 diabetes (95% confidence interval 24, 57%) compared with those in the lowest group (< 14 ng/ml). In post hoc analyses from eight trials among participants with normal glucose tolerance at baseline and in three small underpowered (n = 32–62) trials of patients with established type 2 diabetes, there was no effect of vitamin D supplementation on glycemic outcomes. In two trials among patients with baseline glucose intolerance, vitamin D supplementation improved insulin resistance.
Conclusions
Vitamin D may play a role in type 2 diabetes; however, to better define the role of vitamin D in the development and progression of type 2 diabetes, high-quality observational studies and RCTs that measure blood 25-hydroxyvitamin D concentration and clinically relevant glycemic outcomes are needed.
doi:10.1038/ejcn.2011.118
PMCID: PMC4066381  PMID: 21731035
vitamin D; type 2 diabetes mellitus; systematic review; meta-analysis
3.  Resting energy expenditure and adiposity accretion among children with Down syndrome: a three year prospective study 
European journal of clinical nutrition  2013;67(10):1087-1091.
Background
Children with Down syndrome (DS) have a higher prevalence of obesity than other children. Whether this increased risk for obesity is due to a lower resting energy expenditure (REE) is controversial. Our study assessed whether 1) the REE of children with DS adjusted for fat free mass (FFM) was lower than that of sibling controls and 2) the changes in fat mass (FM) over three years were associated with FFM-adjusted baseline REE.
Methods
This study used cross-sectional and prospective cohort designs. Four annual measurement visits were conducted with 28 children with DS and 35 sibling controls aged 3–10y. REE and serum thyroxine (T4) were measured at baseline. Anthropometry, skinfold thicknesses measures, and, in a subsample, dual energy x-ray absorptiometry (DXA) were used at each visit to calculate FM.
Results
Children with DS had significantly lower REE adjusted for FFM (−78 kcal/day, 95% CI: −133 to −27, p=0.003). The difference remained significant after adjustment for FM, sex, and African ancestry (−49 kcal/day, 95% CI: −94 to −4, p=0.03). In the longitudinal analysis, the baseline REE adjusted for baseline FFM was not predictive of FM accretion over time (p=0.8).
Conclusion
Children with DS have lower REE than sibling controls, but REE was not associated with changes in FM over time. The results suggest that the lower REE of children with DS does not explain their increased risk for obesity.
doi:10.1038/ejcn.2013.137
PMCID: PMC3790863  PMID: 23900244
obesity; fat free mass; fat mass
4.  Effect of a dairy and calcium rich diet on weight loss and appetite during energy restriction in overweight and obese adults: a randomized trial 
Background/Objectives
A diet rich in dairy and calcium (Ca) has been variably associated with improvements in body composition and decreased risk of type 2 diabetes. Our objective was to determine if a dietary pattern high in dairy and Ca improves weight loss and subjective appetite to a greater extent than a low dairy/Ca diet during energy restriction in overweight and obese adults with metabolic syndrome.
Subjects/Methods
49 participants were randomized to one of two treatment groups: CONTROL [low dairy, ~700 mg/day Ca, −500 kcal/d] or DAIRY/CA [high dairy, ~1400 mg/day Ca, −500 kcal/d] for 12wk. Body composition, subjective ratings of appetite, food intake, plasma satiety hormones, glycemic response and inflammatory cytokines were measured.
Results
CONTROL (−2.2±0.5 kg) and DAIRY/CA (−3.3±0.6 kg) had similar weight loss. Based on self-reported energy intake, the percent of expected weight loss achieved was higher with DAIRY/CA (82.1±19.4%) than CONTROL (32.2±7.7%)(P=0.03). Subjects in the DAIRY/CA group reported feeling more satisfied (P=0.01) and had lower dietary fat intake (P=0.02) over 12wk compared to CONTROL. Compared to CONTROL, DAIRY/CA had higher plasma levels of peptide tyrosine tyrosine (PYY, P=0.01) during the meal tolerance test at wk12. Monocyte chemoattractant protein-1 was reduced at 30 min with DAIRY/CA compared to CONTROL (P=0.04).
Conclusions
In conclusion, a dairy and Ca rich diet was not associated with greater weight loss than control. Modest increases in plasma PYY concentrations with increased dairy/Ca intake, however, may contribute to enhanced sensations of satisfaction and reduced dietary fat intake during energy restriction. Registered Trial: ClinicalTrials.gov (NCT00564551).
doi:10.1038/ejcn.2013.52
PMCID: PMC3948984  PMID: 23462943 CAMSID: cams4035
Calcium; dairy; peptide YY; clinical trial; satiety
5.  Prediction of Fat-Free Mass Using Bioelectrical Impedance Analysis in Young Adults from Five Populations of African Origin 
Background/Objectives
Bio-electrical impedance analysis (BIA) is used in population and clinical studies as a technique for estimating body composition. Because of significant underrepresentation in existing literature, we sought to develop and validate predictive equation(s) for BIA for studies in populations of African origin.
Subjects/Methods
Among five cohorts of the Modeling the Epidemiologic Transition Study (METS), height, weight, waist circumference and body composition, using isotope dilution, were measured in 362 adults, ages 25 to 45 with mean BMIs ranging from 24 to 32. BIA measures of resistance and reactance were measured using tetrapolar placement of electrodes and the same model of analyzer across sites (BIA 101Q, RJL Systems). Multiple linear regression analysis was used to develop equations for predicting FFM, as measured by isotope dilution; covariates included sex, age, waist, reactance and height2/resistance, along with dummy variables for each site. Developed equations were then tested in a validation sample; FFM predicted by previously published equations were tested in the total sample.
Results
A site-combined equation and site-specific equations were developed. The mean differences between FFM (reference) and FFM predicted by the study-derived equations were between 0.4–0.6 kg (i.e. 1% difference between actual and predicted FFM) and the measured and predicted values were highly correlated. The site-combined equation performed slightly better than the site-specific equations and the previously published equations.
Conclusions
Relatively small differences exist between BIA equations to estimate FFM, whether study-derived or published equations, although the site-combined equation performed slightly better than other. The study-derived equations provide an important tool for research in these understudied populations.
doi:10.1038/ejcn.2013.123
PMCID: PMC3766444  PMID: 23881006
predictive equation; body composition; epidemiology
6.  Inulin Increases Short-Term Markers for Colonic Fermentation similarly in Healthy and Hyperinsulinemic Humans 
European journal of clinical nutrition  2011;65(12):1279-1286.
Background/Objectives
Colonic fermentation of dietary fibre produces short-chain fatty-acids (SCFA) acetate, propionate and butyrate, which may protect against type 2 diabetes by reducing serum free-fatty acids (FFA). Since hyperinsulinemia is associated with insulin resistance and increased diabetes risk, the main objective was to compare markers of colonic fermentation after acute inulin ingestion in subjects with normal (< 40pmol/L, NI) and high (≥ 40pmol/L, HI) plasma-insulin.
Subjects/Methods
Overnight fasted NI (n = 9) and HI (n = 9) subjects were studied for 4 h on 2 separate days after consuming 300 ml drinks containing 75 g glucose (Glucose) or 75 g glucose plus 24 g inulin (Inulin) using a randomized, single-blind, cross-over design.
Results
Inulin elicited a higher breath hydrogen and methane AUC but the increases in SCFA responses were not statistically significant. Overall mean serum-acetate over the 4 h study period was higher in NI than HI subjects (44.3±6.9 vs 22.5±3.7 μmol/L, p = 0.001). The rate of rebound of FFA was reduced by Inulin, with FFA at 4hr being less after Inulin than Glucose, regardless of insulin status (0.310±0.028 vs 0.432±0.042 mEq/L, p = 0.008).
Conclusions
This suggests that inulin increases short-term markers for colonic fermentation but a longer study period may be necessary to observe differences in SCFA production. The reason for the lower serum-acetate in HI is unclear but may be due to reduced absorption, increased clearance or decreased endogenous production. This suggests the need to compare acetate kinetics in normal and hyperinsulinemic subjects.
doi:10.1038/ejcn.2011.116
PMCID: PMC3937120  PMID: 21712835 CAMSID: cams4024
Colonic fermentation; short chain fatty acids; acetate; inulin; hyperinsulinemia; free fatty acids
7.  Intravenous Acetate Elicits a Greater Free Fatty Acid Rebound in Normal than Hyperinsulinaemic Humans 
Background/Objectives
Colonic fermentation of dietary fiber may improve insulin sensitivity via the metabolic effects of short chain fatty acids (SCFA) in reducing free fatty acids (FFA). The main objectives of this study were to compare peripheral uptake of acetate (AC) in participants with normal (< 40pmol/L, NI) and high (≥ 40pmol/L, HI) plasma-insulin and the ability of AC to reduce FFA in both groups.
Subject/Methods
Overnight fasted NI (n = 9) and HI (n = 9) participants were given an intravenous (IV) infusion of 140 mmol/L sodium acetate at 3 different rates over 90 minutes. The total amount of AC infused was 51.85 mmols.
Results
Acetate clearance in NI participants was not significantly different than that in HI participants (2.11 ± 0.23 vs 2.09 ± 0.24 ml/min). FFA fell in both groups, but rebounded to a greater extent in NI than HI participants (time × group interaction, P = 0.001). Significant correlations between insulin resistance (IR) indices (HOMA-IR, Matsuda and Insulinogenic Index) vs FFA rebound during IV AC infusion were also observed.
Conclusions
These findings suggest that AC uptake is similar in both groups. Participants with lower plasma insulin and lower IR indices had a greater FFA rebound. These results support the hypothesis that increasing AC concentrations in the systemic circulation may reduce lipolysis and plasma FFA concentrations and thus improve insulin sensitivity. More in-depth studies are needed to look at the effects of SCFA on FFA metabolism in insulin resistant participants.
doi:10.1038/ejcn.2012.98
PMCID: PMC3937122  PMID: 22828730 CAMSID: cams4033
Humans; acetate; FFA; insulin sensitivity
8.  Measuring energy expenditure in clinical populations: rewards and challenges 
The measurement of energy expenditure (EE) is recommended as an important component of comprehensive clinical nutrition assessments in patients with altered metabolic states, who failed to respond to nutrition support and with critical illness that require individualized nutrition support. There is evidence that EE is variable in patients with metabolic diseases, such as chronic renal disease, cirrhosis, HIV, cancer cachexia, cystic fibrosis and patients under intensive care. By using appropriate techniques and interpretations of basal or resting EE, clinicians can facilitate the adequate nutrition support with minimum negative impacts from under- or overfeeding in these patients. This review is based on our current understanding of the different components of EE and the techniques to measure them, and to re-examine advances and challenges to determine energy needs in clinical populations with more focuses on the obese, pediatric and elderly patients. In addition, technological advances have expanded the choices of market-available equipments for assessing EE, which also bring specific challenges and rewards in selecting the right equipment with specific performance criteria. Lastly, analytical considerations of interpreting the results of EE in the context of changing body composition are presented and discussed.
doi:10.1038/ejcn.2013.38
PMCID: PMC3928639  PMID: 23443826
basal metabolic rate; indirect calorimetry; oxygen consumption; obesity; children; elderly
9.  European ancestry and resting metabolic rate in older African Americans 
Background/Objectives
Resting metabolic rate (RMR) contributes 60–80% of total energy expenditure and is consistently lower in populations of African descent compared with populations of European populations. Determination of European ancestry (EA) through SNP analysis would provide an initial step for identifying genetic associations that contribute to low RMR. We sought to evaluate the association between RMR and EA in African Americans.
Subjects/Methods
RMR was measured by indirect calorimetry in 141 African American men and women (aged 74.7 ± 3.0 years) enrolled in a substudy of the Health, Aging and Body Composition Study. Ancestry informative markers were used to estimate individual percent EA. Multivariate regression was used to assess the association between RMR and EA after adjustments for soft tissue fat-free mass (STFFM), fat mass, age, study site, physical activity level and sex.
Results
Mean EA was 23.8 ± 16% (range: 0.1% to 70.7%) and there were no differences by sex. Following adjustments, each percent EA was associated with a 1.6 kcal/day (95% Confidence interval: 0.42, 2.7 kcal/day) higher RMR (p = 0.008). This equates to a 160 kcal/day lower RMR in a population of completely African ancestry with one of completely European ancestry. Additional adjustment for trunk STFFM that partially accounts for high-metabolic rate organs did not affect this association.
Conclusions
European ancestry in African Americans is strongly associated with higher RMR. The data suggest that population differences in RMR may be due to genetic variants.
doi:10.1038/ejcn.2011.22
PMCID: PMC3915864  PMID: 21468093
Admixture; energy metabolism; body composition; genetic mapping
10.  Single nucleotide polymorphisms in uracil-processing genes, intake of one-carbon nutrients and breast cancer risk 
Background/Objectives
The misincorporation of uracil into DNA leads to genomic instability. In a prior study, some of us identified four common SNPs in uracil-processing genes (rs2029166 and rs7296239 in SMUG1, rs34259 in UNG, and rs4775748 in DUT) that were associated with significantly altered levels of uracil in human DNA. We investigated whether any of these SNPs are associated with an altered risk of developing breast cancer and if one-carbon nutrients intake can modify their effects.
Subjects/Methods
We genotyped the four SNPs in 1,077 cases of incident breast cancer and 1,910 age and race-matched controls in the Western New York Exposures and Breast Cancer (WEB) Study and examined associations with breast cancer risk and interactions with intake of folate, vitamins B6 and B12.
Results
After adjustment for known risk factors for breast cancer, there was increased risk of breast cancer among postmenopausal women who were heterozygous for either of the SMUG1 SNPs (OR 1.29, 95% CI 1.07–1.56) and (1.29, 1.07–1.55). Among premenopausal women, increased risk associated with the SMUG1 rs2029166 genotype was limited to those with low folate intake. There were no other interactions with vitamins B6 or B12 intake.
Conclusions
Our study suggests that the four selected SNPs are not robust determinants of breast cancer risk, but that the two SNPs in SMUG1 might modestly alter the risk of breast cancer. However, the increase in risk among heterozygotes in the two SNPs in SMUG1, which is thought to be the most active glycosylase in vivo, raises the possibility that subtle ‘heterosis’ effects on cancer risk might be produced by these SNPs.
doi:10.1038/ejcn.2011.29
PMCID: PMC3902360  PMID: 21427733
Uracil-Processing Genes; Single nucleotide polymorphisms; Breast cancer
11.  Family and infant characteristics associated with timing of core and non-core food introduction in early childhood 
Objective
To identify family and infant characteristics associated with timing of introduction of two food types: core foods (nutrient-dense) and non-core foods (nutrient-poor) in a population-based sample of mothers and infants.
Method
Participants were 1861 mothers and infants from the Gemini twin birth cohort (one child per family). Family and infant characteristics were assessed when the infants were around 8 months old. Timing of introducing core and non-core foods was assessed at 8 and 15 months. As the distributions of timing were skewed, three similar-sized groups were created for each food type: earlier (core: 1–4 months; non-core: 3–8 months), average (core: 5 months; non-core: 9–10 months), and later introduction (core: 6–12 months; non-core: 11–18 months). Ordinal logistic regression was used to examine predictors of core and non-core food introduction, with bootstrapping to test for differences between the core and non-core models.
Results
Younger maternal age, lower education level, and higher maternal BMI were associated with earlier core and non-core food introduction. Not breastfeeding for at least 3 months and higher birth weight were specifically associated with earlier introduction of core foods. Having older children was specifically associated with earlier introduction of non-core foods.
Conclusion
There are similarities and differences in the characteristics associated with earlier introduction of core and non-core foods. Successful interventions may require a combination of approaches to target both food types.
doi:10.1038/ejcn.2013.63
PMCID: PMC3674911  PMID: 23486509
Infant feeding; core foods; non-core foods
12.  Effects of high-dose cholecalciferol on serum markers of inflammation and immunity in patients with early chronic kidney disease 
European journal of clinical nutrition  2013;67(3):10.1038/ejcn.2012.217.
Background/Objective
Vitamin D has anti-inflammatory and immune-regulating properties. We aimed to determine if high-dose cholecalciferol supplementation for 1 yr in subjects with early CKD improved circulating markers of inflammation and immunity.
Subjects/Methods
In this double-blind, randomized, placebo-controlled trial, 46 subjects with early CKD (Stage 2–3) were supplemented with oral cholecalciferol (50 000 IU weekly for 12 weeks followed by 50 000 IU every other wk for 40 wks) or a matching placebo for 1 yr. Serum tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1 (MCP-1), interferon gamma-induced protein-10, and neutrophil gelatinase-associated lipocalin were measured at baseline, 12 wks, and 1 yr. Serum cathelicidin (LL-37) was measured at baseline and 12 wks. An in vitro experiment was performed to investigate the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment on MCP-1 secretion in THP-1 monocytes activated with lipopolysaccharide (LPS) and Pseudomonas aeruginosa.
Results
By 12 wks, serum MCP-1 decreased in the cholecalciferol group (66.2 ± 2.5 to 60.8 ± 2.6 pg/mL, group-by-time interaction P = 0.02) but was not different from baseline at 1 yr. Other markers of inflammation and immunity did not change. In vitro, LPS- and Pseudomonas-activated monocytes treated with1,25(OH)2D3 had significantly less MCP-1 secretion compared to untreated cells.
Conclusions
High-dose cholecalciferol decreased serum MCP-1 concentrations by 12 wks in patients with early CKD, although the decrease was not maintained for the remainder of the year. In vitro results confirm an MCP-1-lowering effect of vitamin D. Future studies should determine if vitamin D-mediated reductions in MCP-1 concentrations reflect improved clinical outcomes.
doi:10.1038/ejcn.2012.217
PMCID: PMC3824962  PMID: 23361158
vitamin D; chronic renal insufficiency; cytokines; immune markers; cathelicidin; monocyte chemoattractant protein-1; chronic kidney disease; inflammation
13.  Genetic variation in fatty acid elongases is not associated with intermediate cardiovascular phenotypes or myocardial infarction 
BACKGROUND/OBJECTIVES
Elongases 2, 4 and 5, encoded by genes ELOVL2, ELOVL4 and ELOVL5, have a key role in the biosynthesis of very long chain polyunsaturated fatty acids (PUFAs). To date, few studies have investigated the associations between elongase polymorphisms and cardiovascular health. We investigated whether ELOVL polymorphisms are associated with adipose tissue fatty acids, serum lipids, inflammation and ultimately with nonfatal myocardial infarction (MI) in a Costa Rican population.
SUBJECTS/METHODS
MI cases (n = 1650) were matched to population-based controls (n = 1650) on age, sex and area of residence. Generalized linear and multiple conditional logistic regression models were used to assess the associations between seven common ELOVL polymorphisms and cardiometabolic outcomes. Analyses were replicated in The Nurses’ Health Study (n = 1200) and The Health Professionals Follow-Up Study (n = 1295).
RESULTS
Variation in ELOVL2, ELOVL4 and ELOVL5 was not associated with adipose tissue fatty acids, intermediate cardiovascular risk factors or MI. In the Costa Rica study, the number of the minor allele copies at rs2294867, located in the ELOVL5 gene, was associated with an increase in total and LDL cholesterol (adjusted P-values = 0.001 and <0.0001 respectively). Additionally, the number of the minor allele copies at rs761179, also located in the ELOVL5 gene, was significantly associated with an increase in total cholesterol (adjusted P-value = 0.04). However, the observed associations were not replicated in independent populations.
CONCLUSION
Common genetic variants in elongases are not associated with adipose tissue fatty acids, serum lipids, biomarkers of systemic inflammation, or the risk of MI.
doi:10.1038/ejcn.2012.2
PMCID: PMC3806713  PMID: 22293571
fatty acid elongases; inflammation; cholesterol; triglycerides; myocardial infarction; Costa Rica
14.  Predicted 25-hydroxyvitamin D Score and Change in Fasting Plasma Glucose in the Framingham Offspring Study 
Data on the association between vitamin D status and actual change in glycemic measures are limited. We examined the prospective association between a predicted 25-hydroxyvitamin D (25(OH)D) score and change in fasting plasma glucose concentration over a mean follow-up of 7 years, in 2,571 men and women (mean age 54 yrs) without diabetes in the Framingham Offspring Study cohort. After adjustment for age, sex, BMI and fasting plasma glucose at baseline, higher predicted 25(OH)D score at baseline was associated with a smaller 7-year increase in fasting plasma glucose concentrations (0.23 mmol/l versus 0.35 mmol/l for highest vs. lowest tertile of 25(OH)D score respectively, P-trend=0.007). Vitamin D status may be an important determinant for change in fasting plasma glucose concentration among middle-aged and older adults without diabetes.
doi:10.1038/ejcn.2011.181
PMCID: PMC3796766  PMID: 22009071
15.  Nutrition transition in a middle-income country: 22-year trends in the Seychelles 
BACKGROUND/OBJECTIVES
There is little objective information regarding nutrition transition in African countries. We assessed trends in nutrition patterns in the Seychelles between 1989 and 2011.
SUBJECTS/METHODS
Population-based samples were obtained in 1989, 1994 and 2011 and participants aged 25–44 are considered in this study (n = 493, 599 and 471, respectively). Similar, although not identical, food frequency questionnaires (FFQs) were used in each survey and the variables were collapsed into homogenous categories for the purpose of this study.
RESULTS
Between 1989 and 2011, consumption frequency of fish (5 +/week) decreased from 93 to 74%, whereas the following increased: meat (5 +/week) 25 to 51%, fruits (1 +/week) 48 to 94%, salty snacks (1 +/week) 22 to 64% and sweet snacks (1 +/week) 38 to 67% (P < 0.001 for all). Consumption frequency decreased for home-brewed alcoholic drinks (1 +/week) 16 to 1%, but increased for wine (1 +/week) 5 to 33% (both P < 0.001). Between 2004 and 2011, consumption frequency decreased for rice (2/day) 62 to 57% and tea (1 +/day) 72 to 68%, increased for poultry (1 +/week) 86 to 96% (all P < 0.01), and did not change for vegetables (70.3 to 69.8%, P = 0.65).
CONCLUSIONS
Seychelles is experiencing nutrition transition characterized by a decreased consumption frequency of traditional staple foods (fish, polished rice), beverages (tea) and of inexpensive home brews, and increased consumption frequency of meat, poultry and snacks. Food patterns also became more varied along with a broader availability of products in the 22-year interval. The health impact of these changes should be further studied.
doi:10.1038/ejcn.2012.199
PMCID: PMC3786399  PMID: 23249880
nutrition transition; nutrition trends; food frequency questionnaires; Seychelles; developing countries
16.  Prevalence and energy intake from snacking in Brazil: analysis of the first nationwide individual survey 
Background/Objectives
Snacking has increased globally. We examine snacking patterns and common snack foods in Brazil.
Subjects/Methods
Data from the first of two non-consecutive food diaries from 34,003 individuals (aged ≥10 years) in the first Brazillian nationally representative dietary survey (2008-2009) were used. Meals were defined as the largest (kcal) eating event reported during select times of the day (Breakfast, 6am-10am; Lunch, 12pm-3pm; Dinner, 6pm-9pm); all other eating occasions were considered snacks. We estimate daily energy intake, percent consuming, number of daily snacks, and per capita and per consumer energy from snacks (kcal/d, kcal/snack, and % of daily energy from snacks).
Results
74% of Brazilians (≥10 years) snacked, reporting an average 1.6 snacks/d. 23% of the sample were heavy snackers (≥3 snacks/d). Snacking accounted for 21% of daily energy intake in the full sample, but 35.5% among heavy snackers. Compared to non-snackers (1548 kcal/d), light (1-2 snacks/d) and heavy snackers consumed more daily energy (1929 and 2334 kcal/d, respectively). By time of day, the largest percent of persons reported afternoon/early evening snacking (3:01-5:59 pm, 47.7%). Sweetened Coffee & Tea, Sweets & Desserts, Fruit, Sugar-Sweetened Beverages (SSB), and high-calorie Salgados (Fried/baked dough with Meat/Cheese/Vegetable) were the top 5 most commonly consumed snacks. Differences were observed by age groups. Trends in commercial sales were observed, especially for SSB’s.
Conclusions
Many commonly consumed snack foods in Brazil are classified, in the US, as being high in solid fats and added sugars (SoFAS). The public health impact of snacking in Brazil requires further exploration.
doi:10.1038/ejcn.2013.60
PMCID: PMC3786113  PMID: 23486510
snacking; Brazil; energy intake; adolescents; adults
17.  Determinants of anemia in postpartum HIV-negative women in Dar es Salaam, Tanzania 
OBJECTIVE
The determinants of anemia during both pregnancy and postpartum recovery remain incompletely understood in sub-Saharan African women.
SUBJECTS/METHODS
In a prospective cohort study among pregnant women, we assessed dietary, biochemical, anthropometric, infectious and sociodemographic factors at baseline. In multivariate Cox proportional hazards models, we examined predictors of incident anemia (hemoglobin <11 g/dl) and iron deficiency anemia (anemia plus mean corpuscular volume <80 fL), and recovery from anemia and iron deficiency anemia through 18 months postpartum at antenatal clinics in Dar es Salaam, Tanzania between 2001 and 2005. A total of 2364 non-anemic pregnant women and 4884 anemic women were enrolled between 12 and 27 weeks of gestation.
RESULTS
In total, 292 women developed anemia during the postpartum period and 165 developed iron deficiency anemia, whereas 2982 recovered from baseline anemia and 2044 from iron deficiency anemia. Risk factors for postpartum anemia were delivery complications (RR 1.6, 95% confidence interval (CI) 1.13, 2.22) and low postpartum CD4 cell count (RR 1.73, 95% CI 0.96, 3.17). Iron/folate supplementation during pregnancy had a protective relationship with the incidence of iron deficiency anemia. Absence of delivery complications, education status and iron/folate supplementation were positively associated with time to recovery from iron deficiency.
CONCLUSION
Maternal nutritional status during pregnancy, prenatal iron/folate supplementation, perinatal care, and prevention and management of infections, such as malaria, are modifiable risk factors for the occurrence of, and recovery from, anemia.
doi:10.1038/ejcn.2013.71
PMCID: PMC3775569  PMID: 23612515
anemia; postpartum; iron deficiency; pregnancy
18.  Adherence to the Mediterranean diet and body fat distribution in reproductive aged women 
Background/Objectives
Adherence to the Mediterranean Diet (MD) high in fruits, vegetables and monounsaturated fats, has been associated with lower body mass index. Associations with measured body fat, including regional adiposity, have not been previously investigated. We examined the associations between the alternate Mediterranean Diet Score (aMED), anthropometry and measured adiposity by dual energy x-ray absorptiometry.
Subjects/Methods
This study included 248 healthy females, aged 18–44 years from the BioCycle Study. Each woman’s aMED (range 0–9) was calculated from up to eight 24-hr dietary recalls over 1–2 menstrual cycles (>97% had ≥7 recalls). Multiple linear regression was used to determine whether aMED and its specific components were associated with total and regional adiposity after adjusting for age, race, education, physical activity and energy intake.
Results
Participants had an average (SD) aMED of 4.2 (1.7) and percent body fat of 29.5 (6.0)%. Significant inverse associations were found between aMED and all the examined adiposity measures except waist to hip ratio. Among the DXA measures, a 1-unit increment in aMED was associated with a 0.06 (95% CI:−0.09,−0.02) lower trunk-to-leg fat ratio (T/L), a measure of upper to lower body fat. In an analysis examining T/L as an outcome with the separate components of the aMED, T/L was lower with increased legume consumption (β=−0.280, 95% CI:−0.550,−0.010) but was higher with increased consumption of red and processed meat (β=0.060, 95% CI:0.002,0.117).
Conclusions
Adherence to the aMED was associated with lower total and regional adiposity, adding to the mounting evidence of the health benefits of the MD.
doi:10.1038/ejcn.2013.4
PMCID: PMC3594052  PMID: 23388669
Mediterranean Diet; body fat; trunk fat; regional adiposity; obesity; body mass index; DXA
19.  Impact of vitamin D supplementation on markers of inflammation in adults with cystic fibrosis hospitalized for a pulmonary exacerbation 
Patients with cystic fibrosis (CF) suffer from chronic lung infection and inflammation leading to respiratory failure. Vitamin D deficiency is common in patients with CF, and correction of vitamin D deficiency may improve innate immunity and reduce inflammation in patients with CF. We conducted a double-blinded, placebo-controlled, randomized clinical trial of high-dose vitamin D to assess the impact of vitamin D therapy on antimicrobial peptide concentrations and markers of inflammation. We randomized 30 adults with CF hospitalized with a pulmonary exacerbation to 250 000 IU of cholecalciferol or placebo, and evaluated changes in plasma concentrations of inflammatory markers and the antimicrobial peptide LL-37 at baseline and 12 weeks post intervention. In the vitamin D group, there was a 50.4% reduction in tumor necrosis factor-α (TNF-α) at 12 weeks (P<0.01), and there was a trend for a 64.5% reduction in interleukin-6 (IL-6) (P = 0.09). There were no significant changes in IL-1β, IL-8, IL-10, IL-18BP and NGAL (neutrophil gelatinase-associated lipocalin). We conclude that a large bolus dose of vitamin D is associated with reductions in two inflammatory cytokines, IL-6 and TNF-α. This study supports the concept that vitamin D may help regulate inflammation in CF, and that further research is needed to elucidate the potential mechanisms involved and the impact on clinical outcomes.
doi:10.1038/ejcn.2012.82
PMCID: PMC3638806  PMID: 22805498
cystic fibrosis; vitamin D; inflammation; tumor necrosis factor-α; interleukin-6
20.  Stability of the Framingham Nutritional Risk Score and its component nutrients over 8 years: The Framingham Nutrition Studies 
Background / Objectives
Diet quality indices are increasingly used in nutrition epidemiology as dietary exposures in relation to health outcomes. However, literature on long-term stability of these indices is limited. We aimed to assess the stability of the validated Framingham Nutritional Risk Score (FNRS) and its component nutrients over 8 years as well as the validity of the follow-up FNRS.
Subjects / Methods
Framingham Offspring/Spouse Study women and men (n=1 734) aged 22-76 years wwver 8 years. Individuals' nutrient intake and nutritional risk scores were assessed using 3-day dietary records administered at baseline (1984-1988) and at follow-up (1992-1996). Agreement between baseline and follow-up FNRS and nutrient intakes was evaluated using Bland-Altman method; stability was assessed using intra-class correlation (ICC) and weighted Kappa statistics. The effect of diet quality (as assessed by the FNRS) on cardiometabolic risk factors was evaluated using ANCOVA.
Results
Modest changes from baseline (≤15%) were observed in nutrient intake. Stability coefficients for the FNRS (ICC: women=0.49; men=0.46; P<0.0001) and many nutrients (ICC ≥0.3) were moderate. Over half of women and men (58%) remained in the same or contiguous baseline and follow-up quartile of the FNRS and few (3-4%) shifted >1 quartile. The FNRS was directly associated with BMI in women (P<0.01) and HDL-cholesterol among both women (P<0.001) and men (P<0.01).
Conclusion
The FNRS and its constituent nutrients remained relatively stable over 8 years of follow-up. The stability of diet quality has implications for prospective epidemiological investigations.
doi:10.1038/ejcn.2011.167
PMCID: PMC3736565  PMID: 21970940
long-term stability; dietary quality indices; nutrients
21.  BMI percentiles for the identification of abdominal obesity and metabolic risk in children and adolescents: Evidence in support of the CDC 95th percentile 
Objectives
BMI percentiles have been routinely and historically used to identify elevated adiposity. This paper aimed to investigate the optimal Centers for Disease Control and Prevention (CDC) body mass index (BMI) percentile that predicts elevated visceral adipose tissue (VAT), fat mass and cardiometabolic risk in a biracial sample of children and adolescents.
Participants and Methods
This cross-sectional analysis included 369 white and African American children (5–18 y). BMI was calculated using height and weight and converted to BMI percentiles based on CDC growth charts. Receiver operating characteristic curve analysis identified the optimal (balance of sensitivity and specificity) BMI percentile to predict the upper quartile of age-adjusted VAT (measured by magnetic resonance imaging), age-adjusted fat mass (measured by dual energy x-ray absorptiometry) and elevated cardiometabolic risk (≥ 2 of high glucose, triglycerides and blood pressure and low high density lipoprotein cholesterol) for each race-by-sex group.
Results
The optimal CDC BMI percentile to predict those in the top quartile of age-adjusted VAT, age-adjusted fat mass and elevated cardiometabolic risk were the 96th, the 96th and the 94th percentiles, respectively, for the sample as a whole. Sensitivity and specificity was satisfactory (> 0.70) for VAT and fat mass. Compared to age-adjusted VAT and age-adjusted fat mass, there was a lower overall accuracy of the optimal percentile in identifying those with elevated cardiometabolic risk.
Conclusions
The present findings support the utility of the 95th CDC BMI percentile as a useful threshold for the prediction of elevated levels of VAT, fat mass and cardiometabolic risk in children and adolescents.
The study is registered at clinicaltrials.gov as NCT01595100.
doi:10.1038/ejcn.2012.203
PMCID: PMC3566333  PMID: 23232587
body mass index; visceral adipose tissue; children; adolescents; Centers for Disease Control and Prevention; body fat
22.  The Effects of Phytosterols Present in Natural Food Matrices on Cholesterol Metabolism and LDL-Cholesterol: A Controlled Feeding Trial 
European journal of clinical nutrition  2010;64(12):1481-1487.
Background/Objectives
Extrinsic phytosterols supplemented to the diet reduce intestinal cholesterol absorption and plasma LDL-cholesterol. However, little is known about their effects on cholesterol metabolism when given in native, unpurified form and in amounts achievable in the diet. The objective of this investigation was to test the hypothesis that intrinsic phytosterols present in unmodified foods alter whole-body cholesterol metabolism.
Subjects/Methods
Twenty out of 24 subjects completed a randomized, crossover feeding trial where all meals were provided by a metabolic kitchen. Each subject consumed two diets for 4 weeks each. The diets differed in phytosterol content (phytosterol-poor diet, 126 mg phytosterols/2000 kcal; phytosterol-abundant diet, 449 mg/2000 kcal) but were otherwise matched for nutrient content. Cholesterol absorption and excretion were determined by gas chromatograph/mass spectrometry after oral administration of stable isotopic tracers.
Results
The phytosterol-abundant diet resulted in lower cholesterol absorption [54.2 ± 2.2 % (95% confidence interval, 50.5%, 57.9%) vs. 73.2 ± 1.3% (69.5%, 76.9%), P<0.0001] and 79% higher fecal cholesterol excretion [1322 ± 112 (1083.2, 1483.3) vs. 739 ± 97 mg/day (530.1, 930.2), P<0.0001] relative to the phytosterol-poor diet. Plasma lathosterol/cholesterol ratio rose 82% [from 0.71 ± 0.11 (0.41, 0.96) to 1.29 ± 0.14 μg/mg (0.98, 1.53), (P<0.0001)]. LDL-cholesterol was similar between diets.
Conclusions
Intrinsic phytosterols at levels present in a healthy diet are biologically active and have large effects on whole body cholesterol metabolism not reflected in circulating LDL. More work is needed to assess the effects of phytosterol-mediated fecal cholesterol excretion on coronary heart disease risk in humans.
doi:10.1038/ejcn.2010.180
PMCID: PMC3715129  PMID: 20808333
Diets; Absorption; Mass Spectrometry; Deuterium
23.  Relationships between insulin sensitivity, skeletal muscle mass and muscle quality in obese adolescent boys 
European journal of clinical nutrition  2012;66(12):10.1038/ejcn.2012.142.
We examined the relationships between insulin sensitivity (IS), skeletal muscle (SM) mass and SM quality in youth. Forty obese adolescent boys (body mass index ≥95th percentile, 12–18 years) participated in this study. IS and glucose tolerance was measured by a 3 h hyperinsulinemic–euglycemic clamp and a 2 h oral glucose tolerance test (OGTT), total SM mass and intermusular adipose tissue (IMAT) by whole-body magnetic resonance imaging, and muscular strength by one-repetition maximum leg and bench press. IMAT was associated (P<0.05) with IS (r= −0.53) and OGTT-insulin area under the curve (AUC; r=0.31). Similarly, muscular strength was associated (P<0.05) with both IS (r=0.39) and OGTT-insulin AUC (r= −0.32). By contrast, total SM mass was not associated with IS or any OGTT parameters (P>0.1). After accounting for race and tanner stage, IMAT and muscular strength remained significantly associated with IS, together explaining a total of 41% of the variance in IS. Our findings suggest that SM quality, but not SM mass, is associated with IS in obese adolescent boys.
doi:10.1038/ejcn.2012.142
PMCID: PMC3656505  PMID: 23073260
SM mass; intermuscular adipose tissue; muscular strength; IS; childhood obesity
24.  Fruit and vegetable intake and type 2 diabetes: EPIC-InterAct prospective study and meta-analysis 
European journal of clinical nutrition  2012;66(10):1082-1092.
Background/Objective
Fruit and vegetable intake (FVI) may reduce the risk of type 2 diabetes (T2D), but the epidemiological evidence is inconclusive. The aim of this study is to examine the prospective association of FVI with T2D and conduct an updated meta-analysis.
Subjects/Methods
In the EPIC-InterAct (European Prospective Investigation into Cancer-InterAct) prospective case-cohort study nested within eight European countries, a representative sample of 16 154 participants and 12 403 incident cases of T2D were identified from 340 234 individuals with 3.99 million person-years of follow-up. For the meta-analysis we identified prospective studies on FVI and T2D risk by systematic searches of MEDLINE and EMBASE until April 2011.
Results
In EPIC-InterAct, estimated FVI by dietary questionnaires varied more than two-fold between countries. In adjusted analyses the hazard ratio (95% confidence interval) comparing the highest with lowest quartile of reported intake was 0.90 (0.80-1.01) for FVI; 0.89 (0.76-1.04) for fruit, and 0.94 (0.84-1.05) for vegetables. Among FV sub-types, only root vegetables were inversely associated with diabetes 0.87 (0.77-0.99). In meta-analysis using pooled data from five studies including EPIC-InterAct, comparing the highest with lowest category for FVI was associated with a lower relative risk of diabetes (0.93 (0.87-1.00)). Fruit or vegetables separately were not associated with diabetes. Among FV sub-types, only green leafy vegetable intake (RR: 0.84 (0.74-0.94)) was inversely associated with diabetes.
Conclusions
Sub-types of vegetables, such as root vegetables or green leafy vegetables may be beneficial for the prevention of diabetes, while total FVI may exert a weaker overall effect.
doi:10.1038/ejcn.2012.85
PMCID: PMC3652306  PMID: 22854878
Fruit; vegetables; type 2 diabetes mellitus; epidemiology; meta-analysis; review
25.  Predictors of stunting, wasting, and underweight among Tanzanian children born to HIV-infected women 
European journal of clinical nutrition  2012;66(11):1265-1276.
Background
Children born to HIV-infected women are susceptible to undernutrition, but modifiable risk factors and the time course of the development of undernutrition have not been well characterized.
Objective
To identify maternal, socioeconomic, and child characteristics that are associated with stunting, wasting, and underweight among Tanzanian children born to HIV-infected mothers, followed from 6 weeks for 24 months.
Methods
Maternal and socioeconomic characteristics were recorded during pregnancy, data pertaining to the infant’s birth were collected immediately after delivery, morbidity histories and anthropometric measurements were performed monthly. Multivariate Cox proportional hazards methods were used to assess the association between potential predictors and the time to first episode of stunting, wasting, and underweight.
Results
2387 infants (54.0% male) were enrolled and followed for a median duration of 21.2 months. The respective prevalence of prematurity (<37 weeks) and low birthweight (<2500g) was 15.2% and 7.0%; 11.3% of infants were HIV-positive at 6 weeks. Median time to first episode of stunting, wasting, and underweight was 8.7, 7.2, and 7.0 months, respectively. Low maternal education, few household possessions, low infant birthweight, child HIV infection and male sex were all independent predictors of stunting, wasting, and underweight. In addition, preterm infants were more likely to become wasted and underweight, whereas those with a low Apgar score at birth were more likely to become stunted.
Conclusion
Interventions to improve maternal education and nutritional status, reduce mother-to-child transmission of HIV, and increase birth weight may lower the risk of undernutrition among children born to HIV-infected women.
doi:10.1038/ejcn.2012.136
PMCID: PMC3491141  PMID: 23031850
Child undernutrition; child growth; HIV

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