Cardiometabolic deaths attributable to poor diet among Kuwaiti adults.

BACKGROUND: Nutrition transition towards a Western diet is happening in parallel with the rapidly increasing rates of cardiovascular disease and its risk factors in Kuwait. The cardiometabolic deaths attributable to poor diet have not been quantified among Kuwaiti adults. METHODS: Using a Comparative Risk Assessment model that incorporated dietary intake data from Kuwait's first national nutrition survey, number of cardiometabolic deaths from the World Health Organization, and estimated associations of diet with cardiometabolic deaths from the Global Burden of Disease project, we estimated the number and proportion of cardiometabolic deaths attributable to suboptimal intake of 10 dietary factors among Kuwaiti adults ages 25+ years, and by population subgroups. FINDINGS: An estimated 1,308 (95% uncertainty interval [UI] = 1,228-1,485) cardiometabolic deaths were attributed to suboptimal diet, accounting for 64.7% (95% UI = 60.7%-73.4%) of all cardiometabolic deaths in Kuwait in 2009. The low intake of nuts/seeds was associated with the highest estimated number and proportion of cardiometabolic deaths (n = 380, 18.8%), followed by high intake of sodium (n = 256, 12.6%), low intake of fruits (n = 250, 12.4%), low intake of vegetables (n = 236, 11.7%), low intake of whole grains (n = 201, 9.9%), and high intake of sugar-sweetened beverages (n = 201, 9.9%). The estimated proportions of cardiometabolic deaths attributable to suboptimal diet were higher in men (67.7%) than women (57.8%) and in younger adults aged 25-34 years (84.5%) than older adults aged ≥55 years (55.6%). CONCLUSION: Suboptimal dietary intake was associated with a very substantial proportion of cardiometabolic deaths among Kuwaiti adults in 2009, with young adults and men experiencing the largest proportion of diet-associated cardiometabolic deaths in Kuwait.

Child stunting starts in utero: Growth trajectories and determinants in Ugandan infants.

Childhood stunting remains a public health burden worldwide. Although many studies have examined early life and in-utero risk factors; most have been observational and have used analytic techniques that make inferences limited to population means, thereby obscuring important within-group variations. This study addressed that important gap. Using data from a birth cohort of Ugandan infants (n = 4528), we applied group-based trajectory modelling to assess diverse patterns of growth among children from birth to 1-year old. A multinomial regression model was conducted to understand the relationship between risk factors and observed patterns across groups. We found that the onset of stunting occurred before birth and followed four distinct growth patterns: chronically stunted (Group 1), recovery (Group 2), borderline stunted (Group 3) and normal (Group 4). The average length-for-age z-score (LAZ) at birth was -2.6, -3.9, -0.6 and 0.5 for Groups 1-4, respectively. Although both Groups 1 and 2 were stunted at birth, stunting persisted in Group 1 while children in Group 2 recovered by the fourth month. Group 3 exhibited mild stunting while Group 4 was normal. Wasting and underweight were observed in all groups, with the highest prevalence of underweight in Group 1. Wasting gradually increased among children born already stunted (Groups 1 and 2). This showed the importance of distinguishing children by their growth patterns rather than aggregating them and only comparing population averages against global growth standards. The design of nutrition interventions should consider the differential factors and potential for growth gains relative to different risks within each group.

Effects of Iron and Vitamin A Levels on Pregnant Women and Birth Outcomes: Complex Relationships Untangled Using a Birth Cohort Study in Uganda.

INTRODUCTION: Women and infants are among the most vulnerable groups for micronutrient deficiencies. Pregnancy micronutrient status can affect birth outcomes and subsequent infants' growth. METHODS: We determined the relationship between maternal iron and vitamin A status at delivery using several biomarkers (ferritin, soluble transferrin receptor [sTFR], body iron stores [BIS], hemoglobin and retinol binding protein [RBP]) and birth outcomes (body weight, Z-scores, head circumference, small-for-gestational-age and preterm birth) in rural Uganda. We investigated women who had serum results at the point of delivery and paired them to their infants at birth (n = 1244). We employed multivariable linear and logistic regression, adjusting for clustering at the subcounty level to determine the relationship between maternal micronutrients and birth outcomes. RESULTS: After adjusting for relevant factors, we found that maternal iron status (ferritin and BIS) and anemia (hemoglobin) were not significantly associated with the assessed birth outcomes. However, there was a significant association between serum sTFR and preterm births (AOR: 0.67; 95% CI 0.48-0.94). For Vitamin A, we observed a significant positive association between RBP and length-for-age (LAZ) at birth (ß = 0.12, p < 0.030). DISCUSSION: These findings indicate that the relationship between maternal iron status and birth outcomes needs to be further investigated, because depending on the biomarker used the associations were either in favor of an adverse birth outcome or not significant. Additionally, they confirm that higher maternal RBP levels could be beneficial for birth outcomes. CLINICALTRIALS: gov as NCT04233944.

Consumption of animal source foods, especially fish, is associated with better nutritional status among women of reproductive age in rural Bangladesh.

In rural Bangladesh, intake of nutrient-rich foods, such as animal source foods (ASFs), is generally suboptimal. Diets low in nutrients and lacking in diversity put women of reproductive age (WRA) at risk of malnutrition as well as adverse birth outcomes. The objective of this study was to assess the relationship between maternal dietary diversity, consumption of specific food groups and markers of nutritional status, including underweight [body mass index (BMI) < 18.5 kg/m2 ], overweight (BMI ≥ 23 kg/m2 ) and anaemia (haemoglobin < 120 g/dl) among WRA in Bangladesh. This analysis used data from the third round of a longitudinal observational study, collected from February through May of 2017. Dietary data were collected with a questionnaire, and Women's Dietary Diversity Score (WDDS) was calculated. Associations between WDDS, food group consumption and markers of nutritional status were assessed with separate adjusted logistic regression models. Among WRA, the prevalence of underweight, overweight and anaemia was 13.38%, 40.94% and 39.99%, respectively. Women who consumed dark green leafy vegetables (DGLV) or eggs were less likely to be anaemic or underweight, respectively, and women who consumed ASFs, particularly fish, were less likely to be underweight compared with women who did not consume these foods. WDDS did not show any consistent relationship with WRA outcomes. Interventions that focus on promoting optimal nutritional status among WRA in Bangladesh should emphasise increasing consumption of specific nutrient-rich foods, including ASFs, DGLV and eggs, rather than solely focusing on improving diet diversity in general.

Nutrition Capacity Building to Meet National Priorities: Lessons Learned in Developing and Implementing Malawi's First Dietetics Program.

The current nutrition situation in Malawi, characterized by high rates of malnutrition in communities and hospitals and a rapidly increasing burden of overweight/obesity and diet-related noncommunicable diseases, highlights the urgent need for registered dietitians, who have a proven track record in the prevention and management of all forms of malnutrition and improving patient outcomes. However, dietetics practice has been described as underdeveloped and fragmented in many parts of Africa, exacerbated by a severe and chronic shortage of dietetics professionals and a lack of nutrition and dietetic education programs in most African countries.We share early lessons learned in the development and implementation of the first dietetics program in Malawi. Within 6 years, the program produced 10 graduate dietitians who have filled the first clinical dietitian posts in Malawian public hospitals. This early success can be attributed to the model used to develop and implement the program, which included early stakeholder engagement to define the priority skills and competencies of a Malawian dietitian, the use of internationally recognized training standards, and the development of strategic institutional partnerships that brought together complementary skills and expertise. Furthermore, using existing resources and recruiting students with a nutrition and health background accelerated implementation. The current dietetics curriculum responds to the national nutrition and health policy direction and strategic objectives. Early and sustained government engagement was crucial in creating demand and securing career prospects for graduates. Although still in its infancy, dietitians in Malawi are poised to contribute significantly to alleviating the country's complex nutrition challenges.

Effective nutrition governance is correlated with better nutrition outcomes in Nepal.

BACKGROUND: The public health burden of undernutrition remains heavy and widespread, especially in low-income countries like Nepal. While predictors of undernutrition are well documented, few studies have examined the effects of political will and quality of policy or program implementation on child growth. METHODS: Data were collected from two nationwide studies in Nepal to determine the relationship between a metric of nutrition 'governance' (the Nutrition Governance Index), derived from interviews with 520 government and non-government officials responsible for policy implementation and anthropometry measured for 6815 children in 5556 households. We employed Generalized Estimating Equation (GEE) and multilevel regression models. RESULTS: A higher NGI (more effective nutrition governance) is positively associated with height-for-age as well as weight-for-height in children over 2 years of age compared to younger children (HAZ; ß = 0.02, p < 0.004, WHZ; ß = 0.01, p < 0.37). Results from the hierarchical model show that a one-point increase in the NGI is significantly associated with a 12% increase in HAZ and a 4% increase in WHZ in older children (> 24 months old). Mothers' education, child's age, BMI and no fever in the past 30 days were also protective of stunting and wasting. Seven percent and 17% of the overall variance in HAZ and WHZ, respectively, are accounted for by variations across the 21 district locations in which sampled households were located. Mean HAZ differs considerably across districts (intercept = 0.116, p < 0.001). CONCLUSIONS: These results highlight the importance of effective management of policy-based programming and resource use to bring about nutrition gains on the ground. The NGI explained a non-negligible amount of variation in HAZ and WHZ, which underscores the fundamental role that good governance plays in promoting child nutrition and growth, and the value of seeking to measure it to assist governments in moving policies from paper to practice.

Dietary lycopene attenuates cigarette smoke-promoted nonalcoholic steatohepatitis by preventing suppression of antioxidant enzymes in ferrets.

Cigarette smoke (CS) is an independent risk factor in development of nonalcoholic steatohepatitis (NASH) and fibrosis. Lycopene, a carotenoid naturally occurring in tomatoes, has been shown to be a protective agent against tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced NASH. In the present study using a ferret model we investigated whether CS promotes NASH and whether dietary lycopene can inhibit CS-promoted NASH development, and if so, what potential mechanisms were involved. Ferrets were divided into 4 groups (n=12-16/group): control, NNK/CS exposed, NNK/CS plus low-dose lycopene (2.2 mg/kg BW/day), and NNK/CS plus high-dose lycopene (6.6 mg/kg BW/day) groups, for 26 weeks. Results showed that hepatic steatosis, infiltrates of inflammatory cells, and the number and size of inflammatory foci in liver, together with key genes involved in hepatic fibrogenesis were higher in the NNK/CS group compared to the control group; a lycopene diet reversed these changes to the levels of the control group. Interestingly, a major lycopene cleavage enzyme, beta-carotene 9',10'-oxygenase (BCO2), which recently has been recognized to play metabolic roles beyond cleavage function, was down-regulated by NNK/CS exposure, but this decrease was prevented by lycopene feeding. NNK/CS exposure also downregulated liver expression of antioxidant enzymes and upregulated oxidative stress marker, which were all prevented by lycopene. In conclusion, our results suggest that CS can promote development of NASH and liver fibrosis in ferrets, which is associated with downregulation of BCO2 and impairment of antioxidant system in liver; dietary lycopene may inhibit CS-promoted NASH by preventing suppression of BCO2 and decline in antioxidant network.

Markers of Environmental Enteric Dysfunction Are Associated with Poor Growth and Iron Status in Rural Ugandan Infants.

BACKGROUND: Environmental enteric dysfunction (EED), characterized by altered intestinal permeability/inflammation, microbial translocation, and systemic inflammation (SI), may be a significant contributor to micronutrient deficiencies and poor growth in infants from low-resource settings. OBJECTIVE: We examined associations among EED, SI, growth, and iron status at 6 mo of age. METHODS: We performed a cross-sectional analysis of 6-mo-old infants (n = 548) enrolled in a Ugandan birth-cohort study (NCT04233944). EED was assessed via serum concentrations of anti-flagellin and anti- LPS immunoglobulins (Igs); SI was assessed via serum concentrations of ɑ1-acid glycoprotein (AGP) and C-reactive protein (CRP); iron status was assessed via serum concentrations of hemoglobin (Hb), soluble transferrin receptor (sTfR), and ferritin. Associations were assessed using adjusted linear regression analysis. RESULTS: At 6 mo, ∼35% of infants were stunted [length-for-age z score (LAZ) < -2] and ∼53% were anemic [hemoglobin (Hb) <11.0 g/dL]. Nearly half (∼46%) had elevated AGP (>1 g/L) and ∼30% had elevated CRP (>5 mg/L). EED and SI biomarkers were significantly correlated (r = 0.142-0.193, P < 0.001 for all). In adjusted linear regression models, which included adjustments for SI, higher anti-flagellin IgA, anti-LPS IgA, and anti-LPS IgG concentrations were each significantly associated with lower LAZ [ß (95% CI): -0.21 (-0.41, 0.00), -0.23 (-0.44, -0.03), and -0.33 (-0.58, -0.09)]. Furthermore, higher anti-flagellin IgA, anti-flagellin IgG, and anti-LPS IgA concentrations were significantly associated with lower Hb [ß (95% CI): -0.24 (-0.45, -0.02), -0.58 (-1.13, 0.00), and -0.26 (-0.51, 0.00)] and higher anti-flagellin IgG and anti-LPS IgG concentrations were significantly associated with higher sTfR [ß (95% CI): 2.31 (0.34, 4.28) and 3.13 (0.75, 5.51)]. CONCLUSIONS: EED is associated with both low LAZ and iron status in 6-mo-old infants. Further research on the mechanisms by which EED affects growth and micronutrient status is warranted.

Xanthophyll ß-Cryptoxanthin Inhibits Highly Refined Carbohydrate Diet-Promoted Hepatocellular Carcinoma Progression in Mice.

SCOPE: ß-Cryptoxanthin (BCX) can be cleaved by both ß-carotene 15,15'-oxygenase (BCO1) and ß-carotene 9',10'-oxygenase (BCO2), generating biological active vitamin A and apocarotenoids. We examined whether BCX feeding could inhibit diethylnitrosamine (DEN)-initiated, highly refined carbohydrate diet (HRCD)-promoted hepatocellular carcinoma (HCC) development, dependent or independent of BCO1/BCO2 activity. METHODS AND RESULTS: Two-week-old male wild-type (WT) and BCO1-/- /BCO2-/- double knockout (DKO) mice are given a single intraperitoneal injection of DEN (25 mg kg-1 body weight) to initiate hepatic carcinogenesis. At 6 weeks of age, all animals are fed HRCD (66.5% of energy from carbohydrate) with or without BCX for 24 weeks. BCX feeding increases hepatic vitamin A levels in WT mice, but not in DKO mice that shows a significant accumulation of hepatic BCX. Compared to their respective HRCD littermates, both WT and DKO fed BCX have significantly lower HCC multiplicity, average tumor size, and total tumor volume, and the steatosis scores. The chemopreventive effects of BCX are associated with increased p53 protein acetylation and decreased protein levels of lactate dehydrogenase and hypoxia-inducible factor-1α in tumors. CONCLUSION: This study suggests that BCX feeding may alleviate HRCD-promoted HCC progression by modulating the acetylation of p53, hypoxic tumor microenvironment, and glucose metabolism, independent of BCO1/BCO2.

Dietary Patterns Associated with the Prevalence of Cardiovascular Disease Risk Factors in Kuwaiti Adults.

BACKGROUND: Kuwaiti adults have experienced a rapid increase in cardiovascular disease (CVD) and its risk factors. Dietary patterns in the Kuwaiti diet associated with the increasingly higher CVD burden have not been adequately evaluated. OBJECTIVE: The objective of this study was to identify the major dietary patterns in Kuwaiti adults and examine their associations with CVD risk factors. DESIGN: This cross-sectional study examined data from the 2008-2009 National Nutrition Survey of the State of Kuwait. PARTICIPANTS/SETTING: The study included 555 Kuwaiti adults aged ≥20 years who completed a 24-hour dietary recall. MAIN OUTCOME MEASURES: The outcome measures included CVD risk factors such as obesity (body mass index), abdominal obesity (waist circumference), elevated blood pressure, dyslipidemia (blood lipid levels), diabetes (glucose and glycated hemoglobin levels), and metabolic syndrome. STATISTICAL ANALYSIS: Dietary patterns were identified using principal component analysis. The associations between dietary patterns and CVD risk factors were analyzed using survey-weighted multivariable linear and logistic regression models. RESULTS: Three dietary patterns were identified: vegetable-rich, fast food, and refined grains/poultry. Younger adults had higher adherence to the fast-food or refined-grains/poultry dietary patterns, whereas older adults had higher adherence to the vegetable-rich dietary pattern. The fast-food dietary pattern was positively associated with body mass index (ß=.94, 95% CI 0.08 to 1.79), waist circumference (ß=2.05, 95% CI 0.20 to 3.90 cm), and diastolic blood pressure (ß=1.62, 95% CI 0.47 to 2.77 mm Hg). The refined grains/poultry dietary pattern was positively associated with plasma glucose levels (ß=1.02, 95% CI 1.002 to 1.04 mg/dL [0.056 to 0.058 mmol/L]). Individuals in the highest tertile of the fast-food or refined-grains/poultry dietary patterns had higher odds of metabolic syndrome than those in the lowest tertile. CONCLUSIONS: The fast-food and refined grains/poultry dietary patterns were associated with high prevalence of CVD risk factors among Kuwaiti adults. The current findings underscore the need for prospective studies to further explore dietary pattern and CVD risk factor relationships among at-risk Kuwait adults.

Dietary ß-Cryptoxanthin Inhibits High-Refined Carbohydrate Diet-Induced Fatty Liver via Differential Protective Mechanisms Depending on Carotenoid Cleavage Enzymes in Male Mice.

BACKGROUND: ß-Cryptoxanthin (BCX), a provitamin A carotenoid shown to protect against nonalcoholic fatty liver disease (NAFLD), can be cleaved by ß-carotene-15,15'-oxygenase (BCO1) to generate vitamin A, and by ß-carotene-9',10'-oxygenase (BCO2) to produce bioactive apo-carotenoids. BCO1/BCO2 polymorphisms have been associated with variations in plasma carotenoid amounts in both humans and animals. OBJECTIVES: We investigated whether BCX feeding inhibits high refined-carbohydrate diet (HRCD)-induced NAFLD, dependent or independent of BCO1/BCO2. METHODS: Six-week-old male wild-type (WT) and BCO1-/-/BCO2-/- double knockout (DKO) mice were randomly fed HRCD (66.5% of energy from carbohydrate) with or without BCX (10 mg/kg diet) for 24 wk. Pathological and biochemical variables were analyzed in the liver and mesenteric adipose tissues (MATs). Data were analyzed by 2-factor ANOVA. RESULTS: Compared to their respective HRCD controls, BCX reduced hepatic steatosis severity by 33‒43% and hepatic total cholesterol by 43‒70% in both WT and DKO mice (P < 0.01). Hepatic concentrations of BCX, but not retinol and retinyl palmitate, were 33-fold higher in DKO mice than in WT mice (P < 0.001). BCX feeding increased the hepatic fatty acid oxidation protein peroxisome proliferator-activated receptor-α, and the cholesterol efflux gene ATP-binding cassette transporter5, and suppressed the lipogenesis gene acetyl-CoA carboxylase 1 (Acc1) in the MAT of WT mice but not DKO mice (P < 0.05). BCX feeding decreased the hepatic lipogenesis proteins ACC and stearoyl-CoA desaturase-1 (3-fold and 5-fold) and the cholesterol synthesis genes 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase and HMG-CoA synthase 1 (2.7-fold and 1.8-fold) and increased the cholesterol catabolism gene cholesterol 7α-hydroxylase (1.9-fold) in the DKO but not WT mice (P < 0.05). BCX feeding increased hepatic protein sirtuin1 (2.5-fold) and AMP-activated protein kinase (9-fold) and decreased hepatic farnesoid X receptor protein (80%) and the inflammatory cytokine gene Il6 (6-fold) in the MAT of DKO mice but not WT mice (P < 0.05). CONCLUSION: BCX feeding mitigates HRCD-induced NAFLD in both WT and DKO mice through different mechanisms in the liver-MAT axis, depending on the presence or absence of BCO1/BCO2.

Lycopene Inhibits Smoke-Induced Chronic Obstructive Pulmonary Disease and Lung Carcinogenesis by Modulating Reverse Cholesterol Transport in Ferrets.

Chronic obstructive pulmonary disease (COPD) and lung cancer share the same etiologic factor, cigarette smoking. Higher consumption of dietary lycopene has been associated with lower risks of COPD and lung cancer in smokers. We investigated whether lycopene feeding protects against COPD and lung cancer in ferrets, a nonrodent model that closely mimics cigarette smoke (CS)-induced chronic bronchitis, emphysema, and lung tumorigenesis in human. We also explored whether the protective effect of lycopene is associated with restoring reverse cholesterol transport (RCT), a key driver in persistent inflammation with CS exposure. Ferrets (4 groups, n = 12-16/group) were exposed to a combination of tobacco carcinogen (NNK) and CS with or without consuming lycopene at low and high doses (equivalent to ∼30 and ∼90 mg lycopene/day in human, respectively) for 22 weeks. Results showed that dietary lycopene at a high dose significantly inhibited NNK/CS-induced chronic bronchitis, emphysema, and preneoplastic lesions, including squamous metaplasia and atypical adenomatous hyperplasia, as compared with the NNK/CS alone (P < 0.05). Lycopene feeding also tended to decrease the lung neoplastic lesions. Furthermore, lycopene feeding significantly inhibited NNK/CS-induced accumulation of total cholesterol, and increased mRNA expression of critical genes related to the RCT (PPARα, LXRα, and ATP-binding cassette transporters ABCA1 and ABCG1) in the lungs, which were downregulated by the NNK/CS exposure. The present study has provided the first evidence linking a protective role of dietary lycopene against COPD and preneoplastic lesions to RCT-mediated cholesterol accumulation in lungs.

Maternal aflatoxin exposure during pregnancy and adverse birth outcomes in Uganda.

Aflatoxins are toxic metabolites of Aspergillus moulds and are widespread in the food supply, particularly in low- and middle-income countries. Both in utero and infant exposure to aflatoxin B1 (AFB1 ) have been linked to poor child growth and development. The objective of this prospective cohort study was to investigate the association between maternal aflatoxin exposure during pregnancy and adverse birth outcomes, primarily lower birth weight, in a sample of 220 mother-infant pairs in Mukono district, Uganda. Maternal aflatoxin exposure was assessed by measuring the serum concentration of AFB1 -lysine (AFB-Lys) adduct at 17.8 ± 3.5 (mean ± SD)-week gestation using high-performance liquid chromatography. Anthropometry and birth outcome characteristics were obtained within 48 hr of delivery. Associations between maternal aflatoxin exposure and birth outcomes were assessed using multivariable linear regression models adjusted for confounding factors. Median maternal AFB-Lys level was 5.83 pg/mg albumin (range: 0.71-95.60 pg/mg albumin, interquartile range: 3.53-9.62 pg/mg albumin). In adjusted linear regression models, elevations in maternal AFB-Lys levels were significantly associated with lower weight (adj-ß: 0.07; 95% CI: -0.13, -0.003; p = 0.040), lower weight-for-age z-score (adj-ß: -0.16; 95% CI: -0.30, -0.01; p = 0.037), smaller head circumference (adj-ß: -0.26; 95% CI: -0.49, -0.02; p = 0.035), and lower head circumference-for-age z-score (adj-ß: -0.23; 95% CI: -0.43, -0.03; p = 0.023) in infants at birth. Overall, our data suggest an association between maternal aflatoxin exposure during pregnancy and adverse birth outcomes, particularly lower birth weight and smaller head circumference, but further research is warranted.

Unsafe Drinking Water Is Associated with Environmental Enteric Dysfunction and Poor Growth Outcomes in Young Children in Rural Southwestern Uganda.

Environmental enteric dysfunction (EED), a subclinical disorder of the small intestine, and poor growth are associated with living in poor water, sanitation, and hygiene (WASH) conditions, but specific risk factors remain unclear. Nested within a birth cohort study, this study investigates relationships among water quality, EED, and growth in 385 children living in southwestern Uganda. Water quality was assessed using a portable water quality test when children were 6 months, and safe water was defined as lacking Escherichia coli contamination. Environmental enteric dysfunction was assessed using the lactulose:mannitol (L:M) test at 12-16 months. Anthropometry and covariate data were extracted from the cohort study, and associations were assessed using linear and logistic regression models. Less than half of the households (43.8%) had safe water, and safe versus unsafe water did not correlate with improved versus unimproved water source. In adjusted linear regression models, children from households with safe water had significantly lower log-transformed (ln) L:M ratios (ß: -0.22, 95% confidence interval (CI): -0.44, -0.00) and significantly higher length-for-age (ß: 0.29, 95% CI: 0.00, 0.58) and weight-for-age (ß: 0.20, 95% CI: 0.05, 0.34) Z-scores at 12-16 months. Furthermore, in adjusted linear regression models, ln L:M ratios at 12-16 months significantly decreased with increasing length-for-age Z-scores at birth, 6 months, and 9 months (ß: -0.05, 95% CI: -0.10, -0.004; ß: -0.06, 95% CI: -0.11, -0.006; and ß: -0.05, 95% CI: -0.09, -0.005, respectively). Overall, our data suggest that programs seeking to improve nutrition should address poor WASH conditions simultaneously, particularly related to household drinking water quality.

Biomarkers of maternal environmental enteric dysfunction are associated with shorter gestation and reduced length in newborn infants in Uganda.

Background: Adverse birth outcomes, including preterm birth and stunting at birth, have long-term health implications. The relation between adverse birth outcomes and chronic, asymptomatic gastrointestinal inflammation (environmental enteric dysfunction-EED) is poorly understood. Objective: We aimed to examine the relation between maternal EED and adverse birth outcomes in a sample of pregnant Ugandan women and their newborn infants. Design: We conducted a prospective cohort study in Mukono, Uganda. A total of 258 pregnant women were enrolled at their first prenatal visit (∼18 weeks of gestation). EED was measured by urinary lactulose:mannitol (L:M) ratio and serum concentrations of antibodies to the bacterial components flagellin and LPS. Covariates were obtained from survey data collected at 2 time points. Associations were assessed through the use of unadjusted and adjusted simple linear regression models. Results: Complete birth outcome data were recorded for 220 infants within 48 h of delivery. Mean ± SD gestational age was 39.7 ± 2.1 wk, and 7% were born preterm. Mean ± SD length and length-for-age z score (LAZ) at birth were 48.1 ± 3.2 cm and -0.44 ± 1.07, respectively. L:M ratio was not associated with any birth outcome. In adjusted models, higher concentrations of natural log-transformed anti-flagellin immunoglobin G (IgG) and anti-LPS IgG were significantly associated with shorter length of gestation (ß: -0.89 wk; 95% CI: -1.77, -0.01 wk, and ß: -1.01 wk; 95% CI: -1.87, -0.17 wk, respectively) and with reduced length (ß: -0.80 cm; 95% CI: -1.55, -0.05 cm, and ß: -0.79 cm; 95% CI: -1.54, -0.04 cm, respectively) and LAZ at birth (ß -0.44 z score; 95% CI: -0.83, -0.05, and ß: -0.40 z score; 95% CI: -0.79, -0.01, respectively). Conclusion: Maternal anti-flagellin and anti-LPS IgG concentrations in pregnancy, but not L:M ratio, were associated with shorter gestation and reduced infant length at birth. Further research on the relation between maternal EED and birth outcomes is warranted.

Effect of prior meal macronutrient composition on postprandial glycemic responses and glycemic index and glycemic load value determinations.

Background: The potential impact of prior meal composition on the postprandial glycemic response and glycemic index (GI) and glycemic load (GL) value determinations remains unclear.Objective: We determined the effect of meals that varied in macronutrient composition on the glycemic response and determination of GI and GL values of a subsequent standard test food.Design: Twenty healthy participants underwent 6 test sessions within 12 wk. The subjects received each of 3 isocaloric breakfast meals (i.e., high carbohydrate, high fat, or high protein) on separate days in a random order, which was followed by a standard set of challenges (i.e., white bread and a glucose drink) that were tested on separate days in a random order 4 h thereafter. Each challenge provided 50 g available carbohydrate. Arterialized venous blood was sampled throughout the 2-h postchallenge period. GI, GL, and insulin index (II) values were calculated with the use of the incremental area under the curve (AUCi) method, and serum lipids were determined with the use of standard assays.Results: The consumption of the high-protein breakfast before the white-bread challenge attenuated the rise in the postprandial serum glucose response (P < 0.0001) and resulted in lower glucose AUCi (P < 0.0001), GI (P = 0.0096), and GL (P = 0.0101) values than did the high-carbohydrate and high-fat breakfasts. The high-protein breakfast resulted in a lower insulin AUCi (P = 0.0146) for white bread than did the high-fat breakfast and a lower II value (P = 0.0285) than did the high-carbohydrate breakfast. The 3 breakfasts resulted in similar serum lipid responses to the white-bread challenge.Conclusions: These data indicate that the macronutrient composition of the prior meal influences the glycemic response and the determination of GI and GL values for white bread. Future studies are needed to determine whether the background food macronutrient composition influences mean dietary GI and GL values that are calculated for eating patterns, which may alter the interpretation of the associations between these values and chronic disease risk. This trial was registered at clinicaltrials.gov as NCT01023646.

Ablation of systemic SIRT1 activity promotes nonalcoholic fatty liver disease by affecting liver-mesenteric adipose tissue fatty acid mobilization.

Sirtuin 1 (SIRT1) has been reported to protect against nonalcoholic fatty liver disease (NAFLD) development. The mechanism of how SIRT1 deacetylase activity affects NAFLD has not been well investigated. The current investigation addressed the causal effect of systemic SIRT1 activity on NAFLD development and the underlying mechanism involved in both liver and mesenteric adipose tissue (MAT). Both SIRT1 homozygous mice ablated the catalytic activity (sirt1Y/Y) and their corresponding wild type littermates (WT) were fed a high fat diet (HFD, 60% calories from fat) for 34weeks. Sirt1Y/Y mice showed significantly higher level of hepatic triglyceride which was accompanied with higher levels of SREBP-1 and SCD1and decreased phosphorylation of LKB1 and AMPK in the liver. Compared with WT mice, mRNA expression of lipogenic genes (lxrα, srebp-1c, scd1 and fas) in the MAT increased significantly in sirt1Y/Y mice. Fatty acid oxidation biomarkers (acox1, acox3, cpt, ucp1, sirt3) in both liver and MAT were comparable between groups. Interestingly, we observed that in sirt1Y/Y mice, the mRNA level of hormone sensitive lipase (hsl), adipose triglyceride lipase (atgl) and perilipin-2 (plin-2), all involved in lipolysis, significantly increased in MAT, but not in epididymal adipose tissue. These changes positively correlated with circulating free fatty acid (FFA) concentrations and higher hepatic mRNA expression of cd36 for FFA uptake. The present study has provided novel evidence to suggest that under HFD-induced metabolic surplus, the lack of SIRT1 catalytic activity promotes release of FFA from MAT and escalate NAFLD by interfering with lipid homeostasis in both liver and MAT.

Effect of macronutrients and fiber on postprandial glycemic responses and meal glycemic index and glycemic load value determinations.

Background: The potential confounding effect of different amounts and proportions of macronutrients across eating patterns on meal or dietary glycemic index (GI) and glycemic load (GL) value determinations has remained partially unaddressed.Objective: The study aimed to determine the effects of different amounts of macronutrients and fiber on measured meal GI and GL values.Design: Four studies were conducted during which participants [n = 20-22; women: 50%; age: 50-80 y; body mass index (in kg/m2): 25-30)] received food challenges containing different amounts of the variable nutrient in a random order. Added to the standard 50 g available carbohydrate from white bread was 12.5, 25, or 50 g carbohydrate; 12.5, 25, or 50 g protein; and 5.6, 11.1, or 22.2 g fat from rice cereal, tuna, and unsalted butter, respectively, and 4.8 or 9.6 g fiber from oat cereal. Arterialized venous blood was sampled for 2 h, and measured meal GI and GL and insulin index (II) values were calculated by using the incremental area under the curve (AUCi) method.Results: Adding carbohydrate to the standard white-bread challenge increased glucose AUCi (P < 0.0001), measured meal GI (P = 0.0066), and mean GL (P < 0.0001). Adding protein (50 g only) decreased glucose AUCi (P = 0.0026), measured meal GI (P = 0.0139), and meal GL (P = 0.0140). Adding fat or fiber had no significant effect on these variables. Adding carbohydrate (50 g), protein (50 g), and fat (11.1 g) increased the insulin AUCi or II; fiber had no effect.Conclusions: These data indicate that uncertainty in the determination of meal GI and GL values is introduced when carbohydrate-containing foods are consumed concurrently with protein (equal amount of carbohydrate challenge) but not with carbohydrate-, fat-, or fiber-containing foods. Future studies are needed to evaluate whether this uncertainty also influences the prediction of average dietary GI and GL values for eating patterns. This trial was registered at clinicaltrials.gov as NCT01023646.

Hepatic DNA hydroxymethylation is site-specifically altered by chronic alcohol consumption and aging.

PURPOSE: Global DNA hydroxymethylation is markedly decreased in human cancers, including hepatocellular carcinoma, which is associated with chronic alcohol consumption and aging. Because gene-specific changes in hydroxymethylcytosine may affect gene transcription, giving rise to a carcinogenic environment, we determined genome-wide site-specific changes in hepatic hydroxymethylcytosine that are associated with chronic alcohol consumption and aging. METHODS: Young (4 months) and old (18 months) male C57Bl/6 mice were fed either an ethanol-containing Lieber-DeCarli liquid diet or an isocaloric control diet for 5 weeks. Genomic and gene-specific hydroxymethylcytosine patterns were determined through hydroxymethyl DNA immunoprecipitation array in hepatic DNA. RESULTS: Hydroxymethylcytosine patterns were more perturbed by alcohol consumption in young mice than in old mice (431 differentially hydroxymethylated regions, DhMRs, in young vs 189 DhMRs in old). A CpG island ~2.5 kb upstream of the glucocorticoid receptor gene, Nr3c1, had increased hydroxymethylation as well as increased mRNA expression (p = 0.015) in young mice fed alcohol relative to the control group. Aging alone also altered hydroxymethylcytosine patterns, with 331 DhMRs, but alcohol attenuated this effect. Aging was associated with a decrease in hydroxymethylcytosine ~1 kb upstream of the leptin receptor gene, Lepr, and decreased transcription of this gene (p = 0.029). Nr3c1 and Lepr are both involved in hepatic lipid homeostasis and hepatosteatosis, which may create a carcinogenic environment. CONCLUSIONS: These results suggest that the location of hydroxymethylcytosine in the genome is site specific and not random, and that changes in hydroxymethylation may play a role in the liver's response to aging and alcohol.

Estimating the reliability of glycemic index values and potential sources of methodological and biological variability.

BACKGROUND: The utility of glycemic index (GI) values for chronic disease risk management remains controversial. Although absolute GI value determinations for individual foods have been shown to vary significantly in individuals with diabetes, there is a dearth of data on the reliability of GI value determinations and potential sources of variability among healthy adults. OBJECTIVE: We examined the intra- and inter-individual variability in glycemic response to a single food challenge and methodologic and biological factors that potentially mediate this response. DESIGN: The GI value for white bread was determined by using standardized methodology in 63 volunteers free from chronic disease and recruited to differ by sex, age (18-85 y), and body mass index [BMI (in kg/m2): 20-35]. Volunteers randomly underwent 3 sets of food challenges involving glucose (reference) and white bread (test food), both providing 50 g available carbohydrates. Serum glucose and insulin were monitored for 5 h postingestion, and GI values were calculated by using different area under the curve (AUC) methods. Biochemical variables were measured by using standard assays and body composition by dual-energy X-ray absorptiometry. RESULTS: The mean ± SD GI value for white bread was 62 ± 15 when calculated by using the recommended method. Mean intra- and interindividual CVs were 20% and 25%, respectively. Increasing sample size, replication of reference and test foods, and length of blood sampling, as well as AUC calculation method, did not improve the CVs. Among the biological factors assessed, insulin index and glycated hemoglobin values explained 15% and 16% of the variability in mean GI value for white bread, respectively. CONCLUSIONS: These data indicate that there is substantial variability in individual responses to GI value determinations, demonstrating that it is unlikely to be a good approach to guiding food choices. Additionally, even in healthy individuals, glycemic status significantly contributes to the variability in GI value estimates. This trial was registered at clinicaltrials.gov as NCT01023646.