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Background: Lipid biomarkers, such as HDL-cholesterol concentrations, have been shown to have positive, inverse, and null associations with total, breast, and colorectal cancer risks. Studies of novel lipid biomarkers, such as apolipoprotein A-I (apo A-I) and apolipoprotein B- 100 (apo B-100), and cancer risk have been sparse, to our knowledge. Objectives: We evaluated the prospective association of total, breast, colorectal, and lung cancers and cancer mortality with circulating lipid biomarkers in 15,602 female health professionals in the Women's Health Study (aged ≥45 y, free of cardiovascular disease and cancer, and without hormone replacement therapy or lipid-lowering medications at baseline). Design: Cox regression models estimated HRs of cancer endpoints (19 y median follow-up) across quartiles 1 (reference) to 4 of each lipid biomarker after adjustment for cancer risk factors. Results: Confirmed cases included 2163 incident cancer cases (864 breast, 198 colorectal, and 190 lung cancers) and 647 cancer deaths. Total cancer risk was significantly lower in the highest quartile of apo A-I (adjusted HR: 0.79; 95% CI: 0.70, 0.90; P-trend = 0.0008) and HDL cholesterol (HR: 0.85; 95% CI: 0.75, 0.97; P-trend = 0.01). For site-specific cancers, significant associations included colorectal cancer risk with HDL cholesterol (HR: 0.63; 95% CI; 0.41, 0.98; P-trend = 0.03), triglycerides (HR: 1.86; 95% CI: 1.17, 2.97; P-trend = 0.02), and apo B-100 (HR: 1.60; 95% CI: 1.03, 2.49; P-trend = 0.006) and lung cancer risk with HDL cholesterol (HR: 0.59; 95% CI: 0.38, 0.93; P-trend = 0.01). LDL cholesterol was not significantly associated with risk of total cancer or any site-specific cancers. In time-dependent models that were adjusted for the use of a lipid-lowering medication after baseline, these associations remained. Conclusions: Lipids were associated with total, lung, and colorectal cancer risks in women. Lifestyle interventions for heart-disease prevention, which reduce apo B-100 or raise HDL cholesterol, may be associated with reduced cancer risk. The Women's Health Study was registered at clinicaltrials.gov as NCT00000479. [ABSTRACT FROM AUTHOR]

Background: Maternal and infant undernutrition is associated with poor infant development; however, few studies have examined the impact of combined pre- and postnatal dietary supplementation on infant development. Objective: Our objective was to determine whether provision of small-quantity lipid-based nutrient supplements (SQ-LNSs) to mothers during pregnancy and the first 6 mo postpartum, and to children aged 6-18 mo, improves infant development in Malawi. Design: We randomly assigned 869 pregnant women to receive one of the following daily: an iron and folic acid (IFA) capsule, a multiple micronutrient (MMN) capsule containing 18 micro-nutrients, or a 20-g sachet of SQ-LNSs containing 22 vitamins and minerals, protein, carbohydrates, essential fatty acids, and 118 kcal. Children in the lipid-based nutrient supplement (LNS) group only received SQ-LNSs from 6 to 18 mo of age. We monitored the acquisition of 11 developmental milestones monthly by maternal report; observed the attainment of 7 motor milestones at 6, 12, and 18 mo of age; and conducted a comprehensive assessment of motor, language, and socioemotional development and executive function at 18 mo of age. The primary analysis was by intention-to-treat. Results: By maternal report, children in the LNS group achieved walking alone (B = 0.53; 95% CI: 0.11, 0.94; P = 0.034) and waving goodbye (B = 0.60; 95% CI: 0.12, 1.08; P = 0.040) earlier than the IFA group and standing with assistance earlier than the MMN group (B = 0.51; 95% CI: 0.12, 0.89; P = 0.029). By researcher observation, there was a trend (P = 0.052) for a greater percentage of children in the LNS group (58%) to walk alone at age 12 mo than in the IFA (49%) and MMN (49%) groups. At age 18 mo, there were no significant differences between groups in any scores. Conclusion: Although provision of SQ-LNSs to pregnant women and infants in Malawi may affect the age of acquisition of certain developmental milestones, it did not affect our assessments of motor, language, socioemotional, or executive function skills at 18 mo of age. This trial was registered at clinicaltrials.gov as NCT01239693. [ABSTRACT FROM AUTHOR]

Background: The management of children with moderate acute malnutrition (MAM) is based on food supplementation in outpatient programs. When midupper arm circumference (MUAC) is used as the sole admission criterion, it is common practice to exclude children with lengths <67 cm from treatment. The WHO calls for research to determine the treatment effect among children with MAM included by MUAC and aged ≥6 mo with lengths <67 cm. Objective: We hypothesized that among children given supplementary feeding based on an MUAC of 115-124 mm as the sole criterion, there would be no difference in growth rate between children <67 cm and those ≥67 cm in length at program admission. Design: This was an observational study nested in a randomized trial that investigated the effectiveness of new formulations of corn-soy blend and lipid-based nutrient supplements. Children aged 6-23 mo were included if their MUAC was between 115 and 124 mm but with a weight-for-height z score (WHZ) ≥-2. This cohort was divided into 2 groups by length at admission: <67 cm ("short") and ≥67 cm ("long"). Linear mixed-effects models and regression models were used to compare gains in weight and MUAC while adjusting for intervention, season, sex, age, and site. Results: Weight-gain velocity (expressed as g ⋅ kg-1 ⋅ d-1) and MUAC-gain velocity (expressed as 0.01 mm ⋅ cm-1 ⋅ d-1) were not different between short and long children. Weight-gain velocity was slightly higher in the shortest quartile of length (P = 0.03), whereas there was no effect modification by stunting across length quartiles (P = 0.32). Conclusions: We found no evidence of a difference in percentage of weight gain or weight-gain velocity during supplementary feeding in short or long children aged 6-23 mo. We recommend a policy change to include children <67 cm in supplementary feeding programs if their MUAC is between 115 and 124 mm and their WHZ is ≥-2. This could benefit millions of children currently excluded from supplementary feeding. This trial was registered at www.controlled-trials.com as ISRCTN42569496. [ABSTRACT FROM AUTHOR]

Background: Metabolomics may unravel important biological pathways involved in the pathophysiology of childhood obesity. Objectives: We aimed to 1) identify metabolites that differ significantly between nonobese and obese Hispanic children; 2) collapse metabolites into principal components (PCs) associated with obesity and metabolic risk, specifically hyperinsulinemia, hypertriglyceridemia, hyperleptinemia, and hyperuricemia; and 3) identify metabolites associated with energy expenditure and fat oxidation. Design: This trial was a cross-sectional observational study of metabolomics by using gas chromatography-mass spectrometry and ultrahigh-performance liquid chromatography-tandem mass spectrometry analyses performed on fasting plasma samples from 353 nonobese and 450 obese Hispanic children. Results: Branched-chained amino acids (BCAAs) (Leu, Ile, and Val) and their catabolites, propionylcarnitine and butyrylcarnitine, were significantly elevated in obese children. Strikingly lower lysolipids and dicarboxylated fatty acids were seen in obese children. Steroid derivatives were markedly higher in obese children as were markers of inflammation and oxidative stress. PC6 (BCAAs and aromatic AAs) and PC 10 (asparagine, glycine, and serine) made the largest contributions to body mass index, and PC10 and PC12 (acylcarnitines) made the largest contributions to adiposity. Metabolic risk factors and total energy expenditure were associated with PC6, PC9 (AA and tricarboxylic acid cycle metabolites), and PC10. Fat oxidation was inversely related to PC8 (lysolipids) and positively related to PC 16 (acylcarnitines). Conclusions: Global metabolomic profiling in nonobese and obese children replicates the increased BCAA and acylcarnitine catabolism and changes in nucleotides, lysolipids, and inflammation markers seen in obese adults; however, a strong signature of reduced fatty acid catabolism and increased steroid derivatives may be unique to obese children. Metabolic flexibility in fuel use observed in obese children may occur through the activation of alternative intermediary pathways. Insulin resistance, hyperleptinemia, hypertriglyceridemia, hyperuricemia, and oxidative stress and inflammation evident in obese children are associated with distinct metabolomic profiles. [ABSTRACT FROM AUTHOR]

Background: Public health strategies to lower cardiovascular disease (CVD) risk involve reducing dietary saturated fatty acid (SFA) intake to ≤10% of total energy (%TE). However, the optimal type of replacement fat is unclear. Objective: We investigated the substitution of 9.5-9.6%TE dietary SFAs with either monounsaturated fatty acids (MUFAs) or n-6 (v-6) polyunsaturated fatty acids (PUFAs) on vascular function and other CVD risk factors. Design: In a randomized, controlled, single-blind, parallel-group dietary intervention, 195 men and women aged 21-60 y from the United Kingdom with moderate CVD risk (≥50% above the population mean) followed one of three 16-wk isoenergetic diets (%TE target compositions, total fat:SFA:MUFA:n-6 PUFA) that were rich in SFAs (36:17:11:4, n = 65), MUFAs (36:9:19:4, n = 64), or n-6 PUFAs (36:9:13:10, n = 66). The primary outcome measure was flow-mediated dilatation; secondary outcome measures included fasting serum lipids, microvascular reactivity, arterial stiffness, ambulatory blood pressure, and markers of insulin resistance, inflammation, and endothelial activation. Results: Replacing SFAs with MUFAs or n-6 PUFAs did not affect the percentage of flow-mediated dilatation (primary endpoint) or other measures of vascular reactivity. Of the secondary outcome measures, substitution of SFAs with MUFAs attenuated the increase in night systolic blood pressure (-4.9 mm Hg, P = 0.019) and reduced E-selectin (-7.8%, P = 0.012). Replacement with MUFAs or n-6 PUFAs lowered fasting serum total cholesterol (-8.4% and -9.2%, respectively), low-density lipoprotein cholesterol (-11.3% and -13.6%), and total cholesterol to high-density lipoprotein cholesterol ratio (-5.6% and -8.5%) (P ≤ 0.001). These changes in low-density lipoprotein cholesterol equate to an estimated 17-20% reduction in CVD mortality. Conclusions: Substitution of 9.5-9.6%TE dietary SFAs with either MUFAs or n-6 PUFAs did not significantly affect the percentage of flow-mediated dilatation or other measures of vascular function. However, the beneficial effects on serum lipid biomarkers, blood pressure, and E-selectin offer a potential public health strategy for CVD risk reduction. This trial was registered at www.clinicaltrials.gov as NCT01478958. [ABSTRACT FROM AUTHOR]

Background: Small birth size, often associated with insufficient maternal nutrition, contributes to a large share of global child undernutrition, morbidity, and mortality. We developed a small-quantity lipid-based nutrient supplement (SQ-LNS) to enrich the diets of pregnant women. Objective: The objective was to test a hypothesis that home fortification of pregnant women's diets with SQ-LNS would increase birth size in an African community. Design: We enrolled 1391 women with uncomplicated pregnancies (<20 gestational weeks) in a randomized controlled trial in Malawi. The women were provided with one daily iron-folic acid (IFA) capsule, one capsule containing multiple micronutrients (MMNs), or one 20-g sachet of SQ-LNS (LNS, containing 118 kcal, protein, carbohydrates, essential fatty acids, and 21 micronutrients). Primary outcomes were birth weight and newborn length. Secondary outcomes included newborn weight, head and arm circumference, and pregnancy duration. Analysis was by intention to treat. Results: The mean ± SD birth weight and newborn length were 2948 ± 432, 2964 ± 460, and 3000 ± 447 g (P = 0.258) and 49.5 ± 2.4, 49.7 ± 2.2, and 49.9 ± 2.1 cm (P = 0.104) in the IFA, MMN, and LNS groups, respectively. For newborn weight-for-age, head circumference, and arm circumference, the point estimate for the mean was also highest in the LNS group, intermediate in the MMN group, and lowest in the IFA group, but except for midupper arm circumference (P = 0.024), the differences were not statistically significant. The prevalence of low birth weight (<2500 g) was 12.7%, 13.5%, and 12.1% (P = 0.856), respectively; newborn stunting (length-for-age z score < -2) was 19.2%, 14.0%, and 14.9% (P = 0.130), respectively; and newborn small head circumference (head circumference-for-age z score < -2) was 5.8%, 3.0%, and 3.1% (P = 0.099), respectively. The associations between the intervention and the outcomes were not modified by maternal parity, age, or nutritional status (P > 0.100). Conclusion: The study findings do not support a hypothesis that provision of SQ-LNS to all pregnant women would increase the mean birth size in rural Malawi. The trial was registered at clinicaltrials.gov as NCT01239693. [ABSTRACT FROM AUTHOR]

Background: The potential for small-quantity lipid-based nutrient supplements (LNS) to promote growth and development after 6 mo of age is currently being investigated. Because infants self-regulate energy intake, consumption of LNS may reduce breast milk intake and potentially decrease the beneficial effects of breast milk. Objective: The objective was to test the hypothesis that the breast milk intake of 9- to 10-mo-old rural Malawian infants receiving LNS would not be lower than that of infants receiving no supplementation. Design: This was a substudy of the International Lipid-based Nutrient Supplements (iLiNS) DOSE trial, in which 6-mo-old infants were randomly assigned to receive 10, 20, or 40 g LNS/d containing 56, 117, or 241 kcal/d, respectively, or no LNS until 18 mo of age. A subset was randomly selected to estimate breast milk intake at 9-10 mo of age with the dose-to-mother deuterium oxide dilution method. The noninferiority margin was <10% of total energy requirements. Results: Baseline characteristics (n = 376) were similar across groups. The mean (±SD) daily breast milk intake of unsupplemented infants was 730 ± 226 g. The differences (95% CIs) in mean intake of infants provided with 10, 20, or 40 g LNS/d, compared with controls, were +62 (-18, +143), +30 (-40, +99), and +2 (-68, +72) g/d, respectively. Non-breast milk oral water intake did not differ by group (P = 0.39) and was inversely (r = -0.22, P< 0.01) associated with breast milk intake. Conclusion: In this rural Malawian population, breast milk intake at 9-10 mo of age was not reduced by supplementation with complementary foods with 10-40 g LNS/d. This study was a substudy within the iLiNS DOSE trial, which was registered at clinicaltrials.gov as NCT00945698. [ABSTRACT FROM AUTHOR]

Background: Increased carotid intima-media thickness (c-IMT) is considered a marker of early-onset atherosclerosis and it has been found in obese children and adolescents, but the risk factors associated with this population remain to be elucidated. Objective: To compare and verify the relationship between c-IMT, metabolic profile, inflammatory markers, and cardiorespiratory fitness in obese and non-obese children and adolescents. Method: Thirty-five obese subjects (19 boys) and 18 non-obese subjects (9 boys), aged 10-16 years, were included. Anthropometry, body composition, blood pressure, maximal oxygen consumption (VO2max), and basal metabolic rate were evaluated. Serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), blood lipids, C-reactive protein (CRP), and adiponectin were assessed. c-IMT was measured by ultrasound. Results: The results showed that c-IMT, triglycerides, insulin, HOMA-IR, and CRP values were significantly higher in the obese group than in the non-obese group, and high-density lipoprotein cholesterol (HDL-c), adiponectin, and VO2max values were significantly lower in the obese group than in the non-obese group. The c-IMT was directly correlated with body weight, waist circumference, % body fat, and HOMA-IR and inversely correlated with % free fat mass, HDL-c, and VO2max. Conclusions: Our findings show that c-IMT correlates not only with body composition, lipids, insulin resistance, and inflammation but also with low VO2max values in children and adolescents. [ABSTRACT FROM AUTHOR]

Background: Haiti has experienced rapid urbanization that has exacerbated poverty and undernutrition in large slum areas. Stunting affects 1 in 5 young children. Objective: We aimed to test the efficacy of a daily lipid-based nutrient supplement (LNS) for increased linear growth in young children. Design: Healthy, singleton infants aged 6-11 mo (n = 589) were recruited from an urban slum of Cap Haitien and randomly assigned to receive: 1) a control; 2) a 3-mo LNS; or 3) a 6-mo LNS. The LNS provided 108 kcal and other nutrients including vitamin A, vitamin B-12, iron, and zinc at ⩾80% of the recommended amounts. Infants were followed monthly on growth, morbidity, and developmental outcomes over a 6-mo intervention period and at one additional time point 6 mo postintervention to assess sustained effects. The Bonferroni multiple comparisons test was applied, and generalized least-squares (GLS) regressions with mixed effects was used to examine impacts longitudinally. Results: Baseline characteristics did not differ by trial arm except for a higher mean age in the 6-mo LNS group. GLS modeling showed LNS supplementation for 6 mo significantly increased the length-for-age z score (±SE) by 0.13 ± 0.05 and the weight-for-age z score by 0.12 ± 0.02 compared with in the control group after adjustment for child age (P <0.001). The effects were sustained 6 mo postintervention. Morbidity and developmental outcomes did not differ by trial arm. Conclusion: A low-energy, fortified product improved the linear growth of young children in this urban setting. The trial was registered at clinicaltrials.gov as NCT01552512 [ABSTRACT FROM AUTHOR]

Background: Flexibility in the recommended dosing time for a statin may improve patient compliance. Objective: This study was designed to compare the efficacy and tolerability of morning and evening doses of controlled-release simvastatin in Korean adults with dyslipidemia. It was carried out as a requirement to obtain authorization from the Korean regulatory agency to market the product. Methods: In this prospective, randomized, double- blind, multicenter, placebo-controlled Phase III study, we randomly assigned 132 patients with hypercholes-terolemia to a morning-dose group or an evening-dose group. Patients in the morning-dose group received 20 mg controlled-release simvastatin in the morning and a placebo in the evening, and those in the evening-dose group received a placebo in the morning and 20 mg controlled-release simvastatin in the evening. Results: After 8 weeks of the treatment, the differ-ence in the mean change of LDL-C between the morning-dose and evening-dose groups was --2.78% (95% confidence interval, --7.65 to 2.10). The changes in total cholesterol, triglycerides, HDL-C, apolipoprotein A1, apolipoprotein B, and lipoprotein (a) after treatment did not differ between groups Also, the achievement rates of the target LDL-C goal suggested by the dyslipidemia treatment guideline of the Korean Society of Lipidology and Atherosclerosis were not different. No serious adverse event was observed in either group. Mild and moderate adverse events were observed similarly in both groups. Conclusions: Although controlled-release simvasta-tin significantly reduces LDL-C levels with good tolerability in Korean adults with dyslipidemia, the time of administration does not affect its efficacy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Behavioral research to improve lifestyle in broadly defined populations of patients with type 2 diabetes is limited. Objective: We evaluated a behavioral intervention featuring technology-based self-monitoring on biophysiologic outcomes of glycemic control and markers of cardiovascular risk. Design: In this single-site, randomized clinical trial, participants were stratified by good and poor glycemic control (glycated hemoglobin <8% or ≥8%) and absence or presence of kidney disease, (estimated glomerular filtration rate ≥60 or <60 mL/min) and randomized within strata. Measurements were obtained at 0, 3, and 6 months. Participants/setting: Self-referred, community-dwelling adults with type 2 diabetes mellitus. Intervention: The intervention group received Social Cognitive Theory-based counseling paired with technology-based self-monitoring, and results were compared with an attention control group. Main outcome measures: Glycated hemoglobin, fasting serum glucose, lipid levels, blood pressure, weight, body mass index, and waist circumference were evaluated. Statistical analyses performed: Mean differences within and between randomization groups were compared over time. Intervention effects over time were estimated using random intercept models. Results: Two hundred ninety-six subjects were randomized, 256 (86.5%) completed 3-month and 246 (83.1%) completed 6-month assessments. Glycated hemoglobin was reduced in the intervention group by 0.5% at 3 months and 0.6% at 6 months (P<0.001 for each), and the control group by 0.3% (P<0.001) at 3 months and 0.2% (P<0.05) at 6 months; but between-group differences were not significant. In those with baseline glycated hemoglobin ≥8% and estimated glomerular filtration rate ≥60 mL/min, glycated hemoglobin was reduced in the intervention group by 1.5% at 3 months and 1.8% at 6 months (P<0.001 for each), and the control group by 0.9% (P<0.001) at 3 months and 0.8% (P<0.05) at 6 months; but between-group differences were not significant. In random intercept models, the estimated reduction in glycated hemoglobin of 0.29% was not significant. Conclusions: Two behavioral approaches to improving general lifestyle management in individuals with type 2 diabetes mellitus were effective in improving glycemic control, but no significant between-group differences were observed. [Copyright &y& Elsevier]

Background: Increased consumption of nuts has been advocated because of their health benefits, but the role of nuts in the treatment of obesity is unclear given their high energy density. Objective: This study was designed to evaluate the effects of a hypocaloric, almond-enriched diet (AED) compared with a hypocaloric nut-free diet (NFD) on body weight and cardiovascular disease risk factors in the context of an 18-mo behavioral weight-management program. Design: Overweight and obese individuals [n = 123; age = 46.8 y, BMI (in kg/m2) = 34.0] were randomly assigned to consume an AED or NFD and instructed in traditional behavioral methods of weight control. Anthropometric and metabolic measurements were made at baseline, 6 mo, and 18 mo. Results: Those in the AED group lost slightly but significantly less weight than did those in the NFD group at 6 mo (-5.5 compared with -7.4 kg; P = 0.04), but there were no differences at 18 mo. No significant differences in body composition were found between the groups at 6 or 18 mo. The AED, compared with the NFD, was associated with greater reductions in total cholesterol (P = 0.03), total:HDL cholesterol (p = 0.02), and triglycerides (P = 0.048) at 6 mo, and no differences were observed between the groups at 18 mo. Conclusions: The AED and NFD groups experienced clinically significant and comparable weight loss at 18 mo. Despite smaller weight loss in the AED group at 6 mo, the AED group experienced greater improvements in lipid profiles. This trial was registered at clinical- trials.gov as NCT00I94428. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Obesity is a serious health problem implicated in many metabolic disorders (i.e., hypertension, dyslipidemia, and cardiovascular disease). We examined whether the mRNA of tested genes were linked to blood lipid concentrations and vascular endothelial function as features of obesity. Methods: In healthy subjects (30–69 y old; normal weight, n = 22, body mass index 18.5–23 kg/m2; overweight, n = 25, body mass index ≥23 kg/m2) the following parameters were measured in the blood circulation: total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triacylglycerol, apolipoprotein AI, apolipoprotein B, adiponectin, high-sensitivity C-reactive protein, and soluble intercellular adhesion molecule-1. The mRNA levels of genes (arginase I [ARG1], very low-density lipoprotein receptor [VLDLR], adiponectin receptor-1 [ADIPOR1], ADIPOR2, and nitric oxide synthase-3 [NOS3]) were tested in the subjects’ peripheral blood mononuclear cells. Results: The expression levels of all tested genes were investigated for their associations with the blood concentrations of each parameter. In the expression study, only ARG1 (4.5-fold) and VLDLR (4-fold) expressions were significantly upregulated in the overweight group compared with the normal-weight group. The ARG1 mRNA levels were positively associated with blood concentrations of total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and soluble intercellular adhesion molecule-1. The VLDLR mRNA levels showed a positive relation with triacylglycerol and glucose concentrations and a negative relation with adiponectin levels. Conclusion: Significant upregulations of ARG1 and VLDLR were observed in the overweight condition and their expression levels are likely to be closely linked to the phenotypic biomarkers for obesity (disturbed lipid profiles and endothelial dysfunction). [Copyright &y& Elsevier]