A multicomponent nutrient bar promotes weight loss and improves dyslipidemia and insulin resistance in the overweight/obese: chronic inflammation blunts these improvements.

This study determined if twice-daily consumption of a nutrient-dense bar intended to fill gaps in Western diets, without other dietary/lifestyle requirements, favorably shifted metabolic/anthropometric indicators of dysregulation in a healthy direction. Three 8-wk clinical trials in 43 healthy lean and overweight/obese (OW/OB) adults, who served as their own controls, were pooled for analysis. In less inflamed OW/OB [high-sensitivity C-reactive protein (hsCRP) <1.5], statistically significant decreases occurred in weight (-1.1 ± 0.5 kg), waist circumference (-3.1 ± 1.4 cm), diastolic blood pressure (-4.1 ± 1.6 mmHg), heart rate [HR; -4.0 ± 1.7 beats per minute (bpm)], triglycerides (-72 ± 38.2 mg/dl), insulin resistance (homeostatic model of insulin resistance) (-0.72 ± 0.3), and insulin (-2.8 ± 1.3 mU/L); an increase in HDL-2b (+303 ± 116 nM) and realignment of LDL lipid subfractions toward a less atherogenic profile [decreased small LDL IIIb (-44 ± 23.5 nM), LDL IIIa (-99 ± 43.7 nM), and increased large LDL I (+66 ± 28.0 nM)]. In the more inflamed OW/OB (hsCRP >1.5), inflammation was reduced at 2 wk (-0.66 mg/L), and HR at 8 wk (-3.4 ± 1.3 bpm). The large HDL subfraction (10.5-14.5 nm) increased at 8 wk (+346 ± 126 nM). Metabolic improvements were also observed in lean participants. Thus, favorable changes in measures of cardiovascular health, insulin resistance, inflammation, and obesity were initiated within 8 wk in the OW/OB by replacing deficiencies in Western diets without requiring other dietary or lifestyle modifications; chronic inflammation blunted most improvements.

Dyslipidemia and Food Security in Low-Income US Adolescents: National Health and Nutrition Examination Survey, 2003-2010.

INTRODUCTION: Low levels of food security are associated with dyslipidemia and chronic disease in adults, particularly in women. There is a gap in knowledge about the relationship between food security among youth and dyslipidemia and chronic disease. We investigated the relationship between food security status and dyslipidemia among low-income adolescents. METHODS: We analyzed data from adolescents aged 12 to 18 years (N = 1,072) from households with incomes at or below 200% of the federal poverty level from the National Health and Nutrition Examination Survey (NHANES) 2003-2010. We used logistic regression to examine the relationship between household food security status and the odds of having abnormalities with fasting total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), serum triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), TG/HDL-C ratio, and apolipoprotein B (Apo B). Models included age, sex, race/ethnicity, smoking status, partnered status in the household, and maternal education, with additional adjustment for adiposity. RESULTS: Household food security status was not associated with elevated TC or LDL-C. Adolescents with marginal food security were more likely than food-secure peers to have elevated TGs (odds ratio [OR] = 1.86; 95% confidence interval [CI], 1.14-3.05), TG/HDL-C ratio (OR = 1.74; 95% CI, 1.11-2.82), and Apo B (OR = 1.98; 95% CI, 1.17-3.36). Female adolescents with marginal food security had greater odds than male adolescents of having low HDL-C (OR = 2.69; 95% CI, 1.14-6.37). No elevated odds of dyslipidemia were found for adolescents with low or very low food security. Adjustment for adiposity did not attenuate estimates. CONCLUSION: In this nationally representative sample, low-income adolescents living in households with marginal food security had increased odds of having a pattern consistent with atherogenic dyslipidemia, which represents a cardiometabolic burden above their risk from adiposity alone.

A nutrient-dense, high-fiber, fruit-based supplement bar increases HDL cholesterol, particularly large HDL, lowers homocysteine, and raises glutathione in a 2-wk trial.

Dietary intake modulates disease risk, but little is known how components within food mixtures affect pathophysiology. A low-calorie, high-fiber, fruit-based nutrient-dense bar of defined composition (e.g., vitamins and minerals, fruit polyphenolics, ß-glucan, docosahexaenoic acid) appropriate for deconstruction and mechanistic studies is described and evaluated in a pilot trial. The bar was developed in collaboration with the U.S. Department of Agriculture. Changes in cardiovascular disease and diabetes risk biomarkers were measured after 2 wk twice-daily consumption of the bar, and compared against baseline controls in 25 healthy adults. Plasma HDL-cholesterol (HDL-c) increased 6.2% (P=0.001), due primarily to a 28% increase in large HDL (HDL-L; P<0.0001). Total plasma homocysteine (Hcy) decreased 19% (P=0.017), and glutathione (GSH) increased 20% (P=0.011). The changes in HDL and Hcy are in the direction associated with decreased risk of cardiovascular disease and cognitive decline; increased GSH reflects improved antioxidant defense. Changes in biomarkers linked to insulin resistance and inflammation were not observed. A defined food-based supplement can, within 2 wk, positively impact metabolic biomarkers linked to disease risk. These results lay the groundwork for mechanistic/deconstruction experiments to identify critical bar components and putative synergistic combinations responsible for observed effects.

Nontraditional risk factors and biomarkers for cardiovascular disease: mechanistic, research, and clinical considerations for youth: a scientific statement from the American Heart Association.

The rapid increase in the prevalence and severity of obesity in children is likely to lower the age of onset and increase the incidence of cardiovascular disease worldwide. Understanding the pathophysiology and improving the clinical management of cardiovascular disease involve a knowledge of novel risk factors and biomarkers. The clinical and mechanistic roles of these novel biological factors during childhood are currently being investigated. The goals of this scientific statement are to present the existing knowledge and theoretical framework of nontraditional risk factors for cardiovascular disease as they relate to children and adolescents, to describe the relevance and weight of available experimental and clinical evidence and the therapeutic implications pertaining to nontraditional risk factors in the pediatric population, and to stimulate further research with a goal of developing valid and reliable approaches to identify and validate novel risk factors that will aid in the clinical evaluation and perhaps prediction of cardiovascular disease in the pediatric population. Although several biomarkers are promising, substantial research is required before nontraditional risk factors can be used to identify and reduce cardiovascular disease risk in children and adolescents.

A clinic-based lifestyle intervention for pediatric obesity: efficacy and behavioral and biochemical predictors of response.

AIM: To examine efficacy and predictors of response to a lifestyle intervention for obese youth. METHODS: Retrospective chart review of 214 children and adolescents aged 8-19 years. Linear regression identified baseline predictors of response (delta BMI z-score) at first and ultimate follow-up visits. RESULTS: Mean delta BMI z-score from baseline was -0.04 (p < 0.001) at first follow-up and -0.09 (p < 0.001) at ultimate follow-up (median time 10 mo) among 156 children and adolescents. Higher baseline BMI z-score predicted poor response at first and ultimate follow-up, explaining 10% of variance in response. Fasting insulin explained 6% of response variance at first follow-up. delta BMI z-score at the first visit along with baseline BMI z-score explained up to 50% of variance in response at ultimate visit. CONCLUSION: Clinic-based interventions improve weight status. Baseline variables predict only a small proportion of response; response at the first visit is a more meaningful tool to guide clinical decisions.

Effect of docosahexaenoic acid on lipoprotein subclasses in hyperlipidemic children (the EARLY study).

To test the hypothesis that a dietary omega-3 fatty acid, docosahexaenoic acid, improves the lipoprotein subclass profile of children who have hyperlipidemia, we conducted a randomized, double-blind, placebo-controlled study. Children who had hyperlipidemia (n = 20) were stabilized on a low-fat diet for 6 weeks and then randomized to receive 1.2 g/day of docosahexaenoic acid for 6 weeks or placebo. Supplementation with docosahexaenoic acid significantly increased low-density lipoprotein subclass 1 and high-density lipoprotein subclass 2 (large and buoyant; less atherogenic particles) by 91% and 14%, respectively, compared with the placebo phase. Low-density lipoprotein subclass 3 (small and dense; more atherogenic particles) decreased by 48%.

Childhood obesity: adrift in the "limbic triangle".

The prevalence and severity of childhood obesity have increased steadily over the past three decades. The human species evolved to rigorously defend its lower limit for weight and adiposity but is tolerant of the upper limit, which, until recent times, was rarely approached. Neuroendocrine mechanisms within the limbic core of the brain prevent starvation (ventromedial hypothalamus), heighten reward (ventral tegmental area and nucleus accumbens), and attenuate stress (amygdala), in order to promote food-seeking and ingestive behavior and to conserve energy output. In a stressful modern environment with ready access to calorie-dense, highly palatable foods and limited venues for activity, normal, reflexive responsiveness to these three drives makes weight gain all but inevitable. The obesity that ensues often engenders insulin resistance, which undermines the ability of normal hunger and satiety signals to accurately modulate energy intake versus expenditure. Obesity interventions that rely on cognitive information alone cannot free children from this "limbic triangle." Integrated multidisciplinary family- and community-based education, effective stress reduction, and a societal commitment to alter the food and built environments are all necessary components to battle the global obesity epidemic.

Insulin dynamics predict body mass index and z-score response to insulin suppression or sensitization pharmacotherapy in obese children.

OBJECTIVE: To assess the use of oral glucose tolerance testing (OGTT) to predict efficacy of insulin sensitization (metformin) or suppression (octreotide) because insulin resistance and insulin hypersecretion may impact pharmacotherapeutic efficacy in obese children. STUDY DESIGN: Forty-three and 24 obese children, with and without central nervous system (CNS) insult, underwent OGTT. Insulin sensitivity was expressed as composite insulin sensitivity index (CISI), and secretion as corrected insulin response (CIRgp). Those without CNS insult received metformin (weight-based dosing) for 6 to 16 months. Those with CNS insult received octreotide SQ 15 microg/kg/d for 6 months. Body mass index (BMI) and z-score responses were modeled using CIRgp and CISI. RESULTS: Metformin: With CIRgp and CISI = 1, BMI z-score in white children declined by 0.23 over the first 4 months (P < .001), and by 0.14 over the next year (P = .33). Each 2-fold increase in CIRgp or CISI attenuated BMI z-score reduction, but with wide uncertainty (P = .24). Black children exhibited little response. Octreotide: With CIRgp and CISI = 1, BMI z-score decreased by 0.23 in the first 4 months (P = .052). Efficacy was dependent on an interaction between CIRgp and CISI (P = .051). CONCLUSIONS: Efficacy of metformin was predicted by pretreatment insulin resistance. Efficacy of octreotide was predicted by insulin hypersecretion and sensitivity.

Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults.

BACKGROUND: Dark chocolate derived from the plant (Theobroma cacao) is a rich source of flavonoids. Cardioprotective effects including antioxidant properties, inhibition of platelet activity, and activation of endothelial nitric oxide synthase have been ascribed to the cocoa flavonoids. OBJECTIVE: To investigate the effects of flavonoid-rich dark chocolate on endothelial function, measures of oxidative stress, blood lipids, and blood pressure in healthy adult subjects. DESIGN: The study was a randomized, double-blind, placebo-controlled design conducted over a 2 week period in 21 healthy adult subjects. Subjects were randomly assigned to daily intake of high-flavonoid (213 mg procyanidins, 46 mg epicatechin) or low-flavonoid dark chocolate bars (46 g, 1.6 oz). RESULTS: High-flavonoid chocolate consumption improved endothelium-dependent flow-mediated dilation (FMD) of the brachial artery (mean change = 1.3 +/- 0.7%) as compared to low-flavonoid chocolate consumption (mean change = -0.96 +/- 0.5%) (p = 0.024). No significant differences were noted in the resistance to LDL oxidation, total antioxidant capacity, 8-isoprostanes, blood pressure, lipid parameters, body weight or body mass index (BMI) between the two groups. Plasma epicatechin concentrations were markedly increased at 2 weeks in the high-flavonoid group (204.4 +/- 18.5 nmol/L, p < or = 0.001) but not in the low-flavonoid group (17.5 +/- 9 nmol/L, p = 0.99). CONCLUSION: Flavonoid-rich dark chocolate improves endothelial function and is associated with an increase in plasma epicatechin concentrations in healthy adults. No changes in oxidative stress measures, lipid profiles, blood pressure, body weight or BMI were seen.