Prevalence of NAFLD in Guatemala following exposure to a protein-energy nutrition intervention in early life.

INTRODUCTION AND OBJECTIVES: The global prevalence of non-alcoholic fatty liver disease (NAFLD) is approximately 25%, with Hispanic populations at greatest risk. We describe the prevalence of NAFLD in a cohort of Guatemalan adults and examine whether exposure to a protein-energy supplement from conception to two years is associated with lower prevalence of NAFLD. MATERIALS AND METHODS: From 1969 to 1977, four villages in Guatemala were cluster-randomized to receive a protein-energy supplement (Atole) or a no-protein, low-energy beverage (Fresco). We conducted a follow-up of participants from 2015 to 2017. We assessed blood samples (n=1093; 61.1% women; aged 37-53 years) for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and estimated NAFLD prevalence using the liver fat score. We used generalized linear and logistic models to estimate the difference-in-difference effect of Atole from conception to two years on NAFLD. RESULTS: Median ALT and AST were 19.7U/L (interquartile range, IQR: 14.1, 27.4) and 26.0U/L (IQR: 21.4, 32.8), respectively. The median NAFLD liver fat score was 0.2 (IQR: -1.2, 1.6) in women and -1.2 (IQR: -2.2, 0.5) in men (p<0.0001). The prevalence of NAFLD was 67.4% among women and 39.5% among men (p<0.0001). The association between Atole exposure from conception to two years and NAFLD was not significant (OR: 0.90, 95% CI: 0.50-1.63). CONCLUSIONS: NAFLD prevalence among Guatemalan adults exceeds the global average. Protein-energy supplementation in early life was not associated with later NAFLD. There is a need for further studies on the causes and onset of NAFLD throughout the life course.

Production-related contaminants (pesticides, antibiotics and hormones) in organic and conventionally produced milk samples sold in the USA.

OBJECTIVE: Consumption of cow's milk, which is associated with diet and health benefits, has decreased in the USA. The simultaneous increase in demand for more costly organic milk suggests consumer concern about exposure to production-related contaminants may be contributing to this decline. We sought to determine if contaminant levels differ by the production method used. DESIGN: Half-gallon containers of organic and conventional milk (four each) were collected by volunteers in each of nine US regions and shipped on ice for analysis. Pesticide, antibiotic and hormone (bovine growth hormone (bGH), bGH-associated insulin-like growth factor 1 (IGF-1)) residues were measured using liquid or gas chromatography coupled to mass or tandem mass spectrometry. Levels were compared against established federal limits and by production method. SETTING: Laboratory analysis of retail milk samples. RESULTS: Current-use pesticides (5/15 tested) and antibiotics (5/13 tested) were detected in several conventional (26-60 %; n 35) but not in organic (n 34) samples. Among the conventional samples, residue levels exceeded federal limits for amoxicillin in one sample (3 %) and in multiple samples for sulfamethazine (37 %) and sulfathiazole (26 %). Median bGH and IGF-1 concentrations in conventional milk were 9·8 and 3·5 ng/ml, respectively, twenty and three times that in organic samples (P < 0·0001). CONCLUSIONS: Current-use antibiotics and pesticides were undetectable in organic but prevalent in conventionally produced milk samples, with multiple samples exceeding federal limits. Higher bGH and IGF-1 levels in conventional milk suggest the presence of synthetic growth hormone. Further research is needed to understand the impact of these differences, if any, on consumers.

Effect of a Low Free Sugar Diet vs Usual Diet on Nonalcoholic Fatty Liver Disease in Adolescent Boys: A Randomized Clinical Trial.

Importance: Pediatric guidelines for the management of nonalcoholic fatty liver disease (NAFLD) recommend a healthy diet as treatment. Reduction of sugary foods and beverages is a plausible but unproven treatment. Objective: To determine the effects of a diet low in free sugars (those sugars added to foods and beverages and occurring naturally in fruit juices) in adolescent boys with NAFLD. Design, Setting, and Participants: An open-label, 8-week randomized clinical trial of adolescent boys aged 11 to 16 years with histologically diagnosed NAFLD and evidence of active disease (hepatic steatosis >10% and alanine aminotransferase level ≥45 U/L) randomized 1:1 to an intervention diet group or usual diet group at 2 US academic clinical research centers from August 2015 to July 2017; final date of follow-up was September 2017. Interventions: The intervention diet consisted of individualized menu planning and provision of study meals for the entire household to restrict free sugar intake to less than 3% of daily calories for 8 weeks. Twice-weekly telephone calls assessed diet adherence. Usual diet participants consumed their regular diet. Main Outcomes and Measures: The primary outcome was change in hepatic steatosis estimated by magnetic resonance imaging proton density fat fraction measurement between baseline and 8 weeks. The minimal clinically important difference was assumed to be 4%. There were 12 secondary outcomes, including change in alanine aminotransferase level and diet adherence. Results: Forty adolescent boys were randomly assigned to either the intervention diet group or the usual diet group (20 per group; mean [SD] age, 13.0 [1.9] years; most were Hispanic [95%]) and all completed the trial. The mean decrease in hepatic steatosis from baseline to week 8 was significantly greater for the intervention diet group (25% to 17%) vs the usual diet group (21% to 20%) and the adjusted week 8 mean difference was -6.23% (95% CI, -9.45% to -3.02%; P < .001). Of the 12 prespecified secondary outcomes, 7 were null and 5 were statistically significant including alanine aminotransferase level and diet adherence. The geometric mean decrease in alanine aminotransferase level from baseline to 8 weeks was significantly greater for the intervention diet group (103 U/L to 61 U/L) vs the usual diet group (82 U/L to 75 U/L) and the adjusted ratio of the geometric means at week 8 was 0.65 U/L (95% CI, 0.53 to 0.81 U/L; P < .001). Adherence to the diet was high in the intervention diet group (18 of 20 reported intake of <3% of calories from free sugar during the intervention). There were no adverse events related to participation in the study. Conclusions and Relevance: In this study of adolescent boys with NAFLD, 8 weeks of provision of a diet low in free sugar content compared with usual diet resulted in significant improvement in hepatic steatosis. However, these findings should be considered preliminary and further research is required to assess long-term and clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02513121.

Added Sugars and Cardiovascular Disease Risk in Children: A Scientific Statement From the American Heart Association.

BACKGROUND: Poor lifestyle behaviors are leading causes of preventable diseases globally. Added sugars contribute to a diet that is energy dense but nutrient poor and increase risk of developing obesity, cardiovascular disease, hypertension, obesity-related cancers, and dental caries. METHODS AND RESULTS: For this American Heart Association scientific statement, the writing group reviewed and graded the current scientific evidence for studies examining the cardiovascular health effects of added sugars on children. The available literature was subdivided into 5 broad subareas: effects on blood pressure, lipids, insulin resistance and diabetes mellitus, nonalcoholic fatty liver disease, and obesity. CONCLUSIONS: Associations between added sugars and increased cardiovascular disease risk factors among US children are present at levels far below current consumption levels. Strong evidence supports the association of added sugars with increased cardiovascular disease risk in children through increased energy intake, increased adiposity, and dyslipidemia. The committee found that it is reasonable to recommend that children consume ≤25 g (100 cal or ≈6 teaspoons) of added sugars per day and to avoid added sugars for children <2 years of age. Although added sugars most likely can be safely consumed in low amounts as part of a healthy diet, few children achieve such levels, making this an important public health target.

Carbohydrates and diet patterns in nonalcoholic fatty liver disease in children and adolescents.

PURPOSE OF REVIEW: The primary treatment for nonalcoholic fatty liver disease (NAFLD) in children is lifestyle change, including a healthier diet. However, there are no agreed upon expert recommendations for a specific diet in the prevention or treatment of NAFLD. In this study, we review studies published between 2015 and 2017 contributing to further understanding of the role of diet in the development and progression of NAFLD, particularly those addressing sugars and dietary patterns. RECENT FINDINGS: Multiple recent studies have expanded on earlier evidence that suggests that high intake of sugars plays a causal role in the development of NAFLD, including several recent experimental studies in adults and children that support a unique effect of fructose consumption on liver fat accumulation. Evidence also points to protective effects of dietary patterns that include but are not limited to minimizing sugar intake, Dietary Approaches to Stop Hypertension (DASH), high protein and the Mediterranean diet. The effect of diet may act through its impact on the microbiome, and may be modified by presence or absence of genetic polymorphisms (nutrigenomics) and several new studies demonstrate this. SUMMARY: Diet appears to be a powerful tool in the prevention and treatment of NAFLD. It is imperative that researchers and clinicians continue to hone in on the mechanistic pathways and specific diets to reverse the growing morbidity and mortality of NAFLD.

Arsenic exposure and risk of nonalcoholic fatty liver disease (NAFLD) among U.S. adolescents and adults: an association modified by race/ethnicity, NHANES 2005-2014.

BACKGROUND: While associated with obesity, the cause of the rapid rise in prevalence of nonalcoholic fatty liver disease (NAFLD) in children, which is highest among Hispanics, is not well understood. Animal experiments have demonstrated that arsenic exposure contributes to liver injury. Our objective was to examine the association between arsenic exposure and NAFLD in humans and to determine if race/ethnicity modifies the association. METHODS: Urinary inorganic arsenic concentrations among those ≥12 years in the National Health and Nutrition Examination Survey, 2005-2014 were used to assess the cross-sectional association with serum alanine aminotransferase (ALT) levels, a marker of liver dysfunction. We excluded high alcohol consumers (>4-5 drinks/day; n = 939), positive hepatitis B or C (n = 2330), those missing body mass index (n = 100) and pregnant women (n = 629) for a final sample of 8518. Arsenic was measured using liquid chromatography coupled with mass spectrometry and ALT was measured using standard methods. Sampling weights were used to obtain national estimates. Due to lack of normality, estimates were log transformed and are presented as geometric means. Logistic regression models controlling for age, sex, income, and weight category estimate adjusted odd ratios (aOR) of elevated ALT by quartile of arsenic and tested for effect modification by race/ethnicity and weight. Elevated ALT was defined as >25 IU/L and >22 IU/L for boys and girls ≤17 years, respectively and >30 IU/L and >19 IU/L for men and women, respectively. RESULTS: Among all, aOR of elevated ALT were higher among those in the highest vs. lowest arsenic quartile (referent), 1.4 (95% confidence interval [CI]: 1.1, 1.7) with a borderline significant interaction (p = 0.07) by race/ethnicity but not weight (p = 0.4). In analysis stratified by race/ethnicity, aOR of elevated ALT among those in the 4th quartile were higher among Mexican Americans, 2.0 (CI: 1.3, 3.1) and non-Hispanic whites only, aOR 1.4 (CI: 1.1, 1.8) despite the fact that obesity prevalence was highest among non-Hispanic blacks. CONCLUSIONS: Our findings demonstrate a positive association between urinary arsenic exposure and risk of NAFLD among U.S. adolescents and adults that is highest among Mexican Americans and among those obese, regardless of race/ethnicity.

Lipidome Changes Associated with a Diet-Induced Reduction in Hepatic Fat among Adolescent Boys with Metabolic Dysfunction-Associated Steatotic Liver Disease.

Little is known about lipid changes that occur in the setting of metabolic-dysfunction-associated steatotic liver disease (MASLD) regression. We previously reported improvements in hepatic steatosis, de novo lipogenesis (DNL), and metabolomic profiles associated with oxidative stress, inflammation, and selected lipid metabolism in 40 adolescent boys (11-16 y) with hepatic steatosis ≥5% (98% meeting the definition of MASLD). Participants were randomized to a low-free-sugar diet (LFSD) (n = 20) or usual diet (n = 20) for 8 weeks. Here, we employed untargeted/targeted lipidomics to examine lipid adaptations associated with the LFSD and improvement of hepatic steatosis. Our LC-MS/MS analysis revealed decreased triglycerides (TGs), diacylglycerols (DGs), cholesteryl esters (ChE), lysophosphatidylcholine (LPC), and phosphatidylcholine (PC) species with the diet intervention (p < 0.05). Network analysis demonstrated significantly lower levels of palmitate-enriched TG species post-intervention, mirroring the previously shown reduction in DNL in response to the LFSD. Targeted oxylipins analysis revealed a decrease in the abundance of 8-isoprostane and 14,15-DiHET and an increase in 8,9-DiHET (p < 0.05). Overall, we observed reductions in TGs, DGs, ChE, PC, and LPC species among participants in the LFSD group. These same lipids have been associated with MASLD progression; therefore, our findings may indicate normalization of key biological processes, including lipid metabolism, insulin resistance, and lipotoxicity. Additionally, our targeted oxylipins assay revealed novel changes in eicosanoids, suggesting improvements in oxidative stress. Future studies are needed to elucidate the mechanisms of these findings and prospects of these lipids as biomarkers of MASLD regression.

Increasing prevalence of nonalcoholic fatty liver disease among United States adolescents, 1988-1994 to 2007-2010.

OBJECTIVE: To assess recent trends in nonalcoholic fatty liver disease (NAFLD) prevalence among US adolescents. STUDY DESIGN: Cross-sectional data from 12 714 12-19 year olds (exclusions: chronic hepatitis, hepatotoxic medications) in the National Health and Examination Survey between 1988-1994 and 2007-2010 were used to estimate trends in suspected NAFLD, defined as overweight (body mass index ≥85th percentile) plus elevated alanine aminotransferase levels (boys >25.8 U/L; girls >22.1 U/L). Linear trends in prevalence and the independent effect of demographic indicators and adiposity on NAFLD risk were tested using regression models. Complex sampling methods and P values of <.05 were used to assess statistical significance. RESULTS: Suspected NAFLD prevalence (SE) rose from 3.9% (0.5) in 1988-1994 to 10.7% (0.9) in 2007-2010 (P < .0001), with increases among all race/ethnic subgroups, males and females, and those obese (P trend ≤.0006 for all). Among those obese, the multivariate adjusted odds of suspected NAFLD were higher with increased age, body mass index, Mexican American race, and male sex; the adjusted odds in 2007-2010 were 2.0 times those in 1988-1994. In 2007-2010, 48.1% (3.7) of all obese males and 56.0% (3.5) of obese Mexican American males had suspected NAFLD. CONCLUSION: Prevalence of suspected NAFLD has more than doubled over the past 20 years and currently affects nearly 11% of adolescents and one-half of obese males. The rapid increase among those obese, independent of body mass index, suggests that other modifiable risk factors have influenced this trend.

Infant and young child feeding practices and the factors that influence them: a qualitative study.

BACKGROUND: Early child feeding is important for healthy growth and forming positive eating behaviors. METHODS: This qualitative study sought to describe early childhood feeding behaviors, challenges, and opportunities through four focus group discussions with a diverse group of mothers of at least one child under two years or pregnant with their first child. RESULTS: Although providing healthy foods was a priority, feeding behaviors reflected the mothers' partial understanding of infant and child nutrition. Mothers sought guidance on early child feeding from several sources, including in-person and virtual relationships but made decisions based largely on their own instincts. Participants consulted clinicians the least often, and mothers often felt frustrated by strict guidelines and negative messaging. Mothers were most receptive to suggestions when they felt supported and valued in the decision-making process. CONCLUSIONS: In order to help mothers provide the best nutrition for their young children, clinicians should use positive tones, provide flexibility when possible, and work to create open lines of communication with parents.

The Impact and Burden of Dietary Sugars on the Liver.

NAFLD, or metabolic dysfunction-associated steatotic liver disease, has increased in prevalence hand in hand with the rise in obesity and increased free sugars in the food supply. The causes of NAFLD are genetic in origin combined with environmental drivers of the disease phenotype. Dietary intake of added sugars has been shown to have a major role in the phenotypic onset and progression of the disease. Simple sugars are key drivers of steatosis, likely through fueling de novo lipogenesis, the conversion of excess carbohydrates into fatty acids, but also appear to upregulate lipogenic metabolism and trigger hyperinsulinemia, another driver. NAFLD carries a clinical burden as it is associated with obesity, type 2 diabetes, metabolic syndrome, and cardiovascular disease. Patient quality of life is also impacted, and there is an enormous economic burden due to healthcare use, which is likely to increase in the coming years. This review aims to discuss the role of dietary sugar in NAFLD pathogenesis, the health and economic burden, and the promising potential of sugar reduction to improve health outcomes for patients with this chronic liver disease.

Factors That Influence Sleep Behaviors of High School Students: Findings From a Semi-Rural Community in Georgia.

BACKGROUND: Inadequate sleep has been shown to have detrimental effects on academic performance, physical, mental, and emotional health among adolescents. Factors that influence sleep have been identified. However, most literature is currently limited to urban settings. This study sought to identify factors that influence sleep habits among high school students in a semi-rural community. METHODS: Twelve focus groups were conducted in-person with separate groups of students, parents, and school staff in October 2019. Discussions focused on sleep experiences, knowledge, environment, and factors influencing sleep. Data were coded using grounded theory approach. Themes were identified through summative content analysis. RESULTS: Four major themes were identified: (1) inadequate sleep adversely affects academic performance and emotional health; (2) students face a gap in knowledge regarding sleep duration; (3) academic and nonacademic activities compete with sleep needs; and (4) night-time use of technology negatively influences sleep habits. CONCLUSIONS: Our findings suggest that high school students do not get adequate sleep, largely due to the demands of academic and extracurricular activities and the use of electronics at night. These results can guide the development of targeted sleep education and intervention programs.

Metabolome × Microbiome Changes Associated with a Diet-Induced Reduction in Hepatic Fat among Adolescent Boys.

Dietary sugar reduction is one therapeutic strategy for improving nonalcoholic fatty liver disease (NAFLD), and the underlying mechanisms for this effect warrant further investigation. Here, we employed metabolomics and metagenomics to examine systemic biological adaptations associated with dietary sugar restriction and (subsequent) hepatic fat reductions in youth with NAFLD. Data/samples were from a randomized controlled trial in adolescent boys (11-16 years, mean ± SD: 13.0 ± 1.9 years) with biopsy-proven NAFLD who were either provided a low free-sugar diet (LFSD) (n = 20) or consumed their usual diet (n = 20) for 8 weeks. Plasma metabolomics was performed on samples from all 40 participants by coupling hydrophilic interaction liquid chromatography (HILIC) and C18 chromatography with mass spectrometry. In a sub-sample (n = 8 LFSD group and n = 10 usual diet group), 16S ribosomal RNA (rRNA) sequencing was performed on stool to examine changes in microbial composition/diversity. The diet treatment was associated with differential expression of 419 HILIC and 205 C18 metabolite features (p < 0.05), which were enriched in amino acid pathways, including methionine/cysteine and serine/glycine/alanine metabolism (p < 0.05), and lipid pathways, including omega-3 and linoleate metabolism (p < 0.05). Quantified metabolites that were differentially changed in the LFSD group, compared to usual diet group, and representative of these enriched metabolic pathways included increased serine (p = 0.001), glycine (p = 0.004), 2-aminobutyric acid (p = 0.012), and 3-hydroxybutyric acid (p = 0.005), and decreased linolenic acid (p = 0.006). Microbiome changes included an increase in richness at the phylum level and changes in a few genera within Firmicutes. In conclusion, the LFSD treatment, compared to usual diet, was associated with metabolome and microbiome changes that may reflect biological mechanisms linking dietary sugar restriction to a therapeutic decrease in hepatic fat. Studies are needed to validate our findings and test the utility of these "omics" changes as response biomarkers.

Consumption of added sugars and indicators of cardiovascular disease risk among US adolescents.

BACKGROUND: Whereas increased carbohydrate and sugar consumption has been associated with higher cardiovascular disease risk among adults, little is known about the impact of high consumption of added sugars (caloric sweeteners) among US adolescents. METHODS AND RESULTS: In a cross-sectional study of 2157 US adolescents in the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004, dietary data from one 24-hour recall were merged with added sugar content data from the US Department of Agriculture MyPyramid Equivalents databases. Measures of cardiovascular disease risk were estimated by added sugar consumption level (< 10%, 10 to < 15%, 15 to < 20%, 20 to < 25%, 25 to < 30%, and ≥ 30% of total energy). Multivariable means were weighted to be representative of US adolescents and variances adjusted for the complex sampling methods. Daily consumption of added sugars averaged 21.4% of total energy. Added sugars intake was inversely correlated with mean high-density lipoprotein cholesterol levels (mmol/L) which were 1.40 (95% confidence interval [CI] 1.36 to 1.44) among the lowest consumers and 1.28 (95% CI 1.23 to 1.33) among the highest (P trend = 0.001). Added sugars were positively correlated with low-density lipoproteins (P trend =0.01) and geometric mean triglycerides (P trend = 0.05). Among the lowest and highest consumers, respectively, low-density lipoproteins (mmol/L) were 2.24 (95% CI 2.12 to 2.37) and 2.44 (95% CI 2.34 to 2.53), and triglycerides (mmol/L) were 0.81 (95% CI 0.74, 0.88) and 0.89 (95% CI 0.83 to 0.96). Among those overweight/obese (≥ 85th percentile body-mass-index), added sugars were positively correlated with the homeostasis model assessment (P linear trend = 0.004). CONCLUSION: Consumption of added sugars among US adolescents is positively associated with multiple measures known to increase cardiovascular disease risk.

Impact of a brief training on motivational interviewing and the 5A's approach on weight-related counseling practices of pediatricians.

Background: Pediatric primary healthcare providers are well-positioned to provide healthy lifestyle and weight management related counseling but many lack training in evidence-based messages and methods. Objectives: We assessed the impact of a brief, easy-to-access training for pediatric healthcare providers, (the Strong4Life Provider Training), designed to introduce/review current evidence-based messages and methods and improve healthy weight-related assessment and counseling practices. Methods: Following their well-child visit, a convenience sample of children 12-17 years and parents of children 6-11 years (N = 121) of randomly selected Strong4Life trained (N = 15) and untrained (N = 15) pediatricians were administered a survey designed to assess the frequency, content, and patient satisfaction with weight management-related counseling provided. Results from parents and patients of trained pediatricians (N = 62) compared to those from parents and patients of untrained pediatricians (n = 59) were compared using chi-square tests. Generalized estimating equations were used to account for lack of independence among respondents from the same practice. P-values less than 0.05 were considered to be statistically significant. Results: Parents/patients of trained pediatricians were more likely than those of an untrained pediatrician to report having been asked about child's consumption of fruit/vegetables, 57 (92%) versus 44 (75%), p = 0.04 and sugary drinks, 50 (81%) versus 29 (49%), p = 0.005, and their readiness for behavior change, 47 (76%) versus 29 (49%), p = 0.005, and to set a behavior change goal, 36 (59%) versus. 23 (40%), p = 0.005. Regardless of training status, physical activity, screen time, and weight status were assessed for most patients, and most were satisfied with the discussion. Few (21%) were asked about barriers to behavior change.

Dietary and Health Correlates of Sweetened Beverage Intake: Sources of Variability in the National Health and Nutrition Examination Survey (NHANES).

Recent studies using data from the National Health and Nutrition Examination Survey (NHANES) have used inconsistent approaches to identify and categorize beverages, especially those containing low-calorie sweeteners (LCS), also referred to as low-calorie sweetened beverages (LCSBs). Herein, we investigate the approaches used to identify and categorize LCSBs in recent analyses of NHANES data. We reviewed published studies examining LCS consumption in relation to dietary and health outcomes and extracted the methods used to categorize LCS as reported by the authors of each study. We then examined the extent to which these approaches reliably identified LCSBs using the Internet Archive Wayback Machine to examine beverage ingredients lists across three NHANES cycles (2011-2016). None of the four general strategies used appeared to include all LCSBs while also excluding all beverages that did not contain LCS. In some cases, the type of sweetener in the beverage consumed could not be clearly determined; we found 9, 16, and 18 of such "mixed" beverage identifiers in the periods 2011-2012, 2013-2014, and 2015-2016, respectively. Then, to illustrate how heterogeneity in beverage categorization may impact the outcomes of published analyses, we compared results of a previously published analysis with outcomes when "mixed" beverages were grouped either all as LCSBs or all as sugary beverages. Our results suggest that caution is warranted in design and interpretation of studies using NHANES data to examine dietary and health correlates of sweetened beverage intake.

Associations of maternal diet and nutritional status with offspring hepatic steatosis in the Avon longitudinal study of parents and children.

BACKGROUND: Priming for cardiometabolic diseases, including non-alcoholic fatty liver disease (NAFLD), is hypothesized to begin in utero. The primary objective of this study is to determine whether there is an association between maternal nutritional status and offspring NAFLD. METHODS: Data come from the Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK. The analytic sample included 3353 participants who had maternal information on pre-pregnancy BMI, gestational weight gain, diabetes, and free sugar intake as percent of total energy and were assessed for mild-severe hepatic steatosis at 24 years by transient elastography (controlled attenuation parameter score ≥ 248 dB/m). Multiple logistic regression was used to evaluate the association between maternal factors and offspring hepatic steatosis at 24 years. RESULTS: In confounder-adjusted models the independent associations for each maternal factor with mild to severe vs low hepatic steatosis at 24 years were: pre-pregnancy overweight (OR: 1.84, 95%CL: 1.43-2.38) or obesity (OR: 2.73, 95%CL: 1.84-4.03), more than recommended gestational weight gain (OR: 1.30, 95%CL: 1.04-1.64), diabetes (OR: 1.39, 95%CI: 0.87, 2.21), and high free sugar intake during pregnancy (OR: 1.04, 95% CI: 0.82, 1.33). These associations were largely mediated by BMI at 24 years, but not by birthweight or breastfeeding. CONCLUSIONS: Our results suggest that maternal nutritional status is associated with the development of NAFLD in their adult offspring, although the relationship is largely mediated by offspring BMI in adulthood.

Associations between Free Sugar and Sugary Beverage Intake in Early Childhood and Adult NAFLD in a Population-Based UK Cohort.

(1) Background: High sugar intake is prevalent among children and is associated with non-alcoholic fatty liver disease (NAFLD). The purpose of this study is to determine if a high intake of free sugars and sugary beverages (SB) in childhood is associated with NAFLD in adulthood; (2) Methods: At 24 years, 3095 participants were assessed for severe hepatic steatosis (controlled attenuation parameter >280 dB/m) and had dietary data collected via a food frequency questionnaire at age three years. Multiple logistic regression models adjusted for total energy intake, potential confounders, and a mediator (offspring body mass index (BMI) at 24 years); (3) Results: Per quintile increase of free sugar intake association with severe hepatic steatosis at 24 years after adjusting for total energy was odds ratio (OR):1.07 (95% CL: 0.99-1.17). Comparing the lowest vs. the highest free sugar consumers, the association was OR:1.28 (95% CL: 0.88-1.85) and 1.14 (0.72, 1.82) after full adjustment. The OR for high SB consumption (>2/day) compared to <1/day was 1.23 (95% CL: 0.82-1.84) and OR: 0.98 (95% CL: 0.60-1.60) after full adjustment; (4) Conclusions: High free sugar and SB intake at three years were positively but weakly associated with severe hepatic steatosis at 24 years. These associations were completely attenuated after adjusting for confounders and 24-year BMI.

Longitudinal associations of total and trunk fat in childhood and adolescence and risk of hepatic steatosis at 24 years.

BACKGROUND: The importance of body fat distribution in the development of nonalcoholic fatty liver disease (NAFLD) is unclear. OBJECTIVE: To examine whether total and truncal fat deposition patterns in childhood/adolescence are associated with NAFLD risk at 24 years. METHODS: Data were from 1657 participants in the Avon Longitudinal Study of Parents and Children. Transient elastography was used to assess hepatic steatosis (low/moderate/severe) at 24 years and dual-energy X-ray absorptiometry was used to assess total body fat percent (TBF%) and trunk fat percent (TrF%) at 9, 13, 15, 17, and/or 24 years. Linear mixed models were constructed with quadratic age to examine trajectories of TBF% and TrF% by steatosis at 24 years, adjusting for confounders. RESULTS: In both sexes, TBF% trajectories from 9 to 24 years followed a similar pattern based on steatosis group (P = .83 for boys and P = .14 for girls for age2 *steatosis fixed effect). However, at all ages TBF% was higher for moderate/severe vs low steatosis at 24 years (P < .05). In contrast, TrF% trajectories diverged based on steatosis group (P = .001 for boys and P = .0002 for girls for age2 *steatosis fixed effect), such that, in both sexes, participants with moderate/severe steatosis at 24 yrs exhibited less decline in TrF% from adolescence to adulthood compared to participants with low steatosis at 24 yrs. Similar to TBF%, TrF% was higher at nearly all ages for moderate/severe vs low steatosis. Results were similar after adjusting for BMI category at each age, except in boys some differences for TrF% were attenuated. CONCLUSIONS: These findings suggest that sex-specific body fat distribution patterns in childhood/adolescence may help to identify those at risk of developing NAFLD in adulthood.

Dietary sugar restriction reduces hepatic de novo lipogenesis in adolescent boys with fatty liver disease.

BACKGROUNDHepatic de novo lipogenesis (DNL) is elevated in nonalcoholic fatty liver disease (NAFLD). Improvements in hepatic fat by dietary sugar reduction may be mediated by reduced DNL, but data are limited, especially in children. We examined the effects of 8 weeks of dietary sugar restriction on hepatic DNL in adolescents with NAFLD and correlations between DNL and other metabolic outcomes.METHODSAdolescent boys with NAFLD (n = 29) participated in an 8-week, randomized controlled trial comparing a diet low in free sugars versus their usual diet. Hepatic DNL was measured as percentage contribution to plasma triglyceride palmitate using a 7-day metabolic labeling protocol with heavy water. Hepatic fat was measured by magnetic resonance imaging-proton density fat fraction.RESULTSHepatic DNL was significantly decreased in the treatment group (from 34.6% to 24.1%) versus the control group (33.9% to 34.6%) (adjusted week 8 mean difference: -10.6% [95% CI: -19.1%, -2.0%]), which was paralleled by greater decreases in hepatic fat (25.5% to 17.9% vs. 19.5% to 18.8%) and fasting insulin (44.3 to 34.7 vs. 35.5 to 37.0 µIU/mL). Percentage change in DNL during the intervention correlated significantly with changes in free-sugar intake (r = 0.48, P = 0.011), insulin (r = 0.40, P = 0.047), and alanine aminotransferase (ALT) (r = 0.39, P = 0.049), but not hepatic fat (r = 0.13, P = 0.532).CONCLUSIONOur results suggest that dietary sugar restriction reduces hepatic DNL and fasting insulin, in addition to reductions in hepatic fat and ALT, among adolescents with NAFLD. These results are consistent with the hypothesis that hepatic DNL is a critical metabolic abnormality linking dietary sugar and NAFLD.TRIAL REGISTRYClinicalTrials.gov NCT02513121.FUNDINGThe Nutrition Science Initiative (made possible by gifts from the Laura and John Arnold Foundation, Ambrose Monell Foundation, and individual donors), the UCSD Altman Clinical and Translational Research Institute, the NIH, Children's Healthcare of Atlanta and Emory University's Children's Clinical and Translational Discovery Core, Children's Healthcare of Atlanta and Emory University Pediatric Biostatistical Core, the Georgia Clinical and Translational Science Alliance, and the NIH National Institute of Diabetes, Digestive, and Kidney Disease.

Caloric sweetener consumption and dyslipidemia among US adults.

CONTEXT: Dietary carbohydrates have been associated with dyslipidemia, a lipid profile known to increase cardiovascular disease risk. Added sugars (caloric sweeteners used as ingredients in processed or prepared foods) are an increasing and potentially modifiable component in the US diet. No known studies have examined the association between the consumption of added sugars and lipid measures. OBJECTIVE: To assess the association between consumption of added sugars and blood lipid levels in US adults. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study among US adults (n = 6113) from the National Health and Nutrition Examination Survey (NHANES) 1999-2006. Respondents were grouped by intake of added sugars using limits specified in dietary recommendations (< 5% [reference group], 5%-<10%, 10%-<17.5%, 17.5%-<25%, and > or = 25% of total calories). Linear regression was used to estimate adjusted mean lipid levels. Logistic regression was used to determine adjusted odds ratios of dyslipidemia. Interactions between added sugars and sex were evaluated. MAIN OUTCOME MEASURES: Adjusted mean high-density lipoprotein cholesterol (HDL-C), geometric mean triglycerides, and mean low-density lipoprotein cholesterol (LDL-C) levels and adjusted odds ratios of dyslipidemia, including low HDL-C levels (< 40 mg/dL for men; < 50 mg/dL for women), high triglyceride levels (> or = 150 mg/dL), high LDL-C levels (> or = 130 mg/dL), or high ratio of triglycerides to HDL-C (> 3.8). Results were weighted to be representative of the US population. RESULTS: A mean of 15.8% of consumed calories was from added sugars. Among participants consuming less than 5%, 5% to less than 17.5%, 17.5% to less than 25%, and 25% or greater of total energy as added sugars, adjusted mean HDL-C levels were, respectively, 58.7, 57.5, 53.7, 51.0, and 47.7 mg/dL (P < .001 for linear trend), geometric mean triglyceride levels were 105, 102, 111, 113, and 114 mg/dL (P < .001 for linear trend), and LDL-C levels modified by sex were 116, 115, 118, 121, and 123 mg/dL among women (P = .047 for linear trend). There were no significant trends in LDL-C levels among men. Among higher consumers (> or = 10% added sugars) the odds of low HDL-C levels were 50% to more than 300% greater compared with the reference group (< 5% added sugars). CONCLUSION: In this study, there was a statistically significant correlation between dietary added sugars and blood lipid levels among US adults.