Background: The consumption of added sugars (caloric sweeteners) has been linked to obesity, diabetes, and heart disease. Little is known about recen

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.

Nonalcoholic fatty liver disease (NAFLD) is now thought to be the most common liver disease worldwide. Cardiovascular complications are a leading cause of mortality in NAFLD. Fructose, a common nutrient in the westernized diet, has been reported to be associated with increased cardiovascular risk, but its impact on adolescents with NAFLD is not well understood. We designed a 4-week randomized, controlled, double-blinded beverage intervention study. Twenty-four overweight Hispanic-American adolescents who had hepatic fat >8% on imaging and who were regular consumers of sweet beverages were enrolled and randomized to calorie-matched study-provided fructose only or glucose only beverages. After 4 weeks, there was no significant change in hepatic fat or body weight in either group. In the glucose beverage group there was significantly improved adipose insulin sensitivity, high sensitivity C-reactive protein (hs-CRP), and low-density lipoprotein (LDL) oxidation. These findings demonstrate that reduction of fructose improves several important factors related to cardiovascular disease despite a lack of measurable improvement in hepatic steatosis. Reducing dietary fructose may be an effective intervention to blunt atherosclerosis progression among NAFLD patients and should be evaluated in longer term clinical trials.

Currently, an estimated 1 of 6 deaths in the United States is attributed to coronary heart disease (CHD).¹ Men, people with low income, and non-Hispanic individuals are among those at highest risk.² In multiple experimental and long-term prospective studies, high consumption of dietary sugars, sugar-sweetened beverages (SSBs) in particular, has been associated with several CHD risk factors, including dyslipidemia,³ diabetes,⁴ and obesity,^4,5 but there has been little research to understand if this risk extends to an increase in associated mortality. Yang et al,⁶ using data from the National Health and Nutrition Examination follow-up survey, demonstrated an increase in cardiovascular disease mortality with higher added sugar intake among US adults, but to our knowledge, no one has yet examined the extent to which mortality risk is elevated with sugary beverages, including SSBs and fruit juices.

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. 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. 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. 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.

BACKGROUND. Hepatic 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. METHODS. Adolescent 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. RESULTS. Hepatic 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). CONCLUSION. Our 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 REGISTRY. ClinicalTrials.gov NCT02513121. FUNDING. The 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.