Children with NAFLD Are More Sensitive to the Adverse Metabolic Effects of Fructose Beverages than Children without NAFLD

Context: Dietary fructose induces unfavorable lipid alterations in animal models and adult studies. Little is known regarding metabolic tolerance of dietary fructose in children. Objectives: The aim of the study was to evaluate whether dietary fructose alters plasma lipids in children with nonalcoholic fatty liver disease (NAFLD) and in healthy children. Design and Setting: We performed a 2-d, crossover feeding study at the Inpatient Clinical Interaction Site of the Atlanta Clinical and Translational Science Institute at Emory University Hospital. Participants and Intervention: Nine children with NAFLD and 10 matched controls without NAFLD completed the study. We assessed plasma lipid levels over two nonconsecutive, randomly assigned, 24-h periods under isocaloric, isonitrogenous conditions with three macronutrient-balanced, consecutive meals and either: 1) a fructose-sweetened beverage (FB); or 2) a glucose beverage (GB) being consumed with each meal. Main Outcome Measures: Differences in plasma glucose, insulin, triglyceride, apolipoprotein B, high-density lipoprotein cholesterol, and nonesterified free fatty acid levels were assessed using mixed models and 24-h incremental areas under the time-concentration curve. Results: After FB, triglyceride incremental area under the curve was higher vs. after GB both in children with NAFLD (P = 0.011) and those without NAFLD (P = 0.027); however, incremental response to FB was greater in children with NAFLD than those without NAFLD (P = 0.019). For all subjects, high-density lipoprotein cholesterol declined in the postprandial and overnight hours with FB, but not with GB (P = 0.0006). Nonesterified fatty acids were not impacted by sugar but were significantly higher in NAFLD. Conclusions: The dyslipidemic effect of dietary fructose occurred in both healthy children and those with NAFLD; however, children with NAFLD demonstrated increased sensitivity to the impact of dietary fructose.