Children with NAFLD are more sensitive to the adverse metabolic effects of fructose beverages than children without NAFLD

Abstract

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.

Figures

Fig. 1.

Twenty-four-hour mean plasma glucose (A and B) and insulin (C and D) concentration by consumption of three consecutive meals with FB (solid lines) and GB (dashed lines) in non-NAFLD controls (A and C) and pediatric NAFLD (B and D). Error bars stand for se. In non-NAFLD subjects, the 24-h IAUC of insulin was significantly increased after consuming GB compared with FB (mean ± se, 591.4 ± 239.9 vs. 451.6 ± 228.6; P = 0.021), but there was no significant difference in NAFLD. The 24-h IAUC of plasma insulin was significantly higher in NAFLD subjects compared with non-NAFLD controls during both fructose consumption (mean ± se, 996.3 ± 189.8 vs. 451.6 ± 228.6; P = 0.028) and glucose consumption (mean ± se, 1444.9 ± 247.8 vs. 591.4 ± 239.9; P = 0.008). Although the difference of 24-h IAUC of plasma glucose did not reach the statistical significance, at the end of FB feeding (time point of 23 h), fasting plasma glucose remained significantly higher compared with that after 1-d glucose beverage feeding, for both NAFLD (P = 0.046) and non-NAFLD (P = 0.008) (marked with asterisk).

Fig. 2.

Twenty-four-hour plasma NEFA profile after consumption of FB (solid line) and GB (dashed line) in non-NAFLD controls (A) and pediatric NAFLD (B). Error bars stand for se. In NAFLD children, an overall increased level of plasma NEFA was observed compared with non-NAFLD controls, and there was no difference between FB and GB feeding period (mixed model, beverage, P = 0.260; disease, P = 0.002; beverage × disease interaction, P = 0.558).

Fig. 3.

Twenty-four-hour TG (A and B), apoB (C and D), TG/apoB (E and F) profile during consumption of FB and GB in non-NAFLD controls (A, C, and E) and pediatric NAFLD (B, D, and F). Error bars stand for se. A and B, The 24-h IAUC of plasma TG was significantly increased by consumption of FB in contrast to GB for both children with NAFLD (mean ± se, 1421.2 ± 267.1 vs. 757.3 ± 136.5; P = 0.011) and children without NAFLD (mean ± se, 622.4 ± 110.2 vs. 325.7 ± 87.6; P = 0.027), and NAFLD exacerbated this fructose effect on plasma TG (P = 0.019). At the end of visit (time point of 23 h), fasting plasma TG the next morning was significantly elevated after FB compared with GB for both NAFLD (P = 0.011) and non-NAFLD (P = 0.005) subjects (marked with asterisk). C and D, There was no significant difference in plasma apoB under two beverage-feeding conditions within 24 h, in both non-NAFLD and NAFLD subjects. E and F, Compared with GB, FB consumption was associated with greater postprandial response in TG/apoB, for both NAFLD (P < 0.0001) and non-NAFLD (P = 0.030), and NAFLD exacerbated the effect of fructose (P = 0.018) on TG/apoB (mixed model, beverage, P < 0.0001; disease, P = 0.045; beverage × disease interaction, P = 0.025). At the end of visit (time point of 23 h), fasting plasma TG/apoB the next morning was significantly elevated after FB compared with GB for both NAFLD (P = 0.011) and non-NAFLD (P = 0.016) subjects (marked with asterisk).

Fig. 4.

HDLc trend over 24 h after consumption of FB (solid lines) and GB (dashed lines) in non-NAFLD controls (A) and pediatric NAFLD (B). Error bars stand for se. HDLc had an overall decline during consumption of FB compared with GB, and no difference in HDLc response was found between NAFLD and non-NAFLD subjects (mixed model, beverage, P = 0.0006; disease, P = 0.478; beverage × disease interaction, P = 0.382).