Table 2.

Studies demonstrating effects of fructose feeding or restriction on pediatric NAFLD and/or related parameters

Study population	Study design	Intervention	Main findings	Ref
9 NAFLD/10 matched controls	2-day randomized crossover feeding	Glucose (GB) or fructose beverage (FB)1	Increased TG after FB compared to GB in all children, but greater in children with NAFLD Decrease HDLC in all children with FB, but not GB Higher fasting plasma glucose with FB compared to GB in all children	59
8 NAFLD/7 matched controls	24-hour randomized crossover feeding	GB or FB1	FB produced higher plasma endotoxin levels at 1, 3, and 5 hours and 9-hour IAUC postprandial endotoxin in adolescents with NAFLD compared to non-NAFLD controls No effect of GB on postprandial endotoxin in any adolescents	60
16 NAFLD	4-week randomized, controlled trial	GB or FB2	FB produced higher fasting plasma endotoxin levels at 2 and 4 weeks No effect of GB on endotoxin levels at any time point in any adolescents	60
21 NAFLD	4-week randomized, controlled, double-blinded trial	GB or FB2	GB (i.e.,fructose reduction) improved plasma hs-CRP, adipose IR index, plasma FFA, and circulating oxidized LDL levels. Neither FB or GB had significant effects on body weight, hepatic fat, liver enzymes, fasting TG and PAI-1 levels	61
9 NAFLD/6 controls with obesity/9 lean controls	Cross-sectional	Oral fructose challenge3	Fructose caused higher serum glucose levels in children with NAFLD compared with lean controls and a slower return to baseline compared to both control groups Children with NAFLD had a delayed peak in insulin levels and demonstrated no decline even at 120 minutes in response to fructose compared to control groups. Lean controls had higher fructose levels at 30 and 60 minutes compared to NAFLD and obese controls and children with NAFLD had lower urinary fructose excretion compared with obese and lean controls	34
9 adolescents with NAFLD/13 lean controls	3-, 6-month, cross-sectional, dietary intervention	FRAGILE diet4	Significant reductions in systolic blood pressure (SBP), percent body fat, and plasma ALT and Apo-B100, improved HOMA-IR in children with NAFLD from intervention Fructose reductions were related to improved SBP, percent body fat, ALT, and HOMA-IR No changes in control group, except for Apo-B100 levels	62
41 children with obesity, 25 with high liver fat	9-day randomized, controlled trial	Study-provided meals substituting starch for sugar5	Liver fat and VAT significantly decreased from day 0 to day 10, even in participants who did not lose weight Fractional DNL decreased significantly Significant improvements in insulin sensitivity	63
13 NAFLD	1-year nonrandomized	Nutritional counseling	Intervention group showed lower levels of endotoxin, IL-6, and TNF-a at end of study compared to baseline	58
40 boys with NAFLD	8-week randomized, clinical trial	Study-provided meals restricting sugar intake to <3% of daily calories or usual diet	Mean decrease in hepatic fat was significantly greater for the intervention diet group	65
25 adolescents with obesity and NAFLD	8-week randomized, clinical trial	Carbohydrate-restricted diet (CRD) vs fat-restricted diet (FRD)	CRD resulted in significant reduction in measures of adiposity and hepatic fat, although change in hepatic lipid did not differ with diet Significantly greater decreases in insulin resistance abdominal fat mass, and body fat mass in CRD vs FRD	66

¹33% of total daily calories, isocaloric substitution;

²33 g sugar, isocaloric;

³1 g/kg based on ideal body weight, max 75g;

⁴low fructose (<7% total energy intake), low glycemic index (45–55), and low glycemic load (<80);

⁵sugar and fructose restricted to 10% and 4% of total energy intake