Clinical Intervention to Reduce Dietary Sugar Does Not Affect Liver Fat in Latino Youth, Regardless of PNPLA3 Genotype: A Randomized Controlled Trial

Abstract

Nonalcoholic fatty liver disease (NAFLD) among Latinos is partially attributed to a prevalent C>G polymorphism in the patatin-like phospholipase 3 (PNPLA3) gene. Cross-sectional analyses in Latino children showed the association between dietary sugar and liver fat was exacerbated by GG genotype. Pediatric feeding studies show extreme sugar restriction improves liver fat, but no prior trial has examined the impact of a clinical intervention or whether effects differ by PNPLA3 genotype. We aimed to test effects of a clinical intervention to reduce dietary sugar compared with standard dietary advice on change in liver fat, and secondary-endpoint changes in liver fibrosis, liver enzymes, and anthropometrics; and whether effects differ by PNPLA3 genotype (assessed retrospectively) in Latino youth with obesity (BMI≥95th percentile). This parallel-design trial randomly assigned participants (n=105; mean baseline liver fat: 12.7%; mean age: 14.8 y) to control or sugar reduction (goal of ≤10% of calories from free sugar) for 12 wk. Intervention participants met with a dietitian monthly and received delivery of bottled water. Changes in liver fat, by MRI, were assessed by intervention group via general linear models. Mean free sugar intake decreased in intervention compared with control [11.5% to 7.3% compared with 13.9% to 10.7% (% energy), respectively; P=0.02], but there were no significant effects on liver outcomes or anthropometrics (Pall>0.10), and no PNPLA3 interactions (Pall>0.10). In exploratory analyses, participants with whole-body fat mass (FM) reduction (mean±SD: -1.9±2.4kg), irrespective of randomization, had significant reductions in liver fat compared with participants without FM reduction (median: -2.1%; IQR: -6.5% to -0.8% compared with 0.3%; IQR: -1.0% to 1.1%; P<0.001). In Latino youth with obesity, a dietitian-led sugar reduction intervention did not improve liver outcomes compared with control, regardless of PNPLA3 genotype. Results suggest FM reduction is important for liver fat reduction, confirming clinical recommendations of weight loss and a healthy diet for pediatric NAFLD.This trial was registered at clinicaltrials.gov as NCT02948647.