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

Abstract

Background: 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.

Objectives: 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).

Methods: 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.

Results: 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 ± 2.4 kg), 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).

Conclusions: 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.

Keywords: PNPLA3 genotype; Latino; adolescents; nonalcoholic fatty liver disease; sugar.

© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1

Flow diagram of participant recruitment, enrollment, intervention allocation, follow-up, and analysis for the primary outcome, change in liver fat.

FIGURE 2

Intervention to reduce free sugar intake does not affect liver health as measured by liver fat, liver fibrosis, and liver enzymes. Changes in (A) liver fat fraction and (B) liver fibrosis (intervention group, n = 43; control group, n = 38) and changes in liver enzymes including (C) AST and (D) ALT (intervention group, n = 49; control group, n = 38) for the primary analysis. Outcome variables are represented as the change variable calculated as the postintervention value minus the value at baseline. Each participant's change variable is represented by a solid dot. The medians are represented by horizontal bars. P values for the ANCOVA adjusted for the baseline value of the outcome of interest, sex, change in BMI, and change in physical activity are displayed at the top of each boxplot. ALT, alanine aminotransferase; AST, aspartate aminotransferase.

FIGURE 3

Reduction of TS does not affect liver fat fraction. Changes in liver fat fraction by change in sugar intake group (ΔTS n = 54; ΔTS ≥ 0 group, n = 22). The outcome variable is represented as the change variable calculated as the postintervention value minus the value at baseline. Each participant's change variable is represented by a solid dot. The median is represented by a horizontal bar. The P value for the ANCOVA adjusted for the baseline value of the outcome of interest, sex, and change in physical activity is displayed at the top of the boxplot. TS, total sugar intake.

FIGURE 4

Reducing FM reduces liver fat. Changes in liver fat fraction by change in FM group (Δ FM n = 38; Δ FM ≥ 0 group, n = 43). The outcome variable is represented as the change variable calculated as the postintervention value minus the value at baseline. Each participant's change variable is represented by a solid dot. The median is represented by a horizontal bar. The P value for the ANCOVA adjusted for the baseline value of the outcome of interest, sex, and change in physical activity is displayed at the top of the boxplot. FM, fat mass.