Effect of a Low Free Sugar Diet vs Usual Diet on Nonalcoholic Fatty Liver Disease in Adolescent Boys: A Randomized Clinical Trial

Abstract

Importance: Pediatric guidelines for the management of nonalcoholic fatty liver disease (NAFLD) recommend a healthy diet as treatment. Reduction of sugary foods and beverages is a plausible but unproven treatment.

Objective: To determine the effects of a diet low in free sugars (those sugars added to foods and beverages and occurring naturally in fruit juices) in adolescent boys with NAFLD.

Design, setting, and participants: An open-label, 8-week randomized clinical trial of adolescent boys aged 11 to 16 years with histologically diagnosed NAFLD and evidence of active disease (hepatic steatosis >10% and alanine aminotransferase level ≥45 U/L) randomized 1:1 to an intervention diet group or usual diet group at 2 US academic clinical research centers from August 2015 to July 2017; final date of follow-up was September 2017.

Interventions: The intervention diet consisted of individualized menu planning and provision of study meals for the entire household to restrict free sugar intake to less than 3% of daily calories for 8 weeks. Twice-weekly telephone calls assessed diet adherence. Usual diet participants consumed their regular diet.

Main outcomes and measures: The primary outcome was change in hepatic steatosis estimated by magnetic resonance imaging proton density fat fraction measurement between baseline and 8 weeks. The minimal clinically important difference was assumed to be 4%. There were 12 secondary outcomes, including change in alanine aminotransferase level and diet adherence.

Results: Forty adolescent boys were randomly assigned to either the intervention diet group or the usual diet group (20 per group; mean [SD] age, 13.0 [1.9] years; most were Hispanic [95%]) and all completed the trial. The mean decrease in hepatic steatosis from baseline to week 8 was significantly greater for the intervention diet group (25% to 17%) vs the usual diet group (21% to 20%) and the adjusted week 8 mean difference was -6.23% (95% CI, -9.45% to -3.02%; P < .001). Of the 12 prespecified secondary outcomes, 7 were null and 5 were statistically significant including alanine aminotransferase level and diet adherence. The geometric mean decrease in alanine aminotransferase level from baseline to 8 weeks was significantly greater for the intervention diet group (103 U/L to 61 U/L) vs the usual diet group (82 U/L to 75 U/L) and the adjusted ratio of the geometric means at week 8 was 0.65 U/L (95% CI, 0.53 to 0.81 U/L; P < .001). Adherence to the diet was high in the intervention diet group (18 of 20 reported intake of <3% of calories from free sugar during the intervention). There were no adverse events related to participation in the study.

Conclusions and relevance: In this study of adolescent boys with NAFLD, 8 weeks of provision of a diet low in free sugar content compared with usual diet resulted in significant improvement in hepatic steatosis. However, these findings should be considered preliminary and further research is required to assess long-term and clinical outcomes.

Trial registration: ClinicalTrials.gov Identifier: NCT02513121.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Schwimmer reported receiving research support from Galmed and Intercept. Dr Welsh reported receiving reimbursement from the Crossfit Foundation for travel expenses to attend a conference; and personal fees from the Sugar Association for a presentation. Dr Middleton reported having university contract agreements with Alexion, AstraZeneca, Bioclinica, Biomedical Systems, Bristol-Myers Squibb, Enanta, General Electric, Gilead, Icon, Intercept, NuSirt, Pfizer, Profil, Roche, Shire, Siemens, Synageva, and Virtualscopics; serving as a consultant to Bracco, Kowa, Median, Merge Healthcare, Novo Nordisk, and Quantitative Insights; being a stockholder of General Electric and Pfizer; receiving grant funding from General Electric, Gilead, and Guerbet; and holding a patent with General Electric. Dr Sirlin reported serving as a consultant representative of the University of California Regents for GE Healthcare, Bayer, Boehringer Ingelheim, AMRA, Fulcrum Therapeutics, Medscape, and Resoundant; serving on advisory boards for AMRA, Guerbet, and VitualScopics; receiving research grants from ACR Innovation, Bayer, Gilead, GE Healthcare, General Electric, Philips, and Siemens; serving as a consultant for AMRA, Boehringer Ingelheim, Epigenomics, and Guerbet; being on the speaker’s bureau for Resoundant and General Electric; and having laboratory service agreements with Enanta, Genzyme, Gilead, Icon Medical Imaging, Intercept, Janssen, NuSirt, Shire, Synageva, Takeda, and VitualScopics. Dr Vos reported receiving grant support from Resonance Health, Immuron, Gemphire, Shire, and Target Pharmasolutions; and receiving personal fees from AMRA, Immuron, Intercept, Target Pharmasolutions, Shire, Bristol-Myers Squibb, Boehringer Ingelheim, and Axcella Health. No other disclosures were reported.

Figures

Figure 1.. Consort Flow Diagram of Dietary Treatment Study Participants

aBased on either the alanine aminotransferase level or the magnetic resonance imaging proton density fat fraction percentage measurement.

Figure 2.. Individual-Level Measurements for the Primary and Secondary Outcomes

The primary outcome is magnetic resonance imaging (MRI) proton density fat fraction measurement of hepatic steatosis (panel A) and levels of alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase (panels B-D) are secondary outcomes. Each vertical line represents 1 child sorted by treatment and baseline value. The baseline values are on the dotted line and the 8-week values are represented by the circles.