Dietary sugar restriction reduces hepatic de novo lipogenesis in adolescent boys with fatty liver disease.
Study Goal
The researchers examined the effects of dietary sugar restriction on hepatic de novo lipogenesis (DNL) and its correlation with metabolic outcomes, including alanine aminotransferase (ALT) levels, in adolescents with NAFLD.
Results Summary
The study found that dietary sugar restriction significantly reduced hepatic DNL and fasting insulin, with a notable correlation between changes in DNL and ALT levels (r = 0.39, P = 0.049), suggesting a metabolic link. However, no direct causal relationship between alanine and outcomes was established.
Population
Adolescent boys with nonalcoholic fatty liver disease (NAFLD) (n = 29).
Effective Dosage
Not specified (intervention was a diet low in free sugars).
Duration
8 weeks.
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
dietary sugar restriction | decrease | hepatic de novo lipogenesis (DNL) | adolescent boys with NAFLD | from 34.6% to 24.1% (adjusted week 8 mean difference: -10.6% [95% CI: -19.1%, -2.0%]) | significantly decreased | #1 |
dietary sugar restriction | decrease | hepatic fat | adolescent boys with NAFLD | 25.5% to 17.9% | greater decreases | #2 |
dietary sugar restriction | decrease | fasting insulin | adolescent boys with NAFLD | 44.3 to 34.7 μIU/mL | greater decreases | #3 |
usual diet | no change | hepatic de novo lipogenesis (DNL) | adolescent boys with NAFLD | 33.9% to 34.6% | no significant change | #4 |
usual diet | no change | hepatic fat | adolescent boys with NAFLD | 19.5% to 18.8% | no significant change | #5 |
usual diet | no change | fasting insulin | adolescent boys with NAFLD | 35.5 to 37.0 μIU/mL | no significant change | #6 |
dietary sugar restriction | neutral | percentage change in DNL | adolescent boys with NAFLD | r = 0.48, P = 0.011 | correlated significantly | #7 |
dietary sugar restriction | neutral | percentage change in DNL | adolescent boys with NAFLD | r = 0.40, P = 0.047 | correlated significantly | #8 |
dietary sugar restriction | neutral | percentage change in DNL | adolescent boys with NAFLD | r = 0.39, P = 0.049 | correlated significantly | #9 |
dietary sugar restriction | no change | percentage change in DNL | adolescent boys with NAFLD | r = 0.13, P = 0.532 | did not correlate | #10 |
dietary sugar restriction | decrease | hepatic DNL | adolescents with NAFLD | - | reduces | #11 |
dietary sugar restriction | decrease | fasting insulin | adolescents with NAFLD | - | reductions | #12 |
dietary sugar restriction | decrease | hepatic fat | adolescents with NAFLD | - | reductions | #13 |
dietary sugar restriction | decrease | alanine aminotransferase (ALT) | adolescents with NAFLD | - | reductions | #14 |
BACKGROUNDHepatic de novo lipogenesis (DNL) is elevated in nonalcoholic fatty liver disease (NAFLD). Improvements in hepatic fat by dietary sugar reduction may be mediated by reduced DNL, but data are limited, especially in children. We examined the effects of 8 weeks of dietary sugar restriction on hepatic DNL in adolescents with NAFLD and correlations between DNL and other metabolic outcomes.METHODSAdolescent boys with NAFLD (n = 29) participated in an 8-week, randomized controlled trial comparing a diet low in free sugars versus their usual diet. Hepatic DNL was measured as percentage contribution to plasma triglyceride palmitate using a 7-day metabolic labeling protocol with heavy water. Hepatic fat was measured by magnetic resonance imaging-proton density fat fraction.RESULTSHepatic DNL was significantly decreased in the treatment group (from 34.6% to 24.1%) versus the control group (33.9% to 34.6%) (adjusted week 8 mean difference: -10.6% [95% CI: -19.1%, -2.0%]), which was paralleled by greater decreases in hepatic fat (25.5% to 17.9% vs. 19.5% to 18.8%) and fasting insulin (44.3 to 34.7 vs. 35.5 to 37.0 μIU/mL). Percentage change in DNL during the intervention correlated significantly with changes in free-sugar intake (r = 0.48, P = 0.011), insulin (r = 0.40, P = 0.047), and alanine aminotransferase (ALT) (r = 0.39, P = 0.049), but not hepatic fat (r = 0.13, P = 0.532).CONCLUSIONOur results suggest that dietary sugar restriction reduces hepatic DNL and fasting insulin, in addition to reductions in hepatic fat and ALT, among adolescents with NAFLD. These results are consistent with the hypothesis that hepatic DNL is a critical metabolic abnormality linking dietary sugar and NAFLD.TRIAL REGISTRYClinicalTrials.gov NCT02513121.FUNDINGThe Nutrition Science Initiative (made possible by gifts from the Laura and John Arnold Foundation, Ambrose Monell Foundation, and individual donors), the UCSD Altman Clinical and Translational Research Institute, the NIH, Children's Healthcare of Atlanta and Emory University's Children's Clinical and Translational Discovery Core, Children's Healthcare of Atlanta and Emory University Pediatric Biostatistical Core, the Georgia Clinical and Translational Science Alliance, and the NIH National Institute of Diabetes, Digestive, and Kidney Disease.