Study Linking Fructose Intake to Nonalcoholic Fatty Liver Disease

study entitled “Serum uric acid concentrations and fructose consumption are independently associated with NASH in children and adolescents,” was recently published in the Journal of Hepatology. The purpose of the study was to identify the factors associated with non-alcoholic steatohepatitis (NASH) in children and adolescents with confirmed cases of non-alcoholic fatty liver disease (NAFLD). More specifically, the researchers wanted to determine if uric acid (UA) concentrations and fructose intake were independently associated with NASH and whether fructose consumption was independently associated with UA concentrations.

The study included 271 obese adolescents with a mean age of 12.5 years. Dietary intake was measured through a food frequency questionnaire (FFQ) which each participant completed themselves. All participants had blood drawn to assess their lipid profile, uric acid levels, and liver function. Participants over the age of 10 also underwent an oral glucose tolerance test. The extent of their liver disease was determined using liver biopsies and was categorized using both the NAFLD activity score (NAS); a NAS score of 5 or greater is indicative of NASH. Of the participants, 102 had a NAS score ≥5.

The following findings were reported:

  • Breakfast was the meal that was most often skipped in this population.
  • Morning snacks, afternoon snacks, lunch, and dinner were regularly consumed.

o   The most consumed snacks were crackers, pizza, and salty foods.

  • The foods eaten every day were cereals, vegetables, and fruit.
  • The foods eaten at least 1-2 times per week were meat, fish, and eggs.
  • 89% of participants reported drinking sodas and soft drinks one or more times per week.
  • Those with a NAS score ≥5 had higher waist circumference (WC), transaminase levels, total cholesterol, triglycerides (TG), and UA concentrations and fructose consumption. Additionally, they had higher levels of steatosis, inflammation, and fibrosis compared to the non-NASH group.
  • The homeostatic model assessment of insulin resistance (HOMA-IR), WC, TG, fructose consumption, and UA concentration were independently associated with NAS ≥5.
  • UA concentration was positively, and independently, correlated with fructose consumption. UA concentration was also correlated with BMI, HOMA-IR, fasting insulin, TG, and tumor-necrosis factor α (TNF-α).
  • Fructose consumption was correlated with WC, HOMA-IR, alanine aminotransferase (ALT), TG, interleukin-6 (IL-6), and TNF-α.
  • Fructose consumption was not correlated with daily carbohydrate intake.

Researchers conclude “Our novel data shows that in children and adolescents with NAFLD, serum UA concentrations and dietary fructose consumption are independently associated with NASH…Furthermore, fructose consumption was independently associated with hyperuricaemia and hyperuricaemia occurred more frequently in patients with NASH.”

Points of Consideration

  • Dietary intakes were recorded through FFQs by the 9-13 year old participants which lends itself to error and reporter bias.
  • There is a possibility of reverse causality. Children with NASH could have been instructed to eat more fruits and vegetables as part of a more balanced diet.
  • Researchers did not analyze the correlation between NASH and any other food items or macronutrients.
  • Researchers did not also consider or adjust for total caloric intake in their analysis.
  • This was an observational study which shows correlation but does not confirm causation.