Fructose consumption as a risk factor for non-alcoholic fatty liver disease.
Level 4 - case-series / case-control
Case-control study with supplementary in vitro hepatocyte experiments
PubMed 18395287 · doi:10.1016/j.jhep.2008.02.011
What was done
Researchers conducted a case-control study comparing patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) without cirrhosis (n=49) to controls (n=24) matched for gender, age (±5 years), and body mass index (±3 points). Dietary histories were evaluated, paired serum and liver tissue were obtained to measure mRNA expression of fructokinase (KHK) and fatty acid synthase in a subset of patients (n=6), and in vitro testing was conducted in an AML hepatocyte cell line.
What was found
Fructose consumption was significantly higher in NAFLD patients than in controls (365 kcal vs 170 kcal, p < 0.05). In NAFLD patients (n=6), hepatic mRNA expression of KHK and fatty acid synthase was increased compared to controls (p = 0.04 and p = 0.02, respectively). In the AML hepatocyte cell line, fructose exposure produced a dose-dependent increase in KHK protein and activity.
Why it matters
This study links higher dietary fructose consumption and upregulation of hepatic lipogenic enzymes directly to biopsy-confirmed NAFLD, independent of age, gender, and BMI.
Limits
The human sample size was small (49 cases, 24 controls), and hepatic tissue mRNA analysis was limited to 6 patients. The observational case-control design cannot establish temporal causality, dietary histories are susceptible to recall bias, and control liver tissue characteristics were not detailed in the abstract.
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