Effect of fructose on markers of non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of controlled feeding trials.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of controlled feeding trials
PubMed 24569542 · doi:10.1038/ejcn.2014.8
What was done
Authors conducted a systematic review and meta-analysis of controlled feeding trials (follow-up ≥ 7 days) identified via MEDLINE, EMBASE, CINAHL, and the Cochrane Library through September 3, 2013. Two reviewers independently extracted data. Outcomes were intrahepatocellular lipids (IHCL, expressed as standardized mean difference [SMD]) and alanine aminotransferase (ALT, expressed as mean difference [MD]), pooled using generic inverse variance random-effects models. Trials were separated into isocaloric comparisons (fructose substituted for other carbohydrates) and hypercaloric comparisons (+21% to 35% excess energy from +104 to 220 g/day fructose).
What was found
Thirteen trials from eight reports including 260 healthy participants were analyzed (seven isocaloric, six hypercaloric). In isocaloric trials, fructose had no significant effect on IHCL or ALT. In hypercaloric trials, fructose significantly increased IHCL (SMD = 0.45, 95% CI: 0.18, 0.72) and ALT (MD = 4.94 U/l, 95% CI: 0.03, 9.85).
Why it matters
These findings suggest that fructose-induced elevations in liver fat and ALT in healthy individuals are driven by excess caloric intake rather than a unique property of fructose under isocaloric conditions.
Limits
The evidence base is limited by a small total sample size (n = 260), short trial durations (≤ 4 weeks), poor overall study quality, and reliance on healthy participants without assessment of histopathological NAFLD outcomes.
Cited by
- supports When caloric intake is controlled, meta-analyses of randomized trials substituting sugars or sugar-sweetened beverages isocalorically for other carbohydrates show no differences in fat mass, body weight, or inflammation.