Lee · Nutrients 2022 · systematic review and meta-analysis of controlled trials · n=2059 participants across 51 trials

Important Food Sources of Fructose-Containing Sugars and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Controlled Trials.

Level 1 - systematic review of randomized trials

Systematic review and meta-analysis of controlled trials

PubMed 35889803 · doi:10.3390/nu14142846 · record verified 2026-08-26

What was done

A systematic review and meta-analysis of controlled trials (≥7 days) was conducted across MEDLINE, Embase, and Cochrane Library through January 7, 2022. Investigators analyzed 10 food sources of fructose-containing sugars across four energy models: substitution (isocaloric exchange), addition (hypercaloric excess), subtraction (hypocaloric reduction), and ad libitum intake. The primary outcome was intrahepatocellular lipid (IHCL); secondary outcomes were ALT and AST. Certainty of evidence was graded using GRADE. The analysis included 51 trials (75 comparisons, n = 2059) in predominantly healthy normal-weight or overweight/obese younger adults.

What was found

In addition trials, total fructose-containing sugars increased IHCL (standardized mean difference = 1.72, 95% CI: 1.08 to 2.36, p < 0.001), driven by sugar-sweetened beverages (SSBs), which increased IHCL (high certainty) and ALT (moderate certainty). In subtraction trials, removing energy from mixed sources containing SSBs reduced AST (low certainty). No significant effects on IHCL, ALT, or AST were observed in substitution or ad libitum trials. Certainty for food sources other than SSBs was generally low to moderate.

Why it matters

This review demonstrates that fructose-mediated increases in liver fat and liver enzymes are driven primarily by excess energy intake from sugar-sweetened beverages, rather than fructose itself when substituted isocalorically for other macronutrients.

Limits

The minimum intervention duration was short (≥7 days), which may not reflect chronic NAFLD pathogenesis. Included participants were primarily younger and healthy, limiting direct applicability to patients with established NAFLD or advanced metabolic dysfunction. Evidence for non-SSB food sources had lower certainty due to smaller study numbers.

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