Ayoub-Charette · The Journal of nutrition 2021 · Systematic review and meta-analysis of controlled feeding trials · n=47 trials (2,763 participants)

Different Food Sources of Fructose-Containing Sugars and Fasting Blood Uric Acid Levels: A Systematic Review and Meta-Analysis of Controlled Feeding Trials.

Cited 25 times in the scientific literature.

Level 1 - systematic review of randomized trials

Systematic review and meta-analysis of controlled feeding trials

PubMed 34087940 · doi:10.1093/jn/nxab144 · record verified 2026-08-29

What was done

Authors conducted a systematic review and meta-analysis of controlled feeding trials lasting at least 7 days searching MEDLINE, Embase, and the Cochrane Library through January 11, 2021. They evaluated 47 trials (85 comparisons, N = 2,763 predominantly healthy, mixed-weight adults) assessing the effects of 9 food sources of fructose-containing sugars across 4 energy-control models: substitution, addition, subtraction, and ad libitum feeding. Evidence certainty was evaluated using the GRADE framework.

What was found

Across all sources combined, fructose-containing sugars increased blood uric acid in substitution trials (mean difference: 0.16 mg/dL; 95% CI: 0.06 to 0.27 mg/dL; P = 0.003), with no significant overall effect in addition, subtraction, or ad libitum trials. Significant interactions occurred by food source: sugar-sweetened beverages (SSBs) and sweets/desserts increased uric acid in substitution trials, while in addition trials, SSBs increased uric acid and 100% fruit juice decreased it. The evidence certainty was high for the adverse effect of SSBs (in substitution and addition) and the uric-acid-lowering effect of 100% fruit juice (in addition), but moderate to very low for all other food comparisons.

Why it matters

This review demonstrates that the metabolic impact of dietary fructose on uric acid is driven primarily by the food source and matrix rather than total sugar or energy control alone. It distinguishes harmful sources like sugar-sweetened beverages from potentially neutral or beneficial sources like 100% fruit juice.

Limits

The study population comprised predominantly healthy, mixed-weight adults, limiting direct extrapolation to patients with clinical hyperuricemia or gout. High-certainty evidence was limited strictly to SSBs and 100% fruit juice; all other food sources (including whole fruit, dried fruit, and sweetened dairy) had moderate to very low certainty. The minimum trial duration was only 7 days, which may not capture chronic, multi-year disease outcomes.

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