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

Abstract

Background: Although fructose as a source of excess calories increases uric acid, the effect of the food matrix is unclear.

Objectives: To assess the effects of fructose-containing sugars by food source at different levels of energy control on uric acid, we conducted a systematic review and meta-analysis of controlled trials.

Methods: MEDLINE, Embase, and the Cochrane Library were searched (through 11 January 2021) for trials ≥ 7 days. We prespecified 4 trial designs by energy control: substitution (energy-matched replacement of sugars in diets); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced in diets) designs. Independent reviewers (≥2) extracted data and assessed the risk of bias. Grading of Recommendations, Assessment, Development, and Evaluation was used to assess the certainty of evidence.

Results: We included 47 trials (85 comparisons; N = 2763) assessing 9 food sources [sugar-sweetened beverages (SSBs), sweetened dairy, fruit drinks, 100% fruit juice, fruit, dried fruit, sweets and desserts, added nutritive sweetener, and mixed sources] across 4 energy control levels in predominantly healthy, mixed-weight adults. Total fructose-containing sugars increased uric acid levels in substitution trials (mean difference, 0.16 mg/dL; 95% CI: 0.06-0.27 mg/dL; P = 0.003), with no effect across the other energy control levels. There was evidence of an interaction by food source: SSBs and sweets and desserts increased uric acid levels in the substitution design, while SSBs increased and 100% fruit juice decreased uric acid levels in addition trials. The certainty of evidence was high for the increasing effect of SSBs in substitution and addition trials and the decreasing effect of 100% fruit juice in addition trials and was moderate to very low for all other comparisons.

Conclusions: Food source more than energy control appears to mediate the effects of fructose-containing sugars on uric acid. The available evidence provides reliable indications that SSBs increase and 100% fruit juice decreases uric acid levels. More high-quality trials of different food sources are needed. This trial was registered at clinicaltrials.gov as NCT02716870.

Keywords: food sources of fructose-containing sugars; fruit; fruit juice; gout; meta-analysis; sugar-sweetened beverages; systematic review; uric acid.

© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1

Flow of the literature for the effect of different food sources of fructose-containing sugars on blood uric acid levels.

FIGURE 2

Summary plot for the effects of different food sources of fructose-containing sugars on fasting blood uric acid. Data are weighted mean differences (95% CIs) for summary effects of individual food sources and total food sources on fasting blood uric acid. Analyses were conducted by generic, inverse variance random-effects models (at least 5 trials available) or fixed-effects models (fewer than 5 trials available). Between-study heterogeneity was assessed by the Cochrane Q statistic, where PQ < 0.100 is considered statistically significant, and quantified by the I2 statistic, where I2 ≥ 50% is considered evidence of substantial heterogeneity. The GRADEs of randomized controlled trials are rated as “high” certainty of evidence and can be downgraded by 5 domains and upgraded by 1 domain. The filled black squares indicate a single downgrade and/or upgrade for each outcome, whereas the black squares with a white “2” indicate a double downgrade for each outcome. *Where there was a significant interaction by food source in substitution and addition trials and SSBs and mixed sources were the sole food sources in subtraction and ad libitum trials, we performed the GRADE analysis for each individual food source. To convert uric acid to mmol/L, multiply by 0.0595. Abbreviations: GRADE, Grading of Recommendations, Assessment, Development, and Evaluation; MD, mean difference; PMD, P value for the overall effect; PQ, Cochrane's Q statistic; SSB, sugar-sweetened beverage.