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.

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

“…It is unknown whether the effects seen for SSBs providing excess energy hold for other important food sources of fructose-containing sugars at different levels of energy control on NAFLD markers. There is evidence on other cardiometabolic outcomes that the harmful effects seen for SSBs do not hold for other food sources of fructose-containing sugars, whereas some (fruit) may even show benefit [ 8 , 9 , 10 , 11 ].…”

Effect of Important Food Sources of Fructose-Containing Sugars on Inflammatory Biomarkers: A Systematic Review and Meta-Analysis of Controlled Feeding Trials

“…The lack of harm observed for SSBs alone at all levels of energy control is supported by a previous systematic review and meta-analysis including 7 trial comparisons of fructose versus glucose which showed no overall effect [ 121 ]. Previous systematic reviews and meta-analyses exploring the effect of different food sources of fructose containing sugars on cardiometabolic outcomes in controlled trials have demonstrated harm when SSBs are consumed as a source of excess calories, including on glycemic control, adiposity, blood pressure and uric acid [ 8 , 11 , 139 , 140 ]. It is possible that the lack of harm observed in the present analysis may be the result of fewer trials and those which only comprised of healthy participants free of chronic diseases and with low baseline CRP levels (median 0.4 mg/L, range 0.2–1.22 mg/L).…”

“…Bioactives, including antioxidants and flavonoids, may also interfere with fructose metabolism. For example, antioxidants and flavonoids may reduce oxidative stress and thus fructose-induced uric acid production [ 143 ], which is supported by the lack of harm observed for fruit and fruit juice in a systematic review and meta-analysis of food sources of fructose-containing sugars on uric acid which contrasts the significant increases in uric acid that were observed for SSBs [ 8 ]. In addition to bioactives as mechanisms through which various foods may influence inflammation, these food sources of fructose-containing sugars can be higher in dietary fibre and lower in glycemic index (GI).…”

“…This mechanism is postulated to impair other metabolic signaling and lead to increased adiposity [ 6 , 7 ]. However, the harmful effects of fructose on some cardiometabolic outcomes, including body weight, are only observed when fructose-containing sugars are consumed as excess energy [ 8 , 9 , 10 , 11 , 12 ]. There is some evidence that a diet high in fructose may increase interstitial inflammation, although this comes from animal models [ 13 ].…”

Effect of Processing on Biofunctionality of Selected Tropical Fruit Juices

“…Thereby, orange juice might possibly exert acute and sustainable improvements of cardiovascular health. 74,75 Recently, a systematic review and meta-analysis of controlled feeding trials has corroborated the decreasing effect on uric acid by 100% fruit juice consumption, 76 although a weak but opposite effect had been seen earlier in prospective cohort studies. 77 D'Elia et al 78 reported a systematic review and meta-analyses that found a number of favorable associations of 100% fruit juice intake and cardiovascular health or risk factors.…”