Original Important food sources of fructose-containing sugars and adiposity: A systematic review and meta-analysis of controlled feeding trials

Background: Sugar-sweetened beverages (SSBs) providing excess energy increase adiposity. The effect of other food sources of sugars at different energy control levels is unclear. Objectives: To determine the effect of food sources of fructose-containing sugars by energy control on adiposity. Methods: In this systematic review and meta-analysis, MEDLINE, Embase, and Cochrane Library were searched through April 2022 for controlled trials >= 2 wk. We prespecified 4 trial designs by energy control: substitution (energy-matched replacement of sugars), addition (energy from sugars added), subtraction (energy from sugars subtracted), and ad libitum (energy from sugars freely replaced). Independent authors extracted data. The primary outcome was body weight. Secondary outcomes included other adiposity measures. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the certainty of evidence. Results: We included 169 trials (255 trial comparisons, n = 10,357) assessing 14 food sources at 4 energy control levels over a median 12 wk. Total fructose-containing sugars increased body weight (MD: 0.28 kg; 95% CI: 0.06, 0.50 kg; PMD = 0.011) in addition trials and decreased body weight (MD: -0.96 kg; 95% CI: -1.78, -0.14 kg; PMD = 0.022) in subtraction trials with no effect in substitution or ad libitum trials. There was interaction/influence by food sources on body weight: substitution trials [fruits decreased; added nutritive sweeteners and mixed sources (with SSBs) increased]; addition trials [dried fruits, honey, fruits (<10%E), and 100% fruit juice (<10%E) decreased; SSBs, fruit drink, and mixed sources (with SSBs) increased]; subtraction trials [removal of mixed sources (with SSBs) decreased]; and ad libitum trials [mixed sources (with/without SSBs) increased]. GRADE scores were generally moderate. Results were similar across secondary outcomes. Conclusions: Energy control and food sources mediate the effect of fructose-containing sugars on adiposity. The evidence provides a good indication that excess energy from sugars (particularly SSBs at high doses >= 20%E or 100 g/d) increase adiposity, whereas their removal decrease adiposity. Most other food sources had no effect, with some showing decreases (particularly fruits at lower doses <10%E or 50 g/d). This trial was registered at clinicalt rials.gov as NCT02558920 (https://clinicaltrials.gov/ct2/show/NCT02558920).