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

Objectives Excess calories as fructose may initiate pathways increasing biomarkers of inflammation. Whether this effect is mediated by the food matrix at different energy levels is unknown. We conducted a systematic review and meta-analysis of controlled feeding trials of the effect of food sources of fructose-containing sugars at different energy control levels on biomarkers of inflammation (NCT02716870). Methods We searched MEDLINE, Embase, and the Cochrane Library through January 15 2020 for controlled trials ≥7d. Trial designs were prespecified based on energy control: substitution (energy-matched replacement of sugar in the diet); addition (excess energy from sugar added to diets); subtraction (energy from sugar subtracted from diets); ad libitum (energy from sugar freely replaced in the diet). The primary outcome was C-reactive protein (CRP). Secondary outcomes were tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6). Independent reviewers extracted data and assessed the risk of bias. Certainty of evidence was assessed by GRADE. Results We included 48 trials (109 trial comparisons, n = 2108) assessing the effect of 10 food sources (SSBs, sweetened dairy, sweetened dairy alternatives (soy), fruit, 100% fruit juice, dried fruit, sweetened cereal grains/bars, sweets, added nutritive sweetener, and mixed sources) across the 4 levels of energy control. Total fructose-containing sugars had no effect on any outcome in any level of energy control. There was evidence of interaction by food source; in substitution trials, sweetened dairy alternative (soy) decreased CRP. In addition trials, fruit decreased while added nutritive sweetener increased TNF-α. The certainty of evidence was low for the effect of sweetened dairy alternative (soy) on CRP in substitution trials, and generally moderate for all other comparisons. Conclusions Food source more than energy control appears to mediate the effect of fructose-containing sugars on inflammation. The evidence provides some indication that sweetened dairy alternatives (soy) and fruit decrease and added nutritive sweeteners increase biomarkers of inflammation. More high-quality randomized trials of different fructose containing food sources are needed to improve our estimates. Funding Sources Diabetes Canada.