Effect of Important Food Sources of Fructose-containing Sugars on Cardiometabolic Risk Factors: A Series of Systematic Reviews and Meta-analyses of Controlled Trials to Inform Dietary Guidelines, Public Health Policy, and Future Trial Design

Background: Sugars have emerged as one of the most important public health concerns. Attention has focused particularly on fructose-containing sugars (fructose, sucrose, high fructose corn syrup, honey, etc), which collectively have been indicted as drivers of various cardiometabolic complications. This special view rests on the unique metabolic and endocrine responses to fructose. Unlike glucose, fructose is thought to bypasses negative feedback controls acting as an unregulated substrate for de novo lipogenesis and impair satiety signaling resulting in weight gain. In support of these mechanisms, animal models, low-quality ecological studies, and select human trials of overfeeding at levels of exposure far beyond population intakes have reported adverse metabolic effects of sugars. Higher level evidence from systematic reviews and meta-analyses of controlled trials, however, suggests that any effects of sugars are mediated by excess calories rather than the sugars per se. It remains unclear whether fructose-containing sugars contribute to cardiometabolic complications independent of their calories.

Need for proposed research: High quality systematic reviews and meta-analyses of controlled trials represent the highest level of evidence to support dietary guidelines and public health policy development. As dietary guidelines and public health policy have shifted toward food and dietary-pattern based recommendations, there is an urgent need for systematic reviews and meta-analyses comparing the role of different food sources of sugars in the development of cardiometabolic diseases.

Objective: The investigators will conduct a series systematic reviews and meta-analyses to distinguish the effect of fructose-containing sugars from that of energy on measures of cardiometabolic risk in controlled trials.

Design: Each systematic review and meta-analysis will be conducted according to the Cochrane Handbook for Systematic Reviews of Interventions and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Data sources: MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials (Clinical Trials; CENTRAL) will be searched using appropriate search terms supplemented by hand searches of references of included studies.