Fructose-containing sugars have been implicated in the epidemics of obesity, diabetes and related cardiometabolic disorders. This view is supported by lower quality evidence from ecological observations, animal models, and select human trials. Higher level evidence from controlled trials and prospective cohort studies have been inconclusive. Whether sugars contribute to cardiometabolic complications independent of their calories remains unclear. To address the uncertainties, the investigators propose to conduct a series of systematic reviews and meta-analyses of the totality of the evidence from controlled trials to distinguish the contribution of fructose-containing sugars from that of energy in the development of markers of cardiometabolic risk. The findings generated by this proposed knowledge synthesis will help improve the health of consumers through informing evidence-based guidelines and improving health outcomes by educating healthcare providers and patients, stimulating industry innovation, and guiding future research design.