The Effect of 'Catalytic' Doses of Fructose and Its Epimers on Acute Postprandial Carbohydrate Metabolism and Longterm Glycemic Control: A Series of Systematic Reviews and Meta-analyses of Controlled Feeding Trials

Background: Despite advances in the prevention and treatment of type 2 diabetes, its prevalence continues to rise worldwide. There is a need for new modalities to improve glycemic control in individuals with type 2 diabetes and those who are overweight or obese and at risk for type 2 diabetes. Contrary to the concerns raised about the adverse role of fructose in metabolic health, there may be a role for fructose and its epimers, the rare non caloric sugars allulose (C-3 epimer of fructose), tagatose (C-4 epimer of fructose), and D-sorbose (C-3 and C-4 diastereomer of fructose). All are naturally found in small quantities in dried fruits and maple syrup. Bother allulose and tagatose are generally recognized as safe (GRAS) by the Food and Drug Administration in the US and are marketed as low-calorie sugar substitutes that have anti-hyperglycemic effects. Various lines of evidence suggest that fructose and its epimers may improve the metabolic handling of glucose through inducing glycogen synthesis. Recent small trials in humans suggest that 'catalytic' doses (=<10g/meal) of fructose and its epimers (allulose, tagatose, and sorbose) may reduce postprandial glycemic responses to carbohydrate loads (i.e., oral glucose tolerance test or a starch load) in people with and without type 2 diabetes. These acute effects have been shown to be sustainable over the longer term in several controlled trials of fructose and tagatose.

Need for a review: There is an urgent need to synthesize the evidence of the effects of fructose and its epimers on acute postprandial carbohydrate metabolism and longterm glycemic control. There remains uncertainty in regards to the minimum effective dose (range studied, 2-25g) and the extent to which these benefits translate into meaningful longterm improvements in glycemic control. A systematic review and meta-analysis remains the "Gold Standard" of evidence to support health claims development. It will map the available evidence and, by pooling the totality of that evidence, provide the most precise estimate of the true effect of fructose and its epimers on carbohydrate metabolism and longterm glycemic control.

Objectives: The investigators will conduct two systematic reviews and meta-analyses of the effect of small 'catalytic' doses of fructose and its epimers. The objective of the first systematic review and meta-analysis will be to assess their effect on the postprandial glycemic and insulinemic responses to other carbohydrates in acute feeding trials, while the objective of the second systematic review and meta-analysis will be to update and expand on our previous systematic review and meta-analysis of small catalytic doses of fructose to assess the effect of small catalytic doses of fructose and its epimers on glycemic control in chronic feeding trials.

Design: The planning and conduct of the two proposed systematic reviews and meta-analyses will follow the Cochrane handbook for systematic reviews of interventions. The reporting will follow the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.

Data sources: MEDLINE, EMBASE and The Cochrane Central Register of Controlled Trials will be searched using appropriate search terms.