Effect of fructose and its epimers on postprandial carbohydrate metabolism: A systematic review and meta-analysis

Aims: To synthesize the evidence of the effect of small doses (<= 30-g/meal) of fructose and its epimers (allulose, tagatose, and sorbose) on the postprandial glucose and insulin response to carbohydrate-containing meals. Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through to April 9, 2019. We included randomized (RCTs) and non-randomized acute, single-meal, controlled feeding trials that added <= 30-g of fructose or its epimers either prior to or with a carbohydrate-containing meal compared with the same meal alone. Outcomes included the incremental area under the curve (iAUC) for glucose and insulin, the Matsuda Insulin Sensitivity Index, and the Early Insulin Secretion Index. Data were expressed as ratio of means (RoM) with 95% CIs and pooled using the inverse variance method. The overall certainty of the evidence was evaluated using GRADE. Results: Forty trial comparisons (n = 400) were included (none for sorbose). Allulose significantly reduced the postprandial iAUC glucose response by 10% (0.90 [0.84 to 0.96], P < 0.01). Tagatose significantly reduced the postprandial iAUC insulin response by 25% (0.75 [0.62 to 0.91], P < 0.01) and showed a non-significant 3% reduction in the postprandial iAUC glucose response (0.97 [0.94 to 1.00], P = 0.07). There was no effect of fructose on any outcome. The certainty of the evidence was graded as low to moderate for fructose, moderate for allulose, and low for tagatose. Conclusions: Small doses of allulose and tagatose, but not fructose, lead to modest improvements on postprandial glucose and insulin regulation. There is a need for long-term RCTs to confirm the sustainability of these improvements. (C) 2020 Published by Elsevier Ltd.