Apple polyphenol-rich drinks dose-dependently decrease early-phase postprandial glucose concentrations following a high-carbohydrate meal: a randomized controlled trial in healthy adults and in vitro studies

Background: Previous research demonstrated that a high dose of phlorizin-rich apple extract (AE) can markedly inhibit early-phase postprandial glycemia, but efficacy of lower doses of the AE is unclear. Objective: To determine whether lower AE doses reduce early-phase postprandial glycemia in healthy adults and investigate mechanisms. Design: In a randomized, controlled, double-blinded, cross-over acute trial, drinks containing 1.8 g (HIGH), 1.35 g (MED), 0.9 g (LOW), or 0 g (CON) of a phlorizin-rich AE were consumed before 75 g starch/sucrose meal. Postprandial blood glucose, insulin, C-peptide, glucose-dependent insulinotropic polypeptide (GIP) and polyphenol metabolites concentrations were measured 0-240 min, acetaminophen concentrations to assess gastric emptying rate, and 24 h urinary glucose excretion. Effects of AE on intestinal glucose transport were investigated in Caco-2/TC7 cells. Results: AE significantly reduced plasma glucose iAUC 0-30 min at all doses: mean differences (95% CI) relative to CON were -15.6 ( -23.3, -7.9), -11.3 (-19.6, -3.0) and -8.99 (-17.3, -0.7) mmol/L per minute for HIGH, MEDIUM and LOW respectively, delayed T-max (HIGH, MEDIUM and LOW 45 min vs. CON 30 min), but did not lower C-max. Similar dose-dependent treatment effects were observed for insulin, C-peptide, and GIP. Gastric emptying rates and urinary glucose excretion did not differ. Serum phloretin, quercetin and epicatechin metabolites were detected postprandially. A HIGH physiological AE dose equivalent decreased total glucose uptake by 48% in caco-2/C7 cells. Conclusions: Phlorizin-rich AE, even at a low dose, can slightly delay early-phase glycemia without affecting peak and total glycemic response. (C) 2020 Elsevier Inc. All rights reserved.