Purpose : This study aimed to assess the inter-individual variation in phloretin absorption and metabolism and to seek possible phloretin metabotypes following apple snack consumption. Methods : The excreted phloretin metabolites in 24 h urine samples were determined by UPLC-MS/MS in 62 volunteers after acute and sustained (6 weeks) interventions in a randomized and parallel study with a daily supplementation of 80 g of a low-phloretin (39.5 μmol) or a high-phloretin (103 μmol) freeze-dried apple snacks. Results : absorption estimated as phloridzin equivalents for 62 volunteers varied almost 70-fold ranging from 0.1% to 6.94% of phloretin glycoside intake. Volunteers were stratified into low, medium and high producers and by the balance between glucuronidation and sulphation. For 74% of the volunteers phloretin- O -glucuronide was the dominant urinary metabolite, especially at the higher phloretin glycoside intake and for higher producers. Sulphate conjugation assumed greater significance for the remaining volunteers especially for low producers. Females dominated glucuronide profile (64.1%) and males dominated the low excretion group. Analysis of plasma glucose and insulin at the start and end of the sustained study showed a trend towards modest reductions for high producers. Furthermore, plausible factors contributing to the inter-individual variation in phloretin uptake are discussed. Conclusions : extensive inter-individual variability exists in the excretion of phloretin phase-II conjugates following consumption of apple snacks, which could be related to oral microbiota phloridzin-hydrolysing activity, lactase non-persistence trait or the metabotype to which the subject belongs. There were inconsistent effects on post-prandial serum glucose concentrations but there was a tendency for decreases to be associated with higher excretion of phloretin phase-II conjugates. Trial registration : The acute and sustained studies were registered at ClinicalTrials.gov Identifier: NCT03795324.
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