Association of dietary flavan-3-ol intakes with plasma phenyl-γ-valerolactones: analysis from the TUDA cohort of healthy older adults

Background: Dietary polyphenols, including flavan-3-ols (F3O), are associated with better health outcomes. The relationship of plasma phenyl-γ-valerolactones (PVLs), the products of colonic bacterial metabolism of F3O, with dietary intakes is unclear. Objectives: To investigate whether plasma PVLs are associated with self-reported intakes of total F3O and procyanidins+(epi)catechins. Design: We measured 9 PVLs by uHPLC-MS-MS in plasma from adults (>60y) in the Trinity-Ulster-Department of Agriculture (TUDA study (2008 to 2012; n=5186) and a follow-up subset (2014 to 2018) with corresponding dietary data (n=557). Dietary (poly)phenols collected by FFQ were analyzed using Phenol-Explorer. Results: Mean (95% confidence interval [CI]) intakes were estimated as 2283 (2213, 2352) mg/d for total (poly)phenols, 674 (648, 701) for total F3O, and 152 (146, 158) for procyanidins+(epi)catechins. Two PVL metabolites were detected in plasma from the majority of participants, 5-(hydroxyphenyl)-γ-VL-sulfate (PVL1) and 5-(4ʹ-hydroxyphenyl)-γ-VL-3ʹ-glucuronide (PVL2). The 7 other PVLs were detectable only in 1-32% of samples. Self-reported intakes (mg/d) of F3O (r = 0.113, P = 0.017) and procyanidin+(epi)catechin (r = 0.122, P = 0.010) showed statistically significant correlations with the sum of PVL1 and PVL 2 (PVL1+2). With increasing intake quartiles (Q1-Q4), mean (95% CI) PVL1+2 increased; from 28.3 (20.8, 35.9) nmol/L in Q1 to 45.2 (37.2, 53.2) nmol/L in Q4; P = 0.025, for dietary F3O, and from 27.4 (19.1, 35.8) nmol/L in Q1 to 46.5 (38.2, 54.9) nmol/L in Q4; P = 0.020, for procyanidins+(epi)catechins. Conclusions: Of 9 PVL metabolites investigated, 2 were detected in most samples and were weakly associated with intakes of total F3O and procyanidins+(epi)catechins. Future controlled feeding studies are required to validate plasma PVLs as biomarkers of these dietary polyphenols.