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

Donato Angelino, Aoife Caffrey, Helene McNulty, Chris Ir Gill, Pedro Mena, Alice Rosi, Katie Moore, Leane Hoey, Michelle Clements, Eamon Laird, Kerrie Boyd, Brian Mullen, Bruna Pucci, Harry Jarrett, Conal Cunningham, Mary Ward, J J Strain, Kevin McCarroll, Adrian J Moore, Anne M MolloyDaniele Del Rio

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)476-484
Number of pages9
JournalThe American Journal of Clinical Nutrition
Issue number2
Early online date10 Jun 2023
Publication statusPublished (in print/issue) - 2 Aug 2023

Bibliographical note

Funding Information:
The VALID Project was awarded under the international Joint Programming Initiative a Healthy Diet for a Healthy Life co-funded ERA-HDHL call on ‘Biomarkers for Nutrition and Health,’ involving partners from the United Kingdom, Italy, and Ireland: Ulster University, Northern Ireland, UK – Biotechnology and Biological Sciences Research Council (Grant BB/P028225/1 ; Prof. Helene McNulty, overall Project Coordinator); University of Parma, Italy—Ministry of Agricultural, Food and Forestry Policies (Grant DM 31967/7303/16 ; Prof. Daniele Del Rio, PI); and Trinity College Dublin, Ireland—Science Foundation Ireland (Grant 16/ERA-HDHL/3361 ; Prof. Anne Molloy, PI).

Publisher Copyright:
© 2023 American Society for Nutrition


  • Dietary (poly)phenols
  • (epi)catechins
  • older adults
  • phenyl-γ-valerolactones
  • flavan-3-ols
  • procyanidins


Dive into the research topics of 'Association of dietary flavan-3-ol intakes with plasma phenyl-γ-valerolactones: analysis from the TUDA cohort of healthy older adults'. Together they form a unique fingerprint.

Cite this