Document Type

Journal Article

Publication Title

Journal of Nutrition





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School of Medical and Health Sciences / Nutrition and Health Innovation Research Institute




This is an Authors Accepted Manuscript version of an article published by Elsevier in The Journal of Nutrition. The published article is available at:

Parmenter, B. H., Shinde, S., Croft, K., Murray, K., Bondonno, C. P., Genoni, A., . . . Bondonno, N. P. (2023). Performance of urinary phenyl-γ-valerolactones as biomarkers of dietary flavan-3-ol exposure. The Journal of Nutrition, 153(8), 2193-2204.


Background: Phenyl- -valerolactones (PVLs) have been identified as biomarkers of dietary flavan-3-ol exposure, although their utility requires further characterization. Objectives: We investigated the performance of a range of PVLs as biomarkers indicative of flavan-3-ol intake. Methods: We report the results of 2 companion studies: a 5-way randomized crossover trial (RCT) and an observational cross-sectional study. In the RCT (World Health Organization, Universal Trial Number: U1111-1236-7988), 16 healthy participants consumed flavan-3-ol–rich interventions (of apple, cocoa, black tea, green tea, or water [control]) for 1 d each. First morning void samples and 24-h urine samples were collected with diet standardized throughout. For each participant, 1 intervention period was extended (to 2 d) to monitor PVL kinetics after repeat exposure. In the cross-sectional study, 86 healthy participants collected 24-h urine samples, and concurrent weighed food diaries from which flavan-3-ol consumption was estimated using Phenol-Explorer. A panel of 10 urinary PVLs was quantified using liquid chromatography tandem mass spectrometry. Results: In both studies, 2 urinary PVLs [5-(3ʹ-hydroxyphenyl)- -valerolactone-4ʹ-sulfate and putatively identified 5-(4ʹ-hydroxyphenyl)- -valerolactone-3ʹ-glucuronide] were the principal compounds excreted ( > 75%). In the RCT, the sum of these PVLs was significantly higher than the water (control) after each intervention; individually, there was a shift from sulfation toward glucuronidation as the total excretion of PVLs increased across the different interventions. In the extended RCT intervention period, no accumulation of these PVLs was observed after consecutive days of treatment, and after withdrawal of treatment on the third day, there was a return toward negligible PVL excretion. All results were consistent, whether compounds were measured in 24-h urine or first morning void samples. In the observational study, the sum of the principal PVLs correlated dose dependently (Rs = 0.37; P = 0.0004) with dietary flavan-3-ol intake, with similar associations for each individually. Conclusions: Urinary 5-(3ʹ-hydroxyphenyl)- -valerolactone-4ʹ-sulfate and putatively identified 5-(4ʹ-hydroxyphenyl)- -valerolactone-3ʹ-glucuronide are recommended biomarkers for dietary flavan-3-ol exposure.



Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Available for download on Saturday, August 31, 2024