Quantification of Urinary Phenyl-γ-Valerolactones and Related Valeric Acids in Human Urine on Consumption of Apples

Abstract

Flavan-3-ols are dietary bioactive molecules that have beneficial effects on human health and reduce the risk of various diseases. Monomeric flavan-3-ols are rapidly absorbed in the small intestine and released in the blood stream as phase II conjugates. Polymeric flavan-3-ols are extensively metabolized by colonic gut microbiota into phenyl-γ-valerolactones and their related phenylvaleric acids. These molecules are the main circulating metabolites in humans after the ingestion of flavan-3-ol rich-products; nevertheless, they have received less attention and their role is not understood yet. Here, we describe the quantification of 8 phenyl-γ-valerolactones and 3 phenylvaleric acids in the urine of 11 subjects on consumption of apples by using UHPLC-ESI-Triple Quad-MS with pure reference compounds. Phenyl-γ-valerolactones, mainly as sulfate and glucuronic acid conjugates, reached maximum excretion between 6 and 12 after apple consumption, with a decline thereafter. Significant differences were detected in the cumulative excretion rates within subjects and in the ratio of dihydroxyphenyl-γ-valerolactone sulfate to glucuronide conjugates. This work observed for the first time the presence of two distinct metabotypes with regards to the excretion of phenyl-γ-valerolactone phase II conjugates.