Variation in the Methylation of Caffeoylquinic Acids and Urinary Excretion of 3′-methoxycinnamic acid-4′-Sulfate After Apple Consumption by Volunteers

Abstract

Introduction: It has been reported that the phenolic metabolite 3′-methoxycinnamic acid-4′-sulfate generated from 5-O-caffeoylquinic acid may have potential benefits in human health. However, the variation in 3′- and 4′-methylation of 3′,4′-dihydroxycinnamic acid and its impact on the yield of this sulfate metabolite is unclear and has been poorly studied. Methods and Results: To address this aim, the excreted 3′-methoxy and 4′-methoxy metabolites in urine samples (24-h) are determined in 14 volunteers after an acute intake of 80 g of red-fleshed apple (RFA) or white-fleshed apple (WFA). These methoxy metabolites are also determined in the same volunteers in a second acute intake after a 6-week sustained consumption of the same products. Conclusion: Seven 3′-methoxy and seven 4′-methoxy metabolites are determined, i.e., the free cinnamic and corresponding phenylpropanoic acid, plus their sulfate, glucuronide, and glycine conjugates. In only six volunteers, five females and one male, is 4′-methylation preferred over 3′-methylation, but it is observed that an individual′s 3′- : 4′-methylation ratio can change over time, and that the yield of 3′-methoxycinnamic acid-4′-sulfate is extremely variable, ranging from undetectable to 71% of the total C6-C3 metabolites excreted, and any benefit accruing from this metabolite will not necessarily be available to all consumers.