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.