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

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 C-6-C-3 metabolites excreted, and any benefit accruing from this metabolite will not necessarily be available to all consumers.

Automated summary

The study examines the variability in 3'- and 4'-methylation of 3', 4'-dihydroxycinnamic acid and its impact on the yield of sulfate metabolites. Results show that 4'-methylation is preferred over 3'-methylation in six out of fourteen volunteers, but individual methylation ratios can change over time. The yield of 3'-methoxycinnamic acid-4'-sulfate varies widely among individuals, indicating that the benefits of this metabolite may not be consistent for all consumers.