Avenanthramides and Their Microbial Metabolites As the Novel Biomarkers of Whole Oat Intake

Objectives: It is challenging to measure the intake of whole grains due to inherent limitations of self-reported dietary assessment tools. The study aimed to investigate whether the combined measurement of avenanthramides (AVAs), the unique phytochemicals in WG oat, and their microbial metabolites dihydro-AVAs (DH-AVAs), could serve as reliable biomarkers for WG oat intake. This was achieved by assessing the pharmacokinetics of AVAs and DH-AVAs in human plasma following WG oat consumption. Methods: We conducted a randomized crossover acute pharmacokinetic study to identify the biomarkers of WG oat intake. Twelve healthy volunteers, comprising 5 males and 7 females aged 22-71 years, participated in a controlled-feeding human study. Following the ingestion of a single dose of high-fiber oatmeal containing two-servings of oat bran, blood samples were collected at various time points over 24 hours. LC-MS was used to analyze the metabolic profile of AVAs and quantify the levels of AVAs and DH-AVAs in human plasma. Results: Using authentic standards purified from WG oat or synthesized in-house, we measured the kinetic changes of AVAs and their DH-AVAs. Our results indicate that plasma concentrations of AVA 2p, 2c, and 2f rapidly increased, reached peak levels within 3 hours, and then gradually declined. As for DH-AVAs, the concentration of DH-2f reached peaked at 8 hours and remained quantifiable at 24 hours, while plasma levels of DH-2p and DH-2c continued to rise over the 24-hour period. The plasma elimination half-lives (T1/2) of DH-AVAs are notably higher than those of AVAs. Furthermore, we investigated how variables such as body weight, sex, and age impact the bioavailability of AVAs and DH-AVAs. Conclusions: Our study revealed that DH-AVAs exhibited significantly longer Tmax and T1/2 values compared to their parent forms, indicating that DH-2p, -2f, and -2c are capable of being absorbed into plasma and could serve as medium- to long-term exposure biomarkers for assessing WG oat intake. Consequently, the incorporation of AVAs and DH-AVAs as a panel may provide a more comprehensive reflection of WG oat intake compared to AVAs alone. Funding Sources: This work was supported by funding from The United States Department of Agriculture (USDA) National Institute of Food and Agriculture (NIFA) R01 grant 2018-67001-28265.