Mass spectrometry-based metabolomics for the discovery of candidate markers of flavonoid and polyphenolic intake in adults

Robust biological markers of dietary exposure are essential in improving the understanding of the link between diet and health outcomes. Polyphenolic compounds, including flavonoids, have been proposed to mitigate the risk of chronic diseases where oxidative stress and inflammation play a central role. Biomarkers can provide objective measurement of the levels of polyphenolic compounds. In this study, we provide methodology to identify potential candidate markers of polyphenol intake in human serum. Seventeen participants from the UK arm of the Global Allergy and Asthma Network of Excellence (GA(2)LEN) had their dietary intake estimated using a validated food frequency questionnaire, and serum samples were assessed using mass spectrometry to identify potential candidate markers. 144 features were assigned identities, of these we identified four biologically relevant compounds (rhamnazin 3-rutinoside, 2-galloyl-1,4-galactarolactone methyl ester, 2 '',32 ''-di-O-p-coumaroylafzelin and cyclocommunin), which were significantly increased in the serum of participants with high predicted level of fruit and vegetable intake. 2-galloyl-1,4-galactarolactone methyl ester was strongly correlated with total flavonoids (r = 0.62; P = 0.005), flavan-3-ols (r = 0.67; P. 0.002) as well as with other four subclasses. Rhamnazin 3-rutinoside showed strong correlation with pro-anthocyanidins (r= 0.68; P = 0.001), flavones (r= 0.62; P= 0.005). Our results suggest that serum profiling for these compounds might be an effective way of establishing the relative intake of flavonoids and could contribute to improve the accuracy of epidemiological methods to ascertain flavonoid intake.