A systematic literature review of biomarker methods used to measure total flavonoid intake and intake of selected flavonoid subclasses

A clear understanding of the most appropriate biomarker to measure flavonoid intake is required to inform clinical nutrition studies and epidemiological research. A systematic literature review was conducted to evaluate literature that validated or applied a biomarker method to measure dietary flavonoid intake in adult populations. A comprehensive database and internet search was conducted, alongside hand searching of reference lists of included studies. Potential studies (n=891) were assessed according to inclusion criteria, leaving 17 final papers in the review, with 13 studies validating biomarkers of flavonoid intake against both dietary assessment methods and intervention diets, and 4 applying flavonoid biomarkers as a measure of flavonoid intake. Relevant information relating to the biomarker, assessment method, biological sample, flavonoid sub-group, study design, and the key methodological conclusions was extracted from the studies. There was lack of homogeneity between the study designs however pooling of the correlations (r) in the validation studies was possible. The 13 validation studies identified various biomarkers, including parent flavonoids and phenolic acid metabolites measured in urine and plasma. Pooled 'Sum of flavonoid' biomarkers were strongly correlated with total flavonoid intake (r=0.58). The biomarker quercetin was strongly correlated with quercetin intake (r=0.68) and kaempferol was moderately correlated with kaempferol intake (r=0.44). Four case-control studies measured tea-related flavonoid biomarkers as a measure of tea intake. While multiple biomarkers may correlate with some dietary assessment outcomes, overall there is a lack of biomarker(s) that can accurately reflect dietary flavonoid intake and more studies are needed to inform future clinical research.