Cyanidin-3-glucoside as a possible biomarker of anthocyanin-rich berry intake in body fluids of healthy humans: a systematic review of clinical trials

CONTEXT: Anthocyanins are phenolic compounds found in berries. They exhibit promising health benefits in humans, but no accurate biomarkers of berry intake have been identified thus far. OBJECTIVE: The aim of this systematic review is to propose a biomarker of anthocyanin-rich berry intake in human plasma and urine. DATA SOURCES: PubMed and Cochrane databases were searched from January 2008 to January 2019. STUDY SELECTION: Databases were searched for human intervention studies that assessed the presence of anthocyanins in human body fluids using high-throughput techniques. Non-English articles and studies publishing targeted analyses were excluded. DATA EXTRACTION: Ten clinical trials, in which 203 phenolic compounds were identified, were included and assessed qualitatively. The following criteria were used to identify biomarkers of berry intake: frequency, plausibility, dose-response, time response, robustness, reliability, stability, analytical performance, and reproducibility. Sensitivity and specificity of potential biomarkers were determined by the receiver operating characteristic curve. RESULTS: Of the 203 phenolic compounds identified in human samples, the anthocyanin cyanidin-3-glucoside was the molecule found most frequently in urine (58.06%) and plasma (69.49%). Cyanidin-3-glucoside fulfills the essential criterion of plausibility as well as the dose-response, time response, stability, and analytical performance criteria. Its positive predictive value is 74% (P = 0.210) in plasma, which is acceptable, and 61.7% (P = 0.402) in urine. CONCLUSIONS: Current evidence suggests that cyanidin-3-glucoside is a potential biomarker of anthocyanin-rich berry intake in plasma and urine of healthy humans. PROSPERO REGISTRATION NUMBER: CRD42018096796.