Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a C-13-tracer study

Background: Evidence suggests that the consumption of anthocyanin-rich foods beneficially affects cardiovascular health; however, the absorption, distribution, metabolism, and elimination (ADME) of anthocyanin-rich foods are relatively unknown. Objective: We investigated the ADME of a C-13(5)-labeled anthocyanin in humans. Design: Eight male participants consumed 500 mg isotopically labeled cyanidin-3-glucoside (6,8,10,3',5'-C-13(5)-C3G). Biological samples were collected over 48 h, and C-13 and C-13-labeled metabolite concentrations were measured by using isotope-ratio mass spectrometry and liquid chromatography-tandem mass spectrometry. Results: The mean +/- SE percentage of C-13 recovered in urine, breath, and feces was 43.9 +/- 25.9% (range: 15.1-99.3% across participants). The relative bioavailability was 12.38 +/- 1.38% (5.37 +/- 0.67% excreted in urine and 6.91 +/- 1.59% in breath). Maximum rates of C-13 elimination were achieved 30 min after ingestion (32.53 +/- 14.24 mu g C-13/h), whereas C-13-labeled metabolites peaked (maximum serum concentration: 5.97 +/- 2.14 mu mol/L) at 10.25 +/- 4.14 h. The half-life for C-13-labeled metabolites ranged between 12.44 +/- 4.22 and 51.62 +/- 22.55 h. C-13 elimination was greatest between 0 and 1 h for urine (90.30 +/- 15.28 mu g/h), at 6 h for breath (132.87 +/- 32.23 mu g/h), and between 6 and 24 h for feces (557.28 +/- 247.88 mu g/h), whereas the highest concentrations of C-13-labeled metabolites were identified in urine (10.77 +/- 4.52 mu mol/L) and fecal samples (43.16 +/- 18.00 mu mol/L) collected between 6 and 24 h. Metabolites were identified as degradation products, phenolic, hippuric, phenylacetic, and phenylpropenoic acids. Conclusion: Anthocyanins are more bioavailable than previously perceived, and their metabolites are present in the circulation for <= 48 h after ingestion. This trial was registered at clinicaltrials.gov as NCT01106729. Am J Clin Nutr 2013;97:995-1003.