Protocatechuic Acid Is the Major Human Metabolite of Cyanidin-Glucosides3

Abstract

The metabolic fate of dietary anthocyanins (ACN) has not been fully clarified in humans. In all previous studies, the proportion of total ACN absorbed and excreted in urine was <1% intake. This study aimed to elucidate the human metabolism of cyanidin-glucosides (CyG) contained in blood orange juice (BOJ). One liter of BOJ, containing 71 mg CyG, was consumed by 6 healthy, fasting volunteers. Blood, urine, and fecal samples were collected at baseline and at different times up to 24 h after juice consumption. The content of native CyG, glucuronidated/methylated derivatives, and various phenolic acids was determined by HPLC/MS/MS. The serum maximal concentration of cyanidin-3-glucoside (Cy-3-glc) was 1.9 +/- 0.6 nmol/L and that of protocatechuic acid (PCA) was 492 +/- 62 nmol/L at 0.5 h and 2 h after juice consumption, respectively. The calculated total amounts in plasma corresponded for Cy-3-glc to 0.02% and for PCA to 44% of CyG ingested. CyG and glucuronidated/methylated metabolites, but not PCA, were detected in urine. ACN recovered in 24-h urine collections represented approximately 1.2% of the ingested dose. Both CyG (1.90 +/- 0.04 nmol/g) and PCA (277 +/- 0.2 nmol/g) were recovered in 24-h fecal samples. Data explained the metabolic fate of 74% of BOJ ACN. PCA was for the first time, to our knowledge, identified in humans as a CyG metabolite, accounting for almost 73% of ingested CyG. A high concentration of PCA may explain the short-term increased plasma antioxidant activity observed after intake of cyanidin-rich food and it can also contribute to the numerous health benefits attributed to dietary ACN consumption.

Anthocyanin-rich plum juice reduces ambulatory blood pressure but not acute cognitive function in younger and older adults: a pilot crossover dose-timing study

“…Here they are catabolized by the microbiota, producing an array of phenolic components that are absorbed, and some metabolized to phase II conjugates [61]. Furthermore, our finding that methylated and glucuronidated derivatives of cyaniding-based anthocyanins were the main urinary metabolites is also in agreement with others [62][63][64]. The in vivo glucuronidation, sulfatation and methylation of anthocyanins by UDP-glucuronosyltransferases, sulfotransferase and COMT in the intestinal epithelial cells, liver and kidney is a common metabolic pathway of dietary anthocyanins and other polyphenolic compounds [65].…”

Berries and anthocyanins: promising functional food ingredients with postprandial glycaemia-lowering effects

“…Microbiota can degrade anthocyanins to phenolic acids and aldehydes by splitting the C-ring and modifying the remaining A and B-rings (62) . Some of the main metabolites of microbiota degradation are gallic acid, vanillic acid, homovanilic acid, protocatechuic acid (PCA), syringic acid and 4-hydroxybenzoic acid (55,(65)(66)(67)(68) . Despite knowledge of the high rate of anthocyanin degradation by gut microbiota there is still no consensus about the proportion absorbed into the systemic circulation (45,53,55) .…”

“…For example, a study published in 2007 reported only the recovery of cyanidin-3-glucoside and PCA in the plasma following ingestion of 1 litre blood orange juice (65) . However, de Ferrars et al (55) in 2013 reported twenty-eight total metabolites, seventeen phenolics and eleven anthocyanin conjugates in urine following consumption of an elderberry extract (500 mg mixed anthocyanins) consisting mostly of cyanidin glycosides, while plasma analysis discovered seventeen phenolics and four anthocyanin conjugates.…”

Potential anti-inflammatory, anti-adhesive, anti/estrogenic, and angiotensin-converting enzyme inhibitory activities of anthocyanins and their gut metabolites

“…More recently, it has been established that the intestinal microflora plays a key role in the metabolism of anthocyanins. After ingestion, anthocyanins can be hydrolyzed by intestinal glucosidases and the resulting aglycones are further metabolised in the large intestine to other breakdown metabolites such as protocatechuic, gallic, syringic, and vanillic acids (Avila et al 2009;Forester and Waterhouse 2008;Keppler and Humpf 2005;Vitaglione et al 2007). Moreover, gallic acid has been determined in plasma after its ingestion at levels as high as 1.8 lmol/L in its original form and at 2.2 lmol/L as its derivative 4-Omethylgallic acid (Shahrzad and Bitsch 1998;Shahrzad et al 2001).…”