New insights into the bioavailability of red raspberry anthocyanins and ellagitannins

Abstract

Abbreviations:ADME, absorption, disposition, metabolism and excretion; C max, peak plasma concentration; 2 CID, collision-induced dissociation; ESI, electrospray interface; GIT, gastrointestinal tract; PDA, photodiode array; T max, time to reach peak plasma concentration; UHPLC-MS; ultra high performance liquid chromatography-mass spectrometry 3 ABSTRACT Red raspberries, containing ellagitannins and cyanidin-based anthocyanins, were fed to volunteers and metabolites appearing in plasma and urine were analysed by UHPLC-MS. Anthocyanins were not absorbed to any extent with sub nmol/L concentrations of cyanidin-3-glucoside and a cyanidin-Oglucuronide appearing transiently in plasma. Anthocyanins excreted in urine corresponded to 0.007% of intake. More substantial amounts of phase II metabolites of ferulic acid and isoferulic acid, along with 4′-hydroxyhippuric acid, potentially originating from pH-mediated degradation of cyanidin in the proximal gastrointestinal tract, appeared in urine and also plasma where peak concentrations were attained 1-1.5 h after raspberry intake. Excretion of 18 anthocyanin-derived metabolites corresponded to 15.0% of intake, a figure substantially higher than obtained in other anthocyanin feeding studies. Ellagitannins pass from the small to the large intestine where the colonic microbiota mediate their conversion to urolithins A and B which appeared in plasma and were excreted almost exclusively as sulfate and glucuronide metabolites. The urolithin metabolites persisted in the circulatory system and were excreted in urine for much longer periods of time than the anthocyanin metabolites although their overall urinary recovery was lower at 7.0% of intake. It is events originating in the proximal and distal gastrointestinal tract, and subsequent phase II metabolism, that play an important role in the bioavailability of both anthocyanins and ellagitannins and it is their metabolites which appear in the circulatory system, that are key to elucidating the mode of action(s) underlying the protective effects of these compounds on human health.

Antioxidant Capacity of Anthocyanin Pigments

“…The existing knowledge concerning with the absorption, distribution, metabolism and excretion (ADME) of anthocyanin compounds (including their decomposition within the gastrointestinal lumen) has been the subjects of several recent reviews [81][82][83][84][85][86][87][88][89][90][91][92][93][94][95]. In general, few Flavonoids -From Biosynthesis to Human Healthcomparative studies have been undertaken about their metabolism, physiological availability or biotransformation after intake in comparison with the number of studied devoted to absorption and distribution.…”

“…Pharmacokinetic trial to evaluate the bioavailability of anthocyanins and colonic polyphenol metabolites after consumption of aronia berry extract in plasma and urine [96] Pharmacokinetic characterization and bioavailability of strawberry anthocyanins relative to meal intake [97] Bioavailability studies and anticancer properties of malvidin-based anthocyanins, pyranoanthocyanins and nonoxonium derivatives [98] Effect of red cabbage fermentation on anthocyanin bioavailability and plasma antioxidant capacity in humans [99] Bioavailability of red raspberry anthocyanins and ellagitannins: new insights [82] Bioavailability and uptake of anthocyanins and their metabolites from grape/blueberry juice and smoothie in vivo and in vitro [100] Tissue bioavailability and intake of tart cherry anthocyanins [101] Confirmation and identification of tart cherry anthocyanins in several target tissues of healthy rats [102] Bioactive anthocyanins in 'Queen Garnet' plum: maturity and bioavailability [103] Use of anthocyanins as bioactive colourants in lipstick formulations [104] Application of the developed flavonoid-poor menu meals to the study of the bioavailability of bilberry anthocyanins as model flavonoids [105] Anthocyanin stability, mucus binding, and uptake into epithelial cells in healthy individuals that retained red grape or chokeberry juice in the mouth [106] Absorption and bioavailability of anthocyanins across the gastrointestinal mucosa [107] Effects of processing sour cherry fresh fruit to the final juice product on the content of anthocyanins and other related polyphenols [108] …”

Bioavailability of wild blueberry (poly)phenols at different levels of intake

“…Recent work suggests that the bioavailability of berry (poly)phenols is higher and more complex than previously thought [9,[19][20][21]. Highly unstable anthocyanins are degraded into smaller compounds as early as 1 hour postconsumption, before or after being absorbed in the small intestine, leading to a vast array of phenolic metabolites that can be glucuronidated, sulfated and/or methylated and circulate in much higher concentrations than the structurally related anthocyanin metabolites [19,22,23].…”

Development of obesity is reduced in high-fat fed mice fed whole raspberries, raspberry juice concentrate, and a combination of the raspberry phytochemicals ellagic acid and raspberry ketone

“…In the GI tract, EA is converted into a family of compounds calls the urolithins [27][28][29]. It has been suggested it is the urolithins that mediate the health benefits produced by consumption of ellagitannins and EA [30,31]. On the other hand, raspberry ketone, the aromatic compound that is the hallmark aroma of raspberry, has been minimally-studied in terms of metabolic disease.…”