The metabolism and excretion of (+)-[¹⁴C]cyanidanol-3 in man following oral administration

Abstract

Following administration of a single dose of [U14C]cyanidanol-3 to human volunteers, a mean of 55% of the dose of 14C was excreted in urine; 90% of urine 14C was excreted within 24 h of drug administration. The major urinary metabolites were the glucuronides of (+)-catechin and 3'-O-methyl-(+)-catechin, and the sulphate of the latter. These three conjugates collectively accounted for three quarters of urine 14C. Urinary excretion of unchanged (+)-cyanidanol-3 was 0.1-1.4% dose. (+)-Cyanidanol-3 and metabolites containing the intact flavanol ring system accounted for 90% of urine 14C. Ring scission was, under these conditions, a minor metabolic pathway resulting in the excretion of small amounts of 3-hydroxybenzoic acid, 3-hydroxyhippuric acid and 3-hydroxyphenylpropionic acid. Unchanged (+)-cyanidanol-3 was detected in plasma between 30 min and 12 h after administration. Metabolites (as total 14C) persisted in plasma for at least 120 h after administration.

(–)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans

“…The reasons for these shortcomings are, at least in part, based on the fact that food matrices contain a multitude of phytochemical constituents, of which an unknown number may exert physiological effects. Furthermore, despite the fact that previous work structurally characterized major flavanol metabolites in human plasma (16)(17)(18)(19), the direct proof that, and which of, the absorbed flavanols and their metabolites are causally linked to the observed cardiovascular effects in humans has yet to be established. Importantly, most data available from in vitro studies are based on the use of flavanol forms as present in foods and not as they exist in circulation, potentially limiting the validity of a subsequent data analysis in the context of human physiology.…”

“…Importantly, most data available from in vitro studies are based on the use of flavanol forms as present in foods and not as they exist in circulation, potentially limiting the validity of a subsequent data analysis in the context of human physiology. The extent of this potential drawback becomes apparent when considering that the human metabolism of flavanols gives rise to various O-methylated, O-glucuronidated, and Osulfated flavanol derivatives that are products of phase I͞II biotransformation in intestine and liver (16)(17)(18)(19). Flavanols also undergo biotransformation by the gut micro flora resulting in a large variety of phenolic acid derivatives and ␥-valerolactone-like compounds (20).…”

Procyanidins are not bioavailable in rats fed a single meal containing a grapeseed extract or the procyanidin dimer B<SUB>3</SUB>

“…Procyanidin B 3 dimer and procyanidin polymers can be degraded by microflora in the large intestine into bioavailable phenolic acids similar to those formed from catechin itself (Scheline, 1970;Groenewoud & Hundt, 1986;Déprez et al 2000). Studies have identified mono-and dihydroxylated phenylpropionic, phenylacetic and hippuric acid as well as various phenylvalerolactones as flavanol metabolites in plasma (Das, 1971;Hackett et al 1983;Pietta et al 1998;Li et al 2000). These metabolites may further increase the antioxidant capacity of plasma or may have activity within the intestine.…”

“…The monomers catechin and epicatechin as well as the gallate esters present in green tea are absorbed in both human subjects and animals (Hackett et al 1983;Lee et al 1995;Piskula & Terao, 1998;Donovan et al 1999aDonovan et al , 2002Koga et al 1999;Richelle et al 1999;Baba et al 2000;Rein et al 2000).…”

Cancer Chemoprevention by Dietary Polyphenols

“…Hackett et al, [126] reported that three human volunteers were given 2 g of (+)-catechin and the metabolic changes in it were then examined by looking at their blood and urine. About 55% of the labeled catechin was excreted in urine within 2 h after its uptake.…”