The metabolome of [2-14C](−)-epicatechin in humans: implications for the assessment of efficacy, safety and mechanisms of action of polyphenolic bioactives

Abstract

Diet is a major life style factor affecting human health, thus emphasizing the need for evidence-based dietary guidelines for primary disease prevention. While current recommendations promote intake of fruit and vegetables, we have limited understanding of plant-derived bioactive food constituents other than those representing the small number of essential nutrients and minerals. This limited understanding can be attributed to some extent to a lack of fundamental data describing the absorption, distribution, metabolism and excretion (ADME) of bioactive compounds. Consequently, we selected the flavanol (−)-epicatechin (EC) as an example of a widely studied bioactive food constituent and investigated the ADME of [2-14C](−)-epicatechin (300 μCi, 60 mg) in humans (n = 8). We demonstrated that 82 ± 5% of ingested EC was absorbed. We also established pharmacokinetic profiles and identified and quantified >20 different metabolites. The gut microbiome proved to be a key driver of EC metabolism. Furthermore, we noted striking species-dependent differences in the metabolism of EC, an insight with significant consequences for investigating the mechanisms of action underlying the beneficial effects of EC. These differences need to be considered when assessing the safety of EC intake in humans. We also identified a potential biomarker for the objective assessment of EC intake that could help to strengthen epidemiological investigations.

Anti-inflammatory actions of (−)-epicatechin in the adipose tissue of obese mice

“…Significantly, this occurred at EC/EC metabolites concentrations attainable in human plasma/tissues after dietary consumption (Ottaviani et al, 2011; Mullen et al, 2009; Baba et al, 2000; Holt et al, 2002; Actis-Goretta et al, 2012). Of major physiological relevance, EC metabolites, which constitute the majority of human plasma EC such as glucuronidated, sulphated, and methylated derivatives (Actis-Goretta et al, 2012; Ottaviani et al, 2011, 2016), were also effective in those actions.…”

Oleocanthal-rich extra virgin olive oil demonstrates acute anti-platelet effects in healthy men in a randomized trial

“…If true, both generally phenolic-rich oils and specifically oleocanthal-rich oils would be predicted to have positive impacts on both platelet aggregation and inflammation, and thus have benefits in cardiovascular risk reduction, as has been previously suggested in a 28-day intervention of post-menopausal women (Sánchez-Muniz et al, 1998). While the above associations are intriguing, care must be taken in their final interpretation as phenols and polyphenols are rapidly and extensively metabolized, with circulating metabolites detected in the plasma in significant levels within minutes and lasting for several hours post intake (Ottaviani et al, 2016; Zamora-Ros et al, 2016). Moreover, some studies evaluating dietary flavonoids on plasma flavanols and ex vivo platelet function have shown increases in plasma flavonoids with no effects on platelet function (Hubbard et al, 2003).…”

Bioavailability of Black Tea Theaflavins: Absorption, Metabolism, and Colonic Catabolism

“…The values are corrected for baseline levels of (Table 5). These four 5C-RFMs are known colonic degradation products of flavan-3-ols 258 monomers and possibly to some extent the procyanidin dimer 28,29 a small quantity of which was 259 present in the theaflavin extract (Table 1).…”