Hagen Schroeter, PhD

Global Director of Fundamental Biomedical Research and the Flavanol Research Program, MARS, Inc.
Adjunct Research Professor, Department of Nutrition
University of California Davis, Davis, CA

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Abstract: Necessitated by longer life expectancies globally and by rising health care costs, there is increasing interest in better understanding the impact of diet on health and healthy aging. However, comprehensive understanding of how specific food constituents affect human health is limited to a comparatively small number of essential nutrients. Relatively little is known about the impact on health of a large variety of non-essential dietary constituents (bioactives), which have been proposed to have significant effects on disease risk reduction and primary disease prevention. A critical assessment of available knowledge in this area highlights significant gaps and cross-disciplinary controversies. Examples of such gaps include the urgent need for biomarkers, i.e. objective measures of dietary intake; the need for assessing safety and risks associated with intake of bioactives; and the need for understanding the mechanisms of action of these compounds. Thus, to further advance our knowledge, we submit that we need to gain greater understanding of the absorption, distribution, metabolism and excretion (ADME) of bioactives. We selected here 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 the ADME of EC. Furthermore, we noted species-dependent differences in the metabolism of EC, an insight with perhaps significant consequences for investigating the mechanisms of action underlying the beneficial effects of EC. These differences will also need to be considered when assessing the safety of EC intake in humans. In addition, we identified a potential biomarker for the objective assessment of EC intake that could help to strengthen epidemiological investigations.