Absorption, Metabolism, and Excretion of (-)-[2-14C]Epicatechin in Humans

A Single-Center, Open-Label Study to Evaluate the Absorption, Metabolism, and Excretion of (-)-[2-14C]Epicatechin Following Oral Intake

The purpose of this study is to determine the absorption, metabolism and excretion of (-)-epicatechin using the radiolabeled tracer (-)-[2-14C]epicatechin in healthy male volunteers observing a flavanol-/procyanidin-controlled background diet.

Flavanols and their oligomeric derivatives, the procyanidins, are plant-derived compounds commonly present in the human diet. Accumulating data demonstrate a causal role for dietary flavanols in mediating the cardiovascular benefits associated with the consumption of flavanol-/procyanidin-containing foods. In this context, there exists a great interest in understanding the absorption, distribution, metabolism and excretion (ADME) of flavanols in humans. While significant advances in understanding the ADME of flavanols were made, the data obtained thus far remain fairly preliminary and with significant shortfalls and seeming contradictions. Aimed at addressing the challenges and gaps of previous investigations, this study will investigate the ADME of (-)-epicatechin, one of the most abundant dietary flavanols, following the intake of radiolabeled (-)-[2-14C]epicatechin by healthy humans observing a flavanol-/procyanidin-controlled background diet.

Inclusion Criteria1.

1. males, in good health, between 18 and 50 years of age and between 60 and 100 kg;
2. body mass index (BMI) between 19 and 30 kg/m2.
3. clinical laboratory evaluations (including clinical chemistry [fasted at least 10 hours], hematology, and urinalysis) within the reference range for the testing laboratory, unless deemed not clinically significant by the Investigator;
4. negative hepatitis panel (including hepatitis B surface antigen [HbsAg] and hepatitis C virus antibody [anti-HCV]) and human immunodeficiency virus (HIV) antibody screens;
5. a minimum of 1 bowel movement per day.

Exclusion Criteria:

1. history or clinical manifestations of significant metabolic, hematological, pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic, renal, urological, or psychiatric disorders;
2. allergies to peanuts, nuts, or other foods;
3. lactose intolerance;
4. history of stomach or intestinal surgery, except that appendectomy or hernia were allowed;
5. history of alcoholism or drug addiction within 1 year prior to study entry (ie, at Screening);
6. use of any tobacco products (including cigarette, pipe, cigar, chewing, nicotine patch, or nicotine gum) within 6 months prior to study entry;
7. use of any agents (excluding those provided as part of this study procedure) affecting the liver enzymes;
8. use of aspirin-containing drugs and any other over-the-counter, non-prescription preparations (including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) during the study, unless deemed acceptable by the Investigator;
9. use of any alcohol-containing or caffeine-containing products/medications within 72 hours prior to (-)-[2-14C]epicatechin ingestion;
10. regular consumption of more than 2 alcoholic drinks per day;
11. vegans, vegetarians and/or anyone who consumed less than 1 to 2 servings of fruits and or vegetables per day;
12. participation in more than one other radiolabeled investigational study drug trial within 12 months prior to study entry or exposure to significant radiation within 12 months prior to study entry;