The effect of obesity and repeated exposure on pharmacokinetic response to grape polyphenols in humans

Authors: Novotny, Janet; CHEN, TZU-YING - Purdue University; TEREKHOV, ANTON - Purdue University; GEBAUER, SARAH - Food And Drug Administration(FDA); Baer, David; HO, LAP - The Icahn School Of Medicine At Mount Sinai; PASINETTI, GIULIO - The Icahn School Of Medicine At Mount Sinai; FERRUZZI, MARIO - Purdue University

Submitted to: Molecular Nutrition and Food Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/11/2017
Publication Date: 6/27/2017
Citation: Novotny, J., Chen, T., Terekhov, A., Gebauer, S.K., Baer, D.J., Ho, L., Pasinetti, G., Ferruzzi, M.G. 2017. The effect of obesity and repeated exposure on pharmacokinetic response to grape polyphenols in humans. Molecular Nutrition and Food Research. 61. https://doi.org/10.1002/mnfr.201700043.
DOI: https://doi.org/10.1002/mnfr.201700043

Interpretive Summary: Dietary flavonoids are associated with a number of health benefits, particularly reduction of risk for cardiovascular disease (CVD) and diabetes. Overweight and obese individuals are at increased risk for both CVD and diabetes, and thus may particularly benefit from flavonoid consumption. However, evidence suggests that overweight & obese individuals may have impaired absorption of some nutrients. Previous studies have also demonstrated that prior exposure to flavonoids may influence absorption. Therefore, we recruited a group of lean and overweight/obese individuals to participate in a grape flavonoid absorption study. We found that lean individuals absorbed grape flavonoids better after having consumed grape flavonoids for 10 days prior, while obese individuals had no change in absorption after repeated consumption. When comparing lean and obese individuals, we found that lean individuals absorbed the grape flavonoids better than the obese individuals after 10 days of grape flavonoid consumption. These results will be useful to scientists and health care practitioners.

Technical Abstract: Obesity is associated with lower circulating nutrients, though the reason is unclear. Since obesity may affect intestinal function, differential absorption may play a role. We investigated the pharmacokinetic response of polyphenols in obese/overweight and lean individuals from a dose of grape polyphenols. Pharmacokinetic challenges were administered before and after 10d repeated dosing of polyphenols, since repeated dosing has been found to influence the pharmacokinetic responses of grape polyphenols, Ginkgo flavonoids, and tea flavan-3-ols in rats and tea flavan-3-ols in humans. Six lean and six obese volunteers consumed resveratrol, grape seed extract, and grape juice (2,125 mg total polyphenols) daily for 11 d. On d1 and d11, blood samples were collected for 6h after consumption of the polyphenols and analyzed for deconjugated catechin, epicatechin, resveratrol, and quercetin. Plasma area under the plasma polyphenol mass by time curves (AUCs) were greater for catechin, epicatechin, and quercetin on d11 vs. d1 for low BMI (P<0.039) but not high BMI individuals. Further, AUCs were greater for epicatechin and resveratrol for low BMI vs. high BMI individuals (P<0.041), with a similar trend for catechin (p=0.065), on d11 but not d1. These results suggest that that obesity and repeated exposure may modify polyphenol absorption in humans.