Pharmacokinetics and ex‐vivo bioactivties of pomegranate polyphenols in humans

Pomegranate juice (PJ) contains abundant polyphenols including punicalagin, an ellagitannin (ET) that is largely responsible for its in vitro bioactivities. The pharmacokinetics (PK) of PJ polyphenols in human subjects remains uninvestigated. We evaluated PK parameters of PJ polyphenols in humans (n=19) after ingestion of PJ (180 mL containing 318 mg punicalagin). Blood was collected before and at 0.5, 1, 2, 3, 4, and 6h post administration. Urine (24 h) was collected on the day prior to ingestion, on the intervention day, and on the day after ingestion. Liquid chromatography mass spectroscopy (LC‐MS) plasma analyses revealed ellagic acid (EA), a hydrolysis product of ETs, at Cmax = 18.64 ± 1.69 ng/mL, AUC = 50.07 ± 5.80 ng/h/mL, Tmax = 0.98 ± 0.059 h and T1/2E = 0.75 ± 0.078 h. LC‐MS analyses of urine and plasma showed intact EA and EA‐derivatives on the intervention day while further ET‐breakdown products were detected on the post‐ingestion day. Considerable inter‐individual variability in metabolites was observed. Evaluation of biomarkers of oxidative stress by ex vivo plasma antioxidant status and lymphocyte 8‐hydroxydeoxyguanosine to deoxyguanosine (8‐OHdg/106dG) ratios (damage to lymphocyte DNA), did not show any significant differences after consumption of PJ. Our results provide useful data required for designing doses and dose frequencies in intervention studies with PJ polyphenols for purposes of evaluating their potential health benefits in humans. Supported by the Stewart and Lynda Resnick Revocable Trust.