Pharmacokinetics of 13C‐Lycopene in Healthy Adults

Abstract

Higher plasma lycopene (LYC) concentrations are associated with lower risk of several cancers. (All‐E)‐LYC is the predominant geometrical isomer in tomatoes, yet most plasma and tissue LYC isomers are Z, suggesting greater bioavailability of Z and/or endogenous isomerization of E to Z. To study human LYC pharmacokinetics and isomerization, ~10 mg of 13C‐LYC isolated from tomato cell cultures was consumed with breakfastby 6 healthy adults. The dose was 85% (all‐E)‐LYC, and ~30% uniformly labeled. Plasma was collected at 1–10, 24, 72, and 672 hrs post‐dosing. Native and 13C‐LYC was analyzed by HPLC‐PDA, and LC‐MS (QToF), respectively. No adverse effects of 13C‐LYC were observed. 13C‐LYC Cmax= 0.13±0.03 μM which occurred at 32±8 hr, T1/2 = 6.5 ± 0.3 d, and area‐under‐the‐curve (AUC0–672) = 36.9±7 μM*h. Plasma 13C‐all‐E‐LYC Cmax =0.10 ±0.02 μM at 29±9 h post‐dosing, T1/2 = 5.5±0.3 d, and it constituted 67% of total 13C‐LYC AUC. Total 13C‐Z‐LYC isomers Cmax =0.03 ± 0.005 μM at 56±10 hr post‐dosing with a subsequent T1/2 = 9.3±0.6 days, and constituted 32% of the total 13C‐LYC AUC. Initial plasma 13C‐LYC was 73–87% all‐E, but by 672 hr, had decreased to 46%. The later Z isomer Cmax and longer T1/2 relative to all‐E suggests that endogenous conversion is a source of circulating Z‐LYC isomers. Understanding LYC pharmacokinetics assists in designing anti‐cancer dietary interventions.Grant Funding Source: NCCAM R21AT005166, Pelotonia, OSUCCC NPASR