Compartmental and noncompartmental modeling of 13C-lycopene absorption, isomerization, and distribution kinetics in healthy adults

Abstract

Background: Lycopene, which is a red carotenoid in tomatoes, has been hypothesized to mediate disease-preventive effects associated with tomato consumption. Lycopene is consumed primarily as the all-trans geometric isomer in foods, whereas human plasma and tissues show greater proportions of cis isomers. Objective: With the use of compartmental modeling and stable isotope technology, we determined whether endogenous all-transto- cis-lycopene isomerization or isomeric-bioavailability differences underlie the greater proportion of lycopene cis isomers in human tissues than in tomato foods. Design: Healthy men (n = 4) and women (n = 4) consumed 13C-lycopene (10.2 mg; 82% all-trans and 18% cis), and plasma was collected over 28 d. Unlabeled and 13C-labeled total lycopene and lycopene-isomer plasma concentrations, which were measured with the use of high-performance liquid chromatography-mass spectrometry, were fit to a 7-compartment model. Results: Subjects absorbed a mean 6 SEM of 23% 6 6% of the lycopene. The proportion of plasma cis-13C-lycopene isomers increased over time, and all-trans had a shorter half-life than that of cis isomers (5.3 6 0.3 and 8.8 6 0.6 d, respectively; P , 0.001) and an earlier time to reach maximal plasma concentration than that of cis isomers (28 6 7 and 48 6 9 h, respectively). A compartmental model that allowed for interindividual differences in cis- and all-trans-lycopene bioavailability and endogenous transto- cis-lycopene isomerization was predictive of plasma 13C and unlabeled cis- and all-trans-lycopene concentrations. Although the bioavailability of cis (24.5% 6 6%) and all-trans (23.2% 6 8%) isomers did not differ, endogenous isomerization (0.97 6 0.25 mmol/d in the fast-turnover tissue lycopene pool) drove tissue and plasma isomeric profiles. Conclusion: 13C-Lycopene combined with physiologic compartmental modeling provides a strategy for following complex in vivo metabolic processes in humans and reveals that postabsorptive trans-tocis- lycopene isomerization, and not the differential bioavailability of isomers, drives tissue and plasma enrichment of cis-lycopene. This trial was registered at clinicaltrials.gov as NCT01692340.