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

Authors: MORAN, NANCY - The Ohio State University; CICHON, MORGAN - The Ohio State University; RIEDL, KENNETH - The Ohio State University; GRAINGER, ELIZABETH - The Ohio State University; SCHWARTZ, STEVEN - The Ohio State University; Novotny, Janet; ERDMAN, JOHN - University Of Illinois; CLINTON, STEVEN - The Ohio State University

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/28/2015
Publication Date: 12/1/2015
Citation: Moran, N.E., Cichon, M., Riedl, K., Grainger, E., Schwartz, S., Novotny Dura, J., Erdman, J., Clinton, S. 2015. Compartmental and noncompartmental modeling of 13C-lycopene absorption, isomerization, and distribution kinetics in healthy adults. American Journal of Clinical Nutrition. 102:1436-1449.

Interpretive Summary: Lycopene is a red carotenoid found in tomatoes hypothesized to mediate disease preventive effects associated with tomato consumption. Different forms of lycopene (called cis and trans) are found in tomatoes. Lycopene in tomatoes is primarily in the trans form, while lycopene in blood and body tissues is about half in the cis form. Because of the potential health implications of lycopene consumption, the health community has wondered why half of the lycopene found in the body is cis while the food form is mostly trans. We conducted a study with specially tagged lycopene so we could follow it through human metabolism to determine if cis and trans lycopene are absorbed differently or if trans lycopene is converted to cis after absorption. Eight adults consumed the tagged lycopene and provided blood samples for a month after dosing. The resulting data showed that the intestinal absorption of the two forms was not different. After absorption, the trans form was converted to the cis form in a tissue we believe to be the liver. In conclusion, the body appears to convert the common food form of lycopene (trans) to the cis form for tissue storage. This may indicate that the health benefits of lycopene are provided by the cis form. These results will be useful to scientists and health practitioners.

Technical Abstract: Lycopene is a red carotenoid found in tomatoes hypothesized to mediate disease preventive effects associated with tomato consumption. Lycopene is consumed primarily as the all-trans geometric isomer in foods, while human plasma and tissues demonstrate greater proportions of cis isomers. The objective is to determine, using compartmental modeling and stable isotope technology, if endogenous all-trans-to-cis-lycopene isomerization and/or isomeric bioavailability differences underlie the greater proportion of lycopene cis isomers in human tissues compared to that of tomato foods. 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, measured by HPLC-MS, were fit to a 7-compartment model. Subjects absorbed 23+/-6% of the lycopene. The proportion of plasma cis-13C-lycopene isomers increased over time, and all-trans had a shorter half-life (5.3+/-0.3 vs. 8.8+/-0.6 d, P<0.001) and an earlier Tmax (28+/-7 vs. 48+/-9 h,) than cis isomers. A compartmental model allowing for inter-individual differences in cis- and all-trans-lycopene bioavailability and endogenous trans-to-cis-lycopene isomerization was predictive of plasma 13C and unlabeled cis- and all-trans-lycopene concentrations. While bioavailability of cis- (24.5+/-6%) and all-trans (23.2+/-8%) isomers did not differ, endogenous isomerization (0.97+/-0.25 µmol/d in the fast-turnover tissue lycopene pool) drove tissue and plasma isomeric distributions. In conclusion, 13C-lycopene combined with physiologic compartmental modeling provides a strategy for following complex in vivo metabolic processes in humans, revealing that post-absorptive trans-to-cis-lycopene isomerization, not differential bioavailability of isomers, drive tissue and plasma enrichment of cis-lycopene.