title: 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-trans-to-cis-lycopene isomerization or isomeric-bioavailability differences underlie the greater proportion of lycopene cis isomers in human tissues than in tomato foods.
  
  
  METHODS
  Healthy men (n = 4) and women (n = 4) consumed (13)C-lycopene (10.2 mg; 82% all-trans and 18% cis), and plasma was collected over 28 d. Unlabeled and (13)C-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 ± SEM of 23% ± 6% of the lycopene. The proportion of plasma cis-(13)C-lycopene isomers increased over time, and all-trans had a shorter half-life than that of cis isomers (5.3 ± 0.3 and 8.8 ± 0.6 d, respectively; P < 0.001) and an earlier time to reach maximal plasma concentration than that of cis isomers (28 ± 7 and 48 ± 9 h, respectively). A compartmental model that allowed for interindividual differences in cis- and all-trans-lycopene bioavailability and endogenous trans-to-cis-lycopene isomerization was predictive of plasma (13)C and unlabeled cis- and all-trans-lycopene concentrations. Although the 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 profiles.
  
  
  CONCLUSIONS
  (13)C-Lycopene combined with physiologic compartmental modeling provides a strategy for following complex in vivo metabolic processes in humans and reveals that postabsorptive trans-to-cis-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.
authors.affiliation: The Ohio State University Comprehensive Cancer Center.
authors.forename: Nancy E
authors.identifier: http://orcid.org/0000-0001-7281-9187
authors.initials: NE
authors.lastname: Moran
authors.affiliation: Departments of Food Science and Technology.
authors.forename: Morgan J
authors.identifier: http://orcid.org/0000-0001-9379-0264
authors.initials: MJ
authors.lastname: Cichon
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Departments of Food Science and Technology.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Riedl
authors.affiliation: The Ohio State University Comprehensive Cancer Center.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Grainger
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Departments of Food Science and Technology.
authors.forename: Steven J
authors.identifier: http://orcid.org/0000-0002-1427-5780
authors.initials: SJ
authors.lastname: Schwartz
authors.affiliation: Human Nutrition Research Center, USDA, Beltsville, MD; and.
authors.forename: Janet A
authors.identifier: http://orcid.org/0000-0002-9121-886X
authors.initials: JA
authors.lastname: Novotny
authors.affiliation: Department of Food Science and Human Nutrition and Division of Nutritional Sciences, The University of Illinois, Urbana, IL.
authors.forename: John W
authors.initials: JW
authors.lastname: Erdman
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Internal Medicine-Division of Medical Oncology, and The James Cancer Hospital, The Ohio State University, Columbus, OH; steven.clinton@osumc.edu.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Clinton
mesh_terms: D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D002247:Carbon Isotopes; D002338:Carotenoids / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D019587:Dietary Supplements / Q000032:analysis; D005260:Female; D005638:Fruit / Q000737:chemistry*; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D007700:Kinetics; D000077276:Lycopene; D018551:Solanum lycopersicum / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009753:Nutritive Value; D015203:Reproducibility of Results; D013237:Stereoisomerism; D055815:Young Adult
chemical_list: D000975:Antioxidants; D002247:Carbon Isotopes; D002338:Carotenoids; D000077276:Lycopene
keywords: compartmental modeling; isomers; kinetics; lycopene; tracers