Carotenoid-rich tomatoes and many products derived from tomatoes have been extensively marketed in the last decade for health promotion and disease prevention. Yet, controversy abounds, in large part because so little it known about the bioavailability, metabolism and mechanisms of action of the major tomato carotenoids lycopene (LYC), phytoene (PE) and phytofluene (PF). This grant application describes the characterization and implementation of a novel research tool that will dramatically improve our ability to trace the absorption of metabolites derived from the tomato carotenoids. The new technology, described and tested in this application, is based upon producing 13C labeled LYC, PE, and PF and testing them in humans. These 13C-enriched carotenoids will be used in a cross-over feeding study designed to more precisely define and compare how tomato carotenoids are absorbed and metabolized in men and women.
Specific Aim 1 : To produce pure 13C- phytoene (PE), 13C- phytofluene (PF) and 13C-lycopene (LYC) by utilizing in vitro tomato cell suspension culture technology. For the first time, we will apply tomato cell suspension culture for the reliable production of highly purified non-radioactive 13C-rich tomato carotenoids PE, PF, and LYC for novel bioavailability and metabolism studies in humans.
Specific Aim #2 : To compare and define kinetics of absorption and relative bioavailability of tomato-derived carotenoids in men and women using 13C -PE, 13C -PF, and 13C-LYC. We will use 13C-PE, 13C-PF, and 13C-LYC for characterization of uptake kinetics and relative bioavailability of these tomato carotenoids in healthy adult men (n=12) and women (n=12).
Specific Aim 3 : To identify metabolites of tomato-derived carotenoids in humans over time by employing 13C-PE, 13C-PF, or 13C-LYC. Knowledge and understanding of tomato-derived carotenoid metabolism in humans is speculative at best and essentially nonexistent with regards to both degradation pathways, and production of potentially bioactive compounds. Tracer labeling will allow us to examine the conversion of the orally administered parent compound to metabolites that are characteristic of bioactivation pathways or catabolic/degradation pathways using HPLC-MS/MS. Significance. Only through the development of novel tools to examine the digestion, absorption, bioavailability, tissue distribution, and systemic vs. target tissue metabolism will we be able to understand the mechanisms of action for LYC, PE, and PF in regards to human health. This proposal targets the Program Announcement PAR-08-135 entitled """"""""Exploratory/Developmental Grant for Complementary and Alternative Medicine (CAM) Studies of Humans"""""""" of The National Center for Complementary and Alternative Medicine (NCCAM), NCI, the National Institute on Aging (NIA), and the Office of Dietary Supplements (ODS).

Public Health Relevance

This proposal describes studies that characterize new techniques that will help us understand the absorption and metabolism of the major tomato carotenoids. These studies may help us defined the mechanisms of action for lycopene, phytofluene, and phytoene with regards to human health promotion and disease prevention.

National Institute of Health (NIH)
National Center for Complementary & Alternative Medicine (NCCAM)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZAT1-LD (34))
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Hopp, Craig
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Ohio State University
Internal Medicine/Medicine
Schools of Medicine
United States
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Moran, Nancy E; Novotny, Janet A; Cichon, Morgan J et al. (2016) Absorption and Distribution Kinetics of the 13C-Labeled Tomato Carotenoid Phytoene in Healthy Adults. J Nutr 146:368-76
Moran, Nancy E; Cichon, Morgan J; Riedl, Kenneth M et al. (2015) Compartmental and noncompartmental modeling of ¹³C-lycopene absorption, isomerization, and distribution kinetics in healthy adults. Am J Clin Nutr 102:1436-49
Moran, Nancy Engelmann; Clinton, Steven K; Erdman Jr, John W (2013) Differential bioavailability, clearance, and tissue distribution of the acyclic tomato carotenoids lycopene and phytoene in mongolian gerbils. J Nutr 143:1920-6
Moran, Nancy E; Erdman Jr, John W; Clinton, Steven K (2013) Complex interactions between dietary and genetic factors impact lycopene metabolism and distribution. Arch Biochem Biophys 539:171-80
Moran, Nancy Engelmann; Rogers, Randy B; Lu, Chi-Hua et al. (2013) Biosynthesis of highly enriched 13C-lycopene for human metabolic studies using repeated batch tomato cell culturing with 13C-glucose. Food Chem 139:631-9
Engelmann, Nancy J; Clinton, Steven K; Erdman Jr, John W (2011) Nutritional aspects of phytoene and phytofluene, carotenoid precursors to lycopene. Adv Nutr 2:51-61
Lu, Chi-Hua; Choi, Jin-Ho; Engelmann Moran, Nancy et al. (2011) Laboratory-scale production of 13C-labeled lycopene and phytoene by bioengineered Escherichia coli. J Agric Food Chem 59:9996-10005
Engelmann, Nancy J; Campbell, Jessica K; Rogers, Randy B et al. (2010) Screening and selection of high carotenoid producing in vitro tomato cell culture lines for [13C]-carotenoid production. J Agric Food Chem 58:9979-87