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ARS Home » Northeast Area » Beltsville, Maryland (BHNRC) » Beltsville Human Nutrition Research Center » Food Components and Health Laboratory » Research » Publications at this Location » Publication #145590
Title: A PHYSIOLOGICAL COMPARTMENTAL MODEL DESCRIBING THE DYNAMICS OF LYCOPENE METABOLISM IN HEALTHY MEN.

Author
item DIWADKAR-NAVSARIWALA, V - UNIV. OF ILLINOIS
item Novotny, Janet
item GUSTIN, G - UNIV. OF ILLINOIS
item RODVOLD, K - UNIV. OF ILLINOIS
item SOSMAN, J - UNIV. OF ILLINOIS
item STACEWICZ-SAPUNTZAKI, J - UNIV. OF ILLINOIS
item MURRAY, J - UNIV. OF ILLINOIS
item TILLER, P - UNIV. OF ILLINOIS
item BOWEN, P - UNIV. OF ILLINOIS

Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/30/2003
Publication Date: 7/16/2003
Citation: Diwadkar-Navsariwala, V., Novotny Dura, J., Gustin, G.M., Rodvold, K.A., Sosman, J.A., Stacewicz-Sapuntzaki, J., Murray, J.L., Tiller, P.A., Bowen, P.E. 2003. A physiological compartmental model describing the dynamics of lycopene metabolism in healthy men. Journal of Lipid Research.44(10):1927-39.

Interpretive Summary: The increasing interest in lycopene as a potential anticancer agent has initiated a formal evaluation of this compound. A clinical trial with 25 healthy male subjects was conducted at the University of Illinois to evaluate the dose-dependent kinetics of lycopene delivered as a tomato beverage formulation. Five different doses of lycopene were administered and blood lycopene concentrations were monitored for 28 days. Scientists at the USDA and the U of IL collaborated to develop a compartmental model of lycopene kinetics in humans to determine dose-dependent levels of lycopene absorption and elimination. The predicted % absorption at the lowest dose was significantly greater than that of the higher doses; however, the total amount of lycopene absorbed was similar at all 5 doses. This finding suggests that lycopene absorption may be saturated at high doses, thus reducing the possible health advantages of very large doses compared to small doses. This may have important implications for planning clinical trials with pharmacological doses of lycopene in cancer control and prevention, This information will be useful to carotenoid scientists and health practitioners.

Technical Abstract: A physiological compartmental model was developed to describe the metabolism of lycopene, delivered as a tomato beverage formulation at 5 graded doses (10, 30, 60, 90 or 120 mg), for a Phase I pharmacokinetic study in healthy male subjects (5 per dose). Blood was collected before dose administration (0 hour) and at scheduled intervals until 672 hours. Serum concentrations of carotenoids and vitamins were measured by HPLC analysis. The model was comprised of 7 compartments: gastrointestinal tract, enterocytes, chylomicrons, plasma lipoproteins, liver, extra hepatic tissue and a delay compartment before the enterocytes. The predicted % absorption at the 10 mg dose (33.9 + 8.1 %) was significantly greater than at the higher doses, however, the amount of lycopene absorbed (mg) was similar (mean: 4.69 + 0.55 mg) at all 5 doses, suggesting saturation of absorptive mechanisms. The extra-hepatic tissue compartment served as a slow depleting reservoir for lycopene and the liver represented the fast turnover pool. Independent of dose, 80% of the subjects absorbed less than 6 mg of lycopene. This may have important implications for planning clinical trials with pharmacological doses of lycopene in cancer control and prevention, if absorption saturation occurs at levels that are being consumed in the population.