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The relatively constant carotenoid composition ofleaves in higher plants suggests Arabidopsis leaves could model interactions of P-carotene and lutein ingested in vegetable leaves. We compared liver vitamin A stores in gerbils fed P-carotene in lutein-free (lut2) mutant or wild-type (WT) Arabidopsis leaves. Gerbils were fed a vitamin A-free diet for 4 weeks. They were then fed one of 4 diets for 6 weeks: 1) vitamin A-free diet (n = 8); 2) vitamin A-free diet supplemented with purified P-carotene (22.0 nmol P-carotene/g diet; n = 8); 3) vitamin A-free diet supplemented with /ut2 leaves (61.3 nmol P-carotene/g diet; n = 3); or 4) vitamin A-free diet supplemented with WT leaves (69.1 nmol P-carotene/g diet; n = 3). There were no group differences in body or liver weights. Liver vitamin A stores were 48% higher in gerbils fed /ut2 leaves (2.94 ± 0.14 μmol) than in those fed WT leaves (1.99 ± 0.10 μmol; P = 0.005). Liver vitamin A stores were higher in gerbils fed purified P-carotene (3.80 ± 0.27 μmol) than in those fed WT leaves (P = 0.003) or vitamin A-free diet (0.45 ± 0.08 μmol; P < 0.001). The difference in liver vitamin A stores in gerbils fed purified P-carotene or lut2 leaves was not statistically significant. Although our finding may not extrapolate to humans, for the first time, we have shown carotenoid-carotenoid interactions when ingested within a plant matrix. GENERAL INTRODUCTION Thesis organization There are three chapters in this thesis. The first chapter gives a general background on the protective associations between P-carotene and chronic diseases, as well as between vitamin A and diseases. There is also a review of the low bioavailability of P-carotene in plant matrices and the factors that may affect the bioavailability of P-carotene, particularly, the inhibitory effect of lutein on utilization of P-carotene ingested from dark green leafy vegetables. The lutein-deficient mutant of Arabidopsis plant is addressed. The relative merits of different animal models of human P-carotene metabolism are also discussed in this chapter. The second chapter is a manuscript to be submitted for publication in the journal Nature. It describes an animal study using the Mongolian gerbil (Meriones unguiculatus) as a model and Arabidopsis wild-type (WT) and lutein-deficient lut2 leaves to model interactions of P-carotene and lutein ingested in dark green leafy vegetable leaves. The findings and significance of this study are described in detail. The third chapter gives the general conclusions derived from the study. 1

Bioefficacy of beta-carotene in lutein-free lut2 leaves compared with wild-type Arabidopsis leaves fed to gerbils