Overlapping Vitamin A Interventions with Provitamin A Carotenoids and Preformed Vitamin A Cause Excessive Liver Retinol Stores in Male Mongolian Gerbils

Background: Vitamin A NA) deficiency is a public health problem in some countries. Fortification, supplementation, and increased provitamin A consumption through biofortification are efficacious, but monitoring is needed due to risk of excessive VA intake when interventions overlap. Objectives: Two studies in 28-36-d-old male Mongolian gerbils simulated exposure to multiple VA interventions to determine the effects of provitamin A carotenoid consumption from biofortified maize and carrots and preformed VA fortificant on status. Methods: Study 1 was a 2 x 2 x 2 factorial design (n = 85) with high-beta-carotene maize, orange carrots, and VA fortification at 50% estimated gerbil needs, compared with white maize and white carrot controls. Study 2 was a 2 x 3 factorial design (n = 66) evaluating orange carrot and VA consumption through fortification at 100% and 200% estimated needs. Both studies utilized 2-wk VA depletion, baseline evaluation, 9-wk treatments, and liver VA stores by HPLC. Intestinal scavenger receptor class B member 1 (Scarb1), beta-carotene 15,15'-dioxygenase (Bco1), beta-carotene 9',10'-oxygenase (Bco2), intestine-specific homeobox (lsx), and cytochrome P450 26A1 isoform al (Cyp26a1) expression was analyzed by qRT-PCR in study 2. Results: In study 1, liver VA concentrations were significantly higher in orange carrot (0.69 +/- 0.12 mu mol/g) and orange maize groups (0.52 +/- 0.21 mu mol/g) compared with baseline (0.23 +/- 0.069 mu mol/g) and controls. Liver VA concentrations from VA fortificant alone (0.11 +/- 0.053 mu mol/g) did not differ from negative control. In study 2, orange carrot significantly enhanced liver VA concentrations (0.85 +/- 0.24 mu mol/g) relative to baseline (0.43 +/- 0.14 mu mol/g), but VA fortificant alone (0.42 +/- 0.21 mu mol/g) did not. Intestinal Scarb1 and Bco1 were negatively correlated with increasing liver VA concentrations IP < 0.01, r(2) = 0.25-0.27). Serum retinol concentrations did not differ. Conclusions: Biofortified carrots and maize without fortification prevented VA deficiency in gerbils. During adequate provitamin A dietary intake, preformed VA intake resulted in excessive liver stores in gerbils, despite downregulation of carotenoid absorption and cleavage gene expression.