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Methodology and Mathematical Modeling

Kinetic Analysis Shows that Vitamin A Disposal Rate in Humans Is Positively Correlated with Vitamin A Stores^1,2

³ Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802; ⁴ National Institute for Nutrition and Food Safety, Chinese Centre for Disease Control and Prevention, Beijing, China 100050; ⁵ Institute of Medical Nutrition, Qingdao, China 266021; and ⁶ USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111

^* To whom correspondence should be addressed. E-mail: mhg{at}psu.edu.

Vitamin A (VA) kinetics, storage, and disposal rate were determined in well-nourished Chinese and U.S. adults using model-based compartmental analysis. [²H₈]Retinyl acetate (8.9 µmol) was orally administered to U.S. (n = 12; 59 ± 9 y; mean ± SD) and Chinese adults (n = 14; 54 ± 4 y) and serum tracer and VA concentrations were measured from 3 h to 56 d. Using the Windows version of the Simulation, Analysis and Modeling software, we determined that the average time from dosing until appearance of labeled retinol in serum was greater in U.S. subjects (40.6 ± 8.47 h) than in Chinese subjects (32.2 ± 5.84 h; P < 0.01). Model-predicted total traced mass (898 ± 637 vs. 237 ± 109 µmol), disposal rate (14.7 ± 5.87 vs. 5.58 ± 2.04 µmol/d), and system residence time (58.9 ± 28.7 vs. 42.9 ± 14.6 d) were greater in U.S. than in Chinese subjects (P < 0.05). The model-predicted VA mass and VA mass estimated by deuterated retinol dilution at 3 and 24 d did not differ. VA disposal rate was positively correlated with VA traced mass in Chinese (R² = 0.556), U.S. (R² = 0.579), and all subjects (R² = 0.808). Additionally, VA disposal rate was significantly correlated with serum retinol pool size (R² = 0.227) and retinol concentration (R² = 0.330) in all subjects. Our results support the hypothesis that VA stores are the principle determinant of VA disposal rate in healthy, well-nourished adults.

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