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Porcine Intestinal Metabolism of Excess Vitamin A Differs Following Vitamin A Supplementation and Liver Consumption

Department of Food Toxicology, School of Veterinary Medicine Hannover, D-30173 Hannover, Germany and ^* Center of Anatomy, Medical School Hannover, D-30623 Hannover, Germany

¹To whom correspondence should be addressed. E-mail: thomas.arnhold{at}bc.boehringer-ingelheim.com.

Vitamin A is a well-established teratogen in all animal species. A number of case reports also suggest a teratogenic potential of vitamin A in humans. A possible teratogenic risk of dietary liver vitamin A intake, the kinetics of vitamin A and its metabolites in humans after intake of either a vitamin A supplement or a liver meal have been studied. Major differences were described for the kinetics of all-trans-retinoic acid (all-trans-RA), which occurred at much higher concentrations after supplementation than after liver consumption. Therefore, we investigated whether the intestine may be responsible for the differences in vitamin A metabolism after supplementation or liver feeding. We found that cytosolic fractions of porcine enterocytes oxidized retinol to all-trans-RA in vitro with a K_m of 94–96 µmol/L and a V_max of 7.9–8.6 pmol/(min · mg protein). In an in vivo approach, the portal vein and the central vein (external jugular vein) of a pig were cannulated. In two subsequent experiments, the pig was given a vitamin A supplement or liver. Plasma samples were taken from portal and central veins. Comparison of retinoid levels in these veins indicated that all-trans-RA was already formed from supplemental vitamin A in the intestine and released into the systemic circulation. Two major metabolic pathways were additionally present in the pig, leading to the formation of glucuronides of all-trans-RA and retinol itself. Our results indicate that intestinal metabolism contributes to the elevated levels of all-trans-RA in the systemic circulation after supplementation with vitamin A, but not after consumption of liver.

KEY WORDS: • retinol • retinoic acid • vitamin A • liver • supplementation • intestine • metabolism

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