Exposure to Retinoic Acids in Non-Pregnant Women Following High Vitamin A Intake with a Liver Meal

Author:

Hartmann 1,Brørs 2,Bock 3,Blomhoff 4,Bausch 1,Wiegand 3,Hartmann 3,Hornig 1

Affiliation:

1. DSM Nutritional Products Ltd., Basel, Switzerland

2. The Department of Clinical Chemistry, Ullevål University Hospital, Oslo, Norway

3. The Pharmaceutical Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland

4. Institute for Nutrition Research, University of Oslo, Oslo, Norway

Abstract

Animal liver is a rich source of vitamin A. Due to retinoic acid (RA) metabolites, vitamin A has a teratogenic potential and women are generally advised to avoid or to limit the consumption of liver during pregnancy. In a recent study in non-pregnant female volunteers following single and repeated doses of up to 30,000 IU/day of vitamin A as a supplement, the plasma concentration time curve of all-trans RA acid showed a diurnal-like profile. But, the overall exposure (AUC24h) remained essentially unaltered whereas AUC24h increased linearly with dose for 13-cis and 13-cis-4-oxo RA. The current study in non-pregnant female volunteers showed that a single high vitamin A intake with a liver meal (up to 120,000 IU) exhibited a similar diurnal-like plasma concentration time curve for all-trans RA and its overall exposure remained also unaltered, despite a temporary two-fold increase in peak plasma concentration. Concentrations of 13-cis and 13-cis-4-oxo RA increased several-fold after a liver meal, and exposure (AUC24h) increased three- to five-fold. Pooling our results with data in the literature revealed a linear relation between the mean AUC24h of 13-cis and 13-cis-4-oxo RA and vitamin A intake with liver. Metabolism to all-trans RA of vitamin A with liver seems not to be of safety concern. However, the observed increase of plasma concentrations and the dose-dependent increase in exposure to 13-cis and 13-cis-4-oxo RA support the current safety recommendations on vitamin A intake and suggest that women should be cautious regarding their consumption of liver-containing meals during pregnancy.

Publisher

Hogrefe Publishing Group

Subject

Nutrition and Dietetics,General Medicine,Endocrinology, Diabetes and Metabolism,Medicine (miscellaneous)

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1. Preparatory work for the update of the tolerable upper intake levels for vitamin A;EFSA Supporting Publications;2024-02

2. Vitamin A and Pregnancy: A Narrative Review;Nutrients;2019-03-22

3. Micronutrient supplementation in pregnancy: Who, what and how much?;Obstetric Medicine;2018-05-04

4. Before life begins;Nutrition, health and disease;2015-10-02

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