Exposure to retinoic acids in non-pregnant women following high vitamin A intake with a liver meal

Int J Vitam Nutr Res. 2005 May;75(3):187-94. doi: 10.1024/0300-9831.75.3.187.

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Cattle
  • Diterpenes
  • Female
  • Humans
  • Kinetics
  • Liver*
  • Meat*
  • Retinyl Esters
  • Tretinoin / administration & dosage*
  • Tretinoin / blood
  • Tretinoin / pharmacokinetics
  • Vitamin A / administration & dosage*
  • Vitamin A / analogs & derivatives
  • Vitamin A / blood
  • Vitamin A / pharmacokinetics

Substances

  • Diterpenes
  • Retinyl Esters
  • Vitamin A
  • retinol palmitate
  • Tretinoin