Exposure to retinoic acids in non-pregnant women following high vitamin A intake with a liver meal.
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.
Hartmann
Stefan
S
DSM Nutritional Products Ltd., Basel, Switzerland.
Brørs
Odd
O
Bock
Jürgen
J
Blomhoff
Rune
R
Bausch
Jochen
J
Wiegand
Ulf W
UW
Hartmann
Dieter
D
Hornig
Dietrich H
DH
D000293:Adolescent; D000328:Adult; D000818:Animals; D002417:Cattle; D004224:Diterpenes; D005260:Female; D006801:Humans; D007700:Kinetics; D008099:Liver; D008460:Meat; D000084562:Retinyl Esters; D014212:Tretinoin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D014801:Vitamin A / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics
D004224:Diterpenes; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate; D014212:Tretinoin