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Ann Nutr Metab. 2005 May-Jun;49(3):155-64. Epub 2005 Jul 7.

Exposure to retinyl esters, retinol, and retinoic acids in non-pregnant women following increasing single and repeated oral doses of vitamin A.

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  • 1Roche Vitamins Ltd, Basel, Switzerland.

Abstract

BACKGROUND:

High intakes of vitamin A cause congenital malformations in experimental animals with elevated generation of retinoic acids (RA). Results in humans are conflicting.

OBJECTIVE:

To evaluate plasma concentration-time curves of retinyl esters, retinol and their metabolites at increasing doses of vitamin A.

METHODS:

An open-label dose-response study. Non-pregnant females (3 groups with n = 12; 18-40 years) received once daily oral doses of vitamin A palmitate up to 30,000 IU/day over 21 days. The area under the plasma concentration-time curve (AUC(24h)) served as indicator for exposure.

RESULTS:

AUC(24h) of retinyl esters increased linearly with dose. Retinol concentrations were unaffected. All-trans RA exhibited a diurnal-like concentration-time profile (Cmax at 3 h; Cmin at 8 h), concentrations decreasing below pre-dose levels at 5 h and regaining pre-dose levels at 16 h. The maximum temporary increase in exposure was 33% (single dose) and 19% (repeated doses) above baseline, but AUC(24h) remained unaltered. AUC(24h) increased linearly with dose for 13-cis RA and 13-cis-4-oxo RA. Repeated doses caused a 25% increase in exposure with the highest vitamin A intake. Accumulation of 13-cis-4-oxo RA at 30,000 IU/day doubled compared to the 4,000 IU/day intake.

CONCLUSION:

Repeated oral doses of up to 30,000 IU of vitamin A in addition to dietary vitamin A were without safety concern. Safe doses are probably higher, since plasma concentrations and exposure to RA remained at levels earlier shown to be without increased risk of teratogenicity in pregnant women.

2005 S. Karger AG, Basel

PMID:
16006784
[PubMed - indexed for MEDLINE]
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