[Show abstract][Hide abstract] ABSTRACT: Vitamin A is widely used in cosmetic preparations. Given that oral Vitamin A and its metabolites present a potential reproductive risk, the present study investigated the effect of topical Vitamin A on human endogenous plasma levels of Vitamin A and its metabolites.
Two groups of 14 female volunteers of child-bearing age were kept on a Vitamin A-poor diet and treated topically for 21 days with creams containing 0.30% retinol or 0.55% retinyl palmitate on approximately 3000 cm2 of their body surface area, amounting to a total of approximately 30,000 IU Vitamin A/subject/day. After a 12-day wash-out period, the study groups received single oral doses of 10,000 IU or 30,000 IU retinyl palmitate (RP), corresponding to the maximal EU allowance during pregnancy or three-times higher, respectively. Blood samples were collected over 24h on study days -3 (pre-study), 1, 21 (first and last days of topical treatment) and 34 (oral administration) at 0, 1, 2, 4, 6, 8, 12, 14-16 h and 24 h after treatment for determination of plasma concentrations of retinol (REL), retinyl palmitate (RP), oleate (RO) and stearate (RS), 9-cis-, 13-cis-, all-trans- (AT), 13-cis-4-oxo- or AT-4-oxo-retinoic acids (RAs).
With the exception of transient mild (RP-group) to moderate (REL-group) local irritation on the treatment sites, no adverse local or systemic effects were noted. On days 1 or 21 of topical treatment, no changes were measured in individual or group mean plasma Cmax, AUC0-24 h or other pharmacokinetic parameters of REL, retinyl esters or RAs relative to pre-study data. In contrast, single oral doses of RP at 10,000 IU or 30,000 IU produced dose-related and sustained increases in Cmax and AUC0-24 h values of plasma RP, RO, RS, 13-cis- and 13-cis-4-oxo-RAs, as well as a transient increase in AT-RA. In conclusion, our results provide evidence that human topical exposure to retinol- or retinyl ester-containing cosmetic creams at 30,000 IU/day and maximal use concentrations do not affect plasma levels of retinol, retinyl esters or RAs, whereas single oral doses at 10,000 IU or 30,000 IU produce significant increases in plasma retinyl esters and RAs.
[Show abstract][Hide abstract] 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.
International Journal for Vitamin and Nutrition Research 06/2005; 75(3):187-94. · 1.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: High intakes of vitamin A cause congenital malformations in experimental animals with elevated generation of retinoic acids (RA). Results in humans are conflicting.
To evaluate plasma concentration-time curves of retinyl esters, retinol and their metabolites at increasing doses of vitamin A.
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.
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.
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.
Annals of Nutrition and Metabolism 01/2005; 49(3):155-64. · 1.66 Impact Factor