Abstract
The concentrations of retinoic acid compounds were monitored by a newly developed highly sensitive HPLC procedure in plasma of six volunteers who received 833 IU vitamin A per kg body weight per day during a 20-day period. There was a significant increase of alltrans-retinoic acid (two-fold), 13-cis-retinoic acid (7-fold) and 13-cis-4-oxoretinoic acid (5-fold) over endogenous plasma levels of these retinoids. The same compounds had previously been found after treatment with the teratogenic drug isotretinoin (Roaccutan, Accutane). Our results raise the possibility that high vitamin A intake may carry a teratogenic risk attributable to increased levels of retinoic acid compounds generated from retinol by metabolic processes.
This is a preview of subscription content, log in via an institution to check access.
References
Anonymous (1987) Teratology society position paper: recommendations for vitamin A use during pregnancy. Teratology 35: 269–275
Brazzell RK, Vane FM, Ehmann CW, Colburn WA (1983) Pharmacokinetics of isotretinoin during repetitive dosing to patients. Eur J Clin Pharmacol 24: 695–702
Buggé CJL, Rodriguez LC, Vane FM (1985) Determination of isotretinoin or etretinate and their major metabolites in human blood by reversed-phase high-performance liquid chromatography. J Pharm Biomed Anal 3: 269–277
Eckhoff C, Nau H (1990) Identification and quantitation of all-trans-, 13-cis-4-oxo-retionic acid in human plasma. J Lipid Res (in press)
Eckhoff C, Löfberg B, Chahoud I, Bochert G, Nau H (1989) Transplacental pharmacokinetics and teratogenicity of a single dose of retinol (vitamin A) during organogenesis in the mouse. Toxicol Lett 48: 171–184
Geelen JAG (1979) Hypervitaminosis A induced teratogenesis. CRC Crit Rev Toxicol 6: 351–375
Giguere V, Ong ES, Segui P, Evans RM (1987) Identification of a receptor for the morphogen retinoic acid. Nature 330: 624–629
Giudicelli JF, Tillement JP (1977) Influence of sex on drug kinetics in man. Clin Pharmacokinet 2: 157–166
Kochhar DM, Penner JD, Satre MA (1988) Derivation of retinoic acid and metabolites from a teratogenic dose of retinol (vitamin A) in mice. Toxicol Appl Pharmacol 96: 429–441
Lammer EJ, Chen DT, Hoar RM, Agnish ND, Benke PJ, Braun JT, Curry CJ, Fernhoff PM, Grix AW, Lott IT, Richard JM, Sun SS (1985) Retinoic acid embryopathy. N Engl J Med 313: 837–841
Lucek RW, Colburn WA (1985) Clinical pharmacokinetics of the retinoids. Clin Pharmacokinet 10: 38–62
Nau H, Mirkin BL (1987) Fetal and maternal pharmacology. In: Speight TM (ed) Avery's drug treatment: principals and practice of clinical pharmacology and therapeutics, 3rd edition. ADIS Press, Auckland, New Zealand, chapter III pp 79–117
Rosa FW, Wilk AL, Kelsey FO (1986) Teratogen update: vitamin A congeners. Teratology 33: 355–364
Slavkin HC (1986) Editorial: vitamins acting as hormones during craniofacial morphogenesis? J Craniofac Genet 6: 95–97
Author information
Authors and Affiliations
Additional information
The term vitamin A is used for retinol or retinyl esters
Rights and permissions
About this article
Cite this article
Eckhoff, C., Nau, H. Vitamin A supplementation increases levels of retinoic acid compounds in human plasma: possible implications for teratogenesis. Arch Toxicol 64, 502–503 (1990). https://doi.org/10.1007/BF01977634
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01977634