Vitamin A supplementation increases levels of retinoic acid compounds in human plasma: possible implications for teratogenesis


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 to check access.


  1. Anonymous (1987) Teratology society position paper: recommendations for vitamin A use during pregnancy. Teratology 35: 269–275

    Google Scholar 

  2. Brazzell RK, Vane FM, Ehmann CW, Colburn WA (1983) Pharmacokinetics of isotretinoin during repetitive dosing to patients. Eur J Clin Pharmacol 24: 695–702

    Google Scholar 

  3. 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

    Google Scholar 

  4. 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)

  5. 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

    Google Scholar 

  6. Geelen JAG (1979) Hypervitaminosis A induced teratogenesis. CRC Crit Rev Toxicol 6: 351–375

    Google Scholar 

  7. Giguere V, Ong ES, Segui P, Evans RM (1987) Identification of a receptor for the morphogen retinoic acid. Nature 330: 624–629

    Google Scholar 

  8. Giudicelli JF, Tillement JP (1977) Influence of sex on drug kinetics in man. Clin Pharmacokinet 2: 157–166

    Google Scholar 

  9. 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

    Google Scholar 

  10. 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

    Google Scholar 

  11. Lucek RW, Colburn WA (1985) Clinical pharmacokinetics of the retinoids. Clin Pharmacokinet 10: 38–62

    Google Scholar 

  12. 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

    Google Scholar 

  13. Rosa FW, Wilk AL, Kelsey FO (1986) Teratogen update: vitamin A congeners. Teratology 33: 355–364

    Google Scholar 

  14. Slavkin HC (1986) Editorial: vitamins acting as hormones during craniofacial morphogenesis? J Craniofac Genet 6: 95–97

    Google Scholar 

Download references

Author information



Corresponding author

Correspondence to H. Nau.

Additional information

The term vitamin A is used for retinol or retinyl esters

Rights and permissions

Reprints 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).

Download citation

Key words

  • Retinol
  • Retinoic acid
  • Isotretinoin
  • Teratogenic risk of vitamin A