PERICONCEPTIONAL VITAMIN-A USE - HOW MUCH IS TERATOGENIC

The objective of the review is to determine whether preformed vitamin A (retinol and retinyl esters) is teratogenic at dosages commonly used by women living in industrialized countries, Published human and anim al data and research developed by the authors are reviewed, It is well known that vitamin A is essential for normal reproduction and develop ment, Although doses of 10,000 IU/d or less of preformed vitamin A (re tinyl esters and retinol) are considered safe, doses >10,000 IU/d as s upplements have been reported to cause malformations in a single epide miologic study, Nonhuman primate data show no teratogenicity at doses of 30,000 IU/d. Daily periconceptional exposures greater than 25,000 I U/d of preformed vitamin A have not been sufficiently studied to estab lish specific risk, Because no study reports adverse effects of 10,000 IU/d preformed vitamin A supplements and this dose is more than the R ecommended Dietary Allowance for pregnant women (2670 IU or 800 RE/d), we recommend that women living in industrialized countries or who oth erwise have nutritionally adequate diets may not need to ingest more t han the Recommended Dietary Allowance of preformed vitamin A as supple ments, If periconceptional vitamin A exposures to levels up to 30,000 IU/d (9,000 mu g RE/d) do occur unintentionally, multiple animal studi es do support only very low risk, Human epidemiologic studies do not e stablish at what level vitamin A becomes teratogenic; however, pharmac okinetic data presented in this paper indicate that blood levels of re tinoids from women taking 30,000 IU/d of preformed vitamin A are not g reater than retinoid blood levels in pregnant women during the first t rimester who delivered healthy babies, Interestingly, neither teratoge nicity nor vitamin A toxicity has been observed in multiple species ex posed to high doses of beta-carotene. (C) 1998 Elsevier Science Inc.