Periconceptional vitamin a use: How much is teratogenic?

Richard K. Miller, Andrew G Hendrickx, James L. Mills, Hans Hummler, Ulf W. Wiegand

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

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 animal data and research developed by the authors are reviewed. It is well known that vitamin A is essential for normal reproduction and development. Although doses of 10,000 IU/d or less of preformed vitamin A (retinyl esters and retinol) are considered safe, doses >10,000 IU/d as supplements have been reported to cause malformations in a single epidemiologic study. Nonhuman primate data show no teratogenicity at doses of 30,000 IU/d. Daily periconceptional exposures greater than 25,000 IU/d of preformed vitamin A have not been sufficiently studied to establish specific risk. Because no study reports adverse effects of 10,000 IU/d preformed vitamin A supplements and this dose is more than the Recommended Dietary Allowance for pregnant women (2670 IU or 800 RE/d), we recommend that women living in industrialized countries or who otherwise have nutritionally adequate diets may not need to ingest more than the Recommended Dietary Allowance of preformed vitamin A as supplements. If periconceptional vitamin A exposures to levels up to 30,000 IU/d (9,000 μg RE/d) do occur unintentionally, multiple animal studies do support only very low risk. Human epidemiologic studies do not establish at what level vitamin A becomes teratogenic; however, pharmacokinetic data presented in this paper indicate that blood levels of retinoids from women taking 30,000 IU/d of preformed vitamin A are not greater than retinoid blood levels in pregnant women during the first trimester who delivered healthy babies. Interestingly, neither teratogenicity nor vitamin A toxicity has been observed in multiple species exposed to high doses of β-carotene.

Original languageEnglish (US)
Pages (from-to)75-88
Number of pages14
JournalReproductive Toxicology
Volume12
Issue number1
DOIs
StatePublished - 1998

Fingerprint

Vitamin A
Vitamins
Recommended Dietary Allowances
Retinoids
Developed Countries
Pregnant Women
Epidemiologic Studies
Esters
Animals
Blood
Pharmacokinetics
First Pregnancy Trimester
Carotenoids
Nutrition
Primates
Reproduction
Toxicity
Diet

Keywords

  • Periconceptional vitamin A use
  • Retinol
  • Retinyl esters
  • Tetratogenicity

ASJC Scopus subject areas

  • Toxicology

Cite this

Miller, R. K., Hendrickx, A. G., Mills, J. L., Hummler, H., & Wiegand, U. W. (1998). Periconceptional vitamin a use: How much is teratogenic? Reproductive Toxicology, 12(1), 75-88. https://doi.org/10.1016/S0890-6238(97)00102-0

Periconceptional vitamin a use : How much is teratogenic? / Miller, Richard K.; Hendrickx, Andrew G; Mills, James L.; Hummler, Hans; Wiegand, Ulf W.

In: Reproductive Toxicology, Vol. 12, No. 1, 1998, p. 75-88.

Research output: Contribution to journalArticle

Miller, RK, Hendrickx, AG, Mills, JL, Hummler, H & Wiegand, UW 1998, 'Periconceptional vitamin a use: How much is teratogenic?', Reproductive Toxicology, vol. 12, no. 1, pp. 75-88. https://doi.org/10.1016/S0890-6238(97)00102-0
Miller, Richard K. ; Hendrickx, Andrew G ; Mills, James L. ; Hummler, Hans ; Wiegand, Ulf W. / Periconceptional vitamin a use : How much is teratogenic?. In: Reproductive Toxicology. 1998 ; Vol. 12, No. 1. pp. 75-88.
@article{9812190a2516402d9ee0b11873636e0c,
title = "Periconceptional vitamin a use: How much is teratogenic?",
abstract = "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 animal data and research developed by the authors are reviewed. It is well known that vitamin A is essential for normal reproduction and development. Although doses of 10,000 IU/d or less of preformed vitamin A (retinyl esters and retinol) are considered safe, doses >10,000 IU/d as supplements have been reported to cause malformations in a single epidemiologic study. Nonhuman primate data show no teratogenicity at doses of 30,000 IU/d. Daily periconceptional exposures greater than 25,000 IU/d of preformed vitamin A have not been sufficiently studied to establish specific risk. Because no study reports adverse effects of 10,000 IU/d preformed vitamin A supplements and this dose is more than the Recommended Dietary Allowance for pregnant women (2670 IU or 800 RE/d), we recommend that women living in industrialized countries or who otherwise have nutritionally adequate diets may not need to ingest more than the Recommended Dietary Allowance of preformed vitamin A as supplements. If periconceptional vitamin A exposures to levels up to 30,000 IU/d (9,000 μg RE/d) do occur unintentionally, multiple animal studies do support only very low risk. Human epidemiologic studies do not establish at what level vitamin A becomes teratogenic; however, pharmacokinetic data presented in this paper indicate that blood levels of retinoids from women taking 30,000 IU/d of preformed vitamin A are not greater than retinoid blood levels in pregnant women during the first trimester who delivered healthy babies. Interestingly, neither teratogenicity nor vitamin A toxicity has been observed in multiple species exposed to high doses of β-carotene.",
keywords = "Periconceptional vitamin A use, Retinol, Retinyl esters, Tetratogenicity",
author = "Miller, {Richard K.} and Hendrickx, {Andrew G} and Mills, {James L.} and Hans Hummler and Wiegand, {Ulf W.}",
year = "1998",
doi = "10.1016/S0890-6238(97)00102-0",
language = "English (US)",
volume = "12",
pages = "75--88",
journal = "Reproductigve Toxicoloy",
issn = "0890-6238",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Periconceptional vitamin a use

T2 - How much is teratogenic?

AU - Miller, Richard K.

AU - Hendrickx, Andrew G

AU - Mills, James L.

AU - Hummler, Hans

AU - Wiegand, Ulf W.

PY - 1998

Y1 - 1998

N2 - 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 animal data and research developed by the authors are reviewed. It is well known that vitamin A is essential for normal reproduction and development. Although doses of 10,000 IU/d or less of preformed vitamin A (retinyl esters and retinol) are considered safe, doses >10,000 IU/d as supplements have been reported to cause malformations in a single epidemiologic study. Nonhuman primate data show no teratogenicity at doses of 30,000 IU/d. Daily periconceptional exposures greater than 25,000 IU/d of preformed vitamin A have not been sufficiently studied to establish specific risk. Because no study reports adverse effects of 10,000 IU/d preformed vitamin A supplements and this dose is more than the Recommended Dietary Allowance for pregnant women (2670 IU or 800 RE/d), we recommend that women living in industrialized countries or who otherwise have nutritionally adequate diets may not need to ingest more than the Recommended Dietary Allowance of preformed vitamin A as supplements. If periconceptional vitamin A exposures to levels up to 30,000 IU/d (9,000 μg RE/d) do occur unintentionally, multiple animal studies do support only very low risk. Human epidemiologic studies do not establish at what level vitamin A becomes teratogenic; however, pharmacokinetic data presented in this paper indicate that blood levels of retinoids from women taking 30,000 IU/d of preformed vitamin A are not greater than retinoid blood levels in pregnant women during the first trimester who delivered healthy babies. Interestingly, neither teratogenicity nor vitamin A toxicity has been observed in multiple species exposed to high doses of β-carotene.

AB - 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 animal data and research developed by the authors are reviewed. It is well known that vitamin A is essential for normal reproduction and development. Although doses of 10,000 IU/d or less of preformed vitamin A (retinyl esters and retinol) are considered safe, doses >10,000 IU/d as supplements have been reported to cause malformations in a single epidemiologic study. Nonhuman primate data show no teratogenicity at doses of 30,000 IU/d. Daily periconceptional exposures greater than 25,000 IU/d of preformed vitamin A have not been sufficiently studied to establish specific risk. Because no study reports adverse effects of 10,000 IU/d preformed vitamin A supplements and this dose is more than the Recommended Dietary Allowance for pregnant women (2670 IU or 800 RE/d), we recommend that women living in industrialized countries or who otherwise have nutritionally adequate diets may not need to ingest more than the Recommended Dietary Allowance of preformed vitamin A as supplements. If periconceptional vitamin A exposures to levels up to 30,000 IU/d (9,000 μg RE/d) do occur unintentionally, multiple animal studies do support only very low risk. Human epidemiologic studies do not establish at what level vitamin A becomes teratogenic; however, pharmacokinetic data presented in this paper indicate that blood levels of retinoids from women taking 30,000 IU/d of preformed vitamin A are not greater than retinoid blood levels in pregnant women during the first trimester who delivered healthy babies. Interestingly, neither teratogenicity nor vitamin A toxicity has been observed in multiple species exposed to high doses of β-carotene.

KW - Periconceptional vitamin A use

KW - Retinol

KW - Retinyl esters

KW - Tetratogenicity

UR - http://www.scopus.com/inward/record.url?scp=0031987260&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031987260&partnerID=8YFLogxK

U2 - 10.1016/S0890-6238(97)00102-0

DO - 10.1016/S0890-6238(97)00102-0

M3 - Article

C2 - 9431575

AN - SCOPUS:0031987260

VL - 12

SP - 75

EP - 88

JO - Reproductigve Toxicoloy

JF - Reproductigve Toxicoloy

SN - 0890-6238

IS - 1

ER -