Archives of Toxicology

, Volume 93, Issue 2, pp 227–251 | Cite as

Medicines associated with folate–homocysteine–methionine pathway disruption

  • M. Vidmar
  • J. Grželj
  • I. Mlinarič-Raščan
  • K. Geršak
  • M. Sollner DolencEmail author
Review Article


Folate is vital for cell development and growth. It is involved in one-carbon transfer reactions essential for the synthesis of purines and pyrimidines. It also acts in conjunction with cobalamin (vitamin B12) as a fundamental cofactor in the remethylation cycle that converts homocysteine to methionine. A deficiency in folate or vitamin B12 can lead to elevated homocysteine level, which has been identified as an independent risk factor in several health-related conditions. Adequate folate levels are essential in women of childbearing age and in pregnant women, and folate deficiency is associated with several congenital malformations. Low folate levels can be caused by dietary deficiencies, a genetic predisposition or treatment with medicines that affect folate concentration. Women who are pregnant or of child-bearing age commonly use medicines, so it is important to identify the basic biochemical mechanisms by which medicines interfere with the folate–homocysteine–methionine pathway. This review focuses on prescription medicines associated with folate disruption. It also summarizes their undesirable/toxic effects. Recommendations regarding folate supplementation during medical therapy are also reviewed.


Folate–homocysteine–methionine pathway Folate antagonism Anti-folates Folate supplementation Toxicity 



This work was supported by the Slovenian Research Agency Grant (no. P3-0124). We thank Tomaž Janez Bevec for proofreading the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • M. Vidmar
    • 1
    • 2
  • J. Grželj
    • 2
    • 3
  • I. Mlinarič-Raščan
    • 2
  • K. Geršak
    • 1
  • M. Sollner Dolenc
    • 2
    Email author
  1. 1.Research Unit, Department of Obstetrics and GynecologyUniversity Medical Centre LjubljanaLjubljanaSlovenia
  2. 2.University of Ljubljana, Faculty of PharmacyLjubljanaSlovenia
  3. 3.Krka, d.d., Novo mestoNovo mestoSlovenia

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