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Date of issue: January 2023, Version: 2.0

Note: This monograph should be read in conjunction with the monograph on use of folic acid in pregnancy.

SUMMARY: Methylfolate (L-methylfolate) is the biologically active form of folate which, unlike folic acid, does not require enzymatic reduction by methylenetetrahydrofolate reductase (MTHFR). It is not a licensed medication and there is limited evidence available relating to efficacy or safety.

UKTIS has received a number of enquiries about whether routine use of methylfolate offers a superior alternative to use of folic acid in pregnancy, on the basis that conversion in the body to the biologically active form is not required. However, to date, no studies have addressed rates of neural tube and other birth defects in infants born to women taking methylfolate in pregnancy, while the population-wide data on the beneficial effects of folic acid are unequivocal.

Routine use of prenatal methylfolate in preference to folic acid cannot currently be recommended. In the UK, current guidelines recommend routine use of 400mcg/day of folic acid preconceptually and until at least 12 weeks of gestation. In women considered to be at increased risk of folate deficiency (family history of neural tube defect, concurrent treatment with drugs which interfere with folate metabolism, or maternal obesity), higher dose folic acid (5mg/day) is recommended. Methylfolate supplementation may, however, be advised in individual cases e.g., women with specific metabolic disorders, where benefit of use is likely to outweigh any theoretical or known risks to mother or fetus.

Exposure to methylfolate at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy or any additional fetal monitoring. However, other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.

This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to NHS health care professionals who are logged in.

If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.

If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.

Disclaimer: Every effort has been made to ensure that this monograph was accurate and up-to-date at the time of writing, however it cannot cover every eventuality and the information providers cannot be held responsible for any adverse outcomes of the measures recommended. The final decision regarding which treatment is used for an individual patient remains the clinical responsibility of the prescriber. This material may be freely reproduced for education and not for profit purposes within the UK National Health Service, however no linking to this website or reproduction by or for commercial organisations is permitted without the express written permission of this service. This document is regularly reviewed and updated. Only use UKTIS monographs downloaded directly from to ensure you are using the most up-to-date version.