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This review aims to evaluate the necessity of mandatory folic acid fortification in preventing neural tube defects, highlighting uncertainties and implications.

June 3, 2026Open Access

Reassessing Mandatory Folic Acid Fortification for Neural Tube Defect Prevention: Evidence, Uncertainty, and Policy Implications

Key Points

This review aims to evaluate the necessity of mandatory folic acid fortification in preventing neural tube defects, highlighting uncertainties and implications.
Literature identified via PubMed using keywords like 'fortification' and 'folic acid'.
Focus on three relevant studies published early in 2026.
Critical evaluation of existing evidence regarding fortification and supplementation effects.
Previous studies inadequately account for socioeconomic changes affecting NTD rates.
Improved socioeconomic conditions correlate with decreased NTDs regardless of fortification.
Efficacy of folic acid supplementation is supported, but mandatory fortification evidence remains limited.

Abstract

Background/Objectives: Folate is a water-soluble B vitamin that is essential for DNA synthesis, cell division and proper growth and development, particularly during pregnancy to prevent neural tube defects (NTDs). A large, fully randomized clinical trial (RCT) from the United Kingdom in 1991 (the Medical Research Council (MRC) Vitamin Study), where participants had a prior NTD-affected pregnancy, demonstrated a 72% reduction in NTD recurrence in the folic acid treatment group. Based on this data and the high rate of unplanned pregnancies, about 90 countries fortify cereal grains with folic acid with the goal to prevent NTDs during pregnancy. This critical narrative review and policy perspective addresses the difference between folate and folic acid and between supplementation and food fortification, critically evaluates the data in three recent publications supporting mandatory fortification of food products with folic acid, and presents the case for a more personalized medicine approach to the prevention of NTDs. Methods: Relevant literature was identified through PubMed searches using the keywords “fortification”, “folic acid”, and “systematic review” or by Googe Scholar Alerts. Three studies were identified based on relevance to the topic and publication dates between January and February of 2026. Results: There is a disregard in published studies, which use pre-fortification groups as controls, for the confounding issue of changing socioeconomic factors over time. Improved socioeconomic conditions are associated with subsequent decreases in NTD prevalence regardless of fortification. Conclusions: The efficacy of folic acid supplementation for recurrent NTDs is supported by evidence-based literature, but evidence in favor of mandatory food fortification to prevent NTDs is limited. Food fortification is widely debated, raises numerous ethical issues, and has broad implications for human health.

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