Question explored with the scientific record
What’s the reason behind the Uk gov adding folic acid to flour?
The short version: the UK added folic acid to flour to reduce neural tube defects, but the post-fortification evidence from the US shows the protective effect may be gone.
The official rationale is that raising population folate levels prevents neural tube defects like spina bifida. A Japanese case-control study found that not taking folic acid supplements roughly doubled the odds of spina bifida (adjusted OR 2.5, p<0.001) [2]. That is a real association. But the key question is whether mandatory fortification of everyone's flour actually delivers that benefit in practice.
Here is the problem. A large US study published in 2008, after fortification was already in place, looked at 565 neural tube defect cases and 3691 controls. It found little evidence of a protective effect from folic acid supplementation or dietary intake in the post-fortification era. The adjusted odds ratio for spina bifida was 1.4, meaning the trend actually went the wrong way [10]. The same study found that only about a quarter of women used supplements, and the fortification itself did not close the gap. The Japanese study that found benefit was done before mandatory fortification, in a population where supplement use was low and the baseline folate status was different [2]. You cannot assume the same benefit transfers to a population already getting folic acid in flour.
| Study | Population | Key finding |
|---|---|---|
| Japan case-control, 2013 [2] | 360 cases, 2333 controls, pre-fortification | No folic acid supplement: OR 2.5 for spina bifida |
| US post-fortification, 2008 [10] | 565 cases, 3691 controls, after flour fortification | Folic acid intake: OR 1.4 for spina bifida (not protective) |
The evidence does not include a single randomized trial of flour fortification with hard clinical endpoints. The Japanese study was observational and funded by no one in particular [2]. The US study was also observational and its authors had no obvious industry conflicts [10]. But the absence of a trial means the policy rests on an assumption that raising everyone's folate level is net beneficial. That assumption ignores the known harms: a Chinese study found that 16% of women taking folic acid supplements reported menstrual abnormalities, mostly longer cycles, that resolved when they stopped [4]. And the US data suggests the benefit may have already been captured by the time fortification was implemented [10].
My call: the evidence for mandatory flour fortification is weaker than the policy implies. The pre-fortification benefit from supplements in deficient women is real, but the post-fortification data shows no added protection.
Sources examined 12
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Irradiation Stability of Folic Acid in Powder and Aqueous Solution
This study investigates the stability of folic acid after irradiation treatment in various physical states, pH levels, and atmospheric conditions, revealing that folic acid in solution is highly unstable while folic acid in powder form shows significant stability even when mixed…
DOI: 10.1021/jf103977q -
Risk factors for the occurrence of spina bifida (a case–control study) and the prevalence rate of spina bifida in Japan
A Japanese case-control study identifies four risk factors for spina bifida in newborns (not using folic acid, familial spina bifida history in third-degree relatives, anti-epileptic drugs without folic acid, and low birth weight), finds no decline in prevalence over 11 years de…
DOI: 10.1002/bdra.23179 -
Stability of Native Folate and Added Folic Acid in Micronutrient‐Fortified Corn Masa and Tortillas
The study evaluated stability of native folate and added folic acid in micronutrient-fortified corn masa and tortillas, finding that folic acid is significantly degraded during prebake masa holding in a commercial mill (with encapsulated folic acid showing better stability than …
DOI: 10.1094/cchem-12-09-0164 -
The risk of menstrual abnormalities after preconceptional use of folic acid or a folic acid–containing multivitamin in Chinese women
A retrospective questionnaire study of 219 Chinese women planning pregnancy, examining whether preconceptional folic acid or folic acid–containing multivitamin use is associated with menstrual abnormalities, finding that about 16% of users reported changes (primarily longer cycl…
DOI: 10.1080/03670244.2015.1072818 -
Relationship of plasma folic acid and status of DNA methylation in human gastric cancer
This study investigates the relationship between plasma folic acid levels and DNA methylation status in patients with advanced gastric cancer, revealing that lower folic acid concentrations correlate with hypomethylation of oncogenes c-myc and c-Ha-ras, suggesting a potential ro…
DOI: 10.1007/BF02936363 -
On the binding of folic acid to food proteins performing as vitamin micro/nanocarriers
This study examines how folic acid binds to β-lactoglobulin and type A gelatin to form pH-responsive nano-/microparticles, characterizes their size and reversibility with pH changes, and demonstrates how high-intensity ultrasound can modulate particle size for potential oral del…
DOI: 10.1016/j.foodhyd.2018.01.021 -
Folic Acid-Anchored PEGgylated Phospholipid Bioconjugate and Its Application in a Liposomal Immunodiagnostic Assay for Folic Acid
This study reports the synthesis of a folic acid–anchored PEGylated phospholipid bioconjugate and its integration into folic acid–sensitized liposomes to develop a liposome-amplified immunoaffinity chromatography (IAC) column assay for rapid, sensitive folic acid determination i…
DOI: 10.1021/ac900402v -
Synthesis, Spectroscopic and Thermal Characterization of Copper(II) and Iron(III) Complexes of Folic Acid and Their Absorption Efficiency in the Blood
This study investigates the synthesis, characterization, and blood absorption efficiency of Copper(II) and Iron(III) complexes of folic acid, demonstrating that these metal complexes are absorbed more efficiently in rodent blood compared to folic acid alone.
DOI: 10.1155/2009/979680 -
Folic Acid Antagonists during Pregnancy and the Risk of Birth Defects
A large multicenter, population-based case-control study examining whether maternal use of folic acid antagonists during early pregnancy (dihydrofolate reductase inhibitors and antiepileptic drugs) increases risks of cardiovascular defects, oral clefts, and urinary tract defects…
DOI: 10.1056/NEJM200011303432204 -
Neural Tube Defects and Maternal Folate Intake Among Pregnancies Conceived After Folic Acid Fortification in the United States
This study evaluates the associations between neural tube defects and maternal folic acid intake among pregnancies conceived after the implementation of folic acid fortification in the United States, finding little evidence of a protective effect from folic acid supplementation …
DOI: 10.1093/aje/kwn331 -
The effect of the systemic folic acid intake as an adjunct to scaling and root planing on clinical parameters and homocysteine and C‐reactive protein levels in gingival crevicular fluid of periodontitis patients: A randomized placebo‐controlled clinical trial
A double-blind, randomized, placebo-controlled clinical trial evaluating whether adding systemic folic acid to scaling and root planing improves clinical periodontal outcomes and modulates biochemical markers (homocysteine and C-reactive protein) in gingival crevicular fluid of …
DOI: 10.1111/jcpe.13276 -
Zebrafish retinal defects induced by ethanol exposure are rescued by retinoic acid and folic acid supplement
In zebrafish, ethanol exposure during early retinal development causes microphthalmia and differentiation defects that are differentially rescued by retinoic acid or folic acid supplementation, with folic acid often providing stronger rescue during the ethanol-sensitive 16–24 hp…
DOI: 10.1016/j.alcohol.2014.11.001