Follow-up to: What’s the reason behind the Uk gov adding folic acid to flour?
Question explored with the scientific record
Could the levels mandated be harmful?
The short version: yes, the mandated levels can be harmful, and the evidence shows real risks that the policy discussion mostly ignores.
The strongest signal comes from a 2025 Australian study comparing two large cohorts before and after mandatory fortification. After fortification, median red-cell folate nearly tripled (from 561 to 1490 nmol/L) and the gestational diabetes rate tripled from 5.0% to 15.2% [3]. Women with the highest folate levels had an 18.5% GDM rate versus 12.5% at normal levels. The study also found elevated placental hormones, a plausible mechanism [3].
The B12 masking concern is not theoretical. A US study found that after fortification, the proportion of people with low B12 but no macrocytosis (the red-cell enlargement that normally flags deficiency) rose from 70% to 87% [4]. That means more B12 deficiency goes undetected, and untreated B12 deficiency causes permanent nerve damage.
The cancer signal is worth attention. In the Aspirin/Folate Polyp Prevention Study, folic acid supplementation did not reduce colorectal adenomas but increased advanced lesions (RR 1.67) and multiple adenomas (RR 2.32) [8]. The authors noted a significant increase in non-colorectal cancers. This fits the known biology: folate can feed existing precancerous cells.
| Outcome | Pre-fortification | Post-fortification | Change |
|---|---|---|---|
| Gestational diabetes (Australia) [3] | 5.0% | 15.2% | 3x higher |
| Low B12 without macrocytosis (US) [4] | 70% | 87% | +17 percentage points |
| Median red-cell folate (Australia) [3] | 561 nmol/L | 1490 nmol/L | 2.7x higher |
The cardiovascular meta-analysis of 26 RCTs found no benefit for heart disease or mortality, and the stroke reduction was only in regions without fortification [12]. In fortified populations, even that modest effect disappeared.
My call: the mandated levels produce supraphysiological folate exposures that carry documented risks for gestational diabetes, B12 masking, and potentially cancer promotion, with no demonstrated cardiovascular benefit in fortified populations.
Sources examined 12
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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 -
Infant mortality associated with spina bifida: A systematic review and meta-analysis
A comprehensive systematic review and meta-analysis assessing infant mortality associated with spina bifida across high-income countries, identifying key predictors and showing mortality declines in settings with mandatory folic acid fortification.
DOI: 10.1016/j.ejmg.2018.06.059 -
Maternal Folate Excess, Placental Hormones, and Gestational Diabetes Mellitus: Findings from Prospective Cohorts Before and After Mandatory Folic Acid Food Fortification
In two prospective Australian cohorts spanning before and after mandatory folic acid fortification, the study links maternal folate excess to higher folate status, elevated placental hormones, and a tripling of gestational diabetes risk, suggesting a placental mechanism connecti…
DOI: 10.3390/nu17172863 -
Proportion of individuals with low serum vitamin B-12 concentrations without macrocytosis is higher in the post–folic acid fortification period than in the pre–folic acid fortification period
This study investigates the increase in the proportion of individuals with low serum vitamin B-12 concentrations without macrocytosis following the mandatory folic acid fortification in the United States, revealing a significant rise in such cases post-fortification compared to …
DOI: 10.1093/ajcn/86.4.1187 -
Biochemical indicators of B vitamin status in the US population after folic acid fortification: results from the National Health and Nutrition Examination Survey 1999–2000
This study evaluates the impact of mandatory folic acid fortification on B vitamin status indicators in the US population, revealing significant improvements in serum and red blood cell folate levels and a decrease in the prevalence of low folate concentrations post-fortificatio…
DOI: 10.1093/ajcn/82.2.442 -
Case for Folic Acid and Vitamin B 12 Fortification in Europe
This review advocates for the mandatory fortification of folic acid and vitamin B12 in Europe to effectively reduce the incidence of neural tube defects, highlighting the inadequacy of current dietary recommendations and voluntary fortification efforts.
DOI: 10.1055/s-2005-872400 -
Unmetabolized folic acid prevalence is widespread in the older Irish population despite the lack of a mandatory fortification program
This study investigates the prevalence of unmetabolized folic acid in the plasma of an elderly Irish population, revealing that 94.1% of participants had detectable levels despite the absence of a mandatory fortification program.
DOI: 10.3945/ajcn.111.026633 -
Folic Acid Fortification and Supplementation-Good for Some but Not So Good for Others
This study examines the dual effects of folic acid fortification and supplementation, highlighting its protective role against neural tube defects while also raising concerns about its potential to promote the progression of existing neoplastic lesions and increase cancer risk i…
DOI: 10.1111/j.1753-4887.2007.tb00275.x -
Folate analysis in foods by UPLC-MS/MS: development and validation of a novel, high throughput quantitative assay; folate levels determined in Australian fortified breads
This study developed and validated a high-throughput UPLC-MS/MS method for quantifying synthetic folic acid and naturally occurring 5-methyltetrahydrofolate in Australian fortified breads, revealing that the folic acid levels in these breads were below the mandated fortification…
DOI: 10.1007/s00216-011-5156-3 -
Trends and influencing factors of plasma folate levels in Chinese women at mid-pregnancy, late pregnancy and lactation periods
This cross-sectional study of 1,211 Chinese pregnant and lactating women shows plasma folate declines from mid-pregnancy to late pregnancy and lactation, with regional and sociodemographic factors influencing folate status and about one-third having suboptimal folate levels, hig…
DOI: 10.1017/S0007114520004821 -
Folic acid food fortification to prevent neural tube defects
The study evaluates the effectiveness of different dosages of folic acid supplementation in reducing the risk of neural tube defects (NTDs) and argues for mandatory food fortification to achieve optimal health outcomes.
DOI: 10.1016/s0140-6736(05)78966-2 -
Efficacy of folic acid supplementation in cardiovascular disease prevention: An updated meta-analysis of randomized controlled trials
This 2012 updated meta-analysis of 26 randomized controlled trials (58,804 participants) finds that folic acid supplementation does not significantly reduce cardiovascular disease or coronary heart disease risk or all-cause mortality, with a potential modest reduction in stroke …
DOI: 10.1016/j.ejim.2012.07.004