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To maternity and beyond

By Irish Pharmacist - 29th Sep 2020

While the benefits of folic acid in the prevention of neural tube defects is established, other evidence regarding its efficacy in other areas of health is coming to light

In recent years, pharmacists and other healthcare scientists have been advocating the use of folic acid supplementation, not just for women who are pregnant, but also for women where there is a chance that they may become pregnant.

A Food Safety Authority of Ireland (FSAI) scientific report pointed out that Ireland has one of the world’s highest rates of neural tube defects (NTDs) such as spina bifida and anencephaly, and emphasised the importance of optimal folic acid status through food supplements and fortification, describing it as an “important public health goal in Ireland”.

Mandatory fortification

The report raises the need for a discussion on mandatory folate fortification in Ireland, citing more than 80 other countries as an example and pointing out that there is no evidence of adverse health effects resulting from mandatory fortification. “This report shows that in Ireland, mandatory fortification of bread or flour to provide about 150µg of folic acid per day in women of childbearing age could reduce the prevalence of NTDs by approximately 30 per cent,” wrote the authors. “Provided voluntary fortification of foods was continued, the benefit for reduction in the risk of occurrence of NTD-affected pregnancies by these foods could be retained.
“Mandatory fortification of flour or bread with folic acid would require legislation. An implementation programme would be needed to address legislation, consumer acceptability and consumer choice, technical issues, cost, and trade implications.”

Similarly, in the UK, there have been calls for mandatory folate fortification. It was once suggested by the US Institute of Medicine (IOM) (now known as the National Academy of Medicine) that there might be an ‘upper limit’ for folate consumption, however research published in Public Health Reviews debunked older claims by the IOM that high folic acid consumption could result in neurological damage. Following re-analysis, the researchers wrote that the damage observed was not caused by folic acid, but rather it occurred by not treating B12 deficiency with vitamin B12. Therefore, they concluded, there is no upper limit for the consumption of folate.

Lead author Prof Sir Nicholas Wald from the Wolfson Institute of Preventive Medicine at Queen Mary University, UK, commented: “Failing to fortify flour with folic acid to prevent neural tube defects is like having a polio vaccine and not using it. Every day in the UK, on average two women have a termination of pregnancy because of a neural tube defect and every week, two women give birth to an affected child.”

Folic acid supplementation may enhance blood vessel dilation in older adults, suggesting that folic acid supplements may be an inexpensive therapy for helping older adults to increase skin blood flow during heatwaves and potentially reduce cardiovascular events

In addition, separate research by Penn State University in the US, published in Clinical Science, suggests that folic acid supplementation may enhance blood vessel dilation in older adults, suggesting that folic acid supplements may be an inexpensive therapy for helping older adults to increase skin blood flow during heatwaves and potentially reduce cardiovascular events.

Nitric oxide is produced by blood vessels using an enzyme that requires tetrahydrobiopterin, (BH4). As people get older, BH4 bioavailability decreases, however folic acid supplementation increases nitric oxide production in older blood vessels, according to the authors. Two sub-studies were conducted, using localised and whole-body heating. For the localised heating study, the researchers utilised intradermal microdialysis fibres to deliver a folic acid solution to blood vessels in the skin.

Author Ms Anna Stanhewicz, post-doctoral fellow in kinesiology at Penn State, commented on the findings. “The bottom line is that folic acid supplementation increased nitric oxide production in older blood vessels,” she said. “In the past, studies conducted in our lab showed that we can increase nitric oxide production, and then consequently reflex skin blood flow, in older adults by giving them an expensive pharmaceutical. So in this study, we wanted to test that again, but with an inexpensive treatment that might work the same way.”

Overall health

The benefits of folate supplementation have become apparent in populations other than women who are pregnant or seeking to conceive. The Office of Dietary Supplements at the US National Institutes of Health has stated that the other groups at risk of folate inadequacy include:

? People with alcohol use disorder. These patients may have poor-quality diets that contain insufficient amounts of folate and separately, alcohol interferes with folate absorption and hepatic uptake, accelerates folate breakdown and increases its renal excretion.
? People with malabsorptive disorders. This can include, among others, people with IBD and coeliac disease.
? People with the MTHFR polymorphism. These patients have a genetically-impaired ability to convert folate to its active form, 5-MTHF.

The document also discusses the potential for the benefits of folate supplementation and general health in a number of other conditions, including: Autism spectrum disorder; cancer; cardiovascular disease and stroke; dementia; cognitive dysfunction; Alzheimer’s disease; and depression.

However, the document also cautions healthcare professionals to be aware of the potential for interactions with certain medicines, such as methotrexate, antiepileptic medications and sulfasalazine.


  1. Update Report on Folic Acid and the Prevention of Birth Defects in Ireland. FSAI,
  2. Public health failure in the prevention of neural tube defects: Time to abandon the tolerable upper intake level of folate. Public Health Reviews volume 39, Article number: 2 (2018).
  3. Forbes, ‘Government Urged To Fortify Food With Folic Acid To Prevent Birth Defects’,
    fortify-food-with-folic-acid-to-prevent-birth-defects/, accessed Sept 2020.
  4. NIH, Folate Fact Sheet for Health Professionals.,
    accessed Sept 2020.
  5. Penn State. ‘Folic acid may help elderly weather heat
    waves.’ ScienceDaily, 31 March 2015.






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