Biochemistry Chemistry in the News

What is folic acid, and why is it important during pregnancy?

Infographic titled 'Why is folic acid important during pregnancy?'. Folic acid is a human-made form of folate, vitamin B9. We have to get it from our diet. It's converted into folate in the body. Folate is found naturally in a number of foods, particularly leafy vegetables, seeds, and nuts. It can also be added to some foods including flour, a process known as fortification. Low levels of folate have been linked to neural tube defects (NTDs). These happen when the neural tube, which forms the brain and spinal cord, doesn't develop or close properly, leading to conditions like spina bifida. Taking folic acid before and during early pregnancy reduces the risk of NTDs by about 70%. The mechanism by which folate reduces NTDs isn't known, but folate is important for building nucleic acids, the building blocks of DNA. Large quantities of nucleic acids are required by the developing neural tube for DNA replication, and folic acid deficiency may impact this.
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This week, the UK has confirmed it plans to fortify non-wholemeal flour with folic acid. It’s not the first country to do so: the United States has been fortifying flour with folic acid since 1998. Most countries in South America and a number in Asia also have mandatory fortification programs. This graphic looks at the reasons for fortification with folic acid – and making it also got me wondering why the practice isn’t more widespread in Europe.

Let’s kick off with the (bio)chemistry. Folic acid is the human-made form of folate, otherwise known as vitamin B9. Vitamin B9 is an essential vitamin – that means that our bodies can’t produce it, so we need to get it from our diet.

A number of foods naturally contain folate. Its name comes from the Latin, folium, meaning leaf, giving the clue that it’s found in leafy vegetables such as spinach. Folate is also found in some nuts, seeds, and fruits. In addition to natural sources, some foods can be ‘fortified’ with folic acid, including flour, cereals, rice and pasta. The term ‘fortified’ is just a fancier-sounding way of saying we’ve added nutrients to a food.

Our bodies do a number of things with the folate we get from our food. Our cells need it to make DNA and other genetic material, and it also plays a role in the creation of new red blood cells. But while these roles are undoubtedly important, it’s reasons relating to pregnancy that are behind its addition to some foods.

In the first month of pregnancy, many important structures begin to form, including the brain and spinal cord. These both begin as the neural tube, the precursor to what will become our central nervous system. The neural tube starts off as a groove, and then folds on itself to form a closed tube.

In most pregnancies, closure of the neural tube takes place with no problems. But in a small number of pregnancies, neural tube defects occur. These defects happen when the neural tube doesn’t close properly, leaving an opening in the spine or cranium. The location and size of the opening dictates the type of neural defect. The best known is spina bifida, seen in approximately 0.035% of births in the United States. These defects can lead to babies being stillborn, or having life-long disabilities.

Scientists still aren’t clear on what exactly causes neural tube defects (NTDs for short), but we do know what some of the contributing factors are. This brings us back to folate, because evidence has shown that a deficiency in folate increases the risk of NTDs. That’s why it’s recommended that women should take folic acid supplements before and during early pregnancy. This supplementation reduces the risk of NTDs by about 70%.

So if everyone were to follow this advice, why do we even need to fortify flour with folic acid, too? Firstly, the recommendation to take folic acid supplements before early pregnancy works well for planned pregnancies, but of course not all pregnancies are planned. Additionally, as we’ve all learned in the past year of tackling COVID, not all public health recommendations are followed to the letter by everyone!

Flour fortification with folic acid is already in place in over 60 countries worldwide. The United States has fortified flour with 140 micrograms of folic acid per 100 grams of flour since 1998. Other countries in which mandatory fortification programs exist include in most of South America, Canada, Australia and Indonesia.

Look to Europe, though, and the number of countries fortifying flour with folic acid is strangely small. None of the current EU member states have mandatory flour fortification programs. Only two other European countries have pursued flour fortification to date: Moldova and Kosovo. A recent research paper brands the lack of flour fortification across Europe as “a public health failure” – so why the reluctance to implement it?

It’s certainly not due to a lack of evidence of effectiveness. In the US, it’s estimated that 1300 fewer babies have been born with the NTDs spina bifida or anencephaly since flour fortification began in 1998. And a 2010 analysis of data from countries that fortify flour estimated a 46% drop in the incidence of NTDs. Looking at prevalence of NTDs in Europe (9.1 per 10,000 births) and the United States (5.3 per 10,000 births) further highlights the potential benefits.

One concern that held European countries back from implementing fortification in the early 2000s was fears of a link between folic acid supplementation and some types of cancer. Subsequent research has showed no significant increase in cancers, however. There is a known risk that giving folic acid to people with a deficiency of a different B vitamin, B12, could mask this deficiency, which can ultimately lead to neurological damage. but this could easily be addressed by fortifying with vitamin B12 as well.

Estimates suggest that, if European countries had implemented the practice at the same time, level and extent as the United States, 14,600-19,500 cases of NTDs in pregnancy could have been averted between 1998 and 2017. Ultimately, it’s hard to see why fortification hasn’t been implemented in more European countries sooner. It’ll be interesting to see if further countries in Europe follow the UK’s lead in the coming years.

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