The MTHFR mutation and pregnancy: why standard folic acid isn't always enough

To properly understand the implications of the MTHFR gene mutation, it is first necessary to distinguish between two terms that are often used, incorrectly, interchangeably:

• Folates: these are the natural forms of vitamin B9, found in certain foods such as green vegetables and legumes.
• Folic acid: this is the synthetic form used in the majority of standard food supplements and fortified foods.

What is important to understand: in its existing form, folic acid is not biologically active. To be used by your cells and to cross the placenta, it must first undergo a complex transformation within your body to become 5-MTHF (5-methyltetrahydrofolate). This process is known as methylation.

The conversion of folic acid into active folates depends on a specific enzyme produced by the MTHFR gene. Everyone has two MTHFR genes: one inherited from the mother and one from the father. Some people inherit a variant (or gene mutation) that produces an MTHFR enzyme with impaired function. The most common MTHFR mutations are known as "677C>T" and "1298A>C".

For those who do not carry a mutation, this enzyme functions normally: it converts ingested folic acid into 5-MTHF, which can then fulfil its functions (DNA synthesis, neural tube closure, reduction of homocysteine).

The number of people affected by the MTHFR gene mutation varies across studies. According to some publications, 30–40%[1] to 60–70%[2] of the studied population carries at least one mutation. Other studies estimate that 55%[3] of the European population carries at least one of the 677C>T and 1298A>C mutations. As you can see, this is far from a rare occurrence!

If you carry this genetic variant, it means that the activity of your MTHFR enzyme is reduced by approximately 75% compared to a "normal" enzyme. In other words, it struggles to convert synthetic folic acid into its active form.

This has two major consequences:

• A cellular deficiency despite adequate intake: Even if you take your vitamins conscientiously, your body (and your baby) may be lacking active folates, as the conversion does not happen quickly enough. Standard blood tests can be misleading: they sometimes show a normal vitamin B9 level in the blood, while the cells are actually deficient.
• The accumulation of unmetabolised folic acid: Synthetic folic acid that is not converted remains in the bloodstream. It can then saturate cellular receptors and prevent the "good" natural folates from binding. 

Les taux normaux d'homocystéine, marqueur indirect du bon fonctionnement de la méthylation, se situent entre 5 et 15 μmol/L. Bien qu'il soit possible de réaliser un test génétique ou de doser son homocystéine, vérifier vos dosages sanguins en folates ne vous sera pas forcément d’une grande aide !

En effet, même si vos analyses montrent un taux normal ou élevé d’homocystéine, vous pouvez tout de même faire face à une carence en folates. La faute à l’affinité de liaison, qui correspond à la force avec laquelle une substance se lie à un récepteur. Chose surprenante : l’acide folique (forme synthétique de la B9) se lie plus facilement aux récepteurs de folates que les formes naturelles de folates[4]. Conséquence directe : le folate naturel ne peut pas toujours arriver dans les cellules, car l’acide folique bloque les récepteurs ! On parle dans ce cas de carence fonctionnelle.

Le consensus scientifique actuel va dans le sens du pragmatisme : puisque cette mutation est très fréquente et que les folates actifs (méthylés) sont sûrs et bénéfiques pour tout le monde, il est plus simple et plus avantageux de privilégier directement la bonne forme de vitamine B9. Choisissez donc directement le meilleur complément alimentaire grossesse avec une forme 5-MTHF. 

1. Your plate: the essential foundation

Before taking any supplement, aim to get folates from natural sources, which are found in a highly bioavailable form.

Where to find them? Many foods contain folates directly in the form 5-MTHF [5]. 

For example:

• Legumes (lentils, chickpeas, white beans): lentils contain 71 µg of folates in the active form 5-MTHF, and raw chickpeas contain 125 µg per 100 g.
• Green leafy vegetables (lettuce, spinach, watercress, cabbage…): 100 µg per 100 g for kale, of which half is in active form.
• Broccoli: 100 µg per 100 g, of which 67% is in the active form 5-MTHF.
• Citrus fruits (lemon, orange…): nearly 100% of folates in active form.
• Red berries (strawberries, raspberries, cherries): nearly 100% of folates in active form. For example, strawberries contain 79 µg of active folates per 100 g.

Practical tip: Folates are heat-sensitive and struggle to withstand light and heat. Excessive cooking can destroy up to 30% of them [6]. Where possible and if you can tolerate it, opt for gentle steaming or eating raw.

2. Targeted supplementation

Since diet alone rarely covers the increased folate requirements during pregnancy, supplementation is recommended. However, if you take a folate supplement, avoid folic acid, which requires conversion into its active form by the MTHFR enzyme.

Instead, opt for the following forms:

• (6S)-5-methyltetrahydrofolate as glucosamine salt or calcium salt
• Spinach extract standardised for vitamin B9
• Lemon extract standardised for vitamin B9