About Folate

The terms « Folate » and « folic acid », also known as vitamin B9, are often used interchangeably to indicate a group of water-soluble B-vitamins. Actually, there are differences in the forms:

What is folate

Folate is the natural form of vitamin B9; a water-soluble vitamin that is naturally found in many foods, including dark green leafy vegetables, nuts and legumes.

In order to produce DNA – which we need to grow and repair every cell in our body – we need folate. In fact, folate plays a direct role in the production all DNA in our body.

Folate is also needed in the formation of red blood cells and is vital for cells in our body to grow and divide. Because of this, folate is crucial for fertility and during early pregnancy, where it has been shown to reduce the risk of birth defects.

However, like many essential nutrients, humans cannot produce folate, meaning we must get it from our diet. It is also added to foods and sold as a supplement – often in the form of folic acid, which is a synthetic form of the vitamin that is the inactive precursor to biologically active folate.

Many governments and health authorities recommend folate or folic acid supplementation. Both the European Food Safety Authority (EFSA) and the U.S. Food and Drug Administration (FDA) have set recommendations for folate intake to maintain health at every stage of life.

EFSA has set a dietary reference value (DRV) for folate in healthy adults at 330 micrograms per day and a DRV for pregnancy and lactation at 600 micrograms and 500 micrograms per day, respectively. Meanwhile, the FDA has a Daily Value (DV) of 400 micrograms per day for healthy adults and recommends that women who are pregnant should consume 600 micrograms daily, while those who are breastfeeding should consume 500 micrograms per day.

Some governments also mandate the fortification of foods with folic acid to help ensure people are not deficient.

About Folate

While sometimes used interchangeably, folic acid and active folate are not the same. To become biologically active, folic acid needs to go through several transformation steps in the body.

This multi-step process converts biologically inactive folic acid into the biologically active form of folate that our bodies use, called 5-methyltetrahydrofolate (5-MTHF). Each step of this process is controlled by a different and specific enzyme. Some people, however, have a specific genetic trait (known as MTHFR polymorphism) which means they cannot produce enough of the MTHFR enzyme – which is the important final step in the conversion process. People with MTHFR polymorphism therefore have a lower ability to convert inactive forms of folate and folic acid into the biologically active 5-MTHF form.

Because of this polymorphism, there is also a big variation in how efficiently folic acid is converted to the bioactive form in different people, meaning that even people who take high doses of folic acid can be deficient in folate.

What’s more, because the folic acid they are taking is not being converted, people with these genetic polymorphisms may also be at risk from a condition known as Unmetabolized Folic Acid (UMFA) syndrome – which has potentially serious consequences and might be potentially linked to immune dysfunction and increased cancer risk.

Taking a source of active 5-MTHF folate, like Quatrefolic®, rather than the synthetic form in folic acid means that these conversion steps are not needed, and all of the folate you take is bioavailable for use.

Can we get enough folate from foods?

Naturally occurring food folate can be found in a variety of foods, including vegetables (especially dark green leafy vegetables), fruits and fruit juices, nuts, beans, peas, seafood, eggs, dairy products, meat, poultry, and grains.

However, the folate content in food is unstable and can break down or oxidise during storage and cooking of foods. This means that the levels of folate in foods can drop significantly before we get a chance to eat them! Furthermore, the form folate in food is in a structure known as its polyglutamate form, which means that like folic acid from supplements, it is less soluble, less bioactive, and must still be converted to the active 5-MTHF form in the body.

Both food folate and folic acid need to be converted to active 5-MTHF by the MTHFR enzyme, albeit in slightly different ways. A 2007 study suggested the bioavailability of food folates is 80% that of folic acid, which itself is less bioavailable than the active form of folate 5-MTHF.

For food folates, the initial conversion happens in our small intestines, where an enzyme called glutamate carboxypeptidase II (GCPII) breaks down the links between folate and glutamate so that we can absorb the a form of folate known as tetrahydrofolate (THF).

While folic acid does not need to be converted in the intestines in order to be absorbed, it does need to go through multiple transformation steps, including a step to turn it from dihydrofolate (DHF) into THF.


While it is technically possible for us to get enough folate from food sources, the fact that food folates degrade quickly before consumption, and have to be converted in our intestines, means that many people simply do not get enough through diet alone.

Because of this, major health organizations and governments all recommend the consumption of folic acid or active folate as a supplement. For example, the U.S. Centers for Disease Control and Prevention (CDC), Institute of Medicine, and U.S. Preventive Services Task Force all recommend that women of reproductive age take a folate supplement. Meanwhile, folic acid fortification has been introduced in 78 countries, including the USA, Chile, Canada, South Africa and Australia.

While programmes to fortify flour with folic acid have generally helped to reduce the incidence of developmental birth defects like neural tube defects (NTD) at a population level, research has also shown that these efforts to fortify foods may not benefit people with MTHFR polymorphisms because they are less efficient at converting synthetic folic acid into active 5-MTHF folate.

As such, choosing the supplements that contain biologically active 5-MTHF, like Quatrefolic®, can be a great advantage.

Quatrefolic® The fourth generation folate

As the next-generation solution that bypasses the need for the bioconversion of folic acid in the body, 5-MTHF functions as a nutrient in all applications where folic acid and active folate supplementation are recommended. 

Quatrefolic® is the glucosamine salt of (6S)-5-methyltetrahydrofolate (5-MTHF) and is structurally identical to the reduced and active form of folate found in our bodies. 

Developed by Gnosis by Lesaffre, Quatrefolic® is the fourth-generation folate, providing higher stability, better water solubility, and flexibility for multiple ingredient formulations compared to a third-generation 5-MTHF calcium salt. 


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