Folate and folic acid are often mistakenly used interchangeably for vitamin B9. Folic acid (monopteroylglutamic acid or pteroylmonoglutamic acid) is the oxidized form of vitamin B9; it is not active and is not found in food in this form. This term identifies the chemically synthesized molecule that is present in many vitamin formulations and added into so-called fortified foods. Active folate refers to vitamin B9 in its active form, which is already bioavailable and is in the form that is naturally present in food.  

Folic acid as such is not active in the human body and must be converted to 5-Methyl-TetraHidroFolate (MTHF) in order to act. Active folic acid (5-MTHF) has immediate bioavailability and is not subject to plasma accumulation.

If you are looking to become pregnant or are already pregnant, it is very important to choose the most suitable folic acid formulation for supplementation, especially during the first 15 days after conception.

As mentioned, folic acid as such is not active, but it is the precursor of the active form, 5-methyltetrahydrofolate (5-MTHF), which represents about 98% of all plasma folate. Activation requires two biotransformations in the liver.

Active folic acid (5-MTHF) is naturally occurring vitamin B9, the metabolically active and readily available form. Unlike folic acid, 5-MTHF does not require biotransformations to act.

Several studies have documented that the intake of 400 micrograms (mcg) per day of active folic acid (5-MTHF) allows you to reach the optimal concentration of folate more quickly for preventing the risk of birth defects.

It is important that the intake begins at least one month before conception and continues at least throughout the first trimester of pregnancy.

Folic acid and folate are B vitamins (they are in fact referred to as vitamin B9). They have long been recognized as essential in the prevention of some birth defects. Folate deficiency before conception and during the early stages of pregnancy significantly increases the risk of developing birth defects, particularly neural tube defects (NTD) such as spina bifida (defect involving the spinal cord) or anencephaly (defect in which the brain does not develop).

Our body uses folate to make new cells. Vitamin B9, through mechanisms not yet fully understood, is essential for DNA synthesis and is particularly important for actively growing and differentiating tissues, such as embryonic tissues. Furthermore, folates are involved in the metabolism of homocysteine (sulfur-containing amino acid) and methionine (an essential amino acid that cannot be produced by our body but is only introduced with diet). A folate deficiency can lead to high levels of homocysteine (hyperhomocysteinemia), which appears to be involved in oxidative stress and dysfunction of endothelial cells (vessel lining cells). Vitamin B9 is also involved in the formation of red blood cells, which are responsible for transporting oxygen and some carbon dioxide (CO₂) to and from the tissues.

Folates must necessarily be introduced through food as our body is unable to produce them. The reserves are limited and about half are found in the liver.

The amount of folate introduced by diet - if varied and balanced - is generally adequate, except in situations or periods of increased need (for example in anticipation of pregnancy or during pregnancy itself, particularly in the first months), during which supplementation with active folic acid is suggested.

The main food sources of folate are green leafy vegetables (spinach, broccoli, Brussels sprouts, asparagus, lettuce, turnip greens) from which the name of the vitamin derives, legumes (beans, peas), chickpeas, whole grains, artichokes, fresh fruit (kiwi, strawberries, oranges, avocado), dried fruit (almonds, walnuts, hazelnuts, peanuts) and brewer's yeast. Some foods of animal origin, such as liver, offal and eggs, are particularly rich in folate, but should be consumed in limited and infrequent portions.

According to the Italian Society of Human Nutrition (SINU), the main sources of folate in the Italian diet are the following food groups: “Grains and derivatives” (29%), “Vegetables” (27%), “Fruit” (10%). Fortified foods (breakfast cereals, some baked goods (rusks, crackers), fruit juices) contribute to the average daily intake of adults in very limited percentages (<1%). (Source: LARN, SINU 4th Revision, October 2014).

The absorption of folate from the diet is variable and depends on the food source. Food preparation methods can also affect absorption: prolonged boiling, for example, inactivates much of the vitamin B9, which is a water-soluble vitamin, and therefore sensitive to heat, light, air and acidity. Individual factors and genotypes also influence the ability to absorb folate.

High consumption of alcohol depletes the reserves of folic acid and alters its absorption and use, as does the intake of some drugs, including analgesics such as acetylsalicylic acid, oral contraceptives, and antacids.
A reduction in the absorption of folic acid and/or a consequent increase in the requirement for it can also result from type 1 diabetes mellitus (insulin-dependent), celiac disease, malabsorption diseases or some specific variants of genes involved in the metabolism of folate (methylene-tetrahydrofolate-reductase, folate receptor).

Some studies have shown that active folic acid and arginine amino acid (L-ARG) act synergistically to facilitate a proper start to pregnancy. Together they favor implantation and vascularization during the periconceptional period, starting from ovulation. Choosing a supplement that contains both is advisable: the coexistence of the two substances enables synergistic action at the molecular level, where the activity of L-ARG is enhanced by the presence of folate in the synthesis of nitric oxide or nitric oxide (NO), a gas mediator that regulates endothelium-dependent vasodilation.