Are folic acid and methyl folate the same thing?

The role of folate in the body

Folate plays an important role in maintaining various body functions, including normal cellular function. Consequently, adequate folate intake is required to prevent pregnancy and neurodevelopmental complications, as well as serious medical conditions such as cardiovascular disease or cancer (Scaglione and Panzavolta, 2014).

To maintain optimal health, the recommended dietary allowances (RDAs) for folate are 400 µg/day for adults and 600 µg/day for women of childbearing-age (SCAN, 2006).

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One way to achieve that is through our diet, as the human body is unable to produce folate. To maintain adequate levels, it is important to regularly eat folate-rich foods, such as dar green leafy vegetables, sprouts, fruits, brewer’s yeast and animal liver, or take dietary supplements that contain folic acid – which is a synthetic form of folate. (Scaglione and Panzavolta, 2014).

The differences between methylfolate and folic acid

Folate is a generic term which is used to describe folic acid and naturally-occurring metabolites, including 5-methyltetrahydrofolate (5-MTHF), 5-formyltetrahydrofolate (5-FTHF or folinic acid), 10-formyl-THF, 5,10-methylene-THF and unsubstituted THF (Scaglione and Panzavolta, 2014).

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5-MTHF is a biologically active form of folate (with more than 90% of folate) and is the predominant active metabolite after intake of folic acid (Scaglione and Panzavolta, 2014). Being a natural form of folate, methylfolate has many advantages over synthetic folic acid (Scaglione and Panzavolta, 2014). For example, methylfolate is well absorbed, and its bioavailability is not affected by metabolic defects (Scaglione and Panzavolta, 2014). Methylfolate also has no tolerable upper intake level and will not mask vitamin B12 deficiency (Obeid et al., 2013).

Folic acid, which can be found in many dietary supplements or added to fortified foods (e.g. cereal-based products, pasta, enriched bread, fruit juice) is an oxidized synthetic water-soluble vitamin that belongs to the B-complex group and is not found in nature (Scaglione and Panzavolta, 2014).

Unlike synthetic folate, folinic acid is a 5-formyl derivative of THF, naturally occurring in folate-rich foods. Folinic acid is readily converted to THF without the need for DHFR enzymatic activity, which is required for the conversion of folic acid to tetrahydrofolate, its metabolically active form. (Pietrzik et al., 2010).

Biologically active derivatives of folate, which also include methylfolate, can be found in many food sources, including green leafy vegetables, legumes and eggs, as well as in the certain dietary supplements such as Quatrefolic®.

Quatrefolic® is the fourth generation of folate which, compared to previous generations, contains the glucosamine salt of (6S)-5-methyltetrahydrofolate (5-MTHF) – an active form of folate found in our bodies – instead of synthetic folic acid.

Benefits of dietary supplementation: methylfolate vs folic acid

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Dietary supplements containing 5-MTHF are at least as effective as folic acid in improving folate status, which is assessed using blood folate concentrations and functional indicators, including plasma homocysteine (Pietrzik et al., 2010).

Studies comparing biologically active 5-MTHF form and synthetic folic acid have found that the two compounds have comparable biological activity, including bioavailability and absorption at equal concentrations (Pietrzik et al., 2010).

However, the active form of folate that we can find in the food we eat and in Quatrefolic® seems to have more pronounced effects over supplements containing synthetic folic acid.

The benefits of using methylfolate supplements, like glucosamine salt of (6S)-5-methyltetrahydrofolate (5-MTHF) found in Quatrefolic®, may help to effectively reduce symptoms of vitamin B12 deficiency and prevent the potential negative effects of unconverted folic acid in peripheral circulation (Scaglione and Panzavolta, 2014). In addition, this could also help to reduce probability of any interactions with drugs that could inhibit dihydrofolate reductase, an enzyme required to convert synthetic folic acid to its biologically active form (Pietrzik et al., 2010).

The metabolically active form of folate found in Quatrefolic® appears to have the most potential when it comes to maintaining adequate folate status under high demand conditions, such as pregnancy and/or early-stage development, or in people who are unable to properly metabolize and activate folate. Therefore, dietary supplements containing methylfolate can effectively improve folate status among women in early pregnancy and prevent potential complications, including neural tube defects (Obeid et al., 2013). It is worth noting that a daily intake of 1.13 mg of 5-MTHF over the course of 12 weeks increases red blood cell and plasma folate concentrations in women of childbearing-age, compared to women given 1 mg of folic acid a day (Henderson et al., 2018).

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