Introduction
Folate (vitamin B9) is an essential vitamin for which EFSA has confirmed several health claims: folate contributes to normal amino acid synthesis, normal blood formation, normal homocysteine metabolism, and maternal tissue growth during pregnancy.
In supplements, folate comes in two distinct forms — synthetic folic acid and active methylfolate (5-MTHF). This choice is not merely academic; it significantly affects thousands of people who carry MTHFR gene variants.
What is folic acid?
Folic acid is the synthetic form of vitamin B9, used in most supplements and fortified foods. It is not biologically active — the body must convert it through a multi-step enzymatic process into active methylfolate.
The final step of this conversion is performed by the MTHFR enzyme. If the MTHFR gene is variant, this conversion may be slower.
What is methylfolate (5-MTHF)?
Methylfolate, or 5-methyltetrahydrofolate, is the biologically active form of folate. It is the form that actually circulates in the blood and can be used by cells immediately — without conversion.
Methylfolate is also the natural form of folate found in food (green leafy vegetables, legumes, liver).
MTHFR gene variants — why it matters
MTHFR (methylenetetrahydrofolate reductase) is the enzyme that converts folic acid into active folate. Approximately 30–40% of Europeans carry an MTHFR gene variant (Wilcken et al., 2003) that reduces this enzyme's activity:
- C677T heterozygous (one altered copy) — enzyme activity ~65% of normal
- C677T homozygous (two altered copies) — enzyme activity ~30% of normal
This means a significant portion of the population converts folic acid less efficiently. For these individuals, methylfolate may be directly more beneficial.
Key differences
| Feature | Folic Acid | Methylfolate (5-MTHF) |
|---|---|---|
| Type | Synthetic | Biologically active |
| Requires conversion | Yes (multiple steps) | No — usable immediately |
| For people with MTHFR variants | Less effective | Effective |
| Price | More affordable | More expensive |
| Availability | Very common | Increasingly common |
| Research volume | Very extensive | Growing |
When to choose folic acid
- You have no known MTHFR variant and your body converts folic acid normally
- You are looking for a more affordable option — folic acid is significantly cheaper
- Your doctor has specifically prescribed folic acid — in some clinical contexts folic acid is used specifically
- You consume fortified foods — most fortified foods contain folic acid
When to choose methylfolate
- You have a known MTHFR gene variant (C677T or A1298C) — methylfolate does not require enzymatic conversion
- You are pregnant or planning pregnancy and want to ensure optimal folate levels — consult your doctor about the right form and dose
- You have elevated homocysteine levels — methylfolate may be more effective at supporting homocysteine metabolism
- You generally prefer active vitamin forms
Can you combine them?
Yes, combining folic acid and methylfolate is safe. Some quality prenatal vitamins contain both forms. Just monitor your total intake — the EFSA tolerable upper level is 1000 µg of folic acid per day (this applies to synthetic folic acid, not to food-derived folate or methylfolate).
Frequently asked questions
How do I find out if I have an MTHFR variant? The MTHFR gene variant can be detected through genetic testing. Some healthcare providers offer this as a test. Consult your doctor.
Is folic acid dangerous for people with MTHFR variants? Folic acid is not dangerous but may be less effective. Unconverted folic acid can accumulate in the blood. Many experts recommend methylfolate for people with MTHFR variants.
How much folate should I take daily? EFSA recommends 200 µg per day for adults. During pregnancy, needs are higher (400–800 µg). Consult your doctor.
Is methylfolate better for everyone? Not necessarily. For those without MTHFR variants, folic acid is perfectly adequate and significantly cheaper. Methylfolate is particularly beneficial for those who have conversion issues.
What is folinic acid? Folinic acid is another form of folate that is one step "more active" than folic acid. It does not require the MTHFR enzyme for conversion but does need one other enzymatic step. Some supplements use it as an alternative.
Browse our vitamin selection at MaxFit.ee →
References
- Scaglione, F. & Panzavolta, G. (2014). Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica, 44(5), 480–488.
- Bailey, S.W. & Ayling, J.E. (2009). The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake. Proceedings of the National Academy of Sciences, 106(36), 15424–15429.
- Wilcken, B., Bamforth, F., Li, Z. et al. (2003). Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR). Journal of Medical Genetics, 40(8), 619–625.
- Prinz-Langenohl, R., Bramswig, S., Tobolski, O. et al. (2009). [6S]-5-methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with the homozygous or wild-type 677C→T polymorphism of methylenetetrahydrofolate reductase. British Journal of Pharmacology, 158(8), 2014–2021. See also:
- Folic Acid Guide
- Folic Acid and Methylfolate: In-Depth Comparison
- B Vitamins Guide
Disclaimer
A food supplement is not a substitute for a varied and balanced diet and a healthy lifestyle.
