Folic Acid vs. Methylfolate: Which Type of Folic Acid Is Best?

November 6, 2025 •

4 min read

Studies indicate that up to 40-60% of the population may carry a genetic variant (MTHFR) that impairs the body's ability to efficiently convert folic acid into its active form. This makes the question of which type of folic acid is best a critical one for many, influencing their choice of supplements for optimal health.

Quick Summary

This article explores the differences between synthetic folic acid and the active, bioavailable form, methylfolate (5-MTHF). It details how individual genetics, particularly the MTHFR variant, affect metabolism and influence which form is most beneficial for your body.

Key Points

Folic Acid (Synthetic): The common, synthetic form of B9 found in fortified foods and many supplements that requires enzymatic conversion by the body.
Methylfolate (Active): The bioactive form (5-MTHF) that the body can use directly without conversion, making it more effective for individuals with impaired metabolism.
MTHFR Gene Variant: A common genetic mutation can reduce the body's ability to convert folic acid efficiently, making methylfolate a better choice for those affected.
Standard Recommendation: Folic acid has decades of proven research for preventing neural tube defects and is the standard recommendation for most pregnant women.
Consult a Doctor: It is essential to consult a healthcare provider for personalized advice, especially during pregnancy, to determine the most appropriate form and dosage of vitamin B9.
Cost and Availability: Folic acid is more cost-effective and widely available, whereas methylfolate is often more expensive.
Masked Deficiency: High doses of folic acid can mask a vitamin B12 deficiency, potentially leading to serious neurological damage if left untreated.

The vitamin B9 family is essential for numerous bodily functions, from DNA synthesis to red blood cell formation. While the terms folate, folic acid, and methylfolate are often used interchangeably, they are distinct forms of this crucial nutrient, with different levels of bioavailability and effectiveness for individuals. The choice of supplement—whether synthetic folic acid or active methylfolate—depends heavily on personal metabolic capacity, which for many is influenced by a common genetic variation.

What is Folic Acid?

Folic acid is the synthetic, oxidized form of vitamin B9 that is not naturally found in foods. It was first synthesized in the 1940s and is widely used in dietary supplements and for fortifying foods like cereals, bread, pasta, and rice. This fortification has been highly successful in reducing the incidence of neural tube defects (NTDs) in newborns.

How is Folic Acid Metabolized?

For the body to use folic acid, it must undergo a multi-step conversion process. The dihydrofolate reductase (DHFR) enzyme in the liver converts folic acid into tetrahydrofolate (THF), which is then further converted into the active form, methylfolate (5-MTHF).

Advantages of Folic Acid

Proven Efficacy: Decades of research have confirmed the effectiveness of folic acid supplementation in preventing NTDs, leading to widespread public health recommendations.
Stability: Unlike natural folate from food, synthetic folic acid is stable and retains its potency during food processing and storage.
Cost-Effective: It is generally more affordable and accessible than methylfolate.

What is Methylfolate (5-MTHF)?

Methylfolate, specifically L-methylfolate or 5-MTHF, is the bioactive form of vitamin B9 that the body can use immediately. It is the predominant form of folate found circulating in the bloodstream and is present in leafy greens, legumes, and other natural food sources.

The Role of Methylfolate

Because methylfolate is the active form, it bypasses the need for the enzymatic conversion that folic acid requires. It is directly utilized in essential processes, including the conversion of homocysteine into methionine. Elevated homocysteine levels are associated with an increased risk of cardiovascular disease.

The MTHFR Gene and Methylfolate

An enzyme called Methylenetetrahydrofolate Reductase (MTHFR) is crucial for the final conversion step of folic acid into active methylfolate. Genetic variants in the MTHFR gene, such as C677T and A1298C, can reduce the efficiency of this enzyme. For individuals with these variants, supplementing with methylfolate ensures the body receives usable vitamin B9 without relying on an impaired conversion pathway.

Folic Acid vs. Methylfolate: A Comparison


Feature	Folic Acid (Pteroylmonoglutamic acid)	Methylfolate (5-MTHF)
Source	Synthetic; used in supplements and fortified foods.	Active, bioavailable form; found naturally in food and in supplements.
Metabolism	Requires a multi-step enzymatic conversion in the body.	Already in the active form; requires no conversion.
MTHFR Impact	Metabolism can be impaired in individuals with MTHFR variants.	Bypasses the MTHFR enzyme, making it suitable for those with variants.
Bioavailability	Good absorption, but limited conversion can cause unmetabolized folic acid to accumulate.	High bioavailability, especially beneficial for those with impaired metabolism.
Fortification	The form used for mandatory food fortification programs.	Not used for fortification due to lower stability and higher cost.
Cost	Generally more affordable.	Often more expensive.

Who Should Take Which Type of Folic Acid?

For the General Population

For most people without a known MTHFR gene variant, synthetic folic acid works effectively to raise folate levels and prevent deficiency. It is the most common and cost-effective form used in standard multivitamins and prenatal supplements. The Centers for Disease Control and Prevention (CDC) confirms that folic acid supplementation increases blood folate levels regardless of MTHFR genotype.

For Those With MTHFR Variants

Individuals who know they carry an MTHFR gene variant may benefit more from methylfolate. Since their ability to convert folic acid is compromised, methylfolate ensures direct utilization by the body and helps avoid the accumulation of unmetabolized folic acid in the bloodstream. Some studies also suggest methylfolate may be more effective at lowering high homocysteine levels associated with MTHFR mutations.

During Pregnancy

Folic acid is the form with the most established, decades-long evidence for preventing neural tube defects when taken before conception and throughout early pregnancy. For most women, the standard recommendation is a 400 mcg daily folic acid supplement. However, those with a known MTHFR variant or a history of recurrent miscarriage may be advised by their doctor to take methylfolate, often at a higher dose.

How to Choose the Right Supplement

Talk to Your Doctor: Before starting any supplement, especially at higher doses, consult a healthcare provider. This is crucial for determining the right type and dosage for your specific needs, particularly during pregnancy.
Check the Label: Look for supplements that specify the form of folate. Brands with patented methylfolate, such as Quatrefolic® or Metafolin®, guarantee a bioavailable, active form.
Consider a B-Complex: Folate works synergistically with other B vitamins, especially B12. Taking a balanced B-complex ensures optimal metabolism and prevents one nutrient from masking the deficiency of another.
Dietary Sources: Remember that natural folate from food is always an important part of a healthy diet. Include plenty of leafy greens, legumes, and fortified grains to support your overall folate status.

Conclusion

While both folic acid and methylfolate provide the essential vitamin B9, the distinction matters for optimizing health. For the average person, folic acid is a perfectly effective and cost-efficient supplement. However, for individuals with MTHFR genetic variants, methylfolate offers a superior, more direct pathway to increase usable folate levels. The best type of folic acid is not one-size-fits-all, but rather the form that best matches your body's specific metabolic needs. Always consult a healthcare professional to determine the most suitable option for you. You can learn more about folate and its functions from the NIH Office of Dietary Supplements.

Frequently Asked Questions

Folic acid is a synthetic form of vitamin B9 that needs to be converted by the body into its active form. Methylfolate is the active form of B9 (5-MTHF) and can be used immediately by the body.

Individuals with an MTHFR gene variant, which impairs the enzyme needed to convert folic acid, benefit most from methylfolate because it bypasses this metabolic block.

No, not everyone needs methylfolate. For most of the general population, the body can effectively process synthetic folic acid to meet its needs. Methylfolate is primarily beneficial for those with specific metabolic issues.

Decades of extensive research confirm that folic acid effectively prevents neural tube defects, and it is the standard, well-studied recommendation for pregnancy. Your doctor can advise if methylfolate is a better alternative for your specific situation.

While it is possible to get folate from a diet rich in leafy greens, legumes, and fortified grains, many people find it difficult to meet the recommended daily intake from food alone. Supplementation is often necessary, especially for women of childbearing age.

If you have an MTHFR mutation, your body may struggle to convert folic acid effectively. This can lead to lower-than-optimal levels of active folate and potentially higher levels of unmetabolized folic acid in your blood.

Yes. High doses of folic acid can potentially mask a vitamin B12 deficiency, which can lead to serious neurological damage if the underlying B12 issue is not addressed. High doses may also cause side effects like nausea or stomach upset in some people.