Folic Acid vs. Methylfolate: Which Supplement Is Best for Folic Acid?

December 1, 2025 •

4 min read

According to the CDC, ensuring adequate folic acid intake is crucial for preventing serious neural tube defects in a baby's brain and spine. However, determining which supplement is best for folic acid requires understanding the key differences between the standard synthetic form and its more bioavailable counterpart, methylfolate.

Quick Summary

This article explores the differences between synthetic folic acid and bioavailable methylfolate, explaining which supplement option is most suitable for various individuals, especially those with the MTHFR gene variant.

Key Points

Folic Acid vs. Methylfolate: Folic acid is synthetic and requires conversion, while methylfolate is the active, bioavailable form.
MTHFR Gene Variant: Individuals with an MTHFR gene mutation have reduced ability to convert folic acid to methylfolate, making methylfolate supplements a potential better fit.
Benefits of Methylfolate: Bypasses the MTHFR enzyme issue, ensures better absorption, and has less risk of masking a Vitamin B12 deficiency.
Role of Folic Acid: Decades of research support the efficacy of standard folic acid, particularly for preventing neural tube defects in pregnancy.
Choosing a Supplement: The best choice depends on individual factors like genetics and health goals, making consultation with a healthcare provider important.
Beware of High Doses: Taking excessive amounts of folic acid can mask a Vitamin B12 deficiency, highlighting the importance of correct dosage and B12 monitoring.
Food First Approach: While supplements are important, especially pre-pregnancy, incorporating natural folate from leafy greens, legumes, and eggs is always beneficial.

Folic acid and folate are terms often used interchangeably, but they represent two different forms of vitamin B9. Folate is the naturally occurring form found in foods, while folic acid is the synthetic, man-made version added to supplements and fortified foods. The choice between supplementing with folic acid or methylfolate—the active form of folate—is a critical consideration for many people, especially those with certain genetic predispositions.

Understanding the Forms of Folate

Folic Acid

Folic acid is a stable and inexpensive form of vitamin B9 that has been widely used in dietary supplements and food fortification programs for decades. Before the body can use it, folic acid must undergo a conversion process in the liver to become its biologically active form, L-5-methyltetrahydrofolate (5-MTHF), or methylfolate. For most people, this conversion is efficient, and folic acid supplementation is highly effective. The Centers for Disease Control and Prevention (CDC) cites years of research supporting folic acid's proven effectiveness in preventing neural tube defects.

Methylfolate (5-MTHF)

Methylfolate is the active form of folate, and it can be directly utilized by the body without the need for conversion. This form is naturally found in foods like leafy greens, legumes, and eggs, but it can be less stable than folic acid during cooking. Patented forms of methylfolate, such as Quatrefolic® or Metafolin®, are often used in supplements for their high bioavailability. For individuals with a genetic mutation affecting the MTHFR enzyme, supplementing with methylfolate is often recommended because it bypasses the impaired conversion process.

The MTHFR Gene Variant

The MTHFR (methylenetetrahydrofolate reductase) gene provides instructions for making an enzyme crucial for converting inactive folic acid into active methylfolate. Studies indicate that a significant percentage of the population has a variant of this gene that reduces the enzyme's efficiency. For these individuals, standard folic acid supplementation may not be as effective in raising active folate levels, leading some experts to recommend methylfolate instead. However, the CDC maintains that folic acid supplementation is still beneficial for those with MTHFR variants and should not be avoided.

Comparison of Folic Acid vs. Methylfolate


Feature	Folic Acid (Synthetic)	Methylfolate (Active/Natural)
Source	Lab-made, added to fortified foods and supplements.	Active form naturally present in foods and specialized supplements.
Absorption	Requires conversion by the MTHFR enzyme for activation.	Directly bioavailable and easily absorbed by the body.
Cost	Generally more affordable.	Typically more expensive due to higher processing costs.
MTHFR Relevance	Conversion can be impaired by the MTHFR gene variant.	Bypasses the MTHFR gene, making it effective for those with mutations.
Pregnancy Safety	Well-researched and proven effective for preventing NTDs, as recommended by the CDC.	Considered safe and possibly more effective for those with MTHFR mutations, but less historical NTD prevention data compared to folic acid.
Potential Risks	High doses can potentially mask a Vitamin B12 deficiency.	Lower risk of masking B12 deficiency; no upper intake limit formally established.

Considerations for Choosing a Supplement

For Pregnancy and General Health

For most people without known genetic issues, folic acid is a safe and effective option, especially when taken as part of a daily multivitamin. The CDC's long-standing recommendation is based on years of successful public health interventions. However, some modern prenatal supplements now include a mix of both folic acid and methylfolate to provide broad-spectrum coverage.

For Individuals with MTHFR Gene Variants

For those who know they have an MTHFR variant, particularly when dealing with specific health concerns like recurrent pregnancy loss, many practitioners recommend a methylfolate supplement to ensure proper folate metabolism. High doses of standard folic acid might lead to a build-up of unmetabolized folic acid in the bloodstream, which some studies suggest could have negative health implications.

Combining with Vitamin B12

Folate and vitamin B12 work together closely in the body. A key risk associated with high doses of folic acid is that it can correct the blood picture of megaloblastic anemia caused by a B12 deficiency, but it won't fix the underlying nerve damage. For this reason, many folate supplements are sold in combination with vitamin B12, often in its active form (methylcobalamin), to ensure both nutrients are adequately addressed.

How to Get Natural Folate from Food

While supplements are a reliable way to boost intake, a balanced diet rich in natural folate is always beneficial. Cooking methods like boiling can significantly reduce the folate content in vegetables, but incorporating these foods into your diet is still valuable. Good food sources include:

Dark Leafy Greens: Spinach, kale, and romaine lettuce.
Legumes: Lentils, chickpeas, and kidney beans.
Fruits: Oranges, bananas, and papaya.
Asparagus and Broccoli.
Eggs.

Conclusion: Making the Right Choice

When it comes to selecting the best supplement for folic acid, the decision is not one-size-fits-all. For the general population, a standard folic acid supplement is a cost-effective and proven option, especially for preventing birth defects during pregnancy. However, for those with a known MTHFR gene variant or other specific health considerations, a methylfolate supplement may offer superior absorption and utilization. The safest approach is always to discuss your nutritional needs with a healthcare provider who can evaluate your individual circumstances. They can help determine if a standard prenatal vitamin with folic acid is right for you, or if a specialized supplement with methylfolate is a better choice for your genetic profile and health goals. Ultimately, consistency is key, regardless of the form chosen, and daily intake is necessary to support optimal health.

For further information on recommended intake levels, consult the NIH Office of Dietary Supplements.

Frequently Asked Questions

Folic acid is the synthetic form of Vitamin B9 found in fortified foods and supplements, which the body must convert into its active form. Methylfolate is the active, natural form of Vitamin B9 that the body can use directly without conversion.

Methylfolate is often recommended for individuals with a common MTHFR gene mutation, as it bypasses the impaired enzyme activity that prevents them from efficiently converting folic acid into its active form.

While folic acid has extensive research proving its effectiveness in preventing neural tube defects (NTDs), methylfolate is considered a safe and effective alternative, particularly for those with MTHFR mutations. The CDC still emphasizes folic acid's proven role in NTD prevention for women of childbearing age.

High doses of folic acid can potentially mask the symptoms of a Vitamin B12 deficiency. If left untreated, a B12 deficiency can cause serious nerve damage. This is why many supplements combine folic acid with B12 and why monitoring levels is crucial.

Testing for the MTHFR gene variant is not a standard medical protocol, especially as the CDC states that folic acid supplementation remains effective even for those with the mutation. Discussing your family and personal health history with a doctor is the best way to determine if testing is necessary.

Yes, natural folate can be found in a variety of foods, including leafy green vegetables, legumes, fruits like oranges and bananas, and eggs. However, natural folate can be less stable than synthetic folic acid and is easily destroyed during cooking.

Some prenatal and general health supplements offer a combination of both folic acid and methylfolate. This blended approach ensures adequate folate levels for a wide range of individuals, addressing the needs of those with and without the MTHFR gene variant.