Is it better to take folic acid or methylfolate?

October 31, 2025 •

4 min read

Recent studies suggest that up to 60% of women may have a genetic variation that affects how their body processes folic acid. While both are forms of vitamin B9, the choice between folic acid and methylfolate depends heavily on individual genetic factors, health goals, and how efficiently your body can convert this vital nutrient.

Quick Summary

Folic acid is a synthetic form of vitamin B9 requiring conversion, while methylfolate is the active, more bioavailable form. Genetic factors, particularly the MTHFR gene variant, can impair the conversion process, making methylfolate a better option for some individuals, though folic acid is still effective for most and widely recommended.

Key Points

Conversion Matters: Folic acid is synthetic and must be converted to an active form, while methylfolate is already active and usable by the body.
MTHFR Gene: People with a common MTHFR genetic mutation may have difficulty converting folic acid, making methylfolate a more effective option for them.
Cost vs. Bioavailability: Folic acid is cheaper and widely available, whereas methylfolate is more bioavailable but can be more expensive.
Safety Considerations: High doses of folic acid can potentially mask a vitamin B12 deficiency, while methylfolate is less likely to do so.
Pregnancy Choice: While both are effective for preventing neural tube defects, methylfolate may be a more reliable option for those with genetic variants affecting folate metabolism.
Informed Decision: The best choice depends on individual factors, and consultation with a healthcare provider is recommended to determine the right supplement for you.

What is the difference between folic acid and methylfolate?

Folic acid is the synthetic form of vitamin B9, which is used in dietary supplements and fortifying food products like cereals and bread. Methylfolate, or L-methylfolate (also known as 5-MTHF), is the naturally occurring, active form of folate found in foods like leafy greens, legumes, and eggs. The key distinction lies in how the body processes them. Folic acid is inactive and must be converted by the body into the active form, methylfolate, before it can be used. This conversion is managed by the methylenetetrahydrofolate reductase (MTHFR) enzyme.

The MTHFR genetic mutation and its implications

An estimated 40–60% of people have a genetic variation in the MTHFR gene that can reduce the efficiency of this conversion process. For individuals with this mutation, taking synthetic folic acid may not lead to optimal folate levels, as a significant portion may remain unmetabolized in the bloodstream. This can be a concern for those with certain health conditions or for women trying to conceive, as it can potentially compromise the benefits of folate supplementation. Conversely, methylfolate is already in the active form, allowing it to bypass the MTHFR conversion step entirely. This makes it a more readily available and effective option for those with the MTHFR gene variant.

Advantages and risks of folic acid

Folic acid has been widely used and studied for decades, particularly for its critical role in preventing neural tube defects (NTDs) during pregnancy. It is cost-effective and very stable, making it a common choice for food fortification and over-the-counter multivitamins. However, the primary risks are related to the accumulation of unmetabolized folic acid in the bloodstream, especially with high doses. While the long-term health consequences of this are still under investigation, concerns have been raised about its potential to mask a vitamin B12 deficiency, which can lead to irreversible nerve damage if left untreated. For most people without the MTHFR mutation, standard folic acid supplementation is both safe and effective.

Advantages and risks of methylfolate

Methylfolate offers superior bioavailability, as it does not require enzymatic conversion and is readily absorbed and used by the body. This is a significant advantage for those with the MTHFR mutation, but it also benefits anyone looking for a more direct and efficient form of folate. It does not lead to the accumulation of unmetabolized folic acid and is less likely to mask a vitamin B12 deficiency. Despite its benefits, methylfolate is typically more expensive than folic acid. Some individuals may also experience side effects like anxiety or digestive issues, though this is rare and often dose-dependent. The research on methylfolate's effects in certain populations, while growing, is not as extensive as that for folic acid.

How to choose the right supplement

Making the right choice depends on your personal health needs and genetics. For a pregnant woman with an MTHFR mutation, methylfolate may be the preferred option to ensure optimal folate levels for fetal development. For individuals with a healthy MTHFR gene and no history of folate deficiency issues, the more economical folic acid is often sufficient. It is always best to consult a healthcare provider, especially before and during pregnancy or if you have an underlying health condition. They can help you determine the best course of action and recommend testing, if necessary, to understand your genetic predisposition.

Folic Acid vs. Methylfolate: A comparison


Feature	Folic Acid	Methylfolate (L-methylfolate)
Source	Synthetic	Natural, active form found in food
Processing	Inactive; requires conversion by MTHFR enzyme	Active; requires no conversion
Bioavailability	Lower for individuals with MTHFR mutations	Higher, effective for everyone
Cost	Generally more affordable	Often more expensive
Availability	Very common in fortified foods and supplements	Increasingly available in specialized supplements
Risk of Unmetabolized Folate	Possible buildup with high doses or impaired conversion	No risk of unmetabolized folate buildup
Vitamin B12 Masking	Can potentially mask B12 deficiency symptoms	Less likely to mask B12 deficiency
Best for	Most healthy individuals, general supplementation	Individuals with MTHFR mutations or those seeking maximum bioavailability

Conclusion: Making an informed decision

The long-standing recommendation of folic acid for public health, particularly for neural tube defect prevention, is well-established and effective for the majority of the population. However, the increased understanding of genetic factors like the MTHFR mutation has brought methylfolate to the forefront as a superior alternative for those with compromised conversion pathways. The choice is not a simple one-size-fits-all, but rather an individual assessment based on genetics, absorption efficiency, and overall health status. When in doubt, a discussion with a healthcare professional can provide the clarity needed to select the best form of vitamin B9 for your needs.

Visit the CDC's Folic Acid Information Page for more details on recommendations.

Frequently Asked Questions

The MTHFR gene mutation is a common genetic variation that affects the body's ability to convert synthetic folic acid and dietary folate into its active form, L-methylfolate. Individuals with this mutation may have impaired folate metabolism.

Some studies suggest that methylfolate may help improve depressive symptoms, particularly in individuals with low folate levels or MTHFR gene variants, as it assists in neurotransmitter synthesis. However, research results are inconsistent, and high doses were used in successful studies. Consult a doctor before using it for depression.

It is generally unnecessary and not recommended to take both simultaneously. If you have an MTHFR mutation or choose methylfolate for better absorption, a separate folic acid supplement is not needed. Consult your doctor for personalized advice.

For many, methylfolate may be a better option during pregnancy due to its higher bioavailability, especially for those with MTHFR mutations. While folic acid is the traditional recommendation proven to prevent NTDs, methylfolate ensures optimal folate levels without relying on efficient conversion.

Folic acid is generally safe but high doses can cause side effects such as nausea, bloating, and diarrhea. More importantly, it can mask a serious vitamin B12 deficiency, leading to nerve damage if left unaddressed.

UMFA is folic acid that the body has not converted into its active form. It can accumulate in the bloodstream, particularly with high-dose supplementation or inefficient conversion due to MTHFR mutations. The long-term health effects are still being studied.

While folate is present in many foods, including leafy greens, legumes, and fortified grains, many people, especially those who are pregnant or have certain genetic factors, may not get enough from diet alone. Supplements are often recommended to ensure adequate intake.