Should I Take Folic Acid or Methylfolate? A Guide to Your B9 Supplement

November 2, 2025 •

4 min read

According to the Centers for Disease Control and Prevention (CDC), sufficient folate intake, particularly from folic acid, can prevent up to 70% of neural tube defects. However, for those with a common genetic variant, the conversion process can be less efficient, raising the question: should I take folic acid or methylfolate? The answer depends largely on your individual genetics and how your body processes this vital nutrient.

Quick Summary

This article explains the core differences between synthetic folic acid and the active form, methylfolate, detailing how the body processes each. It explores the role of the MTHFR gene, discusses who might benefit from one form over the other, and compares their bioavailability, cost, and typical uses.

Key Points

Folic Acid is Synthetic: A lab-made form of Vitamin B9 that requires a conversion process in the body to become active.
Methylfolate is Active: The bioavailable, active form of folate (5-MTHF) that bypasses the conversion process entirely.
MTHFR Gene Affects Conversion: Some people have genetic mutations (MTHFR polymorphism) that reduce their ability to convert folic acid to methylfolate.
Consider Methylfolate for MTHFR Variants: If you have a known MTHFR mutation, methylfolate may be a more efficient way to ensure adequate folate levels.
Folic Acid is Well-Researched for NTDs: The CDC and other health organizations primarily recommend folic acid for preventing neural tube defects, with extensive research supporting its efficacy.
Consult a Doctor for Guidance: A healthcare provider can help you decide which supplement is best based on your individual health needs and genetic profile.
Dietary Folate is Crucial: Natural folate is found in foods like leafy greens, legumes, and eggs, and should be part of a balanced diet alongside supplementation.

What is the difference between folate, folic acid, and methylfolate?

To understand the choice between supplements, it's essential to clarify the terminology around Vitamin B9. Folate is the general term for this vital B-vitamin, which is found naturally in many foods. Folic acid is the synthetic, lab-made version used in fortified foods and most standard supplements. Methylfolate, or L-methylfolate (5-MTHF), is the active, readily usable form of folate.

When you ingest folic acid, your body must perform a conversion process to turn it into methylfolate before it can be used for cellular functions. This process is carried out by an enzyme called methylenetetrahydrofolate reductase (MTHFR). Methylfolate, on the other hand, bypasses this conversion step entirely and is immediately available for the body to use.

The role of the MTHFR gene mutation

As much as 40–60% of the population carries a genetic variant of the MTHFR gene that can affect their ability to convert folic acid efficiently. The most common variant, C677T, is associated with a thermolabile (heat-sensitive) MTHFR enzyme with reduced activity. This means that individuals with this genetic makeup may not be able to process folic acid into its active methylfolate form as effectively as others. For these individuals, supplementation with methylfolate may be a more direct and reliable way to increase their folate levels. It is important to note, however, that the CDC states that most people with MTHFR variants can process folic acid and that it is the only form of folate proven to prevent neural tube defects. Consultation with a healthcare provider is recommended for personalized advice.

Benefits of adequate folate levels

Regardless of the form, sufficient folate is crucial for numerous bodily functions. A folate deficiency can lead to a wide range of health issues, including:

Megaloblastic anemia, characterized by large, immature red blood cells.
Fatigue and weakness.
Irritability and neurological symptoms.
Increased risk of neural tube defects during pregnancy, including spina bifida and anencephaly.
Cardiovascular disease risk, linked to elevated homocysteine levels.
Mood disorders like depression.

Which one is right for you? A comparison

Making the choice between folic acid and methylfolate depends on various factors, including genetics, cost, and specific health needs. Here's a comparative overview:


Feature	Folic Acid	Methylfolate (5-MTHF)
Form	Synthetic (lab-made) form of Vitamin B9.	Active, natural form of Vitamin B9.
Conversion	Requires enzymatic conversion by MTHFR in the body to become active.	Readily bioavailable; no conversion required.
Absorption	Can be inefficient for individuals with MTHFR gene variations.	More efficient absorption, particularly for those with MTHFR variants.
Research	Widely studied, especially for preventing neural tube defects.	Newer to the market; less extensive research on broad applications compared to folic acid.
Cost	Generally more affordable and widely available.	Typically more expensive due to the more complex manufacturing process.
Unconverted Folic Acid	Excess intake can lead to unmetabolized folic acid in the bloodstream.	Does not lead to unmetabolized folic acid accumulation.
Masking B12 Deficiency	High doses can potentially mask the hematological symptoms of Vitamin B12 deficiency.	Reduces the potential for masking a Vitamin B12 deficiency.
Typical Use	Standard recommendation for pregnancy prevention of neural tube defects, and general supplementation.	Often recommended for individuals with confirmed MTHFR mutations, recurrent pregnancy loss, or certain mood disorders.

Making an informed choice

For most people without a known MTHFR gene variant, standard folic acid supplementation is effective, affordable, and well-researched, particularly for pregnancy. Food fortification programs have successfully increased folate levels in the population using folic acid. However, if you have a known MTHFR polymorphism, a personal history of recurrent miscarriage, or other health concerns related to folate metabolism, methylfolate might be a more effective option. In some cases, a high intake of folic acid can result in unconverted folic acid circulating in the blood, which some studies suggest could have potential negative effects. Methylfolate sidesteps this issue by providing the active form directly.

Before starting any new supplement, it is crucial to consult with a healthcare provider. They can help determine if genetic testing for the MTHFR variant is appropriate for you and provide personalized recommendations based on your unique health profile, diet, and history. Remember that natural folate can be found in many foods, including green leafy vegetables, legumes, and eggs.

Conclusion

The choice between folic acid and methylfolate is not a one-size-fits-all decision. Folic acid remains the standard, effective, and evidence-based option for the general population, especially for preventing neural tube defects. However, methylfolate offers a compelling alternative for individuals with genetic variations affecting folate metabolism, providing a more bioavailable form that doesn't require conversion. Understanding your personal genetic profile and consulting a health professional are key steps in determining the best path for your nutritional needs. With increasing awareness and research, the personalized approach of choosing methylfolate is gaining traction for specific populations, but the long-standing benefits of folic acid for public health are undeniable.

Authoritative source

For detailed information on folate metabolism and the MTHFR gene, the National Institutes of Health (NIH) Office of Dietary Supplements offers a comprehensive fact sheet.

Frequently Asked Questions

The MTHFR gene provides instructions for making an enzyme that is crucial for processing folate. A mutation or variant in this gene can reduce the enzyme's activity, making it less efficient at converting folic acid into its active form, methylfolate.

Not necessarily. For the majority of people without an MTHFR gene mutation, folic acid supplementation is effective and proven to prevent conditions like neural tube defects. Methylfolate's primary advantage is for individuals with compromised conversion abilities.

Folic acid is widely recommended and has a longer history of extensive research demonstrating its effectiveness in preventing neural tube defects. Fortification programs have used folic acid for decades to successfully increase population-wide folate levels.

High doses of folic acid can lead to the presence of unconverted folic acid in the bloodstream, which some studies suggest may have potential side effects or interactions. It is also known to potentially mask the symptoms of a Vitamin B12 deficiency.

Methylfolate is generally considered safe, but some people report mild and infrequent side effects. These can include stomach upset, nausea, irritability, or altered sleep patterns. It is important to discuss any side effects with a healthcare provider.

You can increase your natural folate intake by consuming foods rich in this nutrient. Good sources include leafy green vegetables (like spinach and kale), legumes (beans, chickpeas, lentils), eggs, and some fruits (oranges and avocados).

Genetic testing for MTHFR variants is not routinely recommended for everyone. If you have a family or personal history of conditions like neural tube defects or recurrent miscarriages, or if you suspect impaired folate metabolism, discussing testing with a healthcare provider is a good idea.