What are other forms of folic acid?

January 12, 2026 •

2 min read

According to the CDC, the fortification of grain products with synthetic folic acid has led to a significant decrease in neural tube defects since its mandate in 1998. However, many people are unaware that folic acid is not the only form of vitamin B9 and that other forms exist, each with unique metabolic properties.

Quick Summary

Folic acid is a synthetic form of vitamin B9, but other forms like L-methylfolate and folinic acid are naturally occurring and have higher bioavailability. Different forms serve various purposes, from general supplementation to targeted therapy for specific genetic factors.

Key Points

L-Methylfolate is the active form: L-methylfolate (or 5-MTHF) is the highly bioavailable, active form of vitamin B9 that the body can use directly without conversion.
Folic acid is synthetic: Folic acid is a synthetic, man-made version of vitamin B9 used in fortified foods and many supplements, which must be converted by the body.
Folinic acid has specific uses: Folinic acid is another reduced folate form, primarily used in clinical settings to counteract the toxicity of drugs like methotrexate.
MTHFR affects metabolism: A common genetic variation in the MTHFR enzyme can impair the body's ability to convert synthetic folic acid, making L-methylfolate a better option for some individuals.
Food folate is less stable: Natural folate found in foods is less stable than synthetic folic acid and can be easily destroyed during cooking.
Bioavailability differs: L-methylfolate offers superior bioavailability for direct use, while folic acid's absorption is efficient but requires enzymatic conversion.
Excess folic acid concerns: High intake of synthetic folic acid can lead to a buildup of unmetabolized folic acid in the blood, which is a subject of ongoing research.

The term "folate" refers to the various forms of vitamin B9, an essential nutrient for DNA synthesis, red blood cell production, and overall cellular health. While folic acid is the most commonly known synthetic form, understanding the differences between it and other forms is crucial for proper supplementation and health management.

Natural Folate (Food Folate)

Naturally occurring folate is found in many foods, particularly dark green leafy vegetables, legumes, eggs, and citrus fruits. Food folate is often in a polyglutamated form and must be converted by the digestive system into a monoglutamate form to be absorbed. The final conversion to the active, usable form, L-methylfolate, involves the MTHFR enzyme. However, natural folate is relatively unstable and can be destroyed by heat during cooking.

L-Methylfolate (5-MTHF)

L-methylfolate, or 5-MTHF, is the biologically active form of folate used directly by the body. Unlike synthetic folic acid, it does not require conversion by the MTHFR enzyme, making it a superior option for individuals with genetic variations in this enzyme. These variations can impair the body's ability to convert folic acid efficiently, leading to potential folate deficiencies even with adequate intake. L-methylfolate is highly bioavailable and is increasingly used in high-quality supplements, including many prenatals. Some brands utilize patented forms of L-methylfolate for enhanced stability and absorption.

Folinic Acid (Leucovorin)

Folinic acid, also known as leucovorin, is another reduced, natural form of folate. It is a 5-formyl derivative of tetrahydrofolate (THF) and is primarily used in a clinical setting as a "rescue" therapy to counteract the toxic effects of high-dose methotrexate, which is a folic acid antagonist used in chemotherapy. Folinic acid is effective in these scenarios because it bypasses the inhibited metabolic pathways. It can also be a non-methylated, bioactive alternative for individuals with certain metabolic disorders or sensitivities.

Folic Acid vs. Other Folates: A Comparison

For a detailed comparison of features including source, conversion requirements, bioavailability, and ideal uses, refer to {Link: droracle.ai https://www.droracle.ai/articles/230694/what-is-difference-between-folic-acid-and-folinic-acid}.

The MTHFR Genetic Variation

A significant number of people have a genetic variation in the MTHFR enzyme, which is vital for converting folic acid into its active form, L-methylfolate. For these individuals, supplementation with synthetic folic acid can be less effective, potentially leading to lower folate levels despite adequate intake. Supplementing with L-methylfolate is often recommended for this group to bypass the inefficient metabolic step. Research suggests that a notable percentage of people have this genetic variation, making the choice of folate form a relevant consideration.

Conclusion

While synthetic folic acid has played a critical public health role, other forms like natural food folate, L-methylfolate, and folinic acid offer unique benefits and uses. Understanding what are other forms of folic acid allows for more informed decisions regarding diet and supplementation.

Outbound Link

For a detailed scientific exploration of folate metabolism, see the comprehensive review provided by the National Institutes of Health.

Toward a better understanding of folate metabolism in health... - National Institutes of Health

Frequently Asked Questions

Folic acid is the synthetic form of vitamin B9, while L-methylfolate is the biologically active form. Folic acid requires a multi-step conversion process in the body to become usable, whereas L-methylfolate can be utilized directly.

Individuals with a genetic variation in the MTHFR enzyme may have difficulty converting folic acid to its active form. L-methylfolate is recommended for these individuals to ensure effective folate supplementation.

While natural food folates are essential for health, their bioavailability is lower and more variable compared to supplemental forms, and they can be degraded by cooking. For some, especially those with MTHFR mutations or specific conditions, supplementation with L-methylfolate is more reliable.

Folinic acid is primarily used in clinical medicine as an antidote to counteract the toxic side effects of high-dose methotrexate, a drug used in chemotherapy. It helps protect healthy cells by bypassing the metabolic pathway that methotrexate inhibits.

Yes, high doses of synthetic folic acid can potentially lead to a buildup of unmetabolized folic acid in the bloodstream. The long-term health implications of this are still under investigation.

Unlike high doses of synthetic folic acid, L-methylfolate does not mask a vitamin B12 deficiency. Excessive folic acid can correct the hematological signs of a B12 deficiency while allowing neurological damage to progress.

High-quality supplements and prenatal vitamins often specify if they contain L-methylfolate. Some products, like those using the patented Quatrefolic® form, use the glucosamine salt of 5-MTHF for superior stability and absorption.

While folic acid has been proven effective at reducing neural tube defects, L-methylfolate is often considered a superior alternative, especially for those with MTHFR mutations, because it is more efficiently utilized by the body and avoids unmetabolized folic acid buildup. It is important to consult a healthcare provider for personalized advice.