Which Folate is Synthetic? Understanding Folic Acid vs. Natural Folate

December 11, 2025 •

3 min read

According to the CDC, mandated folic acid fortification has led to a significant decrease in neural tube defects in the U.S.. This synthetic vitamin is not identical to natural folate found in foods. Understanding which folate is synthetic and its metabolic pathway is crucial for making informed dietary and supplementation decisions.

Quick Summary

Folic acid is the man-made form of vitamin B9, used in supplements and fortified foods, unlike natural folate from vegetables. It is absorbed more easily but requires conversion for use, and high intake can mask vitamin B12 deficiency.

Key Points

Folic Acid is Synthetic: Folic acid is the man-made form of vitamin B9, distinct from natural folate found in whole foods.
Metabolic Conversion is Needed: The body must convert synthetic folic acid into its active form (5-MTHF), a process that some individuals perform inefficiently.
MTHFR Gene Affects Conversion: A common genetic variant of the MTHFR gene can impair the body's ability to metabolize folic acid effectively.
Fortification is a Public Health Strategy: Since 1998, enriched grains in the U.S. have been fortified with folic acid to prevent neural tube defects.
Bioactive Form is More Absorbable: L-methylfolate (5-MTHF) is the active, more bioavailable form that can be directly used by the body, bypassing the need for conversion.
High Doses Can Mask B12 Deficiency: Excessive intake of folic acid can hide the symptoms of a vitamin B12 deficiency, potentially leading to neurological damage.

Folic Acid: The Synthetic Version of Folate

Folic acid is the synthetic, man-made form of vitamin B9, created for supplements and to fortify foods. Its chemical structure is different from the reduced forms of folate found naturally in foods. In 1998, the U.S. Food and Drug Administration required food manufacturers to add folic acid to enriched grain products, such as bread, pasta, and cereals, to help prevent neural tube defects in infants. While this has been highly successful in public health, it has also created a scenario where a significant portion of the population is consuming a nutrient form that is not identical to the one in whole foods.

The Metabolic Differences

When you consume natural folate from food, your body breaks it down into the metabolically active form, 5-methyltetrahydrofolate (5-MTHF), primarily in the gut. Folic acid, however, is a more stable molecule that requires a multi-step enzymatic process, mainly in the liver, to be converted into 5-MTHF. This process is carried out by the dihydrofolate reductase (DHFR) enzyme. The efficiency of this conversion varies widely among individuals, and some researchers suggest that high intakes of folic acid can lead to a buildup of unconverted folic acid in the bloodstream.

MTHFR Gene and Conversion Issues

Compounding this metabolic difference is a genetic variation in the methylenetetrahydrofolate reductase (MTHFR) gene, which is surprisingly common. This gene provides the instructions for making the MTHFR enzyme, which is critical for one of the final steps in converting folic acid to 5-MTHF. Individuals with a variant of the MTHFR gene may have a reduced ability to perform this conversion efficiently. For these people, taking the more bioavailable form, L-methylfolate (the active form), in supplements may be a more effective way to increase their folate status.

Comparison Table: Folic Acid vs. Natural Folate


Feature	Folic Acid	Natural Folate
Source	Synthetic, man-made version	Naturally occurring in foods
Chemical Form	Oxidized monoglutamyl form	Reduced and polyglutamylated forms
Bioavailability	High when isolated; requires conversion	Highly dependent on food source; naturally active
Metabolism	Requires multi-step enzymatic conversion in liver	Converted in the small intestine; active 5-MTHF form
Common Sources	Fortified cereals, bread, supplements	Leafy greens, legumes, citrus fruits
Risk at High Doses	Can mask vitamin B12 deficiency	Does not mask vitamin B12 deficiency

What are the main dietary sources of natural folate?

Leafy Green Vegetables: Spinach, kale, romaine lettuce, and collard greens are excellent sources.
Legumes and Beans: Lentils, black beans, chickpeas, and edamame are packed with folate.
Nuts and Seeds: Peanuts and sunflower seeds contain good levels of natural folate.
Fruits: Citrus fruits like oranges, as well as mangoes and bananas, provide significant amounts.
Animal Products: Liver, seafood, eggs, and dairy products also contain natural folate.

Benefits of Adequate Folate

Both synthetic folic acid and natural folate are forms of vitamin B9 and are crucial for several bodily functions. They play a vital role in DNA synthesis and repair, cell growth, and the formation of healthy red blood cells. Adequate intake helps prevent folate deficiency anemia, which can cause fatigue, weakness, and mood changes. Most importantly, proper folate levels before and during pregnancy are essential for preventing neural tube defects like spina bifida.

Conclusion

In summary, the primary synthetic folate is folic acid, which is routinely added to supplements and fortified foods. While this fortification has been a public health triumph in preventing neural tube defects, it is crucial to understand its metabolic differences from natural food folate. For many people, especially those with MTHFR gene variants, the more bioavailable 5-MTHF form might be a more effective choice for supplementation. When considering supplementation, or if you have specific health concerns, it is always best to consult a healthcare professional to determine the most appropriate course of action for your individual needs. Remember, obtaining folate from a variety of natural food sources remains an essential part of a healthy diet.

Learn more about folate from the National Institutes of Health.

Frequently Asked Questions

Folate is the general term for the naturally occurring forms of vitamin B9 found in food, while folic acid is the synthetic, man-made form used in fortified foods and supplements.

For most people, both are beneficial. However, natural folate is already in a reduced, active state. The synthetic folic acid is more stable and better absorbed but requires conversion, which some people do less effectively, making active folate a better option for them.

The MTHFR gene provides instructions for the MTHFR enzyme, which converts inactive folic acid to its active form (5-MTHF). A genetic variation can make this conversion less efficient, potentially leading to lower folate levels.

Yes, taking very high doses of synthetic folic acid can mask the symptoms of a vitamin B12 deficiency, which can be dangerous as it may allow irreversible neurological damage to progress undetected.

Folic acid fortification in staple foods like cereals and bread has been instrumental in reducing the incidence of neural tube defects in infants. It ensures that a large portion of the population receives adequate intake, particularly in early pregnancy, which is crucial for fetal development.

Excellent food sources of natural folate include dark leafy green vegetables, legumes (beans, lentils), citrus fruits, eggs, liver, and nuts.

You should discuss this with a healthcare provider. Instead of folic acid, many individuals with an MTHFR mutation may be advised to take a supplement containing L-methylfolate (5-MTHF), the active form that does not require enzymatic conversion.