What is Folate Synthetic and How Does it Differ from Natural Folate?

January 13, 2026 •

3 min read

Over 80 countries worldwide, including the United States, mandate or recommend the fortification of certain foods with synthetic folate, known as folic acid, to prevent serious birth defects. This synthetic version of Vitamin B9 is structurally different from its natural counterpart and is intentionally added to a variety of foods and supplements to boost public health. Understanding what is folate synthetic and how it behaves in the body compared to natural folate is crucial for making informed dietary and health choices.

Quick Summary

Synthetic folate, or folic acid, is a man-made form of Vitamin B9 used in supplements and fortified foods like bread and cereals. While chemically different from natural food folate, it is vital for crucial bodily functions, especially during early pregnancy to prevent birth defects. The body processes synthetic folic acid differently than natural folate, a distinction with implications for absorption and metabolism.

Key Points

Folic Acid is Synthetic Folate: The terms 'synthetic folate' and 'folic acid' refer to the man-made form of Vitamin B9 found in supplements and fortified foods.
Metabolic Differences Exist: The body metabolizes synthetic folic acid differently than natural folate, requiring a two-step conversion process in the liver to become biologically active.
High Bioavailability: Synthetic folic acid is more stable and has higher bioavailability than natural folate from food sources, making it a reliable public health tool.
Vital for Pregnancy: Folic acid supplementation is proven to significantly reduce the risk of neural tube defects when taken before and during early pregnancy.
Genetic Considerations: Individuals with an MTHFR gene variation may have reduced ability to process synthetic folic acid, with some opting for a pre-methylated form like 5-MTHF.
Balanced Approach is Best: For most, a combination of natural folate from foods and synthetic folic acid from fortified products ensures adequate intake.

Demystifying Synthetic Folate: Folic Acid Explained

Folate is the general term for a water-soluble B-vitamin, also known as Vitamin B9, essential for cell growth, DNA synthesis, and red blood cell formation. The term 'folate synthetic' refers specifically to folic acid, the man-made version. Folic acid is more stable than natural folates found in foods, making it suitable for fortifying processed grain products.

Folic acid has been used in supplements and food fortification due to its stability and high bioavailability. This has effectively reduced neural tube defects (NTDs), serious birth defects, in areas with widespread fortification.

The Key Differences Between Synthetic Folic Acid and Natural Folate

Synthetic folic acid and natural folate have different chemical structures and metabolic pathways. Natural food folates are typically polyglutamates requiring breakdown for absorption, while folic acid is a monoglutamate absorbed directly.

The conversion to the active form, 5-methyltetrahydrofolate (5-MTHF), also differs.

Activation: Natural folate converts to 5-MTHF during digestion. Folic acid needs a two-step reduction process mainly in the liver, involving the enzyme dihydrofolate reductase (DHFR).
Unmetabolized Folic Acid: Due to limited DHFR capacity, especially with high intake, unmetabolized folic acid can build up in the bloodstream. The long-term health effects are still being studied.
Genetic Factors: A common genetic variation in the MTHFR gene can reduce the enzyme's ability to convert folic acid to 5-MTHF. In such cases, 5-MTHF supplementation might be considered, though folic acid remains the standard for NTD prevention.

Comparison Table: Folate vs. Folic Acid


Feature	Natural Folate	Synthetic Folic Acid
Source	Foods like leafy greens, legumes, citrus fruits.	Supplements and fortified foods.
Chemical Structure	Reduced, unstable, often polyglutamate.	Oxidized, stable, monoglutamate.
Absorption Rate	Variable, less efficient.	Highly bioavailable, easily absorbed.
Metabolism	Converted to 5-MTHF during digestion.	Requires a two-step process in the liver.
Stability	Sensitive to heat, light, processing.	Chemically stable.
Primary Use	Dietary intake.	Supplementation for deficiency and birth defects prevention.

Why We Use Synthetic Folate for Public Health

Synthetic folic acid is used due to its stability and effectiveness in public health. Natural folate is easily destroyed by cooking or processing. Folic acid's robustness ensures a consistent dose through common foods, which has successfully lowered neural tube defect rates, particularly important as these defects occur early in pregnancy.

Key Functions of Synthetic Folate in the Body

Once metabolized, synthetic folate is crucial for health, supporting:

DNA and Red Blood Cell Production: Essential for DNA synthesis/repair and healthy red blood cells.
Homocysteine Metabolism: Works with B12 and B6 to break down homocysteine, high levels of which are linked to cardiovascular risk.
Neurotransmitter Synthesis: Involved in creating neurotransmitters, affecting mood and mental health.

Fortified Foods and Supplementation

Food fortification provides a significant amount of folic acid for many people. However, for groups like women of childbearing age, supplements are often recommended. Consulting a healthcare professional about dosage is important, as high folic acid can hide a Vitamin B12 deficiency.

Common Fortified Foods:

Breakfast cereals
Breads
Pasta
Rice
Flour

Natural Sources of Folate:

Dark leafy greens
Legumes
Asparagus
Broccoli
Citrus fruits
Eggs

Conclusion: Understanding Your B9 Sources

What is folate synthetic? It is folic acid, a stable, absorbable man-made Vitamin B9 vital for public health. Though metabolically different from natural folate, both support essential functions like DNA synthesis and red blood cell production. A varied diet with natural folate and fortified foods usually suffices. However, for specific needs, like pregnancy, targeted folic acid supplementation is often advised by healthcare providers for optimal outcomes. Understanding the difference helps in making informed nutritional choices. For more on metabolism and genetics, researching the MTHFR gene is helpful.

Frequently Asked Questions

The main difference is their source and chemical structure; synthetic folate (folic acid) is a stable, man-made version used in supplements and fortified foods, while natural folate is found in its less stable form in various whole foods like leafy greens and legumes.

Yes, synthetic folate (folic acid) is generally safe at recommended intake levels. Public health measures using folic acid fortification have successfully reduced birth defects without widespread adverse effects. However, excessive intake can mask a Vitamin B12 deficiency.

Some people prefer methylated folate (5-MTHF) because they have a genetic variation (MTHFR polymorphism) that impairs their ability to convert synthetic folic acid into its active form. Methylated folate is already in the active form and doesn't require this conversion.

While uncommon at normal doses, very high intake of synthetic folic acid can potentially lead to mild side effects like nausea or bloating. More importantly, high levels can obscure the neurological symptoms of a Vitamin B12 deficiency, delaying diagnosis and treatment.

Packaged foods that contain synthetic folic acid must list it in the Nutrition Facts or Supplement Facts panel. Look for the term "folic acid" or the inclusion of "micrograms DFE" which indicates the total folate content, including any added folic acid.

Extensive clinical studies have shown that only folic acid supplementation has been proven to prevent neural tube defects. No scientific studies have demonstrated that other forms of folate, such as 5-MTHF, offer the same protection against NTDs.

The main purpose of fortifying foods with synthetic folic acid is to improve public health and prevent neural tube defects in infants. This is a particularly effective strategy because many pregnancies are unplanned, and neural tube development occurs very early, often before a woman knows she is pregnant.