What are Folate and Folic Acid?
Folate and folic acid are two different forms of vitamin B9, an essential nutrient involved in DNA synthesis and cell growth. However, they differ in their origin, chemical structure, and how the body processes them. Folate is the general term for the naturally occurring form of vitamin B9 found in various foods. It exists in different chemical forms called polyglutamates and is often unstable, being sensitive to heat and light during cooking and storage. In contrast, folic acid is the synthetic, oxidized form of vitamin B9 used in dietary supplements and added to fortified foods like cereals, bread, and pasta. This synthetic form is far more stable than natural folate, which is why it is used for food fortification.
Bioavailability: The Key Difference
Bioavailability refers to the proportion of a nutrient that is absorbed and becomes available for use or storage in the body. When it comes to the question of which is more bioavailable, folate or folic acid, the answer is clear: folic acid is significantly more bioavailable.
The difference in absorption is rooted in their chemical structure and metabolic pathway. For natural food folate to be absorbed by intestinal cells, its polyglutamate “tail” must first be enzymatically removed, a process called de-conjugation. This process is inefficient and variable, with only about 50% of food folate typically being absorbed. Folic acid, on the other hand, exists as a monoglutamate and does not require this conversion step in the intestine, leading to much higher absorption rates. When ingested on an empty stomach, supplemental folic acid is nearly 100% bioavailable, while folic acid from fortified foods is about 85% bioavailable.
Once absorbed, folic acid is not biologically active and must undergo a two-step conversion process in the liver, mediated by the enzyme dihydrofolate reductase (DHFR), to become the active form, 5-methyltetrahydrofolate (5-MTHF). Natural food folate, once de-conjugated and absorbed, can enter the folate cycle more directly.
Factors Influencing Bioavailability
- Food Matrix: The physical structure of food can affect how well folate is released for absorption. Different food matrices can have varying impacts on the bioavailability of the folate they contain.
- Cooking and Processing: As a heat- and light-sensitive vitamin, natural food folate can be substantially degraded during cooking, canning, or other processing methods. Folic acid's stability means it is not lost in this way.
- Genetic Factors: An individual's genetics can influence how they metabolize vitamin B9, most notably the MTHFR polymorphism.
- Interaction with Other Nutrients: Nutrients such as vitamin C and B12, as well as an individual's existing folate levels, can affect absorption and metabolism.
What are Dietary Folate Equivalents (DFEs)?
To account for the differences in bioavailability, the Food and Nutrition Board introduced Dietary Folate Equivalents (DFEs). This unit standardizes the intake of both natural folate and synthetic folic acid, allowing for a more accurate comparison of a person's total vitamin B9 consumption.
DFEs are calculated using the following conversions:
- 1 mcg DFE = 1 mcg of food folate
- 1 mcg DFE = 0.6 mcg of folic acid from fortified foods or supplements taken with food
- 1 mcg DFE = 0.5 mcg of folic acid from supplements taken on an empty stomach
For example, 100 mcg of food folate would provide 100 mcg DFE, while 100 mcg of folic acid from a supplement taken with food would provide 170 mcg DFE (100 / 0.6). This system highlights the higher potency of folic acid in raising folate levels in the body.
Folate vs. Folic Acid: A Comparison Table
| Feature | Folate | Folic Acid |
|---|---|---|
| Source | Naturally occurring in foods | Synthetic form (man-made) |
| Chemical Structure | Polyglutamates | Monoglutamate |
| Metabolism | De-conjugated in the intestine for absorption | Metabolized by the liver to the active form (5-MTHF) |
| Absorption Rate | Variable, approximately 50% | High, up to 100% on an empty stomach |
| Stability | Unstable, easily destroyed by heat and light | Very stable, used in fortified foods |
| Presence in Foods | Leafy greens, citrus fruits, beans, liver | Fortified grains like breads, pasta, and cereals |
| Risk of Excess | Extremely low risk from natural food sources | Potential risks with high intake (e.g., masking B12 deficiency) |
The MTHFR Gene and Folate Metabolism
Individuals with a polymorphism in the MTHFR gene may have reduced activity of the enzyme methylenetetrahydrofolate reductase. This enzyme is crucial for the final step of converting folic acid into the biologically active 5-MTHF form. For these individuals, a high intake of folic acid could lead to an accumulation of unmetabolized folic acid (UMFA) in the bloodstream. While the impact of UMFA is not fully understood, some have raised concerns about its potential health effects. For individuals with MTHFR variants, supplementation with L-methylfolate (the active form) may be a more efficient option, though it is not conclusively proven to be more effective than standard folic acid for preventing neural tube defects. The CDC and other health bodies continue to recommend folic acid for all women of childbearing age, including those with MTHFR variations, due to the proven track record in preventing neural tube defects.
Considerations and Potential Risks
While folic acid fortification has been a public health success story in reducing the incidence of neural tube defects (NTDs), it has also created new considerations. High intake of synthetic folic acid can mask the megaloblastic anemia associated with vitamin B12 deficiency. This can delay the diagnosis and treatment of the underlying B12 deficiency, potentially allowing neurological damage to progress irreversibly. This risk is most significant with high-dose supplementation, not typically from fortified foods alone.
Research is ongoing into other potential adverse effects of high folate status or UMFA accumulation, including possible associations with increased cancer risk, cognitive issues, and immune system effects, but evidence remains inconclusive. The Tolerable Upper Intake Level (UL) for folic acid from supplements and fortified foods is set at 1,000 mcg per day for adults, primarily to prevent the masking of B12 deficiency.
How to Ensure Optimal Folate Intake
For most people, a combination of natural folate and folic acid from fortified foods and multivitamins is a healthy approach. Folate-rich foods offer a wide range of other beneficial nutrients, fiber, and antioxidants.
Foods Rich in Natural Folate
- Leafy green vegetables (spinach, romaine lettuce, asparagus, Brussels sprouts)
- Legumes (lentils, chickpeas, beans)
- Citrus fruits (oranges, orange juice)
- Avocado
- Liver
For women of childbearing age, the Centers for Disease Control and Prevention recommends consuming 400 micrograms of folic acid daily from supplements or fortified foods, in addition to dietary folate, to prevent neural tube defects. This is critical because NTDs occur very early in pregnancy, often before a woman knows she is pregnant.
Conclusion
While natural folate is essential, synthetic folic acid has higher and more predictable bioavailability due to its stability and simple chemical form. This high bioavailability is precisely why folic acid is used in fortified foods and supplements, contributing to a significant public health reduction in birth defects. However, this higher absorption rate, combined with potential genetic variations like MTHFR, means that some individuals might benefit from considering L-methylfolate or carefully monitoring their intake. The best approach for most remains a balanced diet of folate-rich foods, supplemented with folic acid as needed, and consulting a healthcare provider for personalized guidance, especially in the context of pregnancy or underlying health conditions. The higher bioavailability of folic acid is a powerful tool, but it requires mindful consumption to optimize health outcomes.
