Folic acid vs folate

Folate is an essential nutrient, especially during pregnancy and when trying to conceive. The benefits of folate, or vitamin B9, are well established. Yet even care practitioners can be unaware of how differently the distinctive forms of folate act in the body. It’s easy to be confused by the various terms or to assume they are interchangeable. Once you know the differences, you’ll understand how important it is to seek out the right form.
 

What is folate?

Folate is a water-soluble B vitamin present in whole foods such as leafy greens, citrus fruits, beans and other legumes, avocados, eggs, and beef liver. Folate is the generic term for food folates as well as folates in supplements and fortified foods like enriched breads and breakfast cereals. Naturally occurring food folates are in the tetrahydrofolate (THF) form. 

Folic acid is the fully oxidized monoglutamate form of the vitamin that is added in fortified foods and most dietary supplements (1). The molecular structure of folic acid is nearly identical to folate, leading to the frequent confusion that they are the same. However, that small difference can make a big difference when it comes to how folate is processed by your body.

Why is folate important?

Folate is a key player in methylation, playing a role in making DNA, gene expression, detoxification of cells in the brain, and regulating homocysteine, a critical factor in heart and neurocognitive health. Because folate is so important for healthy neural tube development, it’s an essential vitamin to look for in a prenatal multivitamin when trying to conceive and during pregnancy, or in a fertility health supplement when facing challenges to conceive. But folate is important for everyone. It goes beyond early development and can influence mood, sleep, memory, and more for both children and parents.

Folate has many benefits, including:

  • Supports healthy neurodevelopment 


  • Supports energy production


  • Supports  memory & brain processing speed


  • Supports the creation of DNA


  • Helps make neurotransmitters 


The different forms of folate

When it comes to understanding folate, an essential point to remember is that folate is the general term for vitamin B9. Folic acid, methylfolate, folinic acid, and food folate are all forms of folate. One common question we hear is, “What’s the difference between folic acid and folate?” Or, “Is folic acid the same as folate?” While all these forms are subtypes of folate, these subtypes are not the same. 

Folic acid is the form commonly found in multivitamins because it is inexpensive and stable. However, those with the MTHFR gene variant (up to 60% of people) aren’t able to metabolize folic acid efficiently.

Methylfolate is the active form found in our bodies. When you take methylfolate, your body can use it immediately because it doesn’t have to convert it to anything else. Quatrefolic® (glucosamine salt of (6S)-5-methyltetrahydrofolate) is one brand of methylfolate that is made in Italy. One advantage of Quatrefolic is that it passes through the stomach and is absorbed mainly in the small intestine. This enables Quatrefolic to ensure a higher folate uptake. Quatrefolic completely bypasses the MTHFR conversion step and delivers a finished folate the body can immediately use without any kind of metabolization.

Folinic acid (5-formyltetrahydrofolate) is a naturally occurring folate. It can convert easily to methylfolate without the enzyme dihydrofolate reductase. This allows your body to regulate the amount of methylfolate it needs.

It is important to note that folinic acid is different from folic acid. Folic acid is synthetic and does not exist in nature, whereas folinic acid exists naturally and is biologically active. Two words that look so alike, yet with a significant difference.
 

Why should I take methylfolate over folic acid?

The synthetic form, folic acid, is processed differently in our bodies. A majority of people (up to 60%) have a variation in their MTHFR gene that doesn’t allow them to properly convert folic acid into active methylfolate.

MTHFR (Methylenetetrahydrofolate reductase) is the key enzyme that regulates this conversion process. This means that those taking folic acid may not be absorbing it as intended. If you are trying to get pregnant, consider getting a genetic test to determine if you have the MTHFR genetic variation. Furthermore, taking folic acid can block the absorption of methylfolate for many people with the MTHFR variant (2). 

Even for people without the MTHFR variant, it’s preferable to get folate from whole food sources and supplements that contain the active form of folate, methylfolate, instead of synthesized folic acid. Folic acid has to go through several steps in the body to become the active form, methylfolate, whereas a supplement with methylfolate is ready to go in the active form.

 Absorption and Transformation Steps between Folic Acid and Methylfolate chart.

What happens to folic acid that isn’t absorbed?

For those with the inability to process folic acid, that excess can be a problem. If your intake of folic acid exceeds your capacity to process it, it can overwhelm the liver and potentially end up in the bloodstream. There are increasing concerns that exposure to unmetabolized folic acid, which results from folic acid intakes that overwhelm the liver's metabolic capacity, may be associated with adverse effects (2).

Other benefits of folate: immunity health

Your body takes the food you eat and converts it into methyl groups. This takes time and energy and, sometimes, your body can’t do this properly. You can shortcut this process when you take methylated vitamins. With them, your body isn’t required to work extra hard to change the vitamins or food you eat into a version with methyl groups. That’s because methylated vitamins come with methyl groups that are ready to go.

Having extra methyl groups at your immune system’s disposal can help it work efficiently without wearing you down.

Why is folate important during pregnancy and preconception?

Folate is especially important for pregnancy. During pregnancy, folate supports a baby’s healthy neural tube development and is very important in the early weeks. Recommended folate intake increases during pregnancy and breastfeeding to fuel rapid growth and help prevent neural tube defects in the fetus.

Demands for folate increase during pregnancy because of folate’s role in nucleic acid synthesis (10), the synthesis of DNA and RNA, which is essential for the growth and proliferation of all body cells. The American College of Obstetricians and Gynecologists (ACOG) recommends a prenatal vitamin supplement for most pregnant women.

An optimal folate status must be achieved before conception and in the first trimester when the neural tube closes. Many neural tube defects (NTDs) can be prevented by increasing maternal folate intake in the pre-conceptional period. Women of childbearing age should ensure a daily intake of at least 400 mcg of folate for at least 4 weeks before and 12 weeks after conception to reduce the risk of having a child with NTD (3).

Although the generally recommended amount of folic acid for all adults is 400 mcg a day, many doctors recommend higher amounts for women who are able to get pregnant (400-800 mcg). The Mama Bird Prenatal Multi+ line has 800 mcg of folate (as methylfolate and folinic acid) to help women meet their nutritional needs. There are also options if you are looking for a prenatal vitamin without iron and iodine or a twice-daily prenatal with extra choline.

Folate is very important when pursuing fertility goals and pregnancy. It is needed for healthy neurodevelopment. It supports the creation of DNA and plays a central role in methylation, a biological process required for healthy eggs (4,5,6,7).

With all of this in mind, we formulated Women's Fertility supplemnt for women facing fertility challenges with L-methylfolate, the active form of folate our body uses. We chose this active form of folate so that you are supported when trying to pursue your fertility goals, whether you have the MTHFR genetic variation or not. If you don’t know if you have the MTHFR gene variation, our fertility formula with methylfolate removes the guesswork.

How much folate?
When taking methylfolate to help with your fertility goals, consume between 400 and 800 mcg daily.

Can I get folate from my diet?

Absolutely, however food folate still has to go through processes to become methylfolate, the form your body uses. There are many good dietary sources of folate. One easy tip is to remember the 3 L’s: legumes, leafy greens, and liver. Some fresh fruits, like citrus, are also a good option. Other food sources include nuts, seafood, eggs, dairy products, meat, poultry, and grains. For foods with some of the highest folate levels, choose spinach, liver, asparagus, and brussels sprouts.

However, the reality is we lead busy lives and often don’t have time to prepare and enjoy diverse, whole-food meals, or to get a recommended 6-8 servings of green vegetables a day. Plus, the depletion of soil can make many of our fruits and vegetables less nutrient-dense than they once were and that nutrients are often lost during food preparation and cooking. Supplementation is often a great way to make sure you’re getting enough folate.
 

What happens when you are low?

All women capable of becoming pregnant should obtain adequate amounts of folate to reduce the risk of NTDs and other birth defects. People with the MTHFR genetic polymorphism have an impaired ability to convert folate to its active form. About 25% of Hispanics, 10% of Caucasians and Asians, and 1% of African Americans are homozygous for the 677C>T MTHFR polymorphism (8). This polymorphism results in less biologically available 5-MTHF (5-MTHF is methylfolate) and, thus, reduced methylation potential, leading to elevated homocysteine levels and an increased risk of NTDs (9,10,11,12) .

Although the research on the benefits of folate supplementation for people with this genetic polymorphism is inconclusive, these people might benefit from supplementation with 5-methyl-THF (another abbreviation for methylfolate) (11,13).

Methylated vitamins

Best Nest Wellness supplements are made with methylated vitamins like methylfolate, the active form of vitamins found in your body that come with attached methyl groups. If you are a woman of childbearing age, it’s a good idea to consider when to start taking prenatal vitamins.

For women just starting to think about trying to conceive or at the beginning of their pregnancy journey, we recommend our Mama Bird Multi+ line. You can find methylated prenatal vitamins in our entire multivitamin line including the Mama Bird Prenatal Multi+, Mama Bird AM/PM, and Mama Bird Prenatal Multi+ Iodine and Iron Free. If you are looking for support for him as you begin your pregnancy journey, the Mama Bird line pairs well with Men’s Fertility supplement.

For women who have been trying to conceive for more than four months, there is Women’s Fertility supplement. This also pairs well with Men’s Fertility supplement.

Or if you need even more methyl support, there is Smart Folate® Methylfolate. 

References

(1) Bailey LB, Caudill MA. Folate. In: Erdman JW, Macdonald IA, Zeisel SH, eds. Present Knowledge in Nutrition. 10th ed. Washington, DC: Wiley-Blackwell; 2012:321-42.

(2) Folic acid handling by the human gut: implications for food fortification and supplementation, National Library of Medicine, National Center for Biotechnology Information, Epub 2014 Jun 18, PMID: 24944062, PMCID: PMC4095662, DOI: 10.3945/ajcn.113.080507.

(3) Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects? De Gruyter, 2013, DOI: https://doi.org/10.1515/jpm-2012-0256.

(4) Folate and neural tube defects, The American Journal of Clinical Nutrition, Volume 85, Issue 1, January 2007, Pages 285S–288S. 

(5) Mitochondrial function and toxicity: Role of the B vitamin family on mitochondrial energy metabolism, Elsevier, Chemico-Biological Interactions, Volume 163, Issues 1-2, 27 October 2006, Pages 94-112.

 (6) Folate and Vitamin B12: Function and Importance in Cognitive Development, Bhutta ZA, Hurrell RF, Rosenberg IH (eds): Meeting Micronutrient Requirements for Health and Development. Nestlé Nutr Inst Workshop Ser Nestec Ltd., Vevey/S. Karger AG., Basel, 2012, vol 70, pp 161–171

 (7) Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate's role. Adv Nutr. 2012;3(1):21-38. doi:10.3945/an.111.000992

(8) Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin Pharmacokinet 2010;49:535-48.

(9) Folate. In: Erdman JW, Macdonald IA, Zeisel SH, eds. Present Knowledge in Nutrition. 10th ed. Washington, DC: Wiley-Blackwell; 2012:321-42.

(10) Modern Nutrition in Health and Disease. 11th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2012:358-68.

(11) Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica 2014;44:480-8.

(12) Genetic risk factors for folate-responsive neural tube defects. Annu Rev Nutr 2017;37:269-91.

(13) Folic acid supplementation and pregnancy: more than just neural tube defect prevention. Rev Obstet Gynecol 2011;4:52-9.

(14) Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 1998.