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Folate vs folic acid vs folinic acid and role of each
Overview
Folate, folic acid, and folinic acid are all forms of vitamin B9, which is essential for healthy pregnancy, especially for the development of the baby’s brain and spine. Each form has unique properties, sources, and roles in the body.
Key Points
Folate
What it is:
- The natural form of vitamin B9 found in foods like leafy greens, legumes, and some fruits.
- Required for DNA synthesis, cell division, and normal growth and development, especially during pregnancy.
Role in Pregnancy:
- Supports the rapid cell growth needed for fetal development.
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Deficiency is linked to neural tube defects (NTDs), anemia, and other complications for both mother and baby.
The Critical Role of Folate in Prenatal Health and a Proposed Shift from Folic Acid to 5-Methyltetrahydrofolate Supplementation | Published in Georgetown Medical ReviewMenezo Y, Elder K, Clement A, Clement P. FolicAcid, FolinicAcid, 5 Methyl TetraHydroFolate Supplementation for Mutations That Affect Epigenesis through the Folate and One-Carbon Cycles. Biomolecules. 2022;12(2):197.Folic Acid Supplementation and Pregnancy: More Than Just Neural Tube Defect Prevention - PMCFolate (vitamin B9) is an essential ... and vitamin metabolism. Demands for folate increase during pregnancy because it is also required for growth and development of the fetus....Folic Acid for a Healthy Baby | Johns Hopkins MedicineThe developing baby needs folate to make healthy new cells, and to make DNA and RNA (genetic material). These are cell-building blocks. Folate also is essential to form normal red blood cells and certain amino acids. These are important functions during pregnancy and infancy.Folate vs. Folic Acid: What's the Difference?For people of all ages, it can be hard to maintain adequate B9 levels and meet the recommended daily amount without taking supplements. People who are pregnant or those planning to conceive need folic acid to reduce the risk of birth defects of the brain and spine (neural tube defects). The terms ...Read full articleSource: Cleveland Clinic
Absorption:
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Folate from food is less stable and less efficiently absorbed than synthetic forms.
Folic Acid for a Healthy Baby | Johns Hopkins MedicineThe developing baby needs folate to make healthy new cells, and to make DNA and RNA (genetic material). These are cell-building blocks. Folate also is essential to form normal red blood cells and certain amino acids. These are important functions during pregnancy and infancy.Folic Acid: Facts for Clinicians | Folic Acid | CDCFolic acid is more stable than folates found naturally in food. It is used in supplements and fortified foods, such as bread, pasta, some breakfast cereals, and some corn masa flour. A woman needs adequate folate in early pregnancy to properly form the neural tube, which becomes a baby's brain ...Folate vs. Folic Acid: What's the Difference?For people of all ages, it can be hard to maintain adequate B9 levels and meet the recommended daily amount without taking supplements. People who are pregnant or those planning to conceive need folic acid to reduce the risk of birth defects of the brain and spine (neural tube defects). The terms ...Read full articleSource: Cleveland Clinic
Folic Acid
What it is:
- The synthetic form of vitamin B9 used in supplements and fortified foods (like cereals and bread).
- More stable and better absorbed than natural folate.
Role in Pregnancy:
- Proven to reduce the risk of neural tube defects (NTDs) when taken before conception and during early pregnancy.
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Recommended daily intake for people who could become pregnant is 400 micrograms (mcg), starting at least one month before conception and continuing through the first trimester.
Folic Acid: Facts for Clinicians | Folic Acid | CDCFolic acid is more stable than folates found naturally in food. It is used in supplements and fortified foods, such as bread, pasta, some breakfast cereals, and some corn masa flour. A woman needs adequate folate in early pregnancy to properly form the neural tube, which becomes a baby's brain ...About Folic Acid | Folic Acid | CDCIt is the only form of folate that's been shown to help prevent serious birth defects called neural tube defects (NTDs). NTDs are major birth defects of the baby's brain (such as anencephaly) and spine (such as spina bifida). NTDs happen in the first few weeks of pregnancy, often before you ...Nutrition During Pregnancy | ACOGDuring pregnancy you need folic acid, iron, calcium, vitamin D, choline, omega-3 fatty acids, B vitamins, and vitamin C. See the below table for recommended amounts. ... Folic acid, also known as folate, is a B vitamin that is important during pregnancy.Folic acid | Office on Women's HealthEveryone needs folicacid to be healthy. But it is especially important for women: Before and during pregnancy. Folicacid protects unborn children against serious birth defects called neural tube defects. These birth defects happen in the first few weeks of pregnancy, often before a woman ...How and when to take folic acid - NHSNHS medicines information on dosage for folic acid, how to take it and what to do if you miss a dose or take too much.Read full articleSource: nhs.ukPrenatal Vitamins: Folate vs. Folic Acid and the MTHFR MutationWomen in intermediate- to high-risk ... risk and the appropriate level of folic acid supplementation. ... While often used interchangeably, folate and folic acid differ slightly....
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Higher doses (up to 4,000 mcg) may be recommended for those with higher risk factors (e.g., previous NTD-affected pregnancy, certain medical conditions).
About Folic Acid | Folic Acid | CDCIt is the only form of folate that's been shown to help prevent serious birth defects called neural tube defects (NTDs). NTDs are major birth defects of the baby's brain (such as anencephaly) and spine (such as spina bifida). NTDs happen in the first few weeks of pregnancy, often before you ...Prenatal Vitamins: Folate vs. Folic Acid and the MTHFR MutationWomen in intermediate- to high-risk ... risk and the appropriate level of folic acid supplementation. ... While often used interchangeably, folate and folic acid differ slightly....
Folinic Acid (and L-methylfolate)
What it is:
- Folinic acid (also called 5-formyltetrahydrofolate) and L-methylfolate (5-methyltetrahydrofolate) are active forms of folate used in the body.
- Folinic acid is available as a supplement and is sometimes used in medical settings, especially for people with specific metabolic or absorption issues.
Role in Pregnancy:
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Folinic acid and L-methylfolate can be used by the body without needing conversion by the MTHFR enzyme, which is important for people with certain genetic variations (MTHFR mutations) that reduce their ability to process folic acid efficiently.
Folic Acid Supplementation and Pregnancy: More Than Just Neural Tube Defect Prevention - PMCFolate (vitamin B9) is an essential ... and vitamin metabolism. Demands for folate increase during pregnancy because it is also required for growth and development of the fetus....Folic acid in pregnancy - ScienceDirectFolate (vitamin B9) is one of thirteen vital vitamins and is found in dietary products, while folic acid is the synthetic supplement used to fortify f…Read full articleSource: sciencedirect.comMultivitamin Supplementation During Pregnancy: Emphasis on Folic Acid and l-Methylfolate - PMCIncreased plasma homocysteine is ... adverse pregnancy outcomes. In a study by Lamers and colleagues,1 healthy women were randomly assigned to consume 400 µg of folicacid, 416 µg of Lmethylfolate (the bioequivalent dose of folicacid), and 208 µg of l-methylfolate (half dose). Each group experienced increases in plasma folate and decreases ...Active Folate Versus Folic Acid: The Role of 5-MTHF (Methylfolate) in Human Health - PMCWhile implementing specific ... the absorption of folate is much more effective with fortified foods and supplements, such as 5-MTHF/folate and folic acid. In fact, in the last decades, the main form of folate supplementation has been FA. Prescription of FA to women in the preconception period ...
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However, only folic acid supplementation has been proven in large studies to prevent neural tube defects. There is not enough evidence to recommend folinic acid or L-methylfolate as a replacement for folic acid for the general population.
Prenatal Vitamins: Folate vs. Folic Acid and the MTHFR MutationWomen in intermediate- to high-risk ... risk and the appropriate level of folic acid supplementation. ... While often used interchangeably, folate and folic acid differ slightly....
How They Work in the Body
Conversion and Activation
- Folic acid must be converted in the body to its active form (L-methylfolate) through several steps, including one that uses the MTHFR enzyme.
- Folate from food is also converted to active forms, but less efficiently.
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Folinic acid and L-methylfolate are already in active forms and can be used directly by the body, which is why they may be considered for people with MTHFR mutations.
Folic acid in pregnancy - ScienceDirectFolate (vitamin B9) is one of thirteen vital vitamins and is found in dietary products, while folic acid is the synthetic supplement used to fortify f…Read full articleSource: sciencedirect.comMultivitamin Supplementation During Pregnancy: Emphasis on Folic Acid and l-Methylfolate - PMCIncreased plasma homocysteine is ... adverse pregnancy outcomes. In a study by Lamers and colleagues,1 healthy women were randomly assigned to consume 400 µg of folicacid, 416 µg of Lmethylfolate (the bioequivalent dose of folicacid), and 208 µg of l-methylfolate (half dose). Each group experienced increases in plasma folate and decreases ...Active Folate Versus Folic Acid: The Role of 5-MTHF (Methylfolate) in Human Health - PMCWhile implementing specific ... the absorption of folate is much more effective with fortified foods and supplements, such as 5-MTHF/folate and folic acid. In fact, in the last decades, the main form of folate supplementation has been FA. Prescription of FA to women in the preconception period ...
Summary
- Folate is the natural form in foods; folic acid is the synthetic, stable, and well-absorbed form in supplements and fortified foods; folinic acid and L-methylfolate are active forms sometimes used for people with absorption or genetic issues.
- Folic acid supplementation before and during early pregnancy is the only intervention proven to reduce the risk of neural tube defects.
- Most guidelines recommend 400 mcg of folic acid daily for anyone who could become pregnant, as it is difficult to get enough from food alone.
- Folinic acid or L-methylfolate may be considered in special cases, but are not standard for NTD prevention in the general population.
If you have questions about which form is best for your individual needs—especially if you have a known MTHFR mutation or other health concerns—it might be beneficial to discuss this with your OB/GYN, who can work with you on your personal course of care.
References:Peer-Reviewed Research
Published, peer-reviewed scientific studies from journals or databases.
Clinical Guidelines & Professional Sources
Clinical recommendations from government, public health organizations, or professional medical provider associations.
Medical & Academic Institutions
Information from hospitals, research institutions, or academic medical centers known for clinical expertise and research contributions.
General Health & Web Sources
Publicly available health-related articles from non-peer-reviewed sources. These may reference research or clinical guidelines, but are not primary sources.
Uncategorized Sources
Information from sources that have not yet been categorized.
What made this response need improvement?
How robust is the evidence on folic acid supplementation?
Overview
The evidence supporting folic acid supplementation for the prevention of neural tube defects (NTDs) in pregnancy is considered extremely robust. This conclusion is based on decades of research, including large randomized controlled trials, systematic reviews, and ongoing recommendations from major health organizations.
Key Points
Strength of Evidence for Neural Tube Defect Prevention
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Convincing and Consistent Results:
Multiple large-scale randomized controlled trials and systematic reviews have shown that taking 400–800 micrograms (mcg) of folic acid daily before conception and during early pregnancy reduces the risk of NTDs (such as spina bifida and anencephaly) by at least 50% or more.Multivitamin Supplementation During Pregnancy: Emphasis on Folic Acid and l-Methylfolate - PMCIncreased plasma homocysteine is ... adverse pregnancy outcomes. In a study by Lamers and colleagues,1 healthy women were randomly assigned to consume 400 µg of folicacid, 416 µg of Lmethylfolate (the bioequivalent dose of folicacid), and 208 µg of l-methylfolate (half dose). Each group experienced increases in plasma folate and decreases ...Folic acid: influence on the outcome of pregnancy - PubMedThe periconceptional use of folicacid-containing supplements reduces the first occurrence, as well as the recurrence, of neural tube defects. Women of populations in which adverse pregnancy outcomes are prevalent often consume diets that contain a low density of vitamins and minerals, including ...Read full articleSource: PubMedFolate vs. Folic Acid: What's the Difference?For people of all ages, it can be hard to maintain adequate B9 levels and meet the recommended daily amount without taking supplements. People who are pregnant or those planning to conceive need folic acid to reduce the risk of birth defects of the brain and spine (neural tube defects). The terms ...Read full articleSource: Cleveland ClinicFolic acid | Office on Women's HealthEveryone needs folicacid to be healthy. But it is especially important for women: Before and during pregnancy. Folicacid protects unborn children against serious birth defects called neural tube defects. These birth defects happen in the first few weeks of pregnancy, often before a woman ...How and when to take folic acid - NHSNHS medicines information on dosage for folic acid, how to take it and what to do if you miss a dose or take too much.Read full articleSource: nhs.ukPrenatal Vitamins: Folate vs. Folic Acid and the MTHFR MutationWomen in intermediate- to high-risk ... risk and the appropriate level of folic acid supplementation. ... While often used interchangeably, folate and folic acid differ slightly....Active Folate Versus Folic Acid: The Role of 5-MTHF (Methylfolate) in Human Health - PMCWhile implementing specific ... the absorption of folate is much more effective with fortified foods and supplements, such as 5-MTHF/folate and folic acid. In fact, in the last decades, the main form of folate supplementation has been FA. Prescription of FA to women in the preconception period ...Folic acid supplementation in pregnancy and implications in health and disease | Journal of Biomedical Science | Full TextIn addition, studies in humans, also reported to have found higher blood folate concentration of unmetabolized FA and naturally occurring folates [78]. To gain a better understanding if maternal supplementation of FA modulates pregnancy related outcomes, much focus has been given to reveal the role ...Folic acid supplementation during pregnancy for maternal health and pregnancy outcomes - PMCThe role of folate deficiency in increasing the risk of spontaneous abortion and birth outcomes such as low birthweight, preterm birth, and perinatal mortality is unclear (Bukowski 2009; Scholl 2000). Hence, the aim of this review is to assess the effect of folicacid supplementation alone in pregnant women on haematological and biochemical parameters, adverse events during pregnancy... -
Global Health Guidelines:
The U.S. Preventive Services Task Force (USPSTF), World Health Organization (WHO), and other major health authorities give an “A” grade (highest certainty and benefit) to the recommendation that all people who could become pregnant take a daily folic acid supplement.Multivitamin Supplementation During Pregnancy: Emphasis on Folic Acid and l-Methylfolate - PMCIncreased plasma homocysteine is ... adverse pregnancy outcomes. In a study by Lamers and colleagues,1 healthy women were randomly assigned to consume 400 µg of folicacid, 416 µg of Lmethylfolate (the bioequivalent dose of folicacid), and 208 µg of l-methylfolate (half dose). Each group experienced increases in plasma folate and decreases ...Folic acid: influence on the outcome of pregnancy - PubMedThe periconceptional use of folicacid-containing supplements reduces the first occurrence, as well as the recurrence, of neural tube defects. Women of populations in which adverse pregnancy outcomes are prevalent often consume diets that contain a low density of vitamins and minerals, including ...Read full articleSource: PubMedFolic acid | Office on Women's HealthEveryone needs folicacid to be healthy. But it is especially important for women: Before and during pregnancy. Folicacid protects unborn children against serious birth defects called neural tube defects. These birth defects happen in the first few weeks of pregnancy, often before a woman ...How and when to take folic acid - NHSNHS medicines information on dosage for folic acid, how to take it and what to do if you miss a dose or take too much.Read full articleSource: nhs.ukActive Folate Versus Folic Acid: The Role of 5-MTHF (Methylfolate) in Human Health - PMCWhile implementing specific ... the absorption of folate is much more effective with fortified foods and supplements, such as 5-MTHF/folate and folic acid. In fact, in the last decades, the main form of folate supplementation has been FA. Prescription of FA to women in the preconception period ...Folic acid supplementation in pregnancy and implications in health and disease | Journal of Biomedical Science | Full TextIn addition, studies in humans, also reported to have found higher blood folate concentration of unmetabolized FA and naturally occurring folates [78]. To gain a better understanding if maternal supplementation of FA modulates pregnancy related outcomes, much focus has been given to reveal the role ...Intestinal absorption of folic acid - new physiologic & molecular aspects - PMC3). [Reprinted with permission from John Wiley & Sons Ltd., UK: Eur J Haematol2006; 76: 200-5]. In order to maintain an adequate folate status, the intake of folates/folic acid should be appropriate and the absorption processes of folates/folic acid in the small intestine should function properly. -
Population Impact:
Countries that have implemented folic acid supplementation and food fortification have seen significant declines in the rates of NTDs.Folic acid supplementation during pregnancy for maternal health and pregnancy outcomes - PMCThe role of folate deficiency in increasing the risk of spontaneous abortion and birth outcomes such as low birthweight, preterm birth, and perinatal mortality is unclear (Bukowski 2009; Scholl 2000). Hence, the aim of this review is to assess the effect of folicacid supplementation alone in pregnant women on haematological and biochemical parameters, adverse events during pregnancy...
Evidence for Other Pregnancy Outcomes
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Other Outcomes Less Clear:
While folic acid is essential for maternal health and fetal development, evidence for benefits beyond NTD prevention—such as reducing the risk of preterm birth, low birth weight, or preeclampsia—is less consistent or conclusive. Some studies and meta-analyses suggest possible benefits, but results are mixed and not as robust as for NTD prevention.Folic Acid Supplementation and Pregnancy: More Than Just Neural Tube Defect Prevention - PMCFolate (vitamin B9) is an essential ... and vitamin metabolism. Demands for folate increase during pregnancy because it is also required for growth and development of the fetus....Nutrition During Pregnancy | ACOGDuring pregnancy you need folic acid, iron, calcium, vitamin D, choline, omega-3 fatty acids, B vitamins, and vitamin C. See the below table for recommended amounts. ... Folic acid, also known as folate, is a B vitamin that is important during pregnancy.Folic acid in pregnancy - ScienceDirectFolate (vitamin B9) is one of thirteen vital vitamins and is found in dietary products, while folic acid is the synthetic supplement used to fortify f…Read full articleSource: sciencedirect.comPregnancy, breastfeeding and fertility while taking folic acid - NHSNHS medicines information on folic acid and whether you can take it while pregnant or breastfeeding.Read full articleSource: nhs.ukIntestinal absorption of folic acid - new physiologic & molecular aspects - PMC3). [Reprinted with permission from John Wiley & Sons Ltd., UK: Eur J Haematol2006; 76: 200-5]. In order to maintain an adequate folate status, the intake of folates/folic acid should be appropriate and the absorption processes of folates/folic acid in the small intestine should function properly.
Safety and Harms
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Safety Profile:
Folic acid supplementation at recommended doses (400–800 mcg daily) is not associated with serious harms to the mother or baby. High-quality studies have found no increased risk of autism, cancer, or other major adverse effects at these doses.Folic acid: influence on the outcome of pregnancy - PubMedThe periconceptional use of folicacid-containing supplements reduces the first occurrence, as well as the recurrence, of neural tube defects. Women of populations in which adverse pregnancy outcomes are prevalent often consume diets that contain a low density of vitamins and minerals, including ...Read full articleSource: PubMedFolic acid supplementation in pregnancy and implications in health and disease | Journal of Biomedical Science | Full TextIn addition, studies in humans, also reported to have found higher blood folate concentration of unmetabolized FA and naturally occurring folates [78]. To gain a better understanding if maternal supplementation of FA modulates pregnancy related outcomes, much focus has been given to reveal the role ...Folic acid | Office on Women's HealthEveryone needs folicacid to be healthy. But it is especially important for women: Before and during pregnancy. Folicacid protects unborn children against serious birth defects called neural tube defects. These birth defects happen in the first few weeks of pregnancy, often before a woman ...How and when to take folic acid - NHSNHS medicines information on dosage for folic acid, how to take it and what to do if you miss a dose or take too much.Read full articleSource: nhs.uk
Limitations and Research Gaps
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Beyond NTDs:
There is inadequate evidence to support benefits of folic acid supplementation for outcomes other than NTD prevention, and more research is needed in these areas.Folic Acid Supplementation and Pregnancy: More Than Just Neural Tube Defect Prevention - PMCFolate (vitamin B9) is an essential ... and vitamin metabolism. Demands for folate increase during pregnancy because it is also required for growth and development of the fetus....Nutrition During Pregnancy | ACOGDuring pregnancy you need folic acid, iron, calcium, vitamin D, choline, omega-3 fatty acids, B vitamins, and vitamin C. See the below table for recommended amounts. ... Folic acid, also known as folate, is a B vitamin that is important during pregnancy.Folic acid | Office on Women's HealthEveryone needs folicacid to be healthy. But it is especially important for women: Before and during pregnancy. Folicacid protects unborn children against serious birth defects called neural tube defects. These birth defects happen in the first few weeks of pregnancy, often before a woman ...Folic acid in pregnancy - ScienceDirectFolate (vitamin B9) is one of thirteen vital vitamins and is found in dietary products, while folic acid is the synthetic supplement used to fortify f…Read full articleSource: sciencedirect.comIntestinal absorption of folic acid - new physiologic & molecular aspects - PMC3). [Reprinted with permission from John Wiley & Sons Ltd., UK: Eur J Haematol2006; 76: 200-5]. In order to maintain an adequate folate status, the intake of folates/folic acid should be appropriate and the absorption processes of folates/folic acid in the small intestine should function properly. -
Optimal Dose and Timing:
Most evidence supports starting supplementation at least one month before conception and continuing through the first trimester. There is less clarity about benefits of continuing supplementation later in pregnancy for other outcomes.Folic acid | Office on Women's HealthEveryone needs folicacid to be healthy. But it is especially important for women: Before and during pregnancy. Folicacid protects unborn children against serious birth defects called neural tube defects. These birth defects happen in the first few weeks of pregnancy, often before a woman ...Active Folate Versus Folic Acid: The Role of 5-MTHF (Methylfolate) in Human Health - PMCWhile implementing specific ... the absorption of folate is much more effective with fortified foods and supplements, such as 5-MTHF/folate and folic acid. In fact, in the last decades, the main form of folate supplementation has been FA. Prescription of FA to women in the preconception period ...
Summary
- The evidence that folic acid supplementation prevents neural tube defects is extremely strong, consistent, and forms the basis for global health recommendations.
- The benefit is greatest when supplementation starts before conception and continues through the first trimester.
- Folic acid supplementation is safe at recommended doses, and no serious harms have been identified.
- Evidence for benefits beyond NTD prevention is less robust and remains an area for further research.
Peer-Reviewed Research
Published, peer-reviewed scientific studies from journals or databases.
Clinical Guidelines & Professional Sources
Clinical recommendations from government, public health organizations, or professional medical provider associations.
Medical & Academic Institutions
Information from hospitals, research institutions, or academic medical centers known for clinical expertise and research contributions.
General Health & Web Sources
Publicly available health-related articles from non-peer-reviewed sources. These may reference research or clinical guidelines, but are not primary sources.
Uncategorized Sources
Information from sources that have not yet been categorized.