Matthew Messer

Matthew Messer

Editor-in-chief

Vitamin B9 is often mistakenly referred to as folic acid, when in fact folic acid is an oxidized form of folate, found in many supplements and vitamin-fortified foods. Folate is an essential B vitamin, necessary for the synthesis of amino acids and DNA, but is also a key player in several other biological processes. (1) 

What does folate do for you? 

Folic acid supplementation has long been recommended during pregnancy, as a lack of folate can lead to a pregnancy disorder called a neural tube defect. This problem can be effectively prevented by folic acid supplementation, although the best idea is actually supplementation with other forms of folate. (2)  

Methylfolate is preferable to folic acid in many ways, particularly because many people have gene mutations that reduce the function of the enzyme converting folic acid into the form utilizable in our bodies. Those with these mutations are at increased risk of diseases that are caused in part by folate deficiency. (3) 

Such conditions include depression and some cancers. Folate deficiency also increases homocysteine levels, which is a risk factor for dementia, Alzheimer's disease, and cardiovascular disease. (4,5,6)  

How much folate do we need? 

The daily recommended folate intake varies from country to country, ranging from 250-400 mcg, increasing to 400-800 mcg during pregnancy. Most people's diet provides them with a fraction of these values, around 100-150 mcg. It's important to consider that food sources of folate have an absorption rate of about 50%. 

While it's impossible to get too much folate from natural foods, it can easily happen with supplements. Over 800 mcg per day, folic acid appears in the blood, indicating a higher intake than the body can convert. (8) 

Excessive folate intake can reduce immune cell function and may also suppress the symptoms of an existing vitamin B12 deficiency. This is dangerous because B12 deficiency causes severe neurological damage over time, and the suppressed symptoms make timely detection difficult. (9) 

Nutritional sources of folate 

Folate is found in many foods, but the best sources are vegetables and pulses. Among foods of animal origin, liver and eggs are the richest sources. Green leafy vegetables such as spinach and lettuce contain 100-200 mcg of folate per 100 grams, similar to cruciferous broccoli and Brussels sprouts. Legumes also contain similar amounts, 10 dkg of lentils, for example, contain 150 mcg of folate. As with many B vitamins, the winner is liver, with 250 mcg of B9 per 100 g. (10) 

Folic acid, the form used as a supplement, is found in many cereal foods, so it is a good idea to mind the ingredients when consuming these. They often contain 100-150 mcg of folic acid per serving. Care should also be taken when taking supplements, as many products on the market mistakenly contain more than 1000 mcg of folic acid, which is an unrealistic dose and can lead to the problems mentioned above.

The advantage of supplements containing methylfolate is that there is no need to worry about gene mutations inhibiting conversion, although an adequate vitamin B2 intake may cancel out that problem for folic acid, as well. (11) Intakes of vitamins B2, B6, and B12, as well as choline, are also important for folate to work properly. Particular attention should be paid to folate intake during and before pregnancy and when consuming large amounts of alcohol.   

The many beneficial effects 

Adequate intake of folate during pregnancy minimizes the risk of prematurity but also reduces the risk of preterm birth, gestational anemia, and autism. (2,12,14) However, methyl folate is more effective than folic acid in preventing anemia. (13)  

Low folate intake has been associated with the development of depression. (4) Folate supplementation, in this case, has led to mixed results but has reduced depressive symptoms in several clinical trials. (15)  

Folate deficiency can increase the levels of homocysteine in the body. Higher levels of homocysteine can increase the incidence of Alzheimer's disease, dementia, and cardiovascular disease. (6,16) Folic acid supplementation has been shown to reduce the risk of stroke in several large studies. (17) 

Could it be harmful? 

Excessive folic acid intake, although not a problem in the short term, can cause issues in the long term. Adequate folate intake is therefore very important, but we need to be careful, partly because of the form of folate and partly because it is one of the micronutrients whose healthy range is relatively narrow. 

In countries where folic acid fortification of food has been introduced, some worrying things have happened. Although there is not much concrete evidence of negative effects, excessive folic acid consumption can accelerate the development of colon and potentially other cancers. These show some correlation with the appearance of fortification. (7)  

In one study, supplementing 1 g of folic acid per day significantly increased the risk of colon cancer. Since it was not blood folate, but specifically methylfolate that was associated with the risk, it is likely worth minding the intake of this form of folic acid, as well as that of folic acid. (19) In addition, excessive folic acid intake may reduce the activity of certain immune cells, and in pregnancy, supplementation of more than 1000 mcg per day may negatively affect the cognitive abilities of the unborn child. (18)  

Interesting facts 

Folate is often referred to as folic acid, but this is only a synthetic form of B9. Although it has a bad reputation, the main problem is excess intake and a simultaneous vitamin B12 deficiency. 

[The cover photo of the note shows Roman lettuce. 100 grams contain 136 μg of vitamin B9, about a third of the required daily intake.]

  1. Merrell BJ, McMurry JP. Folic Acid. [Updated 2021 Nov 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554487/ 

  2. Grosse SD, Collins JS. Folic acid supplementation and neural tube defect recurrence prevention. Birth Defects Res A Clin Mol Teratol. 2007 Nov;79(11):737-42. doi: 10.1002/bdra.20394. PMID: 17990333. 

  3. Gilbody S, Lewis S, Lightfoot T. Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review. Am J Epidemiol. 2007 Jan 1;165(1):1-13. doi: 10.1093/aje/kwj347. Epub 2006 Oct 30. PMID: 17074966. 

  4. Bender A, Hagan KE, Kingston N. The association of folate and depression: A meta-analysis. J Psychiatr Res. 2017 Dec;95:9-18. doi: 10.1016/j.jpsychires.2017.07.019. Epub 2017 Jul 22. PMID: 28759846. 

  5. Zhang D, Wen X, Wu W, Guo Y, Cui W. Elevated homocysteine level and folate deficiency associated with increased overall risk of carcinogenesis: meta-analysis of 83 case-control studies involving 35,758 individuals. PLoS One. 2015;10(5):e0123423. Published 2015 May 18. doi:10.1371/journal.pone.0123423 

  6. Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, Wilson PW, Wolf PA. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med. 2002 Feb 14;346(7):476-83. doi: 10.1056/NEJMoa011613. PMID: 11844848. 

  7. Kim YI. Folate and colorectal cancer: an evidence-based critical review. Mol Nutr Food Res. 2007 Mar;51(3):267-92. doi: 10.1002/mnfr.200600191. PMID: 17295418. 

  8. Paniz C, Bertinato JF, Lucena MR, De Carli E, Amorim PMDS, Gomes GW, Palchetti CZ, Figueiredo MS, Pfeiffer CM, Fazili Z, Green R, Guerra-Shinohara EM. A Daily Dose of 5 mg Folic Acid for 90 Days Is Associated with Increased Serum Unmetabolized Folic Acid and Reduced Natural Killer Cell Cytotoxicity in Healthy Brazilian Adults. J Nutr. 2017 Sep;147(9):1677-1685. doi: 10.3945/jn.117.247445. Epub 2017 Jul 19. PMID: 28724658; PMCID: PMC5712455. 

  9. Johnson MA. If high folic acid aggravates vitamin B12 deficiency what should be done about it? Nutr Rev. 2007 Oct;65(10):451-8. doi: 10.1111/j.1753-4887.2007.tb00270.x. PMID: 17972439. 

  10. https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/ 

  11. McNulty H, Dowey le RC, Strain JJ, Dunne A, Ward M, Molloy AM, McAnena LB, Hughes JP, Hannon-Fletcher M, Scott JM. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism. Circulation. 2006 Jan 3;113(1):74-80. doi: 10.1161/CIRCULATIONAHA.105.580332. Epub 2005 Dec 27. PMID: 16380544. 

  12. Greenberg JA, Bell SJ, Guan Y, Yu YH. Folic Acid supplementation and pregnancy: more than just neural tube defect prevention. Rev Obstet Gynecol. 2011;4(2):52-59. 

  13. Bentley S, Hermes A, Phillips D, Daoud YA, Hanna S. Comparative effectiveness of a prenatal medical food to prenatal vitamins on hemoglobin levels and adverse outcomes: a retrospective analysis. Clin Ther. 2011 Feb;33(2):204-10. doi: 10.1016/j.clinthera.2011.02.010. Epub 2011 Mar 25. PMID: 21440300. 

  14. Levine SZ, Kodesh A, Viktorin A, Smith L, Uher R, Reichenberg A, Sandin S. Association of Maternal Use of Folic Acid and Multivitamin Supplements in the Periods Before and During Pregnancy With the Risk of Autism Spectrum Disorder in Offspring. JAMA Psychiatry. 2018 Feb 1;75(2):176-184. doi: 10.1001/jamapsychiatry.2017.4050. PMID: 29299606; PMCID: PMC5838577. 

  15. Taylor MJ, Carney S, Geddes J, Goodwin G. Folate for depressive disorders. Cochrane Database Syst Rev. 2003;2003(2):CD003390. doi: 10.1002/14651858.CD003390. PMID: 12804463; PMCID: PMC6991158. 

  16. Chrysant SG, Chrysant GS. The current status of homocysteine as a risk factor for cardiovascular disease: a mini review. Expert Rev Cardiovasc Ther. 2018 Aug;16(8):559-565. doi: 10.1080/14779072.2018.1497974. Epub 2018 Jul 17. PMID: 29979619. 

  17. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, Held C, Genest J Jr; Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006 Apr 13;354(15):1567-77. doi: 10.1056/NEJMoa060900. Epub 2006 Mar 12. Erratum in: N Engl J Med. 2006 Aug 17;355(7):746. PMID: 16531613. 

  18. Valera-Gran D, Navarrete-Muñoz EM, Garcia de la Hera M, Fernández-Somoano A, Tardón A, Ibarluzea J, Balluerka N, Murcia M, González-Safont L, Romaguera D, Julvez J, Vioque J; INMA Project. Effect of maternal high dosages of folic acid supplements on neurocognitive development in children at 4-5 y of age: the prospective birth cohort Infancia y Medio Ambiente (INMA) study. Am J Clin Nutr. 2017 Sep;106(3):878-887. doi: 10.3945/ajcn.117.152769. Epub 2017 Jul 19. PMID: 28724645. 

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