Is Folic Acid Toxic?

supplementation Apr 28, 2023
pregnant taking prenatal vitamins


Hint: the answer is no. But make sure you read on to learn why. 


If you’re planning to conceive, you would have heard about folic acid. It’s recommended that all women should take folic acid, 1 month before conceiving and during the first 12 weeks of pregnancy, as it is essential for the development of the neural tube (1). Neural tube defects include anencephaly and spina bifida and are the two most common birth defects worldwide (2). You may have also heard of folate, folinic acid and methyl folate. It’s really important to understand the differences between these types of folate when it comes to preconception and pregnancy supplementation.


The Difference Between Folic Acid + Other Forms of Folate


The terms ‘folic acid’ and ‘folate’ are both used to describe Vitamin B9, but they are not technically the same. 


Folate is a ‘natural’ form of Vitamin B9 found in whole foods including dark leafy green vegetables (spinach), asparagus, Brussel sprouts, legumes (chickpeas, kidney beans, lentils), broccoli, nuts and seeds. 


Folic acid is the ‘synthetic’ form of Vitamin B9 found in supplements and added to processed and fortified foods. It is a favourable form because of its stability, is not degraded by heat (2) and is easily absorbed in the small intestines (3). 


When it comes to folates and conceiving, natural is not always the best choice.


Folic acid is the ONLY form of folate proven by a large body of evidence to reduce the risk of neural tube defects. Folic acid is a stable molecule and is therefore the superior choice for prenatal supplements because of the precision of dosing required.


Folinic acid is a natural form of folate, but not interchangeable with folic acid for neural tube defects. It is the precursor to the biologically active form of folate in the body, however folinic acid hasn’t been proven to reduce neural tube defect risk.


Methyl folate also known as 5-methyltetrahydrofolic acid, is the biologically active form of folate in the body. Being the active form, it doesn’t need converting to be used by the body. Although preliminarily data is promising, methyl folate cannot be recommended at a public health level for the prevention of neural tube defects. Unfortunately, methyl folate isn’t stable over 40 degrees Celsius and therefore the quality can degrade. 


Quatrefolic ®, a type of methyl folate used in supplements, is stable at room temperature and in refrigerated conditions according to the manufacturers data. This sensitivity to heat and degradation means that you may get the protective dose of folate, if the supplement hasn’t been stored and transported in a controlled environment.


Fortification of Foods


Mandatory folic acid fortification was introduced in Australia in 2009 as a public health initiative to reduce the instance of neural tube defects in infants. Fortification of bread and cereal products has had a positive effect on reducing the rates of neural tube defects. However, as research continues to develop there are now concerns that we are getting too much folic acid via food sources, which could have detrimental effects (3). It’s important to be aware of the foods in your diet that are “folic acid fortified”and how many serves you consume daily. 


As an example: According to Food Standards Australia, 3 slices (100g) of commercial bread (not bakery or artisan) contains 120 mcg folic acid (3). Since the 2009 mandatory fortification of refined grain products, there has been an average increase of 247 mcg per day of folic acid (4). This in addition to a prenatal containing 400- 500 mcg of folic acid does not exceed the upper limit of 1000 mcg daily.


Why is Folic Acid / Vitamin B9 Essential? 


Folic acid is not an active nutrient and needs to be converted (or changed) into an “active” form to enter biochemical processes within the body called the “methylation cycle”. The methylation cycle is a metabolic process that regulates the conversion of methionine (an essential amino acid) to the amino acid homocysteine and has effects on DNA methylation as well as in the cardiovascular, neurological, reproductive, and detoxification systems.


Is folic acid toxic? 


You may be feeling a little confused about folate and folic acid. There has been a lot of misinformation spread about it recently, mainly on social media. It’s important to highlight that folic acid is a water-soluble vitamin that can be excreted by the body. It’s not the same as Vitamin A which is a fat-soluble vitamin that stores in the body and has been found to cause congenital disorders and abnormalities in high doses in pregnancy. 


The upper limit of folic acid for a woman of reproductive age is 1000 mcg daily. At a supplemental dose of 400 mcg daily, folic acid is unlikely to cause adverse effects. 


Folic acid when taken in high dosages can remain unmetabolised in the blood. Being a water-soluble vitamin, unmetabolised folic acid is processed by the kidneys and excreted in the urine. Unless vitamin B12 deficiency is present, unmetabolised folic acid it’s not a concern. 


Folic acid is first absorbed by the small intestine. It then travels through the blood to the liver where it is metabolised and converted to “active” form 5-methyltetrahydrofolic acid. This process can be slower for individuals with the MTHFR gene but is only a concern for those with a homozygous (two copies of same gene) or compound variant (meaning one copy of both genes), which only affects 10% of the population. For those with heterozygous, the conversion of folic acid may be slower, but absorption is not compromised (4).

High dose folic acid supplementation can mask vitamin B12 deficiency. B12 deficiency can lead to anaemia and lead to adverse cognitive effects and nerve damage. These adverse effects usually occur with long term high dose folic acid supplementation and chronic B12 deficiency.  Screening for B12 deficiency is simple via a blood test and deficiency is preventable. This is why a prenatal that contains both folic and B12 is preferable.(4) 

The current dietary guidelines set by the Australian National Health and Medical Research Council have set the following guidelines for folate and folic acid intake: 


Life stage 


Folic Acid 

  • Females 



  • Pregnant Females 



  • Lactating Females 



  • Upper limit

No upper limit 

1,000 mcg


Preconception Supplementation 


A large body of evidence (5) exists that 400 mcg folic acid taken in the months prior to pregnancy reduces the risk of neural tube defects. Women planning to conceive should be taking a multivitamin supplement that contains 400 mcg folic acid daily. Vitamin B12 works in synergy with folate in the methylation cycle. Deficiencies on both B9 and B12 mask each other, hence why we recommend a multivitamin, which contains additional B12. 


Should you have concerns about folic acid absorption, please discuss with your healthcare practitioner. The neural tube closes around week 4-6 of pregnancy (this is usually around the time you discover you're pregnant).


Pregnancy Supplementation


Many women may choose to swap to a methyl folate after the first 8-12 weeks of pregnancy or in the second trimester. Given the neural tube has already closed by this time, it is an option if preferred. Bear in mind that the total daily RDI for folate in pregnancy is 600 mcg. Taking a prenatal multi vitamin contains 400 - 500 mcg of folate equivalents, with additional B12. 


So, what’s the take home?

  • Choose a prenatal supplement containing 400- 500 mcg of folic acid. 
  • Consume foods that are high in natural sources of folate (leafy greens and legumes)- you cannot eat too much of these.
  • If you are taking a supplement that contains folic acid, be mindful of your intake of foods fortified with folic acid (breads, pasta and grains) and not to exceed the upper limit of 1000 mcg.
  • If you are concerned about genetic SNPs (such as MTHFR) or have elevated blood homocysteine, reach out to a practitioner who can support you through your fertility journey.  




  1.   Obeid R, Holzgreve W, Pietrzik K. Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects? J Perinat Med [Internet]. 2013 Jan 1 [cited 2020 Feb 19];41(5). Available from:
  2.   Wald NJ, Morris JK, Blakemore C. Public health failure in the prevention of neural tube defects: time to abandon the tolerable upper intake level of folate. Public Health Rev. 2018 Dec;39(1):2. 
  3.   Ledowsky C, Mahimbo A, Scarf V, Steel A. Women Taking a Folic Acid Supplement in Countries with Mandatory Food Fortification Programs May Be Exceeding the Upper Tolerable Limit of Folic Acid: A Systematic Review. Nutrients. 2022 Jun 29;14(13):2715. 
  4.   Wald NJ. Folic acid and neural tube defects: Discovery, debate and the need for policy change. J Med Screen. 2022 Sep;29(3):138–46. 
  5.   De-Regil LM, Peña-Rosas JP, Fernández-Gaxiola AC, Rayco-Solon P. Effects and safety of periconceptional oral folate supplementation for preventing birth defects. Cochrane Pregnancy and Childbirth Group, editor. Cochrane Database Syst Rev [Internet]. 2015 Dec 14 [cited 2023 Feb 28];2015(12). Available from:


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