Folic Acid or Folate?

folate or folic acid MTHFR Agnes Ryu

Epigenetics has taught us that the best time to prevent miscarriage or birth defects is before pregnancy and immediately after conception. Early miscarriage may result from a poor nutritional state or a hormonal imbalance immediately preceding conception. Many serious birth defects originate within the first eight weeks of pregnancy while the foetus is developing.

Folic acid – a harmful synthetic vitamin?

Nearly everyone has heard that pregnant women should take folic acid to prevent birth defects and most prenatal supplements include this. What is not reported is that folic acid is the synthetic form of vitamin B9  and only a small percentage of folic acid converts to 5-methyl tetrahydrofolate, the biologically active form of folate. Synthetic folic acid is not found naturally in food and poorly processed by the body and begins to accumulate in the bloodstream at just 400 micrograms per day with many unwanted side effects.

Pregnancy and folate

Folate is critical for foetal development. Folate is required to synthesize, repair and express DNA.

Folate plays a huge role in cell and tissue growth. It is used to form red blood cells in bone marrow, where it also helps to make antibodies by using sugars and amino acids. Folate works with vitamin B12 in the formation of haemoglobin and is essential for zinc metabolism. It is a fundamental ingredient for good mental and physical health and plays a crucial role in pregnancy because a mother’s body needs a large quantity of it to share with the foetus.

Prevention of foetal abnormalities

Studies suggest that women who supplement with folate during the month of conception and the first eight to ten weeks after conception are less likely to have a malformed baby. Nonetheless, folate deficiency is common during pregnancy. This deficiency can lead to foetal abnormalities like cleft palate, harelip, deformed limbs, neural tube defects like spina bifida, skeletal deformities, lung and kidney underdevelopment, cataracts, brain deformities, and anaemia. Underdevelopment of the heart, diaphragm, urogenital system, blood vessels, adrenals, and eyes can also result.

Problem with the unmetabolized folic acid accumulation

Supplementation with folic acid has been shown to reduce the incidence of neural tube defects. If you do not eat folate-rich foods, synthetic folic acid can benefit but there may be an upper limit, particularly after the first month of pregnancy.

Unmetabolized folic acid, which is elevated in many pregnant women who use these supplements competes with glutamate to bind on neural growth cones in foetuses.

If folic acid outcompetes glutamate, researchers hypothesize it could impair neural development. It has been proposed that excess unmetabolized folic acid from folic acid supplementation could increase the risk of autism.


Genetics: MTHFR gene mutation

 To make matters worse, up to 55% of the European population has the MTHFR gene defect. This gene is responsible for breaking down (methylating) folate in the body.

The effect of this gene defect is to reduce the ability to convert folic acid into the active form and this causes synthetic vitamins to build up in the body. Supplemental and enriched folic acid foods should be avoided by those afflicted with MTHFR C677T mutations because the MTHFR mutation has partially destroyed the MTHFR enzyme which is required to process folic acid completely.

This gene mutation can have a big impact on pregnancy. It has been associated with vitamin B deficiencies, an impaired ability to clear out toxins and an increased risk of blood clots. It also elevates homocysteine levels, which have been associated with difficult pregnancies or miscarriages, birth defects, inflammation and heart disease. A methylation problem can also prevent proper neurotransmitter production and lead to problems with mental health, cellular health, autoimmune disease, infertility, miscarriages and even cancer. If you have a MTHFR gene mutation, you do need to optimize your methylation pathways.

Folate: The Right Form of Folic Acid

For a long time, women of childbearing age have been advised to supplement with folic acid to prevent neural tube defects in their children. However, the use of synthetic folic acid which is frequently recommended is in fact, inadvisable. The biologically active form of folate, which is understood by the body and used in the methylation cycle is what is needed. This active form is sometimes marketed as Methyl-folate or 5-MTHF (5-methyltetrahydrofolate).  This is a form of this critical B vitamin that can be taken in an effort to bypass any gene mutations.

I used to recommend taking 800 micrograms of folate per day but I became increasingly wary of the very concept of supplementation and isolated nutrients after performing nutritional tests.  Folate doesn’t work alone and right form of vitamins B2, B6, and B12, as well as cofactors like magnesium, are required to support the methylation cycle and these are best to take from real food.

Green leafy vegetables can give some folate but their bioavailability is low. Organ meats, especially the liver is by far the best source of folate and other essential nutrients. I recommend the consumption of 200-300 grams per week of beef or lamb liver as the true superfood for pregnancy. This is particularly relevant to ex-vegans and vegetarians.  Also note, a number of medications interfere with folate metabolism and these include metformin and synthetic hormones.

Best Liver Pate recipe can be found here.

For further information on methylation and MTHFR issues, the nutritional biochemist, Chris Masterjohn offers an excellent explanation here.




Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects?

Agnes Ryu

Agnes Ryu

Dr. Ryu is a clinician and biochemist specializing in integrative medicine. Her clinical interests include fertility, hormones, metabolism, healthy ageing, menopause, and natural breast cancer care. As an integrative practitioner, Dr. Ryu aims to uncover the root causes of health issues and strives to empower patients with the knowledge and tools to take charge of their own health.

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