Folic acid vs folate: the dangers of folic acid

[RedFox]

I just watched this interview by Dr John Campbell, and I'm glad I did.
It runs into something that was discussed in the MTHFR mutation community several decades ago - that of (synthetic) folic acid build up in the blood, and it's blocking mechanism to (natural) folate. I didn't think this was a big deal at the time - other than perhaps contributing to fatigue and DNA methylation not working so well. However it seems the research by these two (and others) has is questioning this.
So a quick FYI before digging into this topic.
Folic acid is a synthetic chemical, and not a vitamin. It can have a small percentage converted into folate in the body.
Folate is what the body needs, and is an actual vitamin/naturally occurring product.
Many Dr's, websites, and research papers confuse folic acid (synthetic) for folate (natural) and vice versa.

The 'fortification of food' with things like folic acid since the 80's is potentially causing a great deal of health problems. Most off the shelf vitamins are folic acid. I should also mention that most off the shelf vitamins also contain a form of B12 that is really not good for you (cyanocobalamin - cobalamin combined with cyanide).

The reason given for this public health intervention, was because it could prevent neural tube defects in babies. A better option would be mothers who may be prone to this (i.e. have a MTHFR type mutation), should be getting natural folate from foods - and/or a proper folate supplement (methylated folate).
Please note I am not a doctor and this isn't medical advice - if you are pregnant or attempting to get pregnant, please do your own research.

Here are the links from under the video:

Direct link to the paper, https://www.researchgate.net/public...ning_title_Cerebral_folate_disruption_and_ASDhttps://www.youtube.com/redirect?event=video_description&redir_token=QUFFLUhqbDhBUGcyYjBKLUIwRWx3V1BSdGpCclFoaU13d3xBQ3Jtc0trWkxhaHJVWURGTUhwNEZTWjFZQmxvUHYwSDQxWjVpTGtUSF95VjJwR1RxODdzM1hxLWlBSWpyU3BhYlJReFFkektxRmxtNGRnbjdOX3piSTI1VFp0S1lkMnJkdHBfSkQ5N0U2YWdMZm53eVl5V0xtNA&q=https://www.researchgate.net/publication/396231370_Disruption_of_Cerebral_Folate_Metabolism_as_a_Unifying_Framework_for_Autism_Spectrum_Disorder_Risk_and_Causation_Running_title_Cerebral_folate_disruption_and_ASD&v=4cIIN5-vn5E
Disruption of Cerebral Folate Metabolism as a Unifying Framework for Autism Spectrum Disorder Risk and Causation Running title: Cerebral folate disruption and ASD
Dr Tim Kelly, https://x.com/DrTimothyKelly
Dr Clare Craig, https://x.com/ClareCraigPath
Friend or Faux, https://x.com/fauxlate
Fauxlate: The drug in our food, https://x.com/fauxlate

The paper under the video:

Disruption of Cerebral Folate Metabolism as a Unifying Framework for Autism Spectrum Disorder Risk and Causation Running title: Cerebral folate disruption and ASD​

• October 2025
  
  Autism spectrum disorder (ASD) arises from diverse influences that rarely align into a single explanatory model. Here, we propose a unifying framework centred on disrupted cerebral folate metabolism acting across sensitive developmental windows. Reduced folates are essential for nucleotide synthesis and methylation and their transfer to the developing brain relies on high-affinity folate receptor-α (FRα) transport at the placenta and choroid plexus. Disruption of this pathway, through genetic variants, synthetic folic acid (sFA) producing unmetabolised folic acid (UMFA), or folate receptor autoantibodies (FRAAs), can impair neurodevelopment during critical stages from gestation to infancy and beyond. Using a Capacity-Load-Trigger (CLT) framework, we integrate evidence across genetics, pharmacology, immunology and epidemiology. Capacity reflects intrinsic susceptibility (e.g. folate-pathway polymorphisms) [for example MTHFR]; Load arises from exogenous pressures such as sFA exposure, drugs that deplete one-carbon intermediates, or FRAA-mediated blockade; and Triggers include infection, fever, or metabolic stress that break immune tolerance in predisposed hosts. Regional vulnerability is predicted to follow CSF diffusion distance and metabolic demand, with fronto-parietal association cortex, basal ganglia, long white-matter tracts and cerebellar hemispheres most affected when CSF folate is low in utero. This framework reconciles paradoxical findings, where both folate deficiency and excess sFA/UMFA exposure increase risk and clarifies how timing and 1 location of disruption shape phenotype. It identifies a mechanistically defined, potentially treatable subgroup and generates testable predictions for biomarkers, exposure timing and neuroanatomical patterns.

From the video (if I understand this correctly) they said that folic acid tends to bind to the folate receptors more tightly than folate would - meaning they can block the folate transport receptors for some time. This means cellular folate deficiency, as none is getting through - even though blood levels would read high due to folic acid.
It takes a long time for the body to rid itself of folic acid because of this. It can (see the paper above) also trigger an immune reaction to folate receptors - presumably because that's how the body get's the folic acid out of the receptors. These immune flare ups tend to go away once the body has cleared itself of folic acid.

Many other diseases/problems are associated with the immune system attacking folate receptor-α (or treated by stimulating folate receptor-α, which may be blocked by folic acid) - including a bunch of cancers (ovarian, breast, prostate, epithelial etc), kidney disease, fertility problems (and possibly PCOS), lung and ear infections - to name a few.

 

[thorbiorn]

I just watched this interview by Dr John Campbell, and I'm glad I did.

It is instructive. Below are more notes, some based on the video, some based on other sources. As so often it is complicated.

SOTT carried an article in 2015: The difference between folic acid and folate. See also SOTT articles that mention folic, or folate. Most of them are older.

Folic acid is more chemically stable than folate, and that is at least one reason it is the preferred form when added to foods or included in supplements.

The video says that daily need is 100 mcg but to absorb that much one needs to consume about 200 mcg. In the video, they say that folic acid deficiency is uncommon as most diets have sufficient amounts, and many foods contain folate naturally especially grains, seeds and vegetables. The recommended CDC daily allowance is not 200 mcg but 400 mcg as you can also see in the Wiki:

According to the video, the NIH websites states that People who have cancer, B12, a heart stent, should avoid folic acid, see this time -ttps://youtu.be/4cIIN5-vn5E?t=2405 /app 40 min.

The Wiki describes one problem for some people:

Methyl-THF converts vitamin B12 to methyl-B12 (methylcobalamin). Methyl-B12 converts homocysteine, in a reaction catalyzed by homocysteine methyltransferase, to methionine. A defect in homocysteine methyltransferase or a deficiency of B12 may lead to a so-called "methyl-trap" of THF, in which THF converts to methyl-THF, causing a deficiency in folate. Thus, a deficiency in B12 can cause accumulation of methyl-THF, mimicking folate deficiency.

The Wiki has more examples of disease conditions where folate can be factor.

This paper from New Zealand, (the country that had strict COVID legislation!), lays out the reasoning they maintain legally enforced supplementation of folic acid.

The Health Benefits and Risks of Folic Acid Fortification of Food
A report by the Office of the Prime Minister’s Chief ScienceAdvisor and the Royal Society Te Apārangi June 2018
[...]
Based on an overall assessment of the evidence, and also considering the need to ensure that disadvantaged people including Māori receive benefit, the Expert Panel concludes that the benefits of mandatory fortification of packaged bread with folic acid outweigh any potential adverse effects. In addition, the Panel strongly encourages the continued use of folic acid supplements by as recommended by their healthcare professionals, and encourages all women of child bearing age to ensure that their folate intakes are adequate.

Looking at videos, there is Does folic acid act differently in the body than natural folate? by Chris Masterjohn.
He says that folic acid is transformed by an enzyme, dihydrofolate reductase, DHFR, to give dihydrofolate which is transformed by the same enzyme one more time to create tetrahydrofolate. That is, the enzyme DHFR is doing the same to folic acid as it does to dihydrofolate, (which comes out of DNA synthesis), but the process is repeated twice rather than once. Tetrahydrofolate then has a methyl group added to make methylfolate. The Wiki explains this latter functions and explains further:

Tetrahydrofolate's main function in metabolism is transporting single-carbon groups (i.e., a methyl group, methylene group, or formyl group). These carbon groups can be transferred to other molecules as part of the modification or biosynthesis of a variety of biological molecules. Folates are essential for the synthesis of DNA, the modification of DNA and RNA, the synthesis of methionine from homocysteine, and various other chemical reactions involved in cellular metabolism. These reactions are collectively known as folate-mediated one-carbon metabolism.

More from the video description by Chris Masterjohn.

The question is, does that synthetic folic acid, we call that unmetabolized folic acid, does that cause harm? There are scientific hypotheses that it might, and it might, but there's no conclusive evidence of that. That's one side of the argument against synthetic folic acid. The other side of the argument is now that you are giving the DHFR enzyme more work, that means that might be detracting from the work that it has in recycling dihydrofolate that came out of the DNA synthesis reactions to make tetrahydrofolate.

There is a standard way of explaining the effects of nutrients, but since people have small differences in the way their systems function and metabolize what they take in, there can be overall beneficial effects for a population, but not for all, as usual.