Folate deficiency is very common and it´s not a simple matter. There are different forms of folate, but they are just intermediates in the process of forming the primary biologically active form:

L-methylfolate = Levomefolic acid, 5-MTHF or (6S)-5-methyltetrahydrofolate

It is essential for mental health because it is used in the methylation of homocysteine to form methionine and tetrahydrofolate (THF). The conversion process depends on many enzymes:


Unfortunately, today we don´t find L-methylfolate in our foods anymore, with an exception for berries, especially blueberries. For most of us, supplementation of Folic Acid is enough. However, due to genetic mutations, medications and digestion issues, many people have a hard time converting them to the active form. Major cause are the genetic mutations affecting the MTHFR enzime, needed to produce L-methylfolate. You can memorize the MTHFR acronym by calling it “Monday, THursday, FRiday”.

Those mutations will block your body’s ability to produce SAMe and Gluthatione. Without SAMe, you become under-methylated and without Gluthatione you get heavy metal accumulation.

MTHFR mutations:

The two most known of those mutations affect the MTHFR nucleotide at positions 677 and 1298. Recalling from highschool biology, each position can be defined in terms of it´s nucleobases G–C–A–T (guanine, cytosine, adenine, thymine). The 667 mutation changes that gene from C to T, while 1298 mutation changes that gene from A to C. Hence those mutations are named C667T and A1298C. The 667 mutation is more severe and associated to high levels of high homocysteine.

Recalling again from school, we have a pair of each gene, one given from dad other given from mom. Chances are high you have one gene mutated or even both:


Many people both genes with either 667 or 1298 mutation, as those are common mutations, but we don´t find people with both 667 and 1298 mutations in the SAME gene because those just don´t survive (die during gestation or first years of life). Thus, most common MTHFR types are listed below, in order of severity:

Gene 1 Gene 2
Normal Normal Ok.
Normal 1298 Heterozygous 1298
Normal 667 Heterozygous 667
1298 1298 Homozygous 1298
677 677 Homozygous 677 – 10% of population
677 1298 Compound Heterozygous

Heterozygous mutations make you more susceptible to environmental damage and depression. In the case of homozygous mutations, you get a much worse susceptibility, plus heart disease, especially in case of 667. Finally, those with compound heterozygous are the worst for strokes, heart disease and blood clots.

One easy way of detecting some of your mutations is by purchasing the 23andMe DNA test which costs US$ 100 and is done through your saliva. Results are not user friendly, but are helpful if money is not a problem.

Secondary Deficiencies:

Because of heavy metal accumulation, people with MTHFR mutatations do usually have trouble converting B12 and B6 vitamins to their active forms as well, so active supplementation of those is also recommended.

Synthetic B12 (cyanocobalamin) => methylcobalamin
Synthetic B6 (pyridixine) => P5P (phosphotidy-5-pyrodixine), also known as PLP


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