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The relationship between MTHFR and ADHD

The human body needs folate, or vitamin B9, for several essential functions. Folate activates, synthesizes, and repairs DNA. It converts homocysteine, which you don’t want too much of, into methionine, an essential amino acid. Vitamin B9 also stimulates neurotransmitters. Methylated folate is the active, natural form of folate that the human body uses, and the body cannot produce folate, so it must be obtained through diet.

Methylenetetrahydrofolate reductase (MTHFR) is what helps convert folic acid into L-Methylfolate—the biologically active form of folate. Specifically, this enzyme is required for the multistep process that synthesizes methionine. [1] Methionine is important for the synthesis of neurotransmitters. L-methylfolate is also responsible for other methylation within the cell.

There are genetic polymorphisms or mutations associated with this gene, which may cause methylenetetrahydrofolate reductase deficiency. This may affect the bodies ability to utilize folate and more specifically, folic acid.

MTHFR genotypes were related to ADHD subtypes, particularly for inattentive symptoms. A higher percentage of children identified with the A1298C or C1298C polymorphism were found to meet the criteria for the inattentive subtype. Additionally, the combined genotype category for MTHFR (C677T and A1298C combinations) was also significantly related to increased rates of ADHD symptoms.[2]

Evidence has also shown that behavior related to ADHD is more prevalent in patients with MTHFR than in the general population. [3]

Providing L-methylfolate supplementation to people with MTHFR eliminates problems with folate metabolism. Research has shown that methylfolate can deliver folate immediately, without the need for conversion.


[1] Gokcen, C. et al. “Methylenetetrahydrofolate Reductase Gene Polymorphisms in Children with Attention Deficit Hyperactivity Disorder,” International Journal of Medical Sciences 2011; 8(7):523-528.

[2] Krull KR, et al. “Folate Pathway Genetic Polymorphisms are Related to Attention Disorders in Child-hood Leukemia Survivors,” J Pediatr. 2008 Jan; 152(1):101-5.

[3] Spellicy, C., “Folate Metabolism Gene 5,10-Methylenetetrahydrofolate Reductase (MTHFR) Is Associated with ADHD in Myelomeningocele Patients,” PLOS One, Dec. 2012, Vol. 7, Issue 12.

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