Is MTHFR and Low Folate Related to ADHD?

Attention Deficit Hyperactivity Disorder (ADHD) is a complex neurological disorder with a spectrum of symptoms that vary in severity. The disorder impacts areas of the brain involved in planning, focusing, and executing tasks. Those with ADHD struggle with organization and controlling impulses.

In the past few decades, rates of ADHD have increased significantly around the world, causing much speculation for its causative factors. It affects an estimated 11% of children and almost 5% of adults in the U.S.

There appears to be no single cause for ADHD, and its likely caused by a variety of factors. Still, possible risk factors for ADHD may include exposure to environmental toxins, notably lead, the use of drugs or alcohol during pregnancy, and premature birth. 

Recent research suggests that genetic traits may play a part, particularly those involved in the production of neurotransmitters. For this reason, some researchers have suggested that the MTHFR gene and a corresponding folate deficiency may be linked to a child’s risk of being born with ADHD. 

This article will discuss the possible role of genetics in ADHD and studies supporting this theory. We will explain how folate, neurotransmitters, and MTHFR are related to ADHD and whether supplementation with methylfolate may be advisable.

Although the exact etiology of ADHD has not been determined, many related factors include:

Studies involving families have provided substantial evidence that ADHD may be an inherited condition, with heritability believed to be about 70%.

Gene association studies have provided consistent evidence of an association between ADHD and dopamine receptor genes and that the COMT gene influences the behavioral patterns of those with ADHD.

Methylation is essential for the proper functioning of the Catechol-O-Methyl-Transferase (COMT) enzyme, an enzyme responsible for the breakdown of catecholamines, including dopamine and norepinephrine. If methylation is impaired, the proper functioning of either Histamine N-Methyltransferase (HNMT) or COMT is affected, and the body is less efficient at removing toxins.

For this reason, there may be a link between childhood neuropsychiatric problems, folate metabolism, and the genetic polymorphism MTHFR. MTHFR has been related to neuropsychiatric conditions such as schizophrenia, depression, and bipolar disorder. 

MTHFR is required for converting folic acid into 5-methyltetrahydro­folate, the predominant circulating form of folate. This reaction is required for the multistep process that converts homocysteine to methionine, which is then used to make proteins and other important compounds. 

The relationship between childhood neuropsychiatric problems, folate metabolism, and MTHFR may be central to ADHD. 

Neurotransmitters are chemicals produced by the brain and nervous system, including serotonin, norepinephrine, epinephrine, dopamine, and melatonin. Each of these is responsible for a range of bodily functions: mood, energy, sleep, digestion, muscle and nerve function, memory, and cognition.

The methylation process is necessary to create these neurotransmitters. The brain must have access to sufficient folate for methylation to occur successfully. However, the processing deficiency caused by MTHFR can mean that folate is not produced. 

Methylation is required for over 200 biochemical reactions in the body. It occurs billions of times per second in cells, contributing to detoxification, DNA repair, energy production, mood balancing, glutathione production, and control of inflammation.

Activated folate is also needed for the proper growth and development of cells.

The MTHF effect on neurotransmitters has already been linked to anxiety and depression. Up to 70% of patients with depression test positive for the C677T polymorphism, which is attributed to their inability to process folic acid. 

Methylation is also key to the body’s phase II detoxification pathway, in which toxins are converted into water-soluble compounds so they can be excreted. The MTHFR enzyme is also responsible for the downstream effect of generating glutathione, the body’s 

most potent antioxidant, and detoxifier. Glutathione is the main intracellular antioxidant and is critical for drug and xenobiotic detoxification.

Poor methylation may hinder detoxification in the liver and the production of glutathione. 

Several studies have shown that impaired detoxification may lead to toxic metal accumulation, which has been linked to autism. This may be due to a combination of genetic susceptibility and exposure to environmental toxins at critical periods during brain development, causing a buildup of neurotoxins and associated inflammation of the brain tissue. 

Research has also suggested that ADHD is related to blood lead level, even at background exposure levels typical in western countries. Children with ADHD are found to have slightly elevated blood lead levels. 

As MTHFR mutations are genetic, they cannot be ‘cured.’ However, the health conditions associated with MTHFR may be treated or managed with a range of nutrients - particularly methylfolate. This is crucial for supporting the methylation cycle. 

Methylation is necessary for promoting detoxification, producing glutathione and neurotransmitters, controlling inflammation, and balancing hormones.

The strong association between ADHD and low folate levels has been shown in several studies. Higher hyperactivity and peers relationship problems in children are also associated with low folate in early pregnancy. Folate deficiency is also associated with aggression, and supplementation has been shown to help manage this.  

Stimulants are often the primary treatment for ADD/ADHD. These drugs usually work by helping to maintain neurotransmitter balance by regulating the availability of dopamine.  However, ADHD can be difficult to manage even with these stimulant therapies.

Folate, specifically L-methylfolate, is an important precursor for dopamine synthesis. Scientists have now found that taking methylfolate may be adjuvant to stimulants and can help alleviate the symptoms of ADD/ADHD. L-methylfolate is the naturally occurring metabolite of folate and an important cofactor in the production of neurotransmitters. 

A study in which ADHD patients were treated with a high dose of methylfolate every day for six weeks found that on average, the 32 patients experienced a 27% improvement in their behavior. Also, 21 of the 32 patients experienced a 53% improvement in their behavior.

Numerous studies have shown that methylfolate can help to alleviate neuropsychiatric disorders such as depression by improving response to antidepressants that affect monoamines.

While more research is pending, there are proven benefits in taking methylfolate as a supplement. It should be noted that a methylfolate supplement is not a replacement for ADHD medication but may be used to enhance the benefits of other medications. This should be discussed with a medical practitioner before commencing. 

Methylfolate supplements are now available over-the-counter and online, often labeled as L-MTHF, L-5-Methylfolate, L-5-MTHF, and (6S)-5-Methylfolate.

Some of the most highly recommended methylfolate supplements are in the Methyl-Life® product suite, which includes a range of dosage levels appropriate for both children and adults.

These are formulated especially for people with a heightened need for bioavailable folate due to MTHFR defects, medication side effects, dietary deficiencies (such as vegans or vegetarians), or other conditions in which nutritional absorption is impaired.  

Methyl-life’s® Methylfolate is made with the internationally-patented Magnafolate® PRO, clinically tested as the world’s purest methylfolate. 

Magnafolate® is a methylfolate called L-5-MTHF, which is shown to be the most active form of folate in plasma circulation. When compared with ordinary folate, Magnafolate® PRO was found to be absorbed faster and utilized more quickly in the body.