top of page

Understanding MTHFR and COMT Gene Variations: Unravelling the Link to Mental Health

Updated: Aug 1, 2023


When it comes to our mental health, there are many factors at play, ranging from our environment and experiences to our genetic makeup. In recent years, scientific research has shed light on the role of specific gene variations in influencing mental well-being. Two genes, MTHFR and COMT, have emerged as key players in this arena. In this article, we will explore these gene variations and delve into how they can impact mental health, particularly in relation to anxiety and stress, as a result of nutrient deficiencies stemming from inhibited methylation.

The MTHFR Gene Variation: A Methylation Marvel

Let's start by understanding the MTHFR gene. MTHFR stands for methylenetetrahydrofolate reductase, and it plays a crucial role in a process known as methylation. Methylation is a biochemical process that occurs within our cells, where certain molecules, known as methyl groups, are added to our DNA, proteins, and other molecules. Methylation is essential for various bodily functions, including DNA repair, detoxification, and neurotransmitter synthesis.

The MTHFR gene produces an enzyme that converts folate (a B-vitamin) into its active form, known as 5-MTHF or methylfolate. Methylfolate is crucial for facilitating the methylation process. However, some individuals may carry a genetic variation in the MTHFR gene, which can result in reduced enzyme activity, leading to decreased production of active methylfolate. The most common variations are referred to as C677T and A1298C.

The COMT Gene Variation: Balancing Neurotransmitters

Another gene that plays a role in mental health is COMT, which stands for catechol-O-methyltransferase. This gene encodes an enzyme responsible for breaking down neurotransmitters like dopamine, epinephrine, and norepinephrine in the brain. These neurotransmitters are crucial for regulating mood, cognition, and the body's stress response.

Similar to the MTHFR gene, the COMT gene can also have genetic variations that impact enzyme activity. The most well-known variation is Val158Met, which results in altered COMT enzyme function. Individuals with the Val/Val variation have higher COMT activity, leading to faster breakdown of neurotransmitters, while those with the Met/Met variation have lower COMT activity, resulting in slower neurotransmitter breakdown.

The Impact on Mental Health

Now, you might wonder how these gene variations can influence mental health and contribute to conditions like anxiety and stress. Let's connect the dots.

1. Impaired Methylation and Anxiety:

As mentioned earlier, the MTHFR gene variation can lead to reduced production of active methylfolate, hindering the methylation process. Methylation is essential for the synthesis of neurotransmitters like serotonin, dopamine, and norepinephrine, which play a significant role in mood regulation. Low levels of methylfolate may result in imbalanced neurotransmitter levels, potentially leading to symptoms of anxiety and depression.

2. COMT Variations and Stress Response:

Individuals with the Met/Met variation in the COMT gene have slower breakdown of stress-related neurotransmitters like dopamine and norepinephrine. As a consequence, these neurotransmitters may accumulate in the brain, intensifying the stress response. This heightened stress response could contribute to increased susceptibility to anxiety and difficulty coping with stressors.

3. Nutrient Deficiencies and Mental Health:

The impaired methylation resulting from MTHFR gene variations can lead to nutrient deficiencies, including low levels of vitamin B12 and folate. These deficiencies can further compromise neurotransmitter synthesis and overall mental health, exacerbating symptoms of anxiety and stress. Additionally, a lower quality form of folate named "folic acid" can essentially act as a toxin because it is not well converted into the active form 5-methylfolate (5-MTFH) if you have these variations. As such, folic acid acts more like a toxin and should be avoided.

A Solution

Discover a game-changing solution to boost your mental health: a high-quality methylated B-vitamin complex supplement. If anxiety, stress, or related disorders trouble you, MTHFR and COMT gene variations may be at play. By addressing impaired methylation, these supplements provide active forms of crucial B-vitamins, supporting neurotransmitter synthesis and stress regulation.

When I found out I had both of these genetic variants, I immediately began supplementing with a methylated B-vitamin complex and it has helped me more than any other supplement. Now I just feel anxiety and stress when a anxiety or stress-inducing stimulus is present instead of that constant background stress. This could also be a game changer for you, but be sure to contact your healthcare professional before supplementing with anything new to prevent any potential risks or complications.


In conclusion, understanding the role of genetic variations in the MTHFR and COMT genes is a significant step toward comprehending the intricate relationship between our genes and mental health. While these gene variations can impact our vulnerability to anxiety and stress through inhibited methylation and neurotransmitter imbalances, it's essential to remember that genetics are just one piece of the puzzle.

Environmental factors, lifestyle choices, and emotional support also play crucial roles in our mental well-being. If you suspect you may have these gene variations and experience mental health challenges, consider seeking guidance from a healthcare professional, I'd recommend a functional medicine doctor. By taking a holistic approach to mental health, we can better equip ourselves to lead fulfilling and balanced lives.

23 views0 comments


bottom of page