The Catechol-O-methyltransferase, or COMT, gene plays a role in how our bodies process certain chemical messengers. This gene provides instructions for creating an enzyme that helps manage various neurochemicals related to mood and stress responses. Natural variations in this gene are common among individuals, influencing how a person’s system responds to their environment and daily experiences.
The Role of COMT in the Body
The COMT enzyme’s primary function is to break down a group of brain chemicals known as catecholamines. These include dopamine, norepinephrine, and epinephrine, which are powerful neurotransmitters. Dopamine helps regulate motivation, pleasure, and cognitive functions like attention and memory. Norepinephrine and epinephrine, often called adrenaline, are involved in the body’s “fight or flight” stress response, influencing alertness and heart rate.
COMT is particularly active in the prefrontal cortex, a brain region involved in executive functions such as decision-making and problem-solving. By regulating catecholamine levels, COMT helps maintain a balance that supports various physiological and psychological processes.
Understanding the Val and Met Variants
A frequently studied variation in the COMT gene, rs4680, involves a single change in the gene’s building blocks. This alteration results in two different versions of the COMT enzyme: Val (valine) and Met (methionine). These variants lead to distinct differences in how efficiently the COMT enzyme performs its job.
Individuals can inherit two copies of the Val allele (Val/Val), two copies of the Met allele (Met/Met), or one of each (Val/Met). The Met/Met genotype produces a COMT enzyme with significantly lower activity, reducing its ability to break down catecholamines by approximately 40%. This means catecholamines, especially dopamine, remain in the prefrontal cortex for longer periods. Conversely, the Val/Val genotype is associated with a faster-acting COMT enzyme, which clears catecholamines more quickly, leading to lower baseline levels. The Val/Met genotype typically exhibits intermediate enzyme activity.
Symptoms Associated with Slow COMT (Met/Met)
Individuals with the Met/Met COMT genotype possess a slower-acting enzyme. This leads to higher baseline levels of catecholamines, particularly dopamine, in the prefrontal cortex. This elevated dopamine can offer cognitive advantages, such as enhanced focus, improved working memory, and superior executive function, especially in low-stress environments.
However, the slow breakdown of stress hormones like norepinephrine and epinephrine can also present challenges. People with the Met/Met variant may experience heightened emotional sensitivity, feeling emotions more intensely. They can be more prone to anxiety, rumination, and difficulty disengaging from stressful events. This genotype is also associated with an increased sensitivity to pain and a lower pain threshold. They may also be more sensitive to stimulants, potentially experiencing side effects like jitteriness or increased anxiety from substances that further elevate dopamine.
Symptoms Associated with Fast COMT (Val/Val)
The Val/Val COMT genotype is associated with a faster-acting enzyme, leading to a more rapid breakdown and lower baseline levels of catecholamines in the prefrontal cortex. Individuals with this variant often demonstrate better performance under pressure and a higher capacity for stress resilience. They may also exhibit a higher threshold for pain.
Despite these advantages in high-stress situations, the lower baseline dopamine levels can present other challenges. Individuals with the Val/Val genotype may struggle with sustained focus, motivation, and tasks requiring prolonged concentration. This genetic variation has been linked to attention difficulties and may be associated with conditions like ADHD. They could also experience a reduced emotional reward from positive experiences, potentially contributing to generalized anxiety or a need for higher stimulation.
Managing COMT-Related Tendencies
For slow COMT activity (Met/Met), strategies focus on reducing catecholamine overload. Stress reduction techniques such as mindfulness, meditation, and yoga can help manage anxiety and regulate dopamine levels. Ensuring adequate intake of enzyme cofactors like magnesium and B vitamins (B2, B6, B9, B12) can support the methylation process that COMT relies on.
Those with the Met/Met variant should exercise caution with substances and supplements that might further inhibit COMT or increase catecholamines. This includes limiting caffeine, alcohol, and certain phytonutrients like quercetin and catechins found in green tea, as these can slow COMT activity. Additionally, estrogen can further reduce COMT activity, making dietary support for healthy estrogen metabolism, such as consuming cruciferous vegetables and flaxseeds, beneficial for women with this genotype. Regularly eating small meals can also help maintain stable blood sugar and avoid catecholamine surges from prolonged fasting.
For fast COMT activity (Val/Val), the focus shifts to supporting healthy dopamine levels and improving focus. Regular physical exercise is beneficial as it naturally increases dopamine and can boost mood and motivation. A diet rich in protein, which provides L-Tyrosine—a precursor to dopamine—can also be supportive. Foods like dairy, eggs, lean meats, fish, nuts, and seeds are good sources of tyrosine.
While some caffeine in moderation may help slow COMT activity for those with Val/Val, green tea is often preferred due to its EGCG content, which can mildly inhibit the enzyme and allow dopamine to remain longer in the prefrontal cortex. Creating structured routines and breaking down larger tasks into smaller, manageable steps can aid concentration. Consulting a healthcare provider before considering supplements like L-Tyrosine is always advisable to ensure appropriate dosage and suitability.