Catechol-O-Methyltransferase (COMT) is a fundamental enzyme encoded by the COMT gene. Found throughout the body, COMT performs a necessary metabolic function, acting as a chemical “off-switch” for specific compounds. It plays a significant part in maintaining the balance of signaling molecules in both the central and peripheral nervous systems. Understanding its function is key to grasping the implications of having a version that operates at a slower rate.
The Core Function of COMT
The primary job of COMT is to break down, or inactivate, compounds known as catechols. It achieves this through methylation, transferring a methyl group to the catechol compound, which neutralizes it for excretion.
The most well-known substrates are the catecholamines—neurotransmitters including dopamine, norepinephrine, and epinephrine (adrenaline). COMT regulates the duration and intensity of the signals sent by these powerful signaling molecules. Without this cleanup crew, these compounds would linger in the synapses, causing prolonged effects on mood, cognition, and physical response.
COMT activity is not limited to neurotransmitters; it also plays a role in hormone metabolism. Specifically, COMT helps to process catechol-estrogens, which are metabolic byproducts of estrogen. For methylation to occur, COMT requires specific co-factors, including the methyl donor S-adenosyl methionine (SAM) and the mineral magnesium.
The Genetics Behind “Slow” COMT
The phrase “slow COMT” describes a reduced-function version of the enzyme caused by a specific genetic variation. The most studied and functionally significant variation is a single nucleotide polymorphism (SNP) known as Val158Met (rs4680). This involves a change in the DNA code that substitutes the amino acid valine (Val) with methionine (Met) at position 158.
This change profoundly affects the enzyme’s stability and activity. The Met variant produces an enzyme that is measurably less effective than the Val variant. Studies show that the Met enzyme can be up to 3 to 4 times less active than the Val enzyme, particularly in the brain.
Individuals inherit one copy of the COMT gene from each parent, leading to three possible genotypes. A person can have two copies of the high-activity gene (Val/Val), two copies of the low-activity gene (Met/Met), or one of each (Val/Met). The Met/Met genotype is referred to as “slow COMT,” resulting in the lowest overall enzyme activity.
Implications for Catecholamine Metabolism
The primary consequence of having a slower COMT enzyme is that catecholamines remain active in the body and brain for longer periods. This prolonged presence of signaling molecules, particularly dopamine and norepinephrine, influences an individual’s psychological and physiological profile. Effects are most noticeable in the prefrontal cortex, where COMT is the main mechanism for dopamine inactivation.
For those with slow COMT, higher baseline dopamine levels in the prefrontal cortex can confer cognitive advantages, such as superior executive function and working memory. However, this elevated level means the system is closer to a state of overstimulation. When exposed to stress, the slow clearance rate can quickly lead to feelings of anxiety, irritability, and mental overstimulation.
This difference in dopamine processing contributes to the concept of “worrier” versus “warrior” traits. The Met/Met “worrier” genotype tends to exhibit heightened sensitivity to pain and stress, overthinking, and difficulty filtering thoughts due to sustained neurotransmitter signals. Conversely, the Val/Val “warrior” genotype clears catecholamines quickly, leading to lower baseline levels but potentially better stress resilience.
The slower metabolic rate also affects the processing of catechol-estrogens, contributing to a potential buildup of these estrogen metabolites. This reduced clearance capacity has been linked to issues of estrogen dominance, which can manifest as symptoms like premenstrual syndrome (PMS), mood swings, and breast tenderness.
Supporting COMT Function Through Lifestyle
Individuals with a slow COMT variant can adopt specific lifestyle and nutritional strategies to balance their system. The most direct approach is managing catecholamine input by prioritizing stress reduction techniques. Practices like meditation, deep breathing, and light exercise help prevent the excessive release of norepinephrine and epinephrine that overwhelms the slow enzyme.
Nutritionally, supporting the COMT enzyme’s co-factors is beneficial. Magnesium is necessary for COMT to perform the methylation reaction, and supplementation can help ensure the enzyme operates efficiently. The enzyme also relies on methyl donors, often supplied by B vitamins, particularly folate and Vitamin B12.
Careful attention to diet and supplements is necessary to avoid further enzyme inhibition. High-dose caffeine and concentrated supplements containing polyphenols, such as quercetin or EGCG from green tea extract, can directly inhibit COMT activity. Limiting these substances reduces the burden on an already sluggish enzyme, helping to prevent overstimulation.