What is the COMT Gene?

The COMT gene, also known as catechol-O-methyltransferase, provides instructions for making an enzyme called COMT. This enzyme is involved in the breakdown and elimination of catecholamines, which are neurotransmitters in the brain. Catecholamines include dopamine, norepinephrine, and epinephrine (adrenaline).

The primary function of COMT is to add a methyl group to catecholamines, a process called methylation. This methylation is crucial for regulating the levels of neurotransmitters in the brain. By breaking down and eliminating excess neurotransmitters, COMT helps maintain the balance of these signaling molecules.

Every individual has 2 copies (or alleles) of a gene inherited from each parent.  Genes are made up of DNA and often encode for a protein.  Polymorphisms (variants) are slightly different versions of each gene. 

The COMT gene is located on chromosome 22, and variations in this gene can influence the activity of the COMT enzyme. Genetic variations in COMT have been associated with differences in cognitive function, response to stress, and susceptibility to certain mental health conditions. The enzyme's activity is particularly relevant in brain regions where dopamine signaling is important, such as the prefrontal cortex.  The prefrontal cortex is part of the brain associated with cognitive functions, including thinking, problem-solving, impulsive control, and reasoning.

One common genetic variation in the COMT gene involves a single nucleotide polymorphism (SNP) known as Val158Met. This SNP can lead to variations in COMT enzyme activity, and individuals with different genotypes may exhibit differences in neurotransmitter regulation.

COMT enzyme activity is decreased fourfold in individuals with 2 copies of this genetic polymorphism.  This has been termed the slow COMT genotype, or “worrier gene”.  Individuals with this genotype have higher levels of dopamine in the neuronal synapse.  This can help with improved focus, creativity, attention-based tasks, working memory, cognitive function, and fine motor skills. However, it may result in fixating, high anxiety, chronic pain, OCD, and depression.   

Individuals with no polymorphism of the gene display the highest level of enzyme activity resulting in less catecholamines.  This has been termed the fast COMT genotype, or “warrior gene”.  This genotype is associated with the ability to handle stress and pain better, with higher emotional resilience.  Due to lower levels of catecholamines, however, it is also associated with lack of motivation, less pleasure from life, and worse fine motor skills.  Obesity, food cravings, addictions, and childhood depression can be seen.  Also, under acute extreme stress, these individuals may have worse executive function and be at a higher risk of depression. 

What alters COMT function?

• Childhood trauma

  • Some studies suggest that the interaction between the Val158Met polymorphism and childhood trauma may influence susceptibility to certain mental health conditions. For example, individuals with a history of childhood trauma and the slow genotype may be more vulnerable to conditions like depression or anxiety.

• Sex Hormones

  • Estrogen directly influences COMT activity by inhibiting COMT expression.  Estrogen also directly increases dopamine synthesis and decreases its breakdown. 

  • A decline in estrogen after menopause results in increased COMT activity. 

  • Testosterone speeds up COMT activity.

• Aging

  • Aging magnifies the relationship between COMT genotypes and cognitive performance with a greater performance deficit for fast versus slow genotypes with advanced age.

• MTHFR and COMT

  • COMT uses a compound called SAM-e as its methyl donor during breakdown of catecholamines.  Therefore, having too little SAM-e results in lower COMT enzymatic activity.

  • The MTHFR gene, or methylenetetrahydrofolate reductase gene, provides instructions for making an enzyme called methylenetetrahydrofolate reductase. This enzyme plays a crucial role in the methylation process, which is essential for various bodily functions, including DNA synthesis, repair, folate metabolism and the processing of homocysteine, an amino acid.

  • Polymorphisms in the MTHFR genes are associated with higher levels of homocysteine and lower levels of SAM-e and folate.  Increased levels of homocysteine decrease COMT enzymatic activity. 

  • Thus, MTHFR polymorphisms can interact, and worsen, COMT polymorphisms. 

COMT and Cancer Risk

In addition to its role in catecholamine metabolism, COMT is involved in the breakdown of estrogen.  This includes the body’s production of estrogen as well as xenoestrogens found in our environment.  Sustained exposure to estrogens increases the risk of certain cancers.

Nutritional & Lifestyle Action Plan for COMT

COMT is supported by magnesium, vitamin C, B vitamins, and SAM-e. 

The slow genotype

·        Limit foods high in amino acids that are converted to dopamine (tyrosine, tryptophan, phenylalanine).

·        COMT is involved in processing catechol-containing flavonoids (EGCG, fisetin, rutin, luteolin, quercetin, oleacein), therefore individuals with the slow genotype may have a higher sensitivity to these foods.  These include green & black tea, wine, coffee, capers, olives, and cilantro.

·        Include foods that help remove estrogen including flaxseed and cruciferous vegetables. 

·        Proton pump inhibitor medications used to treat GERD, sugar, and aspartame can decrease COMT expression.

·        Limit exposure to xenoestrogens.

The fast genotype

·        Exercise and fasting increase catecholamines.

·        Caffeine triggers catecholamine release. 

·        Conversely, high amounts of calcium and iron may inhibit the enzyme.

·        Quercetin and green tea may help balance enzymatic function.

While COMT plays a large role in neurotransmitter regulation, there are also several other genes that contribute as well.  In addition, although our genetic makeup may put us at risk of certain diseases and health concerns, it is not our destiny.  Epigenetics is how our environment interacts with our genes to turn them on or off.  This includes MANY aspects of our lives including stress, food, sleep, emotions, adverse childhood events, in utero exposure, physical activity, age, and time in nature. 

Consult with a trained healthcare provider to correctly interpret nutrigenetics results and minimize your health risks through lifestyle and dietary changes.