The COMT gene codes for the enzyme catechol-O-methyltransferase which breaks down (metabolizes) the neurotransmitters dopamine, epinephrine, and norepinephrine. This enzyme adds a methyl group from SAMe to the dopamine, epinephrine, or norepinephrine molecules, thus changing them into a different substance.
COMT is also involved in the metabolism of some drugs used for asthma, Parkinson’s, and high blood pressure.
Researchers link COMT genetic variants to quite a variety of different diseases from mood disorders to heart disease. This variety is due to the COMT variants metabolizing neurotransmitters at different rates.
Some of the psychiatric disorder with increased risk associated with COMT variants include:
Outside of the brain, COMT is also involved in the methylation of catechol estrogens.[ref][ref] This leads to differences in the amount of the COMT available in the prefrontal cortex between males and females after puberty. Estrogens can inhibit COMT, leading to an increase in dopamine in female brains. [ref] This also leads to
The COMT rs4680 A/A variant is found in almost 20% of the population while the G/G variant is found in 35-40% of the population. There are various health websites and Facebook groups dedicated to the negative effects of being ++ or — for this variant.
I want to suggest that instead of focusing on any perceived negative effects, you should look at the various interactions between your genotype and diet/supplements/environment and use the information to optimize for your genes.
One of the most studied variants of the COMT gene is rs4680, often referred to as Val158Met. In looking at research studies, the G is “Val” and the A allele is usually noted as “Met”.
Check your genetic data for rs4680 (23andMe v.4 and v.5):
Here are the findings from a few recent studies on this COMT variant:
This common variant is also involved in the activity level of COMT. T is the less common version with lower COMT enzyme activity; C is the more common version with higher activity. It is linked with the rs4680 polymorphism, and thus most people will have the same activity levels on both.
Check your genetic data for rs4633 (23andMe v4, v5):
Recent studies on this variant have found:
A couple of COMT variants add to the effect of the main variants listed above.
Check your genetic data for rs6267 (23andMe v.4 and v.5):
Check your genetic data for rs165599 (23andMe v.4 and v.5):
Clinicians often suggest that those with the rs4680 A/A genotype (lower COMT levels) avoid going overboard with foods and supplements that are considered methyl donors. Methyl donors include methylcobalamin (methyl-B12), curcumin, TMG, SAMe, theanine, and choline. [ref] The logic behind this suggestion is that overwhelming the pathway with too many methyl groups can lead to a sudden rise and then subsequent fall in dopamine levels — aka mood swings, anger, or anxiety.
Supplements that have a catechol structure are metabolized, or broken down, by COMT; this includes quercetin, EGC/G, and luteolin [ref][ref]. If you have lower COMT enzyme activity, you may want to be careful of stacking too many supplements metabolized by COMT together at the same time.
A study in mice found that COMT deficiency led to glucose intolerance on a high-fat diet. Keeping in mind that this is just a mouse study, if you have blood sugar regulation issues and have COMT rs4680 A/A, you may want to look at the amount of fat in your diet.
Magnesium is a cofactor for the COMT enzyme. A study found positive effects for liver COMT levels along with better heart health from supplementing with magnesium. A good quality magnesium supplement may be worth trying if you aren’t getting enough magnesium from food sources.