COMT (Catechol-O-methyltransferase is a gene involved in the methyaltion pathway. It is responsible for breaking down dopamine, norepinephrine and epinephrine as well as estrogen. It adds a methyl group to the neurotransmitter to deactivate it so that they do not build up and cause harm.
Fast or slow COMT
Fast COMT (V158M val/val GG)can break down estrogen quite quickly, leading to lower levels of estrogen. While this can potentially protect against estrogen-related conditions like breast cancer, it might lead to lower estrogen which potentially influences mood.
Slow COMT (V158M met/met AA) metabolizes estrogen more slowly, which can result in higher levels of circulating estrogen metabolites. Some of these metabolites, such as 4-hydroxyestrone, are potentially carcinogenic if they build up in the body. This slower metabolism could increase the risk of estrogen-dominant conditions such as breast cancer, endometriosis, or fibroids.
Hormone balance
Since COMT plays a key role in estrogen metabolism, a person’s COMT activity can influence their hormonal balance. Women with slow COMT may experience symptoms related to estrogen dominance (e.g., heavy periods, bloating, mood swings), especially if their estrogen levels are high or if they have difficulty clearing excess estrogen through their detoxification pathway. However women with fast COMT can also experience estrogen dominance.
This is NOT only dependent on your variant but more so on what is happening epigenetically. In other words, what is going on in your actual life: what you are eating, your lifestyle, and your environment, all of which influence your genes.
Impact on neurotransmitters
Estrogen also influences dopamine levels by inhibiting COMT activity. This means that during certain phases of the menstrual cycle, when estrogen is higher, this can lead to higher dopamine levels, which may influence mood, motivation, and cognition. And at certain times when estrogen is lower, this may lead to lower dopamine levels affecting motivation, mood, focus and attention.
Support your Methylation pathway
Since COMT is involved in methylation, which helps process both neurotransmitters and estrogens, people with COMT variants might benefit from optimizing their methylation pathways. Ensuring adequate intake of nutrients like methylfolate, vitamin B12, and choline can support better detoxification of estrogen and balance neurotransmitter metabolism.
Estrogen levels may need to be managed through lifestyle changes, dietary adjustments (e.g., cruciferous vegetables that promote estrogen detoxification), and possibly supplements that support COMT activity.
Of course, like any genetic variants, no gene acts alone, but rather genetic variants together with epigenetic factors can all play a part. Need help understanding your DNA test? Contact me for more information.