What is COMT?
COMT (Catechol-O-Methyltransferase) breaks down estrogen, catecholamines and neurotransmitters including dopamine, epinephrine and norepinephrine.
Heterozygous or homozygous variants for the COMT V158M methionine allele slow down the COMT enzyme, affecting estrogen metabolism and the breakdown of dopamine and stress hormones. The valine variant catabolizes dopamine at up to four times the rate of the methionine variant while the methionine variant results in a 40% decrease in functional enzyme activity.
This alteration in enzymatic activity lead to anxiety, impulsiveness, obsessive behavior, ADHD, irritability (especially under stress), hyperactivity and abnormal behavior. From my own observation, I have found that those with higher dopamine levels do better in quiet environments, and are more affected by a lot of external noise and chaos. These are also the people who get easily anxious with coffee or can’t sleep if they have a glass of red wine too late.
However, the wild-type variants in COMT are also relevant. For these people, it is possible for COMT to be going too fast depending on hormonal status and other factors. In this case, it can be beneficial to increase catecholamine intake (berries, bananas, cacao, citrus, coffee, green tea, black tea, red wine) to slow down COMT and increase dopamine levels for an improved mood, concentration and focus.
The Warrior or Worrier Gene
COMT has been called the “warrior” or “worrier” gene based on the genotype. The wild-type COMT V158M genotype has been called the warrior genotype because there is a higher threshold of pressure to perform due to a lower baseline of dopamine. Stress slows down COMT, increasing dopamine and adrenaline levels. For the warrior genotype, certain types of pressure can actually be beneficial to perform at a higher level due to the dopamine boost.
The homozygous COMT V158M genotype has been referred to as the “worrier,” however, I would call this genotype the “problem solver.” The reason is that this genotype has naturally higher dopamine levels, which is an advantage for cognitive function in day to day life, especially complex problem solving. The downside is that this genotype can overreact to stress and pressure, creating dopamine and adrenaline levels that are too high, shutting the brain down.
You can read more about the Warrior or Worrier gene here, including where the heterozygous COMT V158M falls in this spectrum.
Factors that Could Further Slow or Speed Up COMT
Since COMT is working at a reduced rate for the heterozygous and homozygous variants, you want to avoid certain lifestyle and diet factors that can slow down the COMT enzyme even further. These include chronic stress, the use of plastic bottles or aluminum cans, high calcium supplementation, mercury toxicity, certain catechols, high doses of supplemental quercetin, high doses of supplemental methylfolate and estrogen-based medications (like birth control).
- In vitro research has found that bisphenol (BPA) plastic bottles inhibit COMT activity. Other sources include plastic wrap, styrofoam cups, non-organic meat and dairy, non-organic plants sprayed with pesticides, unfiltered tap water, personal care and laundry products that contain parabens, artificial flavors and sweeteners and unfermented soy.
- Magnesium supplementation is necessary for COMT function while COMT activity is inhibited by high amounts of calcium/low magnesium supplementation and high iron.
- Higher doses of supplemental vitamin C may be needed to modulate dopamine and adrenaline levels.
- If you are homozygous +/+, you may be more sensitive to catechols in green and black tea, wine and coffee.
- Beer is estrogenic due to hops, and IPA beers should be avoided by those with a homozygous COMT.
Mercury toxicity also inhibits COMT activity through inhibition of S-adenosylmethionine (SAM), a coenzyme for COMT.
- If S-adenosylhomocysteine (SAH) accumulates, the COMT enzyme may become impaired.
- High homocysteine levels slow down COMT further.
- With a COMT heterozygous or homozygous status, it has been clinically observed by physicians that people may have trouble with methyl donors. This can lead to ADHD, irritability, hyperactivity, or abnormal behavior. They may also be more sensitive to pain. Risk may be increased for some neuropsychiatric disorders and impaired estrogen metabolism.
- Testosterone speeds up the COMT and MAO-A pathway. Therefore, optimizing testosterone levels for men and women can be an excellent strategy for those exhibiting symptoms of high dopamine and adrenaline levels. See this article on the best exercises to target a slow COMT gene and high dopamine and adrenaline levels.
How to Nutritionally Approach COMT?
The COMT enzyme requires the right dosage and type of magnesium based on weight and vitamin C which modulates dopamine and adrenaline. The other pathways to support include b-vitamins, and lowering excess estrogen levels for men or women through daily elimination. Interesting enough, magnesium and vitamin C is also the solution to constipation along with adequate fiber in the diet.
Catecholamine intake will vary depending on the spectrum of COMT function. If you are right in the middle (heterozygous), then catecholamine moderation is key. Remember, diet and environmental factors epigenetically change COMT expression despite your genotype, so it is important to understand your current symptoms and if they are related to dopamine and adrenaline levels.
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