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 can 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 multiple variants in COMT 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.

Factors that Could Further Slow COMT

Since COMT is working at a reduced rate, you want to avoid certain lifestyle and diet factors that can reduce its function 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 +/+, 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.

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 the solution to constipation along with diet.

BH4 Cycle, COMT, MAO-A

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