Catechol-O-Methyltransferase (COMT)

Catechol-O-Methyltransferase (COMT)

The Catechol-O-Methyltransferase (COMT) system helps to break down certain neurotransmitters such as dopamine, norepinephrine and epinephrine and also catechol hormones such as estrogens. Some flavanoids are also metabolised by this enzyme such as Quercetin, Rutin, Luteolin, EGCG (green tea).

COMT is an enzyme that transfers methyl groups and by transferring a methyl group to the catecholamine (dopamine, epinephrine, and norepinephrine), which is donated by S-adenosyl methionine (SAMe). Therefore you need adequate SAMe for COMT to work.

Having too little SAMe (s-adenosylmethionine) and too much SAH (s-adenosylhomocysteine) from undermethylation results in COMT inhibition as well.

For this reason, having MTHFR snps that cause undermethylation and COMT snps that result in lower COMT are a bad combination.

Symptoms of low COMT include:

Anxiety
Chronic Pain
Worry
Delirium
Tachycardia
High Blood Pressure
Insomnia
Paranoia
Schizophrenia/Psychosis

There is one single nucleotide polymorphism or genetic mutation, frequently called SNPs (pronounced “snips”), within the COMT gene that is associated with poor health outcomes – rs4680 or G472A.

COMT rs4680 (G472A) Gene Mutation or SNP

This is one of the most researched SNPs because it plays an important role in intelligence, personality and disease risk.

Both the ‘G’ and ‘A’ allele of G472A in the COMT gene are associated with neurological characteristics associated with altered COMT activity. The COMT enzyme formed from the minor ‘A’ allele has been reported as having approximately a 75% reduction in activity compared to those formed from the major ‘G’ allele.

Therefore those carrying two copies of the ‘A’ allele display lower COMT activity which is associated with increased dopamine levels in the brain. This is thought to lead to a lower pain threshold and increased stress sensitivity, increased anxiety but improved memory and attention to detail, a potential risk for Parkinsons disease has also been described. Carriers are therefore sometimes termed ‘Worriers’.

Conversely those carrying two copies of the ‘G’ allele display higher COMT activity which is associated with decreased dopamine levels in the brain. This increased activity is thought to lead to a higher pain threshold and capacity to deal with stress, at the expense of a reduction in cognitive performance in non-stressful environments. Therefore, carriers of two ‘G’ alleles are sometimes termed ‘Warriors’.

People with AG have COMT levels that is midway between that of AA and GG.

The ‘A’ allele, which is associated with low activity, is linked with increases in the potentially harmful homocysteine; often associated with an elevated cardiovascular risk.As the ‘A’ allele form of COMT displays reduced methylation activity its methyl donor source (methionine) builds up. Methionine is typically formed by the processing of homocysteine using either methionine synthase (MTR) or betaine homocysteine methyltransferase (BHMT). Typically methionine is rapidly used, however when it accumulates it blocks further MTR or BHMT activity leading to a homocysteine accumulation.

Testing for COMT SNP

Genetic tests are available from us which involve the supply a saliva sample to the laboratory to determine if you carry the SNP for the COMT gene. UPDATE: The labs no longer provide COMT only testing and now part of an overall genetic well being profile.

If the tests indicate there is an issue it can be easily treated as indicated below.

Treating lower levels of COMT:

SAM-e – however, this can increase dopamine levels in people who already have high dopamine.
Adequate B6, B12, folate and betaine to support formation of S-adenosylmethionine and prevent elevated homocysteine; S-adenosylhomocysteine inhibits COMT activity
DIM if you have high estrogens because estrogens inhibit COMT
Ensure adequate anti-oxidants to prevent oxidation of dopamine and pro-carcinogenic 4-hydroxyestrogens,
Magnesium (magnesium is a cofactor)
Be careful of the following supplements that are the targets of COMT: quercetin, rutin,luteolin, EGCG, catechins, Epicatechins, Fisetin, Ferulic acid, Hydroxytyrosol
Avoid excessive alcohol consumption. Since alcohol-induced euphoria is associated with the rapid release of dopamine in limbic areas, low activity COMT variant would have a relatively low dopamine inactivation rate, and therefore would be more vulnerable to the development of alcohol dependence.
Avoid stimulants, especially amphetamines. Amphetamines may do worse with people who are AA, but later studies did not replicate this. It could be differences in study design.
Avoid chronic stress (stress hormones require COMT for degradation and compete with estrogens). Mercury is also a COMT inhibitor, so make sure you reduce your load or take supplements that bind to mercury.

If you have higher COMT levels:

Mucuna herb to increase dopamine,
Tyrosine to increase dopamine,
EGCG/Green Tea Extract (COMT inhibitor),
Quercetin (COMT inhibitor),
Ferulic Acid (COMT inhibitor),