COMT GENE Mutations, Symptoms & Treatment Explained (Catechol o Methyltransferase)

Summary

Dr. Janelle Sinclair discusses the COMT gene mutation's impact on mental health, linking it to conditions like depression, anxiety, and insomnia. She explains how the gene's variants affect dopamine, noradrenaline, and adrenaline levels, and the consequent symptoms. The video offers dietary, lifestyle, and supplement recommendations to support COMT enzyme activity, emphasizing the benefits of being heterozygous for the gene. Tailored advice is provided for individuals with different COMT genotypes, including stress management and the use of supplements like magnesium and adaptogenic herbs.

Takeaways

• 🧬 The COMT gene encodes for an enzyme that breaks down catecholamines (dopamine, noradrenaline, and adrenaline) and the estrogen hormone.
• 🧠 Dopamine is associated with reward and pleasure, while noradrenaline and adrenaline are stress hormones linked to the fight-or-flight response.
• 🔍 Variants in the COMT gene, particularly Val158Met, can be linked to mental health conditions like depression, anxiety, and bipolar disorder.
• 🧬 Having two normal copies of the COMT gene can lead to fast breakdown of neurotransmitters, potentially causing low dopamine levels and symptoms like depression and fatigue.
• 🧬 Conversely, having two copies of the 'weak' genetic variant can slow down the breakdown of neurotransmitters, leading to high levels and symptoms like anxiety and insomnia.
• 🥗 For those with fast COMT activity, consuming green tea, coffee, and ensuring adequate protein intake can help balance neurotransmitter levels.
• 🏋️‍♀️ Exercise is recommended to stimulate endorphin and adrenaline production, aiding in balancing neurotransmitter levels.
• 💊 Supplements like EGCG (green tea extract), L-tyrosine, and mucuna can help increase dopamine levels in individuals with fast COMT activity.
• 🧘‍♀️ Stress management techniques such as diaphragm breathing, mindfulness, and maintaining a balanced lifestyle are crucial for those with slow COMT activity.
• 🚫 Reducing exposure to phenols found in cleaning products and certain foods can help support COMT enzyme activity in individuals with slow enzyme activity.

Q & A

What does COMT stand for and what does it do?

COMT stands for catechol-O-methyltransferase, and it is an enzyme encoded by the COMT gene that breaks down catecholamines such as dopamine, noradrenaline, and adrenaline, as well as the estrogen hormone.

Which neurotransmitters are affected by the COMT gene?

The neurotransmitters affected by the COMT gene include dopamine, noradrenaline, and adrenaline.

What are the potential mental health conditions associated with COMT gene mutations?

Mutations in the COMT gene have been linked to conditions such as depression, anxiety, autism, panic disorder, and bipolar disorder.

What is the most well-researched genetic variant of the COMT gene?

The most well-researched genetic variant of the COMT gene is the Val158Met or COMT Val/Met polymorphism.

How does the Val158Met polymorphism affect the COMT enzyme?

The Val158Met polymorphism affects the COMT enzyme's activity. The Val variant results in faster enzyme activity, while the Met variant results in slower enzyme activity.

What are the symptoms of low dopamine levels associated with the COMT gene?

Symptoms of low dopamine levels associated with the COMT gene include a lack of interest in life, decreased motivation, depression, inability to feel pleasure, fatigue, impaired concentration, poor memory, and Parkinson's disease.

What lifestyle changes can help support COMT enzyme activity if you have a genetic weakness?

Lifestyle changes that can support COMT enzyme activity include stress management, avoiding phenols in cleaning products and certain foods, and ensuring a balanced diet with adequate protein intake.

What supplements are suggested for individuals with a genetic weakness in the COMT gene?

Supplements that may help support individuals with a genetic weakness in the COMT gene include green tea extract (EGCG), L-tyrosine, mucuna, magnesium, vitamin C, adaptogenic herbs, and phosphatidylserine.

Why is it important to be cautious with methylation supplements if you have a slow COMT enzyme?

Being cautious with methylation supplements is important because they can increase dopamine levels, which can exacerbate symptoms if you have a slow COMT enzyme and are already struggling with high levels of neurotransmitters.

What is the significance of being heterozygous for the COMT gene?

Being heterozygous for the COMT gene is considered ideal as it provides an intermediate level of dopamine and noradrenaline, which can be beneficial for maintaining a balance between too much or too little neurotransmitter activity.

Outlines

00:00

🧬 Understanding COMT Gene Mutations and Mental Health

Dr. Janelle Sinclair introduces the topic of the COMT gene mutation and its association with mental health issues such as depression, anxiety, and insomnia. She explains that the COMT gene encodes an enzyme responsible for breaking down catecholamines (dopamine, noradrenaline, and adrenaline) and estrogen. The video discusses how variations in the COMT gene, specifically the Val158Met polymorphism, can lead to different enzyme activities and consequently affect neurotransmitter levels, which are linked to various mental health conditions.

05:00

🚫 Effects of COMT Gene Mutations on Neurotransmitter Levels

The video explains the impact of having two normal copies of the COMT gene, which results in fast enzyme activity and can lead to low dopamine levels, causing symptoms like depression, lack of motivation, and poor concentration. On the other hand, having two copies of the mutated gene leads to slow enzyme activity, resulting in high levels of neurotransmitters and increasing the risk of stress, anxiety, and insomnia. Dr. Sinclair suggests that being heterozygous for the COMT gene mutation might be the ideal scenario, providing a balance of neurotransmitter levels.

10:02

🍵 Lifestyle and Supplement Recommendations for COMT Gene Mutations

For individuals with the normal COMT gene variant, Dr. Sinclair recommends strategies to balance neurotransmitter levels, such as drinking green tea, coffee, and supplementing with EGCG to slow down the COMT enzyme. She also suggests regular exercise, adequate protein intake, and l-tyrosine or mucuna supplementation to increase dopamine levels. For those with the mutated variant, stress management, avoiding phenols, and limiting caffeine intake are advised. Additionally, supplementation with magnesium, vitamin C, adaptogenic herbs, and phosphatidylserine is recommended to support stress hormone balance.

15:02

🧠 Sensitivity to Methylating Agents and Genetic Testing

The video addresses the sensitivity of individuals with the mutated COMT gene to methylating agents like methylfolate and methyl B12, suggesting alternatives like 5-MTHF and hydroxy B12. It also touches on the controversy surrounding methylation and the COMT enzyme, cautioning against increasing dopamine levels inadvertently. Dr. Sinclair encourages viewers interested in genetic testing to explore her other videos on the topic, which cover various genetic variations related to mental health, associated health conditions, and treatment considerations.

Keywords

💡COMT gene

The COMT gene encodes for an enzyme that breaks down catecholamines, which include neurotransmitters like dopamine, noradrenaline, and adrenaline. In the video, it's discussed how mutations in the COMT gene can lead to imbalances in these neurotransmitters, resulting in symptoms associated with depression, anxiety, and other mental health conditions. The script explains that changes in the COMT gene, specifically the Val158Met polymorphism, can affect the enzyme's activity, leading to either too fast or too slow a breakdown of these neurotransmitters.

💡Catecholamines

Catecholamines are a class of monoamine neurotransmitters that include dopamine, noradrenaline (also known as norepinephrine), and adrenaline (also known as epinephrine). These neurotransmitters play a crucial role in the brain's reward system, stress response, and fight-or-flight response. The video discusses how the COMT enzyme, influenced by the COMT gene, is responsible for breaking down these neurotransmitters, and imbalances can lead to various mental health symptoms.

💡Dopamine

Dopamine is a neurotransmitter associated with the brain's reward and pleasure centers. In the video, it's mentioned that a deficiency in dopamine can lead to symptoms such as a lack of interest in life, decreased motivation, depression, and fatigue. The script explains how the COMT gene's activity can influence dopamine levels, with a faster breakdown potentially leading to low dopamine levels and associated symptoms.

💡Noradrenaline

Noradrenaline, also known as norepinephrine, is a neurotransmitter involved in the body's stress response and is part of the fight-or-flight mechanism. The video discusses how changes in the COMT gene can affect the breakdown of noradrenaline, which can lead to high stress levels, agitation, anxiety, panic attacks, and insomnia when not properly regulated.

💡Adrenaline

Adrenaline, also known as epinephrine, is a hormone that prepares the body to react to stress and dangerous situations. The video script mentions that the COMT enzyme also breaks down adrenaline, and imbalances due to genetic mutations can result in high levels of this hormone, contributing to stress and anxiety.

💡Estrogen

Estrogen is a hormone that plays a significant role in the female reproductive system but also has effects throughout the body. The video script notes that the COMT enzyme is involved in the breakdown of estrogen, suggesting that the COMT gene's function extends beyond neurotransmitters and includes hormonal regulation.

💡Val158Met polymorphism

Val158Met is a specific genetic variation in the COMT gene, where the amino acid at position 158 can be either valine (Val) or methionine (Met). This polymorphism is well-researched and is associated with differences in the enzyme's activity. The video explains that individuals with the Met variant may have slower enzyme activity, leading to higher levels of neurotransmitters and an increased risk of anxiety and panic disorders.

💡Heterozygous

In genetics, being heterozygous for a particular gene means having two different alleles of that gene. In the context of the COMT gene, being heterozygous for the Val158Met polymorphism suggests having one normal and one variant allele, which the video suggests may provide an intermediate level of neurotransmitter breakdown, potentially offering a balance between the risks associated with the other genotypes.

💡Phenols

Phenols are a group of chemicals found in some foods, cleaning products, and cosmetics. The video script mentions that phenols can slow down the COMT enzyme's activity, which could be detrimental for individuals with certain COMT gene mutations. It advises those with a genetic weakness in the COMT gene to consider a low-phenol diet to support proper enzyme function.

💡Methylation

Methylation is a biochemical process in which methyl groups are added to molecules, often affecting gene expression and enzyme activity. The video discusses the potential sensitivity of individuals with certain COMT gene mutations to methylation agents, such as methylfolate and methyl B12, which could influence neurotransmitter levels. It suggests caution with these supplements due to the potential for increased dopamine levels in those with a slow COMT enzyme.

Highlights

The COMT gene mutation is associated with symptoms like depression, anxiety, and insomnia.

COMT stands for catechol-O-methyltransferase, an enzyme that breaks down catecholamines and estrogen.

Dopamine, noradrenaline, and adrenaline are affected by COMT, impacting mood and stress response.

COMT gene variations are linked to mental health conditions like depression, anxiety, autism, and bipolar disorder.

The most researched COMT gene variation is Val158Met, affecting amino acid changes.

Having two normal COMT gene copies can lead to fast breakdown of neurotransmitters, potentially causing low dopamine levels.

Low dopamine can result in depression, fatigue, and poor concentration.

Two copies of the mutated COMT gene can slow down neurotransmitter breakdown, leading to high stress and anxiety.

Being heterozygous for COMT may provide an optimal balance of neurotransmitters.

Green tea and coffee can slow down the COMT enzyme, potentially helping with dopamine balance.

Exercise can help manage stress and improve neurotransmitter balance.

Protein intake is crucial for providing amino acids needed to produce dopamine.

Supplements like L-tyrosine and mucuna can help increase dopamine levels.

Adrenal support may be beneficial for those with normal COMT gene copies experiencing depression or fatigue.

Stress management is essential for those with two copies of the mutated COMT gene to reduce anxiety and panic.

Phenols found in cleaning products and some foods can slow down COMT activity, potentially increasing anxiety.

Magnesium and vitamin C supplementation can support COMT enzyme function.

Adaptogenic herbs can help balance stress hormones for those with a slow COMT enzyme.

Phosphatidylserine can reduce stress levels and improve sleep quality.

Methylation support should be approached with caution due to potential increases in dopamine levels.

Avoiding EGCG, a green tea extract, may be beneficial for those with a slow COMT enzyme.

Transcripts

are you interested in the county jail

mutation do you suffer from depression

anxiety or insomnia and wonder if it's

related well there's the topic of this

video today I'm going to talk about the

symptoms associated with the comte gene

mutation and I'll explain why changes in

the comte gene lead to these symptoms

finally I'll talk about diet lifestyle

and supplement james's you can make to

help support your conten enzyme activity

if you haven't met me before

I'm dr. Janelle Sinclair and on this

youtube channel we discuss natural

strategies for depression and anxiety if

you're interested in that topic

subscribe and hit that Bell button so

you're notified about our new weekly

videos so let's get into this so Conte

stands for catechol on methyl

transferase and the comte gene encodes

for an enzyme that breaks down at

catecholamines and the catecholamines

are dopamine noradrenaline and adrenalin

compte also breaks down the estrogen

hormone so to really understand the

comte gene and its effect on the body

you really also need to know the

function of dopamine noradrenaline and

adrenaline and dopamine as a reward

giving neurotransmitter and

noradrenaline and adrenaline are the

stress hormones the fight and flight

hormones

changes in the comte have been failed to

be linked with depression anxiety autism

panic disorder and bipolar disorder now

there's quite a few different genetic

snaps for Comte but the one they really

want to look for and the one that's most

well researched as Conti V 1 5 8 m or

Val 1 5 8 met so that Val and meta the

amino acid changes in the iris number 4

this genetic snuper's areas 4 6 8 oh so

if you've got the normal snip you'll

have the code GG if you're a

heterozygous for the snap you have it'll

be a G and if you're homozygous mutant

or you have a mutation or a genetic

weakness in the snap your code will be a

a when it comes to most genetic snips

the normal snip the most common code

that's found in the population is

usually the best one to have and the one

that would be ideal to have but with

Conte it's actually not that simple so

I'm going to talk a little bit about the

differences between being homozygous

wild-type or having the normal snap

versus having the mutant or two copies

of that the weak genetic snap so when it

comes to having two normals and which is

most common the population this results

in an enzyme which breaks down dopamine

noradrenaline in adrenaline fast so I

just thought I'd show you this visually

so let's just imagine your brain as yeah

all your cells are a bucket and you've

got neurotransmitters being made and

that the water coming in asserting those

neurotransmitters and then you've got

holes in the bucket which represent your

neurotransmitters being broken down so

and someone that's our feeling balance

not ant

just but they're happy good mood

motivated they'll have a good balance

between the bucket never being empty in

the bucket never being full but what

happens if you neurotransmitters are

being made at the normal rate so the

water's going in but the

neurotransmitters have been broken down

too fast so there's too many holes in

the bucket well the bucket becomes empty

and you can have low levels of

neurotransmitters well this is the case

when it comes to than the normal arm

snaps the wild type for the Conte the

enzyme is breaking down

neurotransmitters fast so dopamine is

getting broken down fast and you can end

up with low dopamine levels so the

symptoms of a dopamine deficiency

include a lack of interest in life

decreased motivation and drive

depression an inability to feel pleasure

fatigue an ability to focus in impaired

concentration poor memory in Parkinson's

disease so I've created a video

previously on dopamine deficiency

symptoms and if you are feeling like

those symptoms sound like you maybe go

and check out that video

so if you've got the normal snap for

Conte it actually can lead to low

dopamine and it can increase the the

risk of depression poor concentration

and fatigue okay so let's look at the

opposite scenario and which you've got

the genetic weakness and the Conte two

copies of the mutant snap and the this

leads to the enzyme breaking down

dopamine noradrenaline in adrenaline

slowly so visually you can think of your

neurotransmitter being made at a normal

rate the water's going into the bucket

but the the neurotransmitters are being

broken down too slowly so there's very

small holes in the bucket and this is

leading to high levels of

neurotransmitters and so what happens

when you've got too much nor adrenaline

adrenaline adrenaline levels well this

leads to high stress levels agitation

anxiety panic attacks and insomnia so if

having two copies of the normal step can

raise your risk of depression poor

concentration and fatigue and having two

copies of the urine snap or weak genes

can lead to an increased risk of stress

anxiety ins in insomnia then what's the

ideal scenario when it comes to your

genes well is it the ideal scenario is

that you heterozygous for Conti so I've

put this in here because a lot of people

go I'm heterozygous I need to do

something to lower my dopamine levels no

you don't my belief is that being

heterozygous means that you have an

intermediate level of dopamine and

noradrenalin and adrenaline which is

much better than having too much or

having too little

but let's go on and talk about what you

can do if you've got a genetic weakness

and you've got some symptoms that seem

to be correlating with it so if you have

two copies of their wild-type snap and

the the normal snip this means that

we'll just go over this again you've got

fast calm T activity and you're your

break you may be breaking down your

neurotransmitters faster leading to low

dopamine and this can lead to increased

risk of depression fatigue and ADHD

now there is an advantage of having this

genetic snap and it means that you can

perform well under stress because your

body is very good at getting rid of all

your stress hormones but if you do have

some depression or fatigue or poor focus

what can you do to help balance this

this enzyme in your body and improve

your symptoms well firstly one of the

considerations is drinking more green

tea and also perhaps to be a little bit

of coffee as well because the caffeine

will be good at and what it does is it

slows down the content enzyme and it

means that you can hold on to more of

your neurotransmitters there's also a

supplement called EGCG and it's a green

tea extract and and that can be also

good at doing it so exercise is another

good thing for you to do is to get in

your body pumping get the endorphins

and/or the adrenaline going and the body

as well also consider ensuring that

you've got enough protein in your diet

one gram per kilogram of body weight

there's a good thing to aim for so if

you're 60 kilograms to have 60 grams of

protein a day because the you need amino

acids and the amino acids come from

protein and

it's toys ain't specifically that is the

precursor for making dopamine and I have

created our video on this and other ways

to increase dopamine levels in the body

so you could check that video out they

also consider l-tyrosine supplementation

and/or mucuna and these will help

increase the dopamine levels in your

body so this is ideal for you if you are

struggling with symptoms of depression

in low motivation possibly also using

some adrenal support is another good

option for you so let's move on and talk

about the scenario and which you've got

two copies of the week genetics net for

Conti and as I said previously this

results and decrease Conti activity and

this enzyme is between 25 to 40 percent

reduced and that's activity compared to

the wild type so what this means is that

you break down your dopamine

noradrenaline and adrenaline slow slower

which means you can end up having high

levels of these neurotransmitters there

is an advantage of this that means you

have better memory you can have higher

IQ can get more pleasure out of life and

be more creative unfortunately though

often don't do well under stress because

under stress the adrenaline levels rise

and your enzyme your body's just not so

good at getting rid of these stress

levels and there has been xiaolin

studies have shown that if you've got

this genetic weakness there it can

increase your risk of anxiety and panic

disorder now keep in mind this genetic

code doesn't mean you have to have

anxiety it's just more of a increased

risk of environmental factors and

lifestyle factors aren't ideal because I

personally have this genetic weakness

and you know I do have a higher IQ and I

do

have better memory but I'm not so good

under stress that I don't have anxiety

so don't let this you think that this is

a life sentence because it was just

Yujin in a code you can do lots and

you're in your lifestyle and environment

to reduce the risk okay so what can you

do

number one stress management is a big

thing for you what you need to do so

diaphragm breathing mindfulness doing

nice walks just keeping good boundaries

in your life just doing it nice and slow

also doing stimulating activities in the

morning so that at nighttime you're not

you haven't built up all your stress

hormones and you can't sleep

so yeah consider coming activities at

night like massage or Epsom salt bath

sauna and diaphragm breathing most

people with this Conti code are thinkers

and find it so make sure that you find

activities that stimulate your brain or

you'll be bored and also make sure that

you're balanced life because we do seem

to have workaholic tendencies okay

so here's some lifestyle considerations

and avoid phenols and which are found in

cleaning products household chemicals

and cause minutes because phenols seem

to slow down the Conti activity further

so if we can avoid these and get rid of

those that chemicals we we don't affect

our slow down the Conti enzyme so for

some people they may be sensitive to -

our food Sophie knows can be found in

cleaning products and cosmetics but

there are also foods that are high in

phenols so if you are quite anxious and

you have this genetic weakness then you

may consider trying a low phenyl diet

also limit green tea coffee and caffeine

because it's believed that the caffeine

slows down the Conti enso further so

I've personally once I got my genetic

test done and found this out I just

stopped drinking coffee all together and

I suggest that you should do that too

so I've created a video on anxiety and

caffeine and so if you want some more

information on that watch that video

so here's some supplementation and

considerations for someone with a slow

Conti enzyme so consider magnesium in

vitamin C because these actually support

the contact ility consider adaptogenic

herbs because this will help control

your stress hormones and balance them

also phosphatidylserine is a really

great supplement for lowering stress

levels you can take it at night to help

you sleep or if you have a tendency for

high stress during the day as well you

can take it during the day to balance

out those stress levels so usually 100

to 300 milligrams is the standard dose

of that some people with two copies of

the Conti mutant or week snap may be

sensitive to methylating agents so

things like methylfolate in methyl b12

so I would just be mindful of this so if

you've started a new multivitamin or

some new Big B complex but it's just

seeing you just feel like you've your

anxieties increased or something

consider that it could be due to the B

vitamins and that supplement also people

that have the in th ER fire and genetic

weakness and you think that you should

really do well on methylfolate a methyl

b12 but you just don't quite feel so

good on it you might feel bit anxious or

you might get more angry or you might

might increase insomnia it may be

because of your Conti genetic weakness

so my suggestion is if you are sensitive

to it useful Anik acid or hydroxy b12

instead of the methylfolate and instead

of the methyl b12

so there is some controversy because

Conti is the inti part of Conti actually

is methyl transferase so it require a

cofactors for Conti as actually methyl

groups and so it's you know to increase

the contact ility some people were

saying that you should improve your

methylation and the body well yes and no

the problem that that is great but the

problem is that dopamine as as levels

are increased in the body through

improving methylation so by improving

methylation then you can increase your

dopamine and then if you've got a slow

Conti enzyme and you're not very good at

breaking down dopamine noradrenaline and

adrenaline it's it's just a little bit

of a vicious circle so it's not that you

shouldn't have methylfolate or a methyl

b12 but just being a little bit cautious

because you could be sensitive to it

my last recommendation is that you avoid

EGCG which is a green tea extract if

you're interested in genetic testing I

suggest that you check out my video on

genetic testing for depression where I

go over 40 different genetic snips that

are involved in mental health

I've also creative videos on the in th

of our genetics nut and one video on the

health conditions and symptoms that

often correlate with that genetic

weakness and also one on treatment

considerations thanks for watching this

video and I'll see you next time