# Figured out why I have low Dopamine - High COMT enzyme activity



## Beggiatoa

I got the information after doing my gene test with 23andme. I ran the raw data through another software called promethease and that was among the results. I've seen this discussed a few times but it hasn't gotten a lot of attention.

I have a MET158VAL polymorphism in the COMT gene with the genotype VAL/VAL. That means the enzyme catechol-o-methyl transferase is highly active in my body and brain. This enzyme methylates many compounds, rendering them inactive.

Among these, are the catecholamines Dopamine, norepinephrine, epinephrine and others like caffeine and estrogens. Incidentally, I did a hormone panel a few years ago and my estrogen levels were radically low. My doctor didn't make anything of this and I could never figure out why. I think the low estrogen is the culprit behind my chronic joint pain. In support of this, aromatase inhibitors cause joint pain as a side effect because it lowers estrogens. Even supplements with small aromatase inhibition function like resveratrol and mangosteen, worsen this pain for me.

The lower dopamine levels specially in the prefrontal cortex can explain all the dopamine related issues I've had over the years such as lack of motivation, ADD and even the social phobia. Patients with high COMT activity are reported to be less motivated and more prone to ADD symptoms.

The concept of Warrior vs. worrier is directly related to the levels of COMT activity. The val/val genotype makes one a warrior while a met/met a worrier. Each has advantages and disadvantages mediated by low and high dopamine levels, respectively. The warrior tends to have low dopamine levels until said person is under stress. In this case, prefrontal dopamine levels increase (temporarily) improving focus and motivation. In my case, stress is not enough. I need to be angry. It is this anger that's helping me write this post (along with green tea) that I've been putting off for weeks. I've known for a long time that I became more focused and motivated when I was angry and I exploited this reaction to my advantage. I just never knew why.



> Val158 alleles may be associated with an advantage in the processing of aversive stimuli (warrior strategy), while Met158 alleles may be associated with an advantage in memory and attention tasks (worrier strategy). Under conditions of increased dopamine release (eg, stress), individuals with Val158 alleles may have improved dopaminergic transmission and better performance, while individuals with Met158 alleles may have less efficient neurotransmission and worse performance.


I'm not implying that this is the only cause of social phobia but it's definitely one that can be diagnosed and even treated. There are certain compounds that inhibit the COMT enzyme and improve some of these issues. The most effective ones seem to be:


Rhodiola Rosea
EGCG
Oleuropein
Quercetin
Vitamin C

You've probably tried many of these supplements only to find they worsen anxiety.  That's the effect of COMT inhibition. If you can find a way to mitigate the anxiety they provokes, you can probably benefit from the effect of increased dopamine.

Some ideas on how to do this:

Combine with a cholinergic agent to enhance parasympathetic activity
Magnesium and Lysine to keep cortisol low. Cortisol stimulates PNMT.
Inhibit the enzyme dopamine beta hydroxylase to inhibit conversion of Dopamine to Norepinephrine.
Inhibit the enzyme PNMT which converts Norepinephrine to epinephrine.

The COMT enzyme uses magnesium and SAMe as co-factors which could explains low levels or a high demand for these substances. SAMe is also a cofactor for the PNMT enzyme so it increases epinephrine production and worsen anxiety for some. I get anxiety from SAMe every single time.


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## Beggiatoa

You can read more about the Warrior vs worrier idea here:

http://www.cnsspectrums.com/aspx/articledetail.aspx?articleid=642
http://www.snpedia.com/index.php/Rs4680
http://www.selfgrowth.com/articles/Warrior_or_Worrier_Which_One_Are_You.html
http://www.ncbi.nlm.nih.gov/pubmed/17008817

There are some studies that show an association between a COMT polymorphism and social phobias:

http://www.ncbi.nlm.nih.gov/pubmed/15337664

There are also other genes that are linked to anxiety disorders such as MAO-A and 5-HTT, SLC6A4, BDNF.

To give you an idea, Manganese is a potent MAO inhibitor and it can explain why I reacted so well to it.


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## misread

in general genotype VAL/VAL (higher COMT-activity) is associated with low neuroticsm, low anxiety and high extraversion. so in your case it would not make sense..


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## podizzle

great post and interesting info on COMT and choline. cortisol gives me a feeling of GAD instead of SAD. SAD i believe to be buried deep within the psyche.

i also find when i harness anger i can get motivated. sometimes i'll start ****ing throwing around the ****ing f word every other ****ing word and it seems like people respect me more. perhaps they're entertained by the perceived spiral out of control. in the end anger cannot be an answer for me. it is a negative mental condition.

im still working it out but i believe the real answer to social anxiety is complete honesty, faith and selflessness. with these traits there can be no shame. obviously you have neural pathways to rewrite and as we know ours are dug deep.


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## Beggiatoa

misread said:


> in general genotype VAL/VAL (higher COMT-activity) is associated with low neuroticsm, low anxiety and high extraversion. so in your case it would not make sense..


As ironic as it sounds, I used to be a very outgoing friendly guy. This SA problems only kicked in in my early 20's. That aspect of me is still there. The anxiety issues (non-phobic) have a lot to do with my upbringing and with family problems I've had. However, having the VAL/VAL polymorphism IS associated with social phobia. You can see that in some of the studies I posted above and there were more that I found. It's all about the dopamine and having a high COMT activity predisposes one to low dopamine resulting in not only different degrees of social phobia, but also ADD, lack of movitation, depression and other problems.

Maybe as a whole, Val/val has less anxiety and less neuroticism but it's not completely absent. Keep in mind though, that most people are not VAL/VAL or MET/MET. We are the minority. The majority of people are VAL/MET and are as normal as anyone can be.

I took this information and checked other people I suspected had similar traits. (within my family). Ran their gene tests and alas, VAL/VAL was the result everytime. In one particular case, I thought someone was MET/MET because they had the high trait anxiety and neuroticism but was able to focus well when it came to academic tasks. I was surprised to find this person was VAL/VAL but brilliant. All the genes that are linked to intelligence supported this. So the COMT gene alone, doesn't account for academic performance and success. Where in my case, I'm dumb and slow and when you add ADD and lack of motivation, geez..

However, I'm a warrior in every way the articles describes it. I finally put a name to the type of personality I have. I always welcome challenges, hence why I've picked the hardest things, the road less traveled by. I took all AP classes in high school and always chose the tough courses in college. I even went to Medical school. Ofcourse, I struggled given some of my limitations but I was able to graduate in very good standing. I never let problems get the best of me, I always focus on trying to solve them. Hence, why most of my posts are in the supplements forum, not anyone of the many "I hate having SA" subforums.

I found an old post here where someone looked at the COMT idea and was actually trying to RAISE the enzyme. NONONO! You want MORE dopamine, not less. Don't get stuck in the anxiety and neuroticism characteristics because it's only part of the problem and one that wasn't clearly defined.

I hope other people will try to find out if they are affected by this. I'm easy to figure out and not impossible to treat. One thing is knowing that low dopamine causes SA, another is knowing WHY you have low dopamine.


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## Tucker3

*Interesting*

Hey Beggiatoa,Interesting stuff!How's treating the overactive comt enzyme working out for you?What approach are you using i.e egec,rhodiola,quercetin?Also I'm a little confused about the magnesium bit.You claimed that the comt enzyme was reliant on magnesium but also suggested to use magnesium for the resultant anxiety of inhibiting comt enzyme.Anyway thanks for the post and previous posts.If everyone was as dedicated as you are we would of figured this **** out years ago!


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## hoddesdon

Beggiatoa said:


> I even went to Medical school. Ofcourse, I struggled given some of my limitations but I was able to graduate in very good standing.


So you are a doctor?

I agree with another post that it can be difficult to follow what you are saying. Some of the jargon e.g. VAL\VAL I do not understand.


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## Beggiatoa

I don't fully understand what this mean and the magnesium part is a bit of speculation on my part. Magnesium and SAMe are cofactors for the enzyme and anxiety tends to deplete magnesium from your body faster than non-anxious people so it would make sense to keep some at hand. What is clear, however, is the association between high COMT activity/low dopamine and social anxiety. My contribution to this is how there are ways to partly inhibit the enzyme to allow a higher pre-frontal dopamine concentration. This should alleviate some of the low Dop. related problems. 

I'm trying to figure out the best way (for me) to do this. There are medications that inhibit COMT but they are all liver toxic. I think I'll try a combination of Rhodiola and white tea and see how that goes.

Again, this is only one cause of social phobia like behavior but not the only one. If you want to understand more, read the links in the first post.


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## Define Me

Have you tried not fapping? Worked wonders for me.


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## hoddesdon

Define Me said:


> Have you tried not fapping? Worked wonders for me.


What is fapping?


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## Dystopia

hoddesdon said:


> What is fapping?


A disease.

That we've all got to fight against to prevent SA.


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## Define Me

hoddesdon said:


> What is fapping?


Masturbating.


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## hoddesdon

^ this is disgusting.


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## Beggiatoa

Define Me said:


> Have you tried not fapping? Worked wonders for me.


Actually, I have. It does works wonders :clap


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## mark555666

Beggiatoa, I just want to say you are the damn man. You describe my in detail. ADD, lack of motivation and those other problems happen as well. 

Rhodiola Rosea, Manganese, Magnesium, Vitamin C do wonders for me. I'm going to order some supplements again  Better than Xanax I guess.


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## Owtsgmi

You need to check out the CILTEP stack discovered at another forum:
http://www.longecity.org/forum/topic/51732-chemically-induced-ltp/page__st__180#entry516708
It worked to decrease my SA big time. It is basically quercetin and forskolin taken once or twice a day with some sort of stimulant.


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## Beggiatoa

Thanks for the link Owtsgmi. I write on that forum as well. My nick there is Lufega. I'll have to give that thread a read again. I was interesting in inducing LTP before. I got great effects from carnosine.


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## Owtsgmi

Beggiatoa said:


> Thanks for the link Owtsgmi. I write on that forum as well. My nick there is Lufega. I'll have to give that thread a read again. I was interesting in inducing LTP before. I got great effects from carnosine.


Ha..just read your post over "there" and had a feeling Lufega was the same poster. Your posts offer great insight... I appreciate the well thought out research. Plus, it's nice to get some cross talk among the forums to share ideas. I'll look into carnosine...that's one I haven't tried yet. What does it do for you?


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## Beggiatoa

It helped in terms of retaining information when I studied. Like I wrote there, i can't remember what else I was using it with but I reacted very well. I have some left I'll pick again soon. I'm trying to go through the bin of retired supplements. Might as well, since I paid for them all


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## Beggiatoa

pyridoxal-5'-phosphate is also a comt inhibitor. Very cool !
PMID:3004168


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## The Professor

good stuff. And you must have been on adderall if you could write all that so knowledgeably with low dopamine


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## Beggiatoa

The Professor said:


> good stuff. And you must have been on adderall if you could write all that so knowledgeably with low dopamine


I wasn't actually. If you read over it again, I mentioned that I was angry and that was helping me write this. Don't think for a second that having no motivation or being ADD has anything to do with intelligence. It has absolutely nothing to do with it. The low dopamine holds you back a lot but it doesn't make you stupid even though you might feel or even act that way sometimes.


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## Beggiatoa

Beggiatoa said:


> pyridoxal-5'-phosphate is also a comt inhibitor. Very cool !
> PMID:3004168


PLP is the active form of Vitamin B6. I forgot to mention why this was important to me. I have a gene that predisposes me to lower levels of PLP than normal people. So on top of having high COMT enzyme activity, I also have low levels of that vitamin that helps inhibit it. I have PLP here and started using it again.

The plot thickens..


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## tbone

Maybe Kava or chamomile would help


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## misread

is ginkgo also a comt inhibitor?


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## Tucker3

Any updates Beggiatoa?I tried rhodiola.Seemed to improve my mood but nothing too drastic.Any luck with the p5p?


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## hoddesdon

Beggiatoa said:


> PLP is the active form of Vitamin B6. I forgot to mention why this was important to me. I have a gene that predisposes me to lower levels of PLP than normal people. So on top of having high COMT enzyme activity, I also have low levels of that vitamin that helps inhibit it. I have PLP here and started using it again.
> 
> The plot thickens..


So would taking vitamin B6 help?


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## timtron

Man this is so interesting! I have to go back and read it again because I couldnt concentrate I was so excited by all these enzymes! Woohoo I hope the answer to all my problems is in that first post


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## timtron

so high comt = low dopamine?

I must have low comt, most MAOI herbs and rhodiola make me worse. SAMe makes me worse as well. 

Anything that raises comt??


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## Kls2303

*My genetic test also shows low dopamine due to COMT*

I saw others posting that they have found out that their low dopamine is due to high COMT activity. I have tried explaining this to my psychiatrist but she will not listen and says I just need to keep taking ritalin to give me dopamine. How can I make her understand that the COMT is inhibiting me from getting enough dopamine? Has anyone else taken something to help with their high COMT activity? Maybe a COMT inhibitor like entacapone? Any response would be greatly appreciated.


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## jackbarrett

Sorry but this company 23andme is a ripoff. You can do simple research.


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## Owtsgmi

Nope. They are not a ripoff. A genetic test yields valuable results about yourself. And you get it for a measly $100. You may not like the results you get, but you cannot say they are a ripoff.


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## derpresion

wait a minute, you mean brain works with being continuously affected by genetic program? i thought that genetics only make our brain while it develops but our thoughts isnt straight product of our genetics? so its not the case.. 
can you please explain?

sorry for noob question but i wonder :T


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## hoddesdon

derpresion said:


> wait a minute, you mean brain works with being continuously affected by genetic program? i thought that genetics only make our brain while it develops but our thoughts isnt straight product of our genetics? so its not the case..
> can you please explain?
> 
> sorry for noob question but i wonder :T


You are right that our thoughts are not a straight product of our genetics.

What the OP means is that the enzyme COMT makes the neurotransmitter dopamine less effective. A lack of dopamine contributes to Social Anxiety Disorder. You can compare what the OP means to how a car works. The brain is the motor, and dopamine is the petrol. If you add water to the petrol, then the motor can not work properly. COMT is the water that makes dopamine less effective, and then the brain does not work properly.


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## derpresion

thanks for answer


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## jackbarrett

Owtsgmi said:


> Nope. They are not a ripoff. A genetic test yields valuable results about yourself. And you get it for a measly $100. You may not like the results you get, but you cannot say they are a ripoff.


Give me 100 dollars and I assure you, I will make you full-micro-genealogic test.

This is how it works. I will make up a story and say you have asian roots and buy mcdonalds with your money. You can't say I'm wrong since you have no idea about your ancients, in all cases I win.

Jeez.


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## millenniumman75

We have a low self-esteem because we allowed it to happen. 
The best way to "get back" at people is to rise above the crap they shoveled and STILL be nice to other people!!!


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## Dolly35

*MTHFR and COMT*

I did some lab tests and found out I am homozygous MTHFR - C677T and homozygous COMT - rs4680 Val. Every time I try to take the l-methylfolate to help with the MTHFR mutation, I get anxious. What I don't understand is if I am COMT - rs4680 val, why do I get the anxiety, if my body breaks down dopamine faster than normal. Thank you for your help.


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## Dolly35

*MTHFR and COMT*

I did some lab tests and found out I am homozygous MTHFR - C677T and homozygous COMT - rs4680 Val. Every time I try to take the l-methylfolate to help with the MTHFR mutation, I get anxious. What I don't understand is if I am COMT - rs4680 val, why do I get the anxiety, if my body breaks down dopamine faster than normal. Thank you for your help


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## Dolly35

I did some lab tests and found out I am homozygous MTHFR - C677T and homozygous COMT - rs4680 Val. Every time I try to take the l-methylfolate to help with the MTHFR mutation, I get anxious. What I don't understand is if I am COMT - rs4680 val, why do I get the anxiety, if my body breaks down dopamine faster than normal. Thank you for your help


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## InTheWorldOfNiM

Beggiatoa said:


> As ironic as it sounds, I used to be a very outgoing friendly guy. This SA problems only kicked in in my early 20's. That aspect of me is still there. The anxiety issues (non-phobic) have a lot to do with my upbringing and with family problems I've had. However, having the VAL/VAL polymorphism IS associated with social phobia. You can see that in some of the studies I posted above and there were more that I found. It's all about the dopamine and having a high COMT activity predisposes one to low dopamine resulting in not only different degrees of social phobia, but also ADD, lack of movitation, depression and other problems.
> 
> Maybe as a whole, Val/val has less anxiety and less neuroticism but it's not completely absent. Keep in mind though, that most people are not VAL/VAL or MET/MET. We are the minority. The majority of people are VAL/MET and are as normal as anyone can be.
> 
> I took this information and checked other people I suspected had similar traits. (within my family). Ran their gene tests and alas, VAL/VAL was the result everytime. In one particular case, I thought someone was MET/MET because they had the high trait anxiety and neuroticism but was able to focus well when it came to academic tasks. I was surprised to find this person was VAL/VAL but brilliant. All the genes that are linked to intelligence supported this. So the COMT gene alone, doesn't account for academic performance and success. Where in my case, I'm dumb and slow and when you add ADD and lack of motivation, geez..
> 
> However, I'm a warrior in every way the articles describes it. I finally put a name to the type of personality I have. I always welcome challenges, hence why I've picked the hardest things, the road less traveled by. I took all AP classes in high school and always chose the tough courses in college. I even went to Medical school. Ofcourse, I struggled given some of my limitations but I was able to graduate in very good standing. I never let problems get the best of me, I always focus on trying to solve them. Hence, why most of my posts are in the supplements forum, not anyone of the many "I hate having SA" subforums.
> 
> I found an old post here where someone looked at the COMT idea and was actually trying to RAISE the enzyme. NONONO! You want MORE dopamine, not less. Don't get stuck in the anxiety and neuroticism characteristics because it's only part of the problem and one that wasn't clearly defined.
> 
> I hope other people will try to find out if they are affected by this. I'm easy to figure out and not impossible to treat. One thing is knowing that low dopamine causes SA, another is knowing WHY you have low dopamine.


So it doesn't have much to do with serotonin? Why are so many psychiatrists unaware of the dopamine theory for social phobia???


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## jonny neurotic

InTheWorldOfNiM said:


> So it doesn't have much to do with serotonin? Why are so many psychiatrists unaware of the dopamine theory for social phobia???


Because you can't get high on SSRI's. They don't want to be handing out pep pills that make you feel all bouncy and nice in case you abuse them...


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## Sacrieur

I do suspect I'm a MAOA variant, I'll look into it.


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## jonny neurotic

Dolly35 said:


> I did some lab tests and found out I am homozygous MTHFR - C677T and homozygous COMT - rs4680 Val. Every time I try to take the l-methylfolate to help with the MTHFR mutation, I get anxious. What I don't understand is if I am COMT - rs4680 val, why do I get the anxiety, if my body breaks down dopamine faster than normal. Thank you for your help.


Can you be absolutely certain that methylfolate makes you feel anxious? I mean absolutely certain. Have you tried doing a placebo test to see?

I remember one time when I was litttle my mum made a pizza with kidney beans on it. The next day I came down with a tummy bug and was very sick. For years after it I couldn't eat kidney beans. I loved them before but afterwards even thinking about them made me feel sick. Why? Because our brain s try to make these kinds of connections to keep use from consuming things that make us sick. But It wasn't the kidney beans that made me sick. Our brains sometimes make connections between things that are unrelated. There is a good chance that methylfolate had no impact on your mood whatsoever but your brain associated you taking it with you feeling anxious. Just a thought...


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## Wileykit

*Val/Val too*

Hi
Thanks for your post. I am also Val/Val so probably low in dopamine. I also have no motivation and feel ADHD at times. I've taken L-tyrosine the last few nights and found i slept well, altho could be a coincidence. Have you thought of trying this to increase dopamine?

I also have tried Rhodiola Rosea in the past and thought it worked better for me than St Johns wort, SAMe and 5htp.

I'm also heterozygous for the MTHFR C6something mutation. Did you say that that combined with COMT Val/Val makes things worse?

I will definately try the supplements you suggest anyhow! Cheers for interesting post.


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## Wileykit

jonny neurotic said:


> Can you be absolutely certain that methylfolate makes you feel anxious? I mean absolutely certain. Have you tried doing a placebo test to see?
> 
> I remember one time when I was litttle my mum made a pizza with kidney beans on it. The next day I came down with a tummy bug and was very sick. For years after it I couldn't eat kidney beans. I loved them before but afterwards even thinking about them made me feel sick. Why? Because our brain s try to make these kinds of connections to keep use from consuming things that make us sick. But It wasn't the kidney beans that made me sick. Our brains sometimes make connections between things that are unrelated. There is a good chance that methylfolate had no impact on your mood whatsoever but your brain associated you taking it with you feeling anxious. Just a thought...


Have you looked at the MTHFR site and joined forums? I think its complicated how you dose the methly folate, i need to look into it but only have one mutation. Think its more difficult to fix if you have more... they are the best people to ask, there are lots of facebook groups on it.


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