COMT +/+: COMT +/-: COMT -/-:
COMT stands for Catechol-O-Methyltransferase. AKA “The Janitor”.
The Lazy Janitor (May have more mood fluctuations and volatility) The Good Janitor (A more suitable balance; not all defects are negative)
The Hardworking Janitor (May have higher burdens of metals, aluminum & virus).
The COMT V158M +/+ can be a big problem! Though it isn’t the most important area to address first, it is critical to consider the COMT enzyme as this defect can contribute to many challenges when adding in supplements, particularly methyl donors (see methyl groups list below). This is one of the second priority mutations. The COMT H62H also reduces activity leading to “super COMT ++ status” in those with a V158M ++
This enzyme defect allows you to spare dopamine and nor-epinephrine, also known as the “feel good hormones”. A partial defect can be useful in maintaining these important neuro-talkers within the community, particularly when bacteria are present. Bacteria often deplete tyrosine, the major precursor to dopamine so that anyone with bacterial issues (history of recurrent infections, gut issues, etc.), tend to have lower levels. Nevertheless, a full defect can lead to more dopamine and nor-epi sparing, even while these levels remain low.
In fact, full blocks may lead to mood swings and volatility. Why? Well, when an area becomes saturated with too much hormone, a feedback system is in place to slow down its’ production. Just as most refrigerators have a built in system for regulating ice production, your body has an inherent alarm system for controlling excessive hormone levels. For instance, as dopamine levels rise, an alarm bell goes off, relaying the risk of system overload. Consequently, dopamine production drops and you have more potential for extreme highs and lows.
Dopamine deficiency often leads to symptoms of depression, poor focus, and addictive behavior (smoking, drinking, gambling, etc), to name only a few. Conversely, the nor-epi levels (adrenalin) tend to remain elevated. This may be one of many issues contributing to Bipolar Disorder, also known as “manic depression.” This depression tends to be more agitated and irritable than those who have the classic anhedonia, or loss of all pleasure.
Those with the COMT defect are also known to detox more readily than others. However, those who have both the COMT defect and the MTR 11 will detox easily and heavily, dumping both good and bad elements. For this reason, it is important to be very cautious when adding in new supplements. There are also many associations with COMT -/- and COMT +/+ folks in regards to personal traits and characteristics. For instance, those who are COMT -/- are known to be stoic, more even tempered and usually have a much higher pain tolerance.
Conversely, those with the COMT +/+ defects are often volatile, have a lower pain tolerance, and are prone to mood swings. The latter issues are due to the COMT +/+ Janitor not cleaning up the dopamine, nor-epinephrine, and estrogen that is coming through the cycle. This leads to fluctuating levels with these neuro-talkers, particularly when taking in high dopamine foods or supplements. Nevertheless, this also coincides with VDR Taq status as well as other enzyme defects within the system.
For instance, the CBS C699T defect also has an immense impact on the COMT. Subsequently, those with both the COMT and CBS defects should be approached carefully. Based on the research conducted by Dr. Pfeiffer MD and Dr. Yasko PhD, it appears that the COMT defect is one of the culprits behind those referred to as “overmethylators” or “undermethylators”. Nevertheless, it is not quite as simple as “over” or “under” methylator since the VDR Taq enzyme may also figure into this significantly. Also, it is important to consider that those with the CBS defect may have low homocysteine AND low histamine levels.
While we have come to believe that a “defect” is always harmful, in some cases, the COMT +/- or +/+ defect may actually be advantageous. For kids with autism, preliminary data suggest that this enzyme is one of the main predictors of speech. Since this Lazy Janitor preserves dopamine, a crucial neuro-talker used in speech, it appears to be one of several factors that influence apraxia (lack of speech). Nevertheless, a defect that can be helpful usually comes with a price, such as the moodiness and roller coaster mood swings that often occurs in these folks.
The problem with this defect comes in when you take or eat anything that has natural dopamine (tyrosine) in it since your body tries to down regulate, or reduce the dopamine levels in order to maintain balance. This down regulation often leads you from higher dopamine levels in which you have a sense of wellbeing and happiness to suddenly plummeting dopamine levels where you may feel depressed, angry, negative, and irritable. This, along with the MAO A defect, are sort of the "Dr. Jekyll & Mr. Hyde" defects. This also explains why many cannot tolerate SAMe as well and should only take this in small doses such as that found in the Ultimate B caps & some other combination supplements.
Moreover, the COMT shares a promoter site with another enzyme called thioredoxin reductase, which is necessary for managing oxidative stress and is regulated by lithium. Dr. Yasko provides an excellent road construction analogy for this process. When there is roadwork in progress, only one lane is able to move forward at any given time. Therefore both COMT and thioredoxin reductase must take turns. When a COMT ++ defect is present, there is much greater potential for dysfunction in both dopamine and nor epinephrine clearance as well as thioredoxin activity. Therefore, we have another avenue for increasing oxidative stress and free radicals in addition to increasing neurotransmitter imbalances. Since Nor-epinephrine contributes to the stress response, this could lead to a vicious cycle. Yasko states “It appears that lithium may help to regulate thioredoxin reductase, so the net effect may be to increase COMT activity and over time get more even COMT activity which may translate to more even dopamine and less mood swings and aggression. Also, articles show that lithium may help to increase B12 transport and that can play a role as we know in detox”. In addition to impacting the MTR/MTRR enzyme, thimerosol has been proven to inhibit thioredoxin reductase activity (Deth).
Finally, if there has been a longstanding lithium deficiency, B12 transport may have been considerably hindered. Therefore, even while lithium supplementation may be beneficial in balancing COMT function, it may also increase B12 transport and lead to “detox”. In the end, it may take several weeks to see the benefits of lithium amid the “start up” symptoms. Nevertheless, for those who are Sympathetic Nervous System Dominant, B-12 support may be problematic. It is important to discuss this with your practitioner.
You can now see why knowing your genetic mapping makes a difference. It is the combined result of the VDR Taq & COMT status that determines how much of a "methyl Budget" you have, meaning how many methyl donor type supplements that you can take.
Red or purple berries and herbs:
The COMT enzyme processes the colors red and purple so that consuming red or purple herbs or foods and drinks actually slows this enzyme down further. This is a side issue from those with the CBS having difficulty processing phenols. For those with a complete COMT mutation, the simple act of eating too many delicious summer fruits and herbs often leads to more neurotransmitter peaks and valleys. For some, this leads to roller coaster mood or “dopamine swings,” while for others it translates toward more nor- epinephrine surges and restlessness or anxiety. Even so, the synthetic phenols used as coloring agents are even more problematic. *Many become irritable or agitated and struggle with insomnia, and/or develop flushed, red cheeks and ears. In many cases, those with a complete mutation are more sensitive to berries and may develop allergies to them.
Additionally, headaches, insomnia, and heat intolerance are also commonly seen in those with phenol sensitivities. This may be considerably aggravated in the presence of a CBS defect, as it impacts the PST enzyme (please see phenol discussion).
*For instance, a physician colleague of mine would eat red licorice for an afternoon snack. Within the hour his ears would be bright red, and while he was normally very easy going, he would soon become irritable and more easily frustrated with the daily hassles of medical bureaucracy. Yet when he cut the red licorice out of his afternoon routine, he was more pleasant and sociable once again.
* In spite of the fact that CoQ10, carnitine and idebenone are all methyl donors, except in rare circumstances, most with a history of chronic illness will need to use them. Though dosing should be much lower with COMT +/+. Please do not eliminate everything that is on a list, as moderation is key. It is better to be aware of how these various supplements can impact each defect in a positive or negative manner. This is also instrumental in maintaining balance rather than using high doses of any one supplement.
If you have a COMT +/+ defect and the VDR Taq status supports this, you will need to watch your methyl donors, though you do require some. The goal is choosing carefully and finding the best balance for your needs. Generally, the most ideal supports are those that provide some benefit in several areas. In this manner, you get more “bang for your buck.”
#overmethylators #undermethylators #CBS #homocysteine #lhistamine #B12 #MTR #MTRR
To learn more about COMT Gene:
Dr. Richard Deth PhD
Dr. Jill James PhD
1) http://www.ucdmc.ucdavis.ed... (2006 lectures, please scroll down for oxidative Stress Lecture as well).
2) http://www.ucdmc.ucdavis.ed... (2010 Lecture Methylation/Oxidative stress). http://www.youtube.com/watc...
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