S2E31: COMT Fast

The COMT fast picture, as you can imagine, is the flip-side of COMT slow. This enzyme works too well, eliminating crucial substances before they have the chance to act. The most well researched polymorphism that contributes to this picture is the COMT Val158Met Val/Val pattern, but again total COMT activity is additive across all the COMT polymorphisms and is best determined by symptoms and personality.

Signs and Symptoms of Fast COMT

In terms of neurotransmitters, low dopamine, epinephrine, and norepinephrine looks like:

  • Lack of enthusiasm
  • Relaxed, laid-back personality
  • Low motivation
  • Difficulty remaining focused on one task
  • ADD/ADHD
  • Addictive tendencies.

These neurotransmitters do double-duty as stress hormones and so we also see:

  • Suddenly shine in stressful situations, like they are at their best under pressure.
  • Stimulation-seeking – want lots of noise, lights, chatter in the work environment, and chaos to get their neurotransmitters fired up.
  • Sleep easily
  • Tendency toward restless legs and constipaton
  • Typically better with caffeine or other stimulants.

COMT also affects estrogens – meaning it lowers them – and so people with fast COMT often have:

  • Dry skin
  • More prone to osteoporosis
  • Often started their menses later than their peers
  • Symptoms related to low estrogen such as .moodiness, irregular periods, absent periods,
  • Lower tendency toward hormonal cancers including breast and prostate. 
  • Potentially lower sex drive

Remember that other gene SNPs can affect these same neurotransmitters,  and hormones, but if you have this symptom pictures then addressing the situation is appropriate no matter what your gene report says.

The COMT fast genotype carries with it some superpowers as well. On a surface level, the COMT variants get divided into Warrior and Worrier pictures.  COMT fast, because of the lower level of stress hormones, falls into the warrior category.

We say warrior, because stressful situations truly do make people with the COMT fast genotype shine. While others are overwhelmed or overstimulated, these folks are in the zone, at peak performance, and completely on-point. COMT fast folks are well suited to working in emergency rooms, the trading floor on Wall Street, or possibly on the race track. They also have a gift in terms of shifting between topics or areas of focus quickly. None of us are good at multitasking, but COMT fast folks can switch between tasks and activities with ease. This remarkable skill is called cognitive flexibility.

Managing a Fast COMT

Step 1: Balance Your Methylation.

As we discussed, the COMT enzyme is dependent on healthy methylation, so the first thing you would do in this situation, just like in COMT slow, is to optimize your methylation. Get your basic B vitamins, find the best B12 for you, and add a methylation driver like 5-LMTHF or SAMe. Optimize your doses of those things based on how you actually feel and how your symptoms look on a symptom tracker. If you don’t have one yet, you can get a free symptom tracker by signing up for the newsletter at tohealthwiththat.com.

Keep in mind that with a fast COMT your neurotransmitters are naturally low and pushing methylation drivers in this case can make a huge and immediate difference to your mood and affect. Getting good methylation drivers into the works will help tremendously.

Step 2: Optimize Your Diet

Protein boosts dopamine, which is exactly what you want with fast COMT. In a fast COMT situation eating a high protein diet will keep those flagging neurotransmitters up for a good mood and focus. Focus on a higher protein meal at breakfast, and lunch, and have a moderate protein dinner so the neurotransmitters don’t interfere with sleep.

Adding in high magnesium foods helps as well because magnesium is one of the best nutrients for a fast COMT. Look for dark green leafy veggies, low-fat dairy, nuts, and legumes. The magnesium will also balance the tendency toward constipation, muscle cramps, and restless legs.

Step 3: Stimulate

Such a big part of this picture involves stress hormones, and so balancing the helps to optimize performance. This means:

  • Like the slow COMT counterparts, declutter your home and keep it tidy. A calm, chaos-free environment reduces stress hormones, which is not as crucial for COMT fast folks, but it also makes focus easier.
  • Interrupting work with activities that give your brain a dopamine boost, like video games or a quick burst of exercise. Just make sure you’re keeping it in check because these things can become addictive in low-dopamine brains.

Step 4: Balance the Hormones.

As I said last week, balancing hormones is an entire podcast series in itself. Still there are a few things you can do in low hormone states as well:

  • Seed cycling. It’s too much to get into right here, but here’s a link to a detailed article. It’s a lovely way to help balance and regulate hormones safely.
  • Herbal medicines. Shatavari, black cohosh, and red clover are all known to boost estrogens in a relatively safe way, but it is best to work with a knowledgeable practitioner.
  • Exercise to build muscle mass and reduce fat. Dropping estrogens can decrease lean muscle mass and gaining muscle mass helps to balance and regulate all of your hormones.

Thanks so much for listening today and next week we’ll review glutathione before we talk about some of the SNPs that can affect levels. Please subscribe so you don’t miss any episodes and if you like what we’re doing here, I’d really appreciate it if you’d leave a review. Thanks so much!

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S2E30: Slow COMT

This week, let’s talk about our first of two COMT pictures. COMT slow. Remember, this means the COMT enzyme is less efficient than normal so the catecholamines it is supposed to break down stay in circulation longer. This leads to high neurotransmitters including dopamine, norepinephrine, and epinephrine. It also means high levels of hormones, including stress hormones, which are really those same neurotransmitters when they operate outside of the brain, and also estrogens.

This is not dependent on one COMT polymorphism, but rather the sum of all COMT polymorphisms but again I want to caution you against assuming you know what is going on based on a piece of paper. A genetics report can only show you the genes as written, and not the ways your body has activated or silenced those genes (which is called epigenetics) – that can only be observed in real life. So if you’re trying to determine if your COMT is fast or slow, the most helpful thing to look at is personality and symptoms.  Also, there is research showing that the presence of estrogen may inhibit the COMT enzyme further, meaning that women with slow COMT would be more strongly affected than men.

Signs and Symptoms of Slow COMT

In terms of neurotransmitters, high dopamine, epinephrine, and norepinephrine looks like:

  • Enthusiasm
  • Exuberance
  • Self-confidence. 
  • Ability to focus for long periods of time
  • Workaholism

These neurotransmitters do double-duty as stress hormones and so we also see:

  • Difficulty calming down in stressful situations
  • Dislike of overstimulation – lots of noise, lights, chatter in the work environment, chaotic or messy spaces.
  • Hard time falling asleep
  • Easy irritability
  • Often worse with caffeine or other stimulants.

COMT also affects estrogens and so people with slow COMT often have:

  • Glowing skin
  • Strong bones
  • Often started their menses younger than their peers
  • Symptoms related to high estrogen such as fibroids, PMS, and fibrocystic breasts.
  • Higher tendency toward hormonal cancers including breast and prostate. 
  • Higher estrogen status is generally harder to see in men, but in extreme cases it can cause swelling of breast tissue, erectile dysfunction, and delayed puberty but milder cases may be harder to detect.

Remember that other gene SNPs can affect these same neurotransmitters,  and hormones, but if you have these symptom pictures then addressing the situation is appropriate no matter what your gene report says.

The COMT Slow genotype carries with it some superpowers as well. On a surface level, the COMT variants get divided into Warrior and Worrier pictures.  COMT slow, because of the high level of stress hormones, falls into the worrier category.

That doesn’t sound like a superpower, but stick with me. People with slow COMT actually have higher levels of dopamine in their prefrontal cortex, which is associated with executive function, decision making, understanding consequences, impulse control, coordinating complex behaviors, and creativity. 

In studies, higher dopamine in this area of the brain allowed people to excel at these tasks, especially in creativity. Those with the COMT Val158Met Met/Met allele (COMT slow) showed greater abilities in divergent thinking, meaning they were able to create more different  solutions to a given problem in a short amount of time than someone without that polymorphism.

So while those of us with the COMT slow variant (you can’t see it but my hand is up here), have the potential to feel stress more acutely than our COMT fast counterparts but we can also think of 50 ways to solve a problem in no time at all.

Interestingly, the slow COMT state also has better cognitive stability, meaning the ability to stay focused on a task for long periods of time, where COMT fast is better at flipping between tasks effectively.

Managing a Slow COMT

Step 1: Balance Your Methylation.

As we discussed last week, the COMT enzyme is dependent on healthy methylation, so the first thing you would do in this situation, just like in COMT fast, is optimize your methylation. Get your basic B vitamins, find the best B12 for you, and add a methylation driver like 5-LMTHF or SAMe. Optimize your doses of those things based on how you actually feel and how your symptoms look on a symptom tracker. You can get a free symptom tracker by signing up for my newsletter at tohealthwiththat.com.

Keep in mind that with a slow COMT your neurotransmitters look a lot like you’re on small doses of uppers all the time and so overdoing your methylation drivers can take that away, flipping your COMT slow to a COMT fast, and frankly nobody likes anything that downs their uppers. So beware of taking too much or pushing this process too hard. We’ve got to be flexible and responsive in dosing methylation drivers and not get stuck on a target amount we’re “supposed” to take.

Step 2: Optimize Your Diet

Protein boosts dopamine, which is something that you don’t need if you’ve got a slow COMT. Especially at night when you’re trying to get to sleep. Focus on a higher protein meal at breakfast, but lower at lunch and dinner. Slow COMT folks do best with a veggie and carb weighted dinner.

Adding in high magnesium foods helps as well because magnesium is one of the best nutrients for a slow COMT. Look for dark green leafy veggies, low-fat dairy, nuts, and legumes. Fortunately, these are also foods that are high in natural folate, so you’re eating them anyway, right?

Boost your fiber. Help your body to eliminate those excess estrogens by eating lots of fiber that can help to bind them in your gut and make sure they get eliminated.

Step 3: Calm.

Such a big part of this picture involves high stress hormones, and so minimizing stress is crucial to keeping balance. This means:

  • Declutter your home and keep it tidy. A calm, chaos-free environment helps reduce stress hormones.
  • Go for quiet environments or soothing background music when you’re trying to focus or wind down.
  • Meditate, take a minute to breathe deeply, or try the technique Martha Beck outlines in this episode of her Bewildered podcast with Rowan Mangan.

Step 4: Balance the Hormones.

While balancing hormones is an entire podcast series in itself, there are a few constants. I mentioned fiber in the diet section and if there is only one thing you can do, fiber should be it. Otherwise:

  • Seed cycling. It’s too much to get into right here, but here’s a link to a detailed article. It’s a lovely way to help balance and regulate hormones safely.
  • Bump up your broccoli. Broccoli and other cruciferous veggies like cabbage, brussels sprouts, cauliflower, and kale specifically help to detoxify estrogen. If you’re going for bonus points, then look to broccoli sprouts for the win.
  • Avoid plastics and pesticides, many of which mimic estrogen in your body. Getting these artificial estrogens out will help your body deal with your natural estrogens more easily.

Thanks so much for listening today and next week we’ll dive right in to the COMT fast picture. Please subscribe so you don’t miss any episodes and if you like what we’re doing here, I’d really appreciate it if you’d leave a review. Thanks so much!

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S2E28: COMT and MTHFR.

To kick off our series on other polymorphisms, I’m starting with another heavy-hitter that is deeply entwined with MTHFR.  This polymorphism is also in a gene that codes for an enzyme by the name of catechol-O-methyltransferase.

I’m hoping that right off the bat, you noticed the word “methy”l in there as part of the enzyme name. That is important in terms of how it ties in with MTHFR. So let’s break this name down.

Catecholamine = the group of compounds that this enzyme acts on. In fact, it metabolizes these substances as part of the break-down process.” Catecholamines are a very important group of hormones, many of which do double duty as neurotransmitters, that have a similar structure and are all highly biologically active.  They include dopamine, norepinephrine, epinephrine, and a group of estrogenic compounds called catecholestrogens.

It doesn’t take a vast wealth of biomedical knowledge to know that an enzyme that affects stress hormones, neurotransmitters, and estrogens is going to matter. Really matter.

Catechols are also found in foods, drinks, and supplements and the COMT gene can change the way we respond to those as well. Coffee, beer, buckwheat, green and black tea, chocolate, peppermint, parsley, thyme and many other fruits, vegetables, and herbs all contain catechols. In terms of supplements, EGCG (from green tea), green coffee-bean extract, rutin, and quercetin.

A quick note on the supplements – they generally act as COMT inhibitors, which can be a good thing if your COMT is overly fast, but not so good if you have a slow COMT.

As for the next part of the name, “O-methyltransferase” – this refers to the specific action taken at this particular step in the breakdown process. We’re transfering a methyl group to a particular location (designated “O”). And by methyl group, I mean from a SAMe, made by your MTHFR.  So if your MTHFR is limping along, then COMT is by  nature compromised because there isn’t enough SAMe or enough methyl donors to go around.  So these two enzymes are highly tied together. This is also a big part of why MTHFR folks often have issues with estrogens.

There is one other breakdown pathway for these neurotransmitters, which is via the MAO series of enzymes, all of which can also have polymorphisms, so there is a lot of symptom overlap between COMT and MAO mutations.

It may sound like COMT isn’t important because it isn’t about formation of these products, it’s about breakdown, but in reality, breakdown is just as important.  Overly efficient breakdowns means that the substance is cleared too quickly and you don’t get all the benefit, while breakdown that is too slow means the substance hangs around for too long doing damage. 

There are several COMT mutations and they have additive effects to make the overall activity of the enzyme either faster or slower than the wild type genetics. The most studied so far is COMT Val158Met.

COMT Val158Met (or rs4680, or G158A because genetics can’t keep its names straight).

This is a really interesting polymorphism because it can take a person either faster or slower, depending on it’s presentation. In the next two weeks we’ll dive into the idea of faster and slower and what that means for the person experiencing it.

Met/Met = estimated to be 40% slower than “wild type”

Val/Met = intermediate activity

Val/Val = faster than average COMT activity

There are other COMT polymorphisms as well, but I do want to caution you from trying to figure out your fast/slow status from a genetic report. The symptoms and signs of fast and slow COMT are very clear and easy to see and they’re far more accurate than us doing theoretical math on gene SNPs. Remember that genes can actually have a polymorphism, but they can also act like they have a polymorphism because of nutrition, lifestyle, and epigenetic factors so the most important factor in figuring out whether you’re fast or slow is your symptoms and personality.

COMT and MTHFR

There is a really strong link between your MTHFR status (and more importantly, how well you’re methylating) and your COMT activity. Remember the O-methyltransferase part? Well, we can only transfer methyl groups if we have methyl groups and in order to have a healthy supply, methylation needs to be happening well.

This might sound simple, but it essentially means that healthy COMT function depends entirely on healthy methylation, so without doing your methylation background you can work on COMT until you’re blue in the face and it isn’t going to fix things.

This also means that if you’re pushing methylation too hard – say you’re taking great big doses of methyl folate or SAMe and (somehow) tolerating it well but not really needing it? That has the potential to push your COMT into too-fast territory.

The supplements that can push COMT too fast are:

  • methyl-cobalamin (this is one that I see people take far too much of really frequently).
  • betaine / TMG
  • 5-LMTHF or methyl folate
  • SAMe

You’ll notice these are all the drivers of methylation and your big methyl donors.

COMT, also needs a cofactor and that is magnesium. Just like MTHFR needs B2, or riboflavin, to do anything at all, COMT needs magnesium. Fast or slow, this is a great addition to your routine, especially at bedtime because magnesium is physically and mentally relaxing.

Thanks so much for listening and next week we’ll dive into the COMT slow personality type and picture and also what you can do if you have COMT slow. Thanks so much for listening, and if you might be interested in a 6 Weeks to Amazing MTHFR course and workbook, then you’d better get into Genetic Rockstars or sign up for the mailing list at tohealthwiththat.com right now.

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