Slow COMT, Menopause, and Insomnia

Hi all, let me go ahead and talk about one aspect of the Slow COMT + menopause intersection. I’ve already addressed an element of post-menopausal insomnia in a video on our private Facebook group on March 10th, and that is indeed relevant to this discussion, but let’s focus now on menopause’s interaction with Slow COMT.

With menopause, among of course other things, you get a drop in estrogen levels. Estrogen is not an inert molecule but an EXTREMELY broad-ranging molecule with regards to its regulation of 100s of different bodily pathways.

That’s of course what hormones do: They are regulatory molecules that the body makes to change how different body processes run.

One of those processes that estrogen regulates is NEUROTRANSMITTER BREAKDOWN.

Estrogen affects the way that your body processes neurotransmitters, i.e. those molecules that signal within your brain and skew it towards different “modes” of cognition and function.

With regards to sleep, specifically, estrogen reduces serotonin breakdown. So PRE-menopausally, a young woman will lean towards more serotonin in the synapses of her brain.

After menopause, when estrogen comes down, you get less of that estrogen-mediated inhibition of serotonin breakdown, which has the net effect of reducing overall serotonin levels.

This is especially relevant for people with FAST MAO-A variants!

If you’ve been with me long enough, you may know that the MAO enzyme is involved in breaking down all types of “amines,” including not only catecholamines (like adrenalines and dopamine) but also serotonin in the form of 5-hydroxytryptamine!

There are two key types of the MAO enzymes, and it’s the MAO-A form that’s involved in breaking down serotonin.

Estrogen inhibits MAO-A, making it break down serotonin less, and thereby increases serotonin (and through other mechanisms).

If you have the fast version of MAO-A, that’s going to make you even more susceptible to low serotonin levels. You can check this yourself in your genetic data: The “G” allele at rs6323 is the faster form (if you don’t have that data, you can look at my Mood Panel).

So post-menopause means less estrogen, and that in turn means less serotonin in the brain synapses.

And that of course affects sleep because of the way serotonin is involved in both the onset as well as the structure of your sleep.

By the way all, if you’re not a Roadmaps member yet and want to get into my private cohort on the Facebook group and receive all my videos/articles I make for my members, join here please:

Carry on:

With regards to onset, serotonin is the precursor to melatonin! So if you don’t have enough serotonin, you’ll likewise have difficulty producing melatonin, which is central to sleep onset.

And with regards to sleep structure, melatonin is involved in “contouring” your sleep, so to speak.

What does that mean?

Your sleep, as you know, is divided into stages: N1, N2, N3, and REM. Simply put:

• N1 is a “transition” stage of sorts. It’s the shift from wakefulness to sleep.

• N2 is mid-range light sleep, between light stages and deeper stages.

• N3 is deep, slow-wave sleep. It’s characteristically restorative and it’s often what people have less of as they get older.

• REM is where dreams happen and your body is, quite interestingly, neurologically paralyzed.

How is serotonin involved here? It does a couple things:

1. It actually SUPPRESSES REM sleep. That is, if you have serotonin being released in the brain, your body doesn’t want to go into REM sleep and will therefore favor other phases like N3 deep sleep.

2. It helps to sort of smooth the transitions between the phases.

Therefore, if you don’t have enough serotonin, you will:

1. Have too much REM relative to deeper more restorative sleep.

2. and you’ll have rougher transitions between the sleep stages, making you more likely to wake up!!

That obviously implicates estrogen too, because too little estrogen will mean less serotonin and therefore more of the above sleep disturbances.

Where does COMT come into play here?

Slow COMT yet further worsens the serotonin-decreasing effects of menopause!

To make a long story short, it does this by shifting your body more towards a dopaminergic state and away from a serotonergic state, thereby making you more vulnerable to the effects of menopause on sleep!

What you need to do (educationally speaking) is therefore:

1. Address COMT first and foremost.

   It’s worth testing methylation biomarkers like SAMe, SAH, homocytsteine, sarcosine, etc. to assess the availability and usability of methyl-groups for COMT. This will help make sure you’re not shifted into the dopaminergic state that makes you more vulnerable here.

2. Address serotonin availability and usability!

   This is yet another reason (to reiterate what I said in the recent progesterone/sleep video) to test B6 status using an organic acid test and test zinc status. Look at tryptophan levels in the plasma, ideally. Check iron status.

3. Be very careful with low carb dieting,

   and at the very least, shift more carbs towards the nighttime before bed, ideally in a lower protein meal. i.e. your nighttime snack (or even dinner) can be a higher complex carb, lower protein snack.

4. Consider supplements that work on serotonin. Inositol is a no brainer here.

   Though the dosages people use for inositol are usually way too low. You need 3 grams as a bare minimum, and work upwards from there.

   I like the Jarrow one depicted below. Or if you want to be a little more biologically “correct” about things, you could do one with a proper 40:1 ratio of myo- to d-chiro inositol, like this one.

Hope that helps you all! Let me know your thoughts in the Facebook group please!

~ Dr. Malek

This is all purely educational! Nothing on this website should be construed as medical advice! I am not your doctor. Check with your doctor before making any changes to anything.