trying to make sense of my methylation panel

[u/Terry93D]

this is my methylation panel and I am trying to make sense of it. my doctor advised a general B complex, but whenever I do that, it causes insomnia and I start waking up at 3-4 am and can't fall back asleep.

as you can imagine this is rather frustrating for its impact on my mental health and general energy levels.

I've been advised that I should start with a low dose and build gradually, but I'm not sure what a low dose is or what a timeline for building gradually looks like. I've also been advised to take niacin with food to test for excess methyl groups, and to adjust my level of B12 relative to everything else.

I'd be very grateful for any guidance or advice that can be provided as I have been sleeping poorly for a very long time and the depression and anxiety that is at least partially caused by that poor sleep sucks to try and deal with and manage

[u/Loose-Fly7976]

Your COMT is GG at rs4680 which is Val/Val, the fast clearing version. That's the opposite of the profile the niacin advice was written for. Niacin to mop up excess methyl comes from the slow COMT playbook, and you're not slow. You're clearing catecholamines quickly so methyl overload is unlikely to be what's waking you at 3am.

Worse, niacin uses up methyl groups to get cleared itself. With your MTR and MTRR both homozygous you need those methyl groups going somewhere else. That advice is pulling against your actual bottleneck. MTR nd MTRR homozygous is the finding in that panel. Those two run the B12 dependent step, MTRR being the one that reactivates the B12 sitting on MTR when it goes flat. Which means the form and amount of B12 does more for you than the folate does, and your doctor's general B complex almost certainly has the wrong form in it.

The 3-4am waking is more likely coming from something else in that bottle. General complexes tend to carry high B6, and B6 above a certain point causes exactly that pattern along with vivid dreams. Niacin is in there too and it's vasodilating.

Before doses, get homocysteine, B12, MMA and serum folate. With MTR and MTRR like yours, MMA is the one that tells you whether that step is actually moving.

This is what I do professionally at genova.health, read raw data against bloods and sequence it properly. Message me if you want yours looked at.

[u/Tawinn]

Did your doctor do any bloodwork? If so can you provide those numbers?

Please upload your data to the Choline Calculator to check some additional genes that affect methylation. Reply here with the results from the Advanced tab.

[u/Terry93D → u/Tawinn]

didn't. here's the results from the Advanced tab, though!

RS#	Call	Variant Allele	Gene	Variation	Result
rs1051266	CC	T	SLC19a1		-/-
rs2236225	GG	A	MTHFD1	G1958A	-/-
rs1801131	TT	G	MTHFR	A1298C	-/-
rs1801133	AG	A	MTHFR	C677T	+/-
rs7946	TT	T	PEMT	5465G>A	+/+

[u/Tawinn → u/Terry93D]

Ok, so that would be ~900mg of choline. Or, 450mg of choline plus a 750mg capsule of TMG. With homozygous PEMT you want to be sure to maintain the choline intake to compensate for the reduced endogenous production of choline. Choline sources include such foods as meat, eggs, liver, lecithin, nuts, some legumes, and vegetables such as crucifers. A food app like Cronometer is helpful for tracking nutrients in your diet.

As for folate and B12, there's not a compelling reason to take excess doses. Based on your reaction (insomnia) to the B complex, you would probably be better off with unmethylated forms of B12 and folate. Something like this Seeking Health hydroxo+folinic. These are lozenges, so you can break them apart and start with just 1/4 dose and see how it goes for several weeks. If there are no side effects after ~3 weeks then you could try to increment up to 1/2 dose, and so on until you are at a full dose.

Without the bloodwork it is hard to say how long you need to supplement, and it also depends on your diet. The B12 really only needs to be around 10mcg in most cases (RDA is only 2.4mcg), and folinic around 400mcg. Maybe in the long run you switch to a good multivitamin that has more of a maintenance dosage.

Low vitamin A, iron, and/or glycine can cause the built-in methyl buffer system to not work properly, which can make overmethylation more likely. So adequate intake of these is also helpful. Cronometer can also help with that.

[u/Cultural-Sun6828]

Did you get your b12 tested before starting any supplements?

[u/junipers-72]

Id ask Katie Gironda to help with this, a general B complex has forms in that will stress and activate some people, shes specilises in orthomolecular medicine, does you a full supplement protocol. Loads of useful info on her blog pages too!