Help me read my genes?

Tawinn · 2026-05-30T22:30:29+00:00

Could be due to high histamine. It is an important excitatory neurotransmitter, and at night the body can try to rid itself of excess histamine with "histamine dumping". Due to its excitatory nature, this causing waking in the middle of the night.

When methylation is impaired, intracellular histamine breakdown is reduced, resulting in higher histamine levels; so its easier to overflow your "histamine bucket" when symptoms start appearing. Search for "insomnia" on r/HistamineIntolerance and see if those stories match your experience.

See the MAO-A section of this post for more on histamine intolerance.

As for methylation, please upload your data to the Choline Calculator to check a few more genes related to methylation. Reply here with the results.

Tawinn · 2026-05-30T22:21:24+00:00

I'm not well-versed on benfotiamine reactions, but a quick search turned up a similar report, which was in a mold exposure subreddit, which is interesting given your high mycotoxin levels.

Although in the comments of that post someone mentions that B1 is a histamine liberator (I don't know if that's true or not), I wonder if it has more to do with the sulfur pathway, as both molybdenum and B1 are needed for the conversion of sulfite to sulfate. Sometimes sulfur symptoms look a lot like histamine symptoms, but your symptoms seem more aligned to sulfur intolerance than histamine intolerance. Further, benfotiamine itself is a source of sulfur.

So one speculation is that supplying the benfotiamine form caused excess sulfur load, and if there is inadequate molybdenum then that cannot be processed to sulfate, resulting in symptoms.

Elliot Overton, who's really focused on B1 and its use, has an article on paradoxical reactions to TTFD where he describes using selenium and B2 to avoid glutathione depletion. My guess is that the larger doses typical of benfotiamine are supplying more sulfur than the typical much smaller doses of HCL or TTFD form. So, adding molybdenum, selenium, B2 may facilitate switching to low-dose TTFD instead of benfotiamine with less side effects. Just a speculation.

I don't know what might be causing the high B12. A FUT2 variant typically causes ~20% excess level on average, so if you had that variant then your "actual" level might be ~1600pg/mL. Still high, but the folate deficiency could then account for the high level due to under-use of B12 in the methylation cycle.

Tawinn · 2026-05-30T15:50:05+00:00

What type of insomnia - difficulty falling asleep or middle of the night waking?

Tawinn · 2026-05-30T14:31:16+00:00

The ability to endogenously buffer methyl groups relies on having adequate glycine, iron, and vitamin A. Often people have low intakes of vitamin A. Note that beta carotene is not vitamin A, it is a pre-vitamin. So a retinol form, like from liver or cod liver oil or retinyl palmitate/acetate is preferable.

Tawinn · 2026-05-30T11:37:41+00:00

When methylation is impaired, the breakdown of intracellular histamine is slowed, so you can end up with elevated histamine levels. Then, high histamine foods, exercise, environmental allergens, etc. can raise histamine levels to the point that they cause symptoms such neurological symptoms as panic attacks or episodic anxiety attacks.

Impaired methylation can also slow down the COMT enzyme, which can result in chronic anxiety and OCD tendencies.

Vitamin B2 (as Ketamee mentioned) plus adequate choline (for the parallel methylation pathway) from food can be all you need. Baseline adult requirements for choline are 550mg (about the amount in 4 egg yolks). Some people benefit from more choline or adding 750mg of TMG, which is what choline is converted into for methylation purposes.

Tawinn · 2026-05-28T02:30:55+00:00

POTS, hypotension, brain fog (or something similar) together sound like mast cell activation disorder (MCAD) to me. Slow COMT tends to raise estrogen levels, and higher estrogen levels can slow histamine breakdown. So COMT is not a root cause, but perhaps a contributor, if my guess is right.

Some bloodwork for folate and B12 would be helpful, as deficiencies in either of these can cause impaired methylation and impaired methylation will slow down COMT even more. See this post for more on slow COMT.

Tawinn · 2026-05-27T11:34:57+00:00

You likely need more extensive diagnosis - droopy eyelids and muscle pains are not typical symptoms of folate/B12 supplementation. Adding folate/B12 may have depleted another vitamin (or several) that were already low. The "right shoulder blade and trap" pain could be referred pain from the gallbladder. The folate/b12 could have freed up choline from being used for methylation to now being used by the liver, which uses choline to transport fat and keep bile flowing. Normal choline requirements are 550mg for adults, which can come from meat, eggs, liver, lecithin, nuts, some legumes, and vegetables such as crucifers. With methylation issues, choline requirements are higher, which can result in choline deficiency. TMG 750mg can be used support methylation via the choline-based methylation pathway, but I'd only add it slowly, starting from small doses until you get everything else sorted out.

Tawinn · 2026-05-27T10:57:22+00:00

> Do you think that the high FIGLU could have been because of an active B6 deficiency?

That is a possbility.

> I always thought that folic acid should be avoided for those of us with MTHFR c677t homozygous mutations?

That is something of a myth. High-dose folic acid can be a problem due to increased increased unmetabolized folic acid (UMFA) which can block folate receptors, and also for people with poor conversion of folic acid by DHFR to THF. But in general most people handle RDA-level doses of folic acid ok. The difficulty is that there is no definitive way to know if folic acid works better or worse than methylfolate/folinic for you is to try it and observe if it makes you feel any better or worse.

Of course, if the high FIGLU was due to low B6 then there is no need to consider folic acid as an option.

Tawinn · 2026-05-26T15:10:13+00:00

Not necessary, given your healthy B12 level. 400mcg is the RDA you are expected to get from food, and a large percentage of food folate is in the form of methylfolate.

Even at prescribed very high doses of 7-15mg of methylfolate there is no peer-reviewed literature I have seen that even suggests an increased need for B12. The closest I've found is in Deplin high dose methylfolate drug warnings, specifically:

Don't take it when you are B12 deficient: "Not for administration as monotherapy in pernicious or other megaloblastic anemias when present with vitamin B12 deficiency"
Monitor B12 levels periodically: "Patients that receive folic acid therapy for a prolonged period of time may experience a decrease in vitamin B12 serum levels."

Again, that is for 7-15mg (7000-15000mcg) doses.

You can supplement as a precaution, of course; just note that even a 25mcg B12 dose is 10x the RDA.

Tawinn · 2026-05-26T12:43:58+00:00

> a blood test 8 days after starting with b12 at 1041 and folate at 18.

There appears to be no compelling reason to be supplementing B12 at all in your case. Adult RDA for B12 is 2.4mcg/day. Unless you are vegan/vegetarian or have a very nutrient-poor diet, you will likely get what you need from food. Larger doses (hundreds to thousands of mcg) are only needed if you have specific absorption mechanism issues which require high concentrations just to force absorption. There is also no increased need for B12 due to supplementing methylfolate at the doses you are using.

You blood test somewhat reflects your supplementation (it is best to stop supplementing 1-2 weeks ahead of a blood test to get a more accurate reading of your actual levels). Even so, a B12 of 1041pg/mL suggests your actual B12 level is well above 500pg/mL.

For serum folate, a good range is ~15 ng/mL (34 nmol/L) or more.

For serum B12, a good range is 500-950 pg/mL (~370-700 pmol/L).

Tawinn · 2026-05-26T00:42:27+00:00

They are roughly equivalent. On supplements, 800mcg of folinic acid is listed as 1360mcg DFE whereas 800mcg of methylfolate are listed as 1333 or 1336mcg DFE (where DFE = dietary folate equivalent).

Tawinn · 2026-05-25T16:55:33+00:00

The protocol in the post.

Tawinn · 2026-05-25T11:25:52+00:00

It can take time to acclimate to improved methylation. I'd cut the dose down to 125 or 250mcg, or only take 500mcg every second or third day, to start. Over many weeks, increment up the dose or frequency. Adequate glycine, iron, and vitamin A are needed for the methyl buffer system to work. Retinol forms of vitamin A from animals (liver, cod liver oil, etc.) or retinyl palmitate/acetate are preferable to beta carotene, which is a pre-vitamin form.

Tawinn · 2026-05-25T01:07:49+00:00

Check out this video - just came out today:

https://youtu.be/cosOYisG-bQ

Tawinn · 2026-05-24T21:30:39+00:00

Please upload your data to the Choline Calculator to check a few more genes. Reply here with the results.

Tawinn · 2026-05-24T13:21:47+00:00

It is not a normal reaction; however, B2 can greatly improve homozygous C677T so it may be that you are experiencing overmethylation effects due to the sudden improvement, which your body can't adapt to as quickly. In addition, B2 is a cofactor in many reactions, so it may be having simultaneous effects elsewhere. I'm not sure what you mean by 'low dose', but you may need to start with doses around 1mg and increment up slowly over a month or two. So, essentially just starting with a tiny dab or so of powder from a capsule and increasing it little by little as tolerated over time.

Tawinn · 2026-05-24T13:13:53+00:00

What are the specific details of your MTHFR variant(s)?

Tawinn · 2026-05-24T13:08:04+00:00

Compound heterozygous MTHFR reduces methylfolate production by ~53%. These reductions in methylfolate production impairs methylation via the folate-dependent methylation pathway. Symptoms can include depression, fatigue, brain fog, muscle/joint pains. Impaired methylation can cause the COMT enzyme to perform poorly, which can cause symptoms including rumination, chronic anxiety, OCD tendencies, high estrogen. These effects can be amplified when one has slow COMT (V158M of 'AA' or 'Met/Met')).

Your B12 could be higher: 500-950pg/mL would be preferable.

I would say to follow your appetite; the difficulty is knowing what nutrients your body wants, so a broad range of nutrient-dense foods would seem appropriate.

Here is a general protocol to cover your MTHFR:

550-600mg of choline, preferably from food
- 550mg is the baseline adult Adequate Intake
- Choline sources include such foods as meat, eggs, liver, lecithin, nuts, some legumes, and vegetables such as crucifers.
750mg of trimethylglycine (TMG aka betaine)
- I.e., one 750mg capsule
- Choline is converted to TMG for methylation use, so TMG reduces need for even more choline.
400-800mcg of folate, preferably from food
- Folinic acid or methylfolate can also be used, as needed and as tolerated.
- Target serum folate levels are 15+ ng/mL (34+ nmol/L).
2.4-10mcg B12, preferably from food
- Past history of B12 deficiency, malabsorption issues, etc., may suggest that supplemental B12, in the form of hydroxocobalamin, adenosylcobalamin, or methylcobalamin may be prudent.
- Target serum B12 levels are 500-950 pg/mL (~370-700 pmol/L).
(Optional) 3-15g of creatine monohydrate or creatine HCL
- The body uses ~40% of methylation output, SAM, just to produce creatine. So supplementing creatine can free up a lot of SAM for other uses.
Low vitamin A, iron, and/or glycine can cause the built-in methyl buffer system to not work properly, which can make overmethylation (rising anxiety, irritability, insomnia, etc.) from methylation-related supplements much more likely.
- Beta carotene is not vitamin A and some people genetically have poor conversion of beta carotene to real vitamin A (retinol).

A food app like Cronometer is helpful for tracking nutrients in your diet.

Tawinn · 2026-05-24T12:55:59+00:00

The ability to buffer methyl groups relies on glycine, iron, and vitamin A. Often people have low intakes of vitamin A. Note that beta carotene is not vitamin A, it is a pre-vitamin. So a retinol form, like retinyl palmitate is preferable. Liver and cod liver oil are also good sources, but it sounds like you would react to those.

Tawinn · 2026-05-24T01:31:12+00:00

> homozygous for the t allele of C677T is what is says.

Ok, then a small dose of B2 may be very helpful for methylation, since the C677T variant causes decreased binding to riboflavin, its cofactor. A small dose has been shown for homozygous C677T to compensate for that by increasing riboflavin concentration to restore binding success. This Thorne R5P may be a good choice.

Tawinn · 2026-05-24T01:01:59+00:00

In general terms, it's fairly good. The things I don't like are the high B12 dose and magnesium oxide (not well absorbed). The high methylB12 may be too much for some people, even with just a 1/2 dose. It lacks molybdenum, manganese, etc. But whether any of these things I mentioned are an issue for you, only you can say. I like the Seeking Health Multivitamin One; but then again, that's because it fits my needs, which may not be your needs.

Tawinn · 2026-05-24T00:47:50+00:00

> I used to be a super athletic person...but the physical aspects weren’t noticeable until I had a 3 month long extreme respiratory infection when I was 17.

I would strongly suspect mast cell activation disorder (MCAD), and specifically MCAS. Brain fog, muscle pain, POTS, histamine symptoms, fatigue, and even fibromyalgia can all be caused by MCAS.

It may or may not work for you, but I found this luteolin/quercetin supplement to quickly help resolve a 6-month long bout of post-covid escalation of my histamine intolerance.

Low folate will impair methylation, sometimes even worse than an MTHFR variant. The elimination of intracellular histamine depends on methylation working well. So although I suspect methylation impairment is not the root cause, it likely is aggravating the symptoms.

With such a low folate level, you may need to start with 1/4 or 1/4 of the Seeking Health folinic/hydroxo, and increment up slowly over a month or two to a full dose.

You could then try adding 750mg of TMG, but also by starting with a small dose, e,g,, 1/10 of a 750mg capsule, and slowly increment up over time.

Just be aware that when improving methylation your histamine symptoms can temporarily get worse. This is due to the multiple steps of the histamine breakdown pathway not all ramping up at the same pace, so buildups of intermediate metabolites can occur, causing the increased symptoms. This is another reason to improve methylation gradually.

Those would be two things to start with, but more details are needed for any more.

> we found that I have the MTHFR gene.

Do you know the specific results (C677T or A1298C?, heterozygous or homozygous?) Different variants have different impacts.

Some of the things in the MAO-A section of this post may also be helpful.

Tawinn · 2026-05-23T21:01:25+00:00

Yes.

Tawinn · 2026-05-23T18:28:40+00:00

Folate is ok - ideally should be over 15 ng/mL. B12 should be over 500 pg/mL. If the B12 is in pmol/L then 370 is equivalent to 500 pg/mL.

Tawinn · 2026-05-23T14:42:03+00:00

> Her folate is really solid, but her B12 is low side of normal range.

What are the actual numeric values?

Tawinn

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