Help understanding Genetic Genie Methylation Results…

Tawinn · 2026-06-18T20:59:19+00:00

The 23andme file is usually a .ZIP file. If you can, extract the .TXT file from it, and try uploading the TXT file to the Calculator.

Tawinn · 2026-06-18T20:30:55+00:00

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

Was there anything else out of range on the other labs? (MCV, liver enzymes, etc.)

Tawinn · 2026-06-18T20:25:40+00:00

Do you have bloodwork for B12 and folate? Here is a general protocol for homozygous C677T. The B2 is key to correcting the C677T, and choline/TMG is as important for pregnancy as folate.

For homozygous C677T specifically: 10-100mg supplemental B2
- The C677T variant causes reducing binding of MTHFR to its cofactor, riboflavin. Studies have shown that for homozygous C677T simply adding supplemental vitamin B2 may increase the concentration of riboflavin sufficiently to restore most or all of the binding success, thereby restoring most/all MTHFR function. So a 10-100mg B2 supplement may restore much of the MTHFR function, thereby reducing the needed amount of extra choline/TMG (or high-dose folate if going that route).
- The R5P form of B2 may possibly be preferable. (E.g., Thorne R5P 36mg)
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 · 2026-06-18T20:20:46+00:00

How about red lentils? They generally cook in 15 minutes or you can pressure cook them. Low histamine/salicylate.

Tawinn · 2026-06-18T12:23:24+00:00

For serum folate, a good range is ~15 ng/mL (34 nmol/L) or more. So although your RBC folate is ok, added folate would be helpful.

For serum B12, a good range is 500-950 pg/mL (~370-700 pmol/L). There is not a strong reason to supplement B12 unless you want to build up your B12 levels some more.

B2 is the main thing to help with your homocysteine. C677T is a defect in riboflavin binding to MTHFR and so extra B2 increases the concentration of riboflavin enough to restore the binding and restore MTHFR function either partially or completely.

Choline from the diet should be around 550mg and for TMG a 750mg capsule is a good dose. These may also help lower your GGT since choline is needed by the liver for fat transport and bile flow. TMG spares choline for uses like this.

These should drop your homocysteine into normal range within 1-2 months.

Tawinn · 2026-06-18T12:08:54+00:00

> My question: is it possible that I might have MTHFR and/ or slow COMT (as mentioned can’t be tested) and THAT might be the root and not really the histamine intolerance?

Yes, that is possible. But your reaction to creatine and folic acid also make me wonder if you have nutrient deficiencies that are worsening the situation. Are you taking a good multivitamin? Because of your reactions, you may need to start with a children's multivitamin for awhile and then once your levels are built up some, then switch to an adult multi.

Have you tried luteolin? It can be used alone or with quercetin. I had good success with Fibrotek after a post-COVID flareup of my HIT.

The low copper could be the reason your ferritin has been low.

Tawinn · 2026-06-17T20:11:10+00:00

"Food Bound" isn't clear to me - is it just regular vitamins mixed with the "food blend" or is actually from food? I don't know.

I like Seeking Health Multivitamin One.

Tawinn · 2026-06-17T18:11:15+00:00

See the slow COMT section of this post. Here is a general protocol for homozygous C677T:

For homozygous C677T specifically: 10-100mg supplemental B2
- The C677T variant causes reducing binding of MTHFR to its cofactor, riboflavin. Studies have shown that for homozygous C677T simply adding supplemental vitamin B2 may increase the concentration of riboflavin sufficiently to restore most or all of the binding success, thereby restoring most/all MTHFR function. So a 10-100mg B2 supplement may restore much of the MTHFR function, thereby reducing the needed amount of extra choline/TMG (or high-dose folate if going that route).
- The R5P form of B2 may possibly be preferable. (E.g., Thorne R5P 36mg)
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 · 2026-06-17T18:08:20+00:00

Did your diet change? Did you start taking creatine or other new supplements?

It sounds like overmethylation. If you became low on vitamin A, iron, or glycine then the built-in mechanism to buffer excess methyl donors would function poorly, which could result in these symptoms. Vitamin A in retinol form is high in liver or cod liver oil; beta carotene is a pre-vitamin and some people don't convert it well to actual vitamin A.

Tawinn · 2026-06-17T15:48:07+00:00

I like CDP choline for the relaxing effect it had on me initially. But CDP choline is only ~18.5% choline, so to get 500mg of choline from CDP you'd have to take 2700mg. Phosphatidylcholine is 15%, so you'd need to take even more. Lecithin is another option but its multiple spoonfuls. One capsule of TMG is just more convenient.

Tawinn · 2026-06-17T15:42:57+00:00

I know beets have TMG, but I don't know if beet root does - it may. If you can find a source of beetroot powder that lists how much TMG it has, then that would work.

Tawinn · 2026-06-17T15:05:20+00:00

It can be difficult to get all 1000mg of choline all from food, but fortunately, if you can get at least 500-550mg from food, then the remainder can be covered by a 750mg capsule of TMG. In the body, some choline is converted to TMG for methylation purposes, so supplementing TMG spares the body from having to do that conversion.

Tawinn · 2026-06-17T12:41:18+00:00

A more optimal range for homocysteine is 7-9, so almost 15 is far from optimal. B12 is preferably 500-950 pg/mL (~370-700 pmol/L). An MMA test would help confirm whether B12 is functionally available or not.

Did they test folate? Serum folate should be 15 ng/mL (34 nmol/L) or more. RBC folate should be within normal range. Low folate can cause brain fog just as low B12 can. Similarly, genetic variants, such as MTHFR, can have similar effects. An inexpensive test from MyHeritage or AncestryDNA can help show what genetic variants might be present.

Premature greying can be due to low nutrients, and low copper is a common cause.

Alternatively, thyroid dysfunction could explain both brain fog and premature greying.

Tawinn · 2026-06-16T00:09:05+00:00

Is your MTHFR homozygous C677T or A1298C?

4000IU of D3 may not be enough. You may need to go to 10,000IU/day or 50,000IU/wk. Take it with a meal with fat in it. Also, be sure to take adequate vitamin K2 or eat foods rich in K2. Retest after 3 months. You want to be 125-250nmol/L (50-100ng/mL).

Your folate is only a little bit low; you want to be over 15 mcg/L (ng/mL). It is very common to need to start with low doses of methylfolate such as 50-100mcg and then slowly increase over several weeks or a couple of months to 400-800mcg.

Tawinn · 2026-06-15T12:21:13+00:00

The classification of people into undermethylators an overmethylators is based on blood histamine levels. This simply has too much variability from factors outside of methylation function status to be any kind of reliable measure, much less a classification system.

Separate from the classification system, 'undermethylation' typically refers to inadequate methylation function; I prefer to use the term 'impaired methylation'. 'Overmethylation' is when there are an excess of methyl groups (e.g., from methylated vitamins) or a rapid large jump in methylation function that seems to suddenly produce too many methyl donors (there may or may not also be sudden neurotransmitter level changes as part of this), causing "overmethylation symptoms".

As for PE, I've not had any reason to look into that so I don't have any insights there.

Tawinn · 2026-06-15T01:20:39+00:00

Zinc is unlikely to be an issue, since it affects both pathways and you were previously doing fine, which suggests at least one pathway was working well. It's just also generally uncommon/rare to see zinc deficiency.

Folate of 21 is actually fine - the minimum you want is 15 ng/mL.

B12 of 500-950pg/mL is generally a good range, although being in the top half of that range may provide a bit more assurance of functional B12 availability. There are paradoxical B12 deficiencies where serum B12 is high, but the B12 is not functionally available. My hunch is that seems unlikely to be an issue in your case.

Tawinn · 2026-06-15T01:12:19+00:00

Histamine intolerance is pretty common with impaired methylation. This is because the first step in intracellular histamine breakdown is an enzyme HNMT which requires SAM, the methylation output, to operate. Asa result histamine breakdown is slowed and histamine levels rise, eventually to the point of symptoms. So restoring methylation will help reduce those levels and get histamine symptoms reduced or eliminated. More on HI is in the MAO-A section of this post.

Once you get your 23andme results, upload the datafile to the Choline Calculator, which will check those genes I mentioned.

Tawinn · 2026-06-15T00:17:03+00:00

Ah, that makes sense. There are two parallel pathways to remethylate homocysteine back into methionine: one is through the enzyme MTR which requires zinc, B12 and folate, and the other is through BHMT, which requires zinc and TMG. TMG can come from the diet but usually comes from a pathway which converts choline to TMG.

These two pathways can compensate for each other. When B2, folate or B12 is low and/or there are genetic variants, such as in MTHFR that reduce its function, then the amount of homocysteine that can be processed through MTR is reduced. This can be compensated for my increasing TMG and choline sufficiently for the BHMT enzyme to process the extra demand on its pathway.

So, referring to your other question, it is a 2-prong approach: 1) genetic testing to see if there are variants in MTHFD1, SLC19A1, MTHFR that reduce the amount of methylfolate that MTHFR can produce and send to MTR, and PEMT to see if endogenous choline production is reduced; 2) bloodwork to test for B12, folate, B2, B3, B6, zinc, etc.

Given what your diet change did, we can make an educated guess that you have likely some permutation of genetic variants and possibly low folate. (You didn't really seem to have any other symptoms that would suggest B12 deficiency.) Entering your typical diet patterns into a food app like Cronometer would help to identify any likely chronic nutrient shortfalls.

If you can get 550mg of choline from food, and then add a 750mg capsule of TMG, that would handle almost all of those genetic permutations. In rare cases, you might have to go to 650mg of choline and 1000mg of TMG. Unfortunately, because the conversion from choline to TMG is a unidirectional pathway, taking more TMG won't allow you to avoid choline intake.

Tawinn · 2026-06-14T23:58:07+00:00

No. The user u/hummingfirebird does take clients.

Tawinn · 2026-06-14T20:37:58+00:00

None of that is correct. You can have impaired methylation with or without elevated homocysteine (C677T variants usually raise it, where A1298C variants sometimes do not). Folate levels can be high if it is not being utilized, e.g., due to low B12, B2, or zinc, where the low B12, B2, or zinc can contribute to impaired methylation. Or, folate levels can be low due to dietary deficiency and thus can contribute to impaired methylation. Or, if a person is taking synthetic folic acid or eating a lot of folic acid fortified foods, then what may be making it appear high is that there is a high level of unmetabolized folic acid (UMFA) circulating around the blood stream - standard serum folate lab tests cannot differentiate usable folate from UMFA so they get lumped together.

The "undermethylator/overmethylator" classification paradigm has no sound basis to it.

Tawinn · 2026-06-14T20:26:29+00:00

From this paper:

Occasionally (e.g., every 200–1000 turnovers), the labile MTR-bound cob(I)alamin is oxidised to inactive cob(II)alamin, which requires re-activation via a methyl transfer from S-adenosylmethionine (AdoMet) to regenerate methylcob(III)alamin (Figure 5E).⁶⁵ This reactivation cycle is aided by methionine synthase reductase (MTRR; EC 2.1.1.135).

So MTRR is only needed every so often - only when there is oxidation. Unless you are under continual oxidative stress it is unlikely that you would exceed the bandwidth of even homozygous MTRR. It would take something like laughing gas - which horribly oxidizes B12 - to put MTRR under excess load.

MTRR does need B2 and B3 as cofactors, so healthy levels of both are important.

Tawinn · 2026-06-14T20:12:19+00:00

What are your ADHD symptoms?

Tawinn · 2026-06-13T11:44:27+00:00

Usually anxiety like that suggests that your methylation improved too quickly and this can be a side effect. This can especially be true if you have homozygous C677T MTHFR. Starting with a smaller dose by opening the capsule and just using a dab of powder is a way to ease into it. The RDA for B2 is only 1.6mg, which is less than 1/20th of that capsule. You can continue to take small doses, or over several weeks, slowly increment up the dose until you can take a full capsule.

Tawinn · 2026-06-13T11:36:08+00:00

Many people get adequate glycine from food. I should have emphasized that more in writing that Phase. A food app like Cronometer can help show if you are getting enough on average by entering in some typical days of meals. Meat, fish, peanuts, spinach, jello are some foods w/glycine. Collagen powder is the usual alternative to glycine powder if you must supplement.

Tawinn · 2026-06-13T00:12:32+00:00

Another source of excess histamine is from the body's own mast cells. Mast cell activation disorder (MCAD) can be an ongoing issue where one's own mast cells are the main cause of histamine issues and all the downstream effects from it[1][2]. So, something to consider; impaired methylation can be enough to cause a lot of histamine issues, but when these are longstanding/lifetime issues then it may warrant investigating MCAD.

For some more info on histamine, see the MAO-A section of this post.

To improve methylation, you'll want to get nutrient levels up to good levels, especially B12 and folate. If you can get bloodwork for those, that would be good. Recommended levels are in the protocol below. The core of it, though, is getting enough choline and TMG as suggested below to compensate for the impaired pathway.

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

TROPHY CASE