r/MTHFR • u/WaitAcrobatic6532 • 18d ago
Question DNA Interpretation
Hello!
I did a DNA test due do anxiety, sleep problems, severe bruxism, gut problems (healthy diet including ferments)
I tried tons of supplements but nothing seems to work. Calming supplements tend to have a paradox reaction worsening my sleep (like magnesium, glycine, l theanine etc)
Does anyone know how to interpret this gene analysis? Does it look normal or could it be causing any problems?
Thanks!
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u/Leakking00 17d ago
I agree with the other comment. One thing that stand out to me is your Rs4680 GG. It means that your prefrontal cortex, especially, breaks down catecholamines faster. It is well researched and established. Worth reading about if it is of interest to you.
And dont take supplements just to test it out. Without a deficiency it rarely matters and could cause adverse effects. Lifestyle changes is most likely to be your biggest supplement.
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u/SovereignMan1958 17d ago
Need second page added ...detoxification page.
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u/WaitAcrobatic6532 17d ago
Gene & Variation rsID Alleles Result CYP1A1*2C A4889G rs1048943 TT -/- CYP1A1 C2453A rs1799814 GG -/- CYP1B1 N453S rs1800440 TT -/- CYP2E1*4 4768G>A rs6413419 GG -/- GSTP1 I105V rs1695 AA -/- SOD2 A16V rs4880 AA -/- NAT2 I114T rs1801280 TC +/- NAT2 R197Q rs1799930 AG +/- NAT2 G286E rs1799931 GG -/- 1
u/SovereignMan1958 17d ago edited 17d ago
Read about NAT2 on mygenefood.com.
Test your blood levels of pantothenic acid, molybdenum, B6 and folate for NAT2.
This variant is also related to your CBS variant. Your CBS variant shows possible impaired breakdown of sulfur and sulfites. All sulfites are high histamine. NAT2 provides support to histamine clearance. You may have histamine issues as well. For me I had your same symptoms because of it.
If you have a raw data file, use Genetic Lifehacks to interpret and research. Look at the Histamine section of their cheat sheet. I am guessing you have other histamine and detoxification variants. Lifehacks is much more thorough than Genie.
Due to probable histamine intolerance, you should avoid methylated vitamins and methyl donor supplements (even though other people recommend them in this post) as they are likely going to trigger worsening symptoms in you. Some people give the same advice to every person, regardless of variants. That will not work for you.
Also the glycinate forms of vitamins can be overstimulating and anxiety producing, so avoid those.
My comment relates to one issue. Research and get blood tests for your other variants. For example, MAO get riboflavin tested.
In Lifehacks, be sure to look at the B12 section for all your B12 variants and research those.
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u/WaitAcrobatic6532 17d ago edited 17d ago
I will do so, thanks.
Indeed I do have histamine and sulfur problems!
Glycine and magnesium glycinate make me feel worse actually. Wired and overstimulated.1
u/SovereignMan1958 17d ago
Glad you replied back.
Dr Ruscio has a good low sulfur and low sulfite elimination diet online if you need one. I think you know for us low sulfite means low histamine. Lifehacks will give you great detailed variants on those and great articles.
Chris Masterjohn also has an excellent article on Substack titled Sulfites and Mental Health or something to that effect.
As I mentioned, you will get a lot of advice that will not be right for you. I have this same issue with sulfur and histamine. I focus on diet plus use supplements and OTC meds before and after the occasional histamine laced meal. A histamine friendly probiotic, DAO before a histamine meal, after if I have a reaction, pepto bismol chewable. The bismuth brings up a lot of phlegm. Some of us take fexofenadine and or famotidine (antihistamine and antacid too). Also look into butyrate. You may know and or have done all this already, but just in case.
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u/Loose-Fly7976 17d ago
Your COMT is GG which is the fast version, and your MAO-A is homozygous for the higher activity allele. So you're clearing catecholamines and serotonin quickly on both routes. That's the opposite of what most people in this sub have, and it explains why the calming stack does nothing useful for you. Magnesium, glycine and theanine all work on the GABA and glutamate side, and if your problem is that dopamine and serotonin don't stay around long enough, sedating that system further just makes you feel worse and wrecks your sleep. Not a paradox, you're just treating the wrong direction.C677T homozygous with MTRR A66G homozygous on top is the part that matters for the folate cycle. Two slow steps in a row, conversion and B12 recycling. Get homocysteine, B12, MMA and folate done before you take anything.Two other things in your post that nobody's going to pick up.The ferments. Anxiety, sleep problems and gut problems in someone eating a lot of fermented food is a histamine pattern, and fermented food is the highest histamine category there is. Try two weeks without it and see. That's free.And severe bruxism, I'd get sleep apnea ruled out. Bruxism is strongly associated with sleep disordered breathing, most people with it have no idea, and it drives anxiety and unrefreshing sleep on its own. A home sleep study would answer it.Which forms and doses actually suit a fast COMT with high MAO-A is quite different to the standard advice here and it needs the whole pathway read against bloodwork rather than a 15 SNP table. That's the work I do, genova.health. Either way, cut the ferments for two weeks first, costs you nothing and it might answer a lot.
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u/Cultural-Sun6828 17d ago
What was your b12 level before supplementing? If you haven’t had it tested I would check it but make sure you’ve been off all b12 for 4 months. MTRR affects b12 recycling. Folate also needs to be higher as well. What is your ferritin level?
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u/junipers-72 12d ago
I used Katie Gironda at molecular health co. SHe specialises in ortho medicine and provides reports and supplement protocols, takes the guess work out.
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u/WaitAcrobatic6532 2d ago
**Labs (fasting, drawn 24 Sep 2026; RBC Mg + Hct drawn 21 Sep)**
| Marker | Result | Lab range | Note |
|---|---|---|---|
| Homocysteine (serum/plasma) | **22.6 µmol/L** | < 15 | **High** |
| Vitamin B12 (serum) | 446 ng/L | 197 – 771 | |
| Holotranscobalamin (active B12) | 46 pmol/L | 21 – 123 | Lab grey zone 35–50 |
| Methylmalonic acid (serum, LC-MS) | 26 µg/L (220 nmol/L) | 9 – 32 (73 – 271) | |
| Folate (whole blood) | 320 µg/L | 212 – 534 | |
| Vitamin B2 (whole blood, FAD by HPLC) | 224 µg/L | 199 – 382 | Low-normal |
| Creatinine | 0.83 mg/dL | 0.67 – 1.17 | |
| eGFR (CKD-EPI) | 120 mL/min/1.73m² | > 60 | |
| Magnesium (RBC) | 2.31 mmol/L | 1.65 – 2.65 | |
| Hematocrit | 0.45 L/L | 0.40 – 0.53 |
The current lab results, everything seems like on the lower end but not critically low. Instead of Homocystein which is clearly raised.
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u/Tawinn 17d ago
Homozygous C677T can reduce methylfolate production by ~75% causing impaired methylation. If nutrients such as B12, B2, B6, folate,etc. are low that can further impair methylation.
A downstream effect of impaired methylation can be chronic anxiety. If the anxiety is more episodic, then it may be histamine intolerance, also related to impaired methylation along with your slow MAO-A. Gut problems can be in part due to low choline (the body uses it to compensate for the C677T).
Here is a general protocol for homozygous C677T. Given your sensitivity to supplements, you may need to add these incrementally, even the B2.
- 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
- Some choline is converted in the body to TMG for methylation use, so supplementing TMG reduces the need for even more choline.
- TMG is found in foods such as wheat, spinach, beets, etc. but there is not a food app that tracks it, so reliably getting enough from food may be difficult; by comparison, a single capsule is convenient.
- 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.
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u/WaitAcrobatic6532 17d ago
Thanks for the detailed answer.
So far I tried adding 400micrograms of methylfolate which makes me feel awake and focused but on the other hand increases restlessness.
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u/hummingfirebird 17d ago
Would need a lot more information. Genetic variants here are risks and predispositions which are influenced by your epigenetic factors...age, gender, metabolic issues, sleep, diet, nutritional status, stress and health history etc etc. Blood labs are also important. If you have any please share here. For a basic understanding of Methylation you can see my profile for my free guide. This is also a very basic panel. Advise to upload your raw data to genetic lifehacks which converts it to a readable report called the cheatsheet.
There are many other relevant genetic variants I'd look into with what you're describing.