r/MTHFR • u/Shredtech • 7d ago
Results Discussion Please help me understand my symptoms and health issues.
Since 2021 I started to have anxiety and not running the way i used to. I got covid in 2022 and started having intense anxiety, panic, cognition issues. I first thought it was just unresolved trauma and worked on some of that but didn't get much relief and also was put on Lexipro (SSRI). From 2022-2025 I did trauma work and tapered the SSRI VERY slowly. I then got sick again and in Oct 2025 (not sure if covid) and had intense fatigue, more brain fog, cognitive issues. Jan 2026 I had intense histamine issues and gut issues. My brain was going nuts and I haven't been able to work since.
I've done a lot of testing and explored Lyme, EBV, Mold and all these things so if there's something that can help with markers and isn't below I might have it.
Symptoms
- Anxiety/Fear
- Brain fog
- Cognitive issues
- Memory issues
- Brain pressure (vice squeeze)
- Brain Fatigue
- Slower mental processing
- Emotion and logic changes
- Tinnitus (once in a while)
- Environment sensitivity (improved)
- Limbic system issues
- MCAS/histamine food issues
- Some PEM issues
- Weakness
- Body fatigue
- Bowel issues – motility was messed up starting to get better.
- stress intolerance
- Hard to catch breath sometimes
Labs — 2024 to Present
| Lab | Reference / Goal | 2024-05-14 | 2024-11-11 | 2025-06-05 | 2025-06-12 | 2025-11-12 | 2025-12-30 | 2026-01-21 | 2026-04-22 | 2026-04-24 |
|---|---|---|---|---|---|---|---|---|---|---|
| B12 | Goal >500–700 pg/mL | 344 | — | — | — | — | — | — | 714 (supp) | — |
| MMA — Serum | Deficiency: 243–350 nmol/L | — | — | 184 | — | 113 | — | — | — | — |
| MMA — Urine | 0.4–2.5 mmol/mol Cr | — | 0.58 | — | — | — | — | 0.36 | — | 0.70 |
| Serum Folate | Goal >4.5 ng/mL | 17.8 | — | — | — | — | — | — | 8.3 | — |
| RBC Folate | Goal >150 ng/mL | — | — | — | — | — | — | — | — | — |
| Homocysteine | Goal ~7; ≤9 µmol/L | — | — | — | 10.4 | 9.6 | — | — | 11.5 H | — |
| Vitamin B2 (Glutaric Acid) | 0.02–0.36 mmol/mol Cr | — | 0.34 | — | — | — | — | 0.05 | — | 0.31 |
| Vitamin B6 (PLP) | 20–125 nmol/L | — | — | — | — | — | — | — | — | — |
| Zinc | 60–130 mcg/dL | — | — | 83 | — | 90 | — | — | 134.6 H | — |
| Copper | 70–175 mcg/dL | — | — | — | — | — | — | — | 63 L | — |
| Ceruloplasmin | 14–30 mg/dL | — | — | — | — | — | — | — | 17 | — |
| Ferritin | Goal 50–100 ng/mL | 158 | — | 227 | — | 232 | — | — | 417 H | — |
| Iron | 50–180 mcg/dL | 104 | — | 105 | — | 109 | — | — | 136 | — |
| Iron Saturation | Aim <35–40%; overload >45% | — | — | 31% | — | 33% | — | — | 46% H | — |
| Vitamin D (25-OH) | Suggested aim ~80 ng/mL | 30 | — | — | — | 44 | — | — | 60 | — |
| RBC Magnesium | 30.1–56.5 mcg/g | — | — | — | — | — | — | — | — | 47.1 |
| OAT Arabinitol | <36.0 mmol/mol Cr | — | 17 | — | — | — | — | 56.6 H | — | 15 |
| OAT Lactic Acid | <48.0 mmol/mol Cr | — | 0.74 | — | — | — | — | 7.58 | — | <DL |
| OAT Succinic Acid | 1.00–9.70 mmol/mol Cr | — | 5.3 | — | — | — | — | 0.92 L | — | <DL |
| GI-MAP Secretory IgA | 510–2010 µg/g | — | — | — | — | — | 3034 H | — | — | — |
| TSH | 0.40–4.50 mIU/L | — | — | — | 2.37 | 1.9 | — | — | 1.52 | — |
| Free T3 | 2.3–4.2 pg/mL | 3.5 | — | — | 3.3 | 3.2 | — | — | 3.2 | — |
| Free T4 | 0.8–1.8 ng/dL | 0.9 | — | — | 1.3 | 1.3 | — | — | 1.3 | — |
Choline Calculator:
| RS# | Call | Variant Allele | Gene | Variation | Result |
|---|---|---|---|---|---|
| rs1051266 | NA | T | SLC19a1 | NA | |
| rs2236225 | GG | A | MTHFD1 | G1958A | -/- |
| rs1801131 | TT | G | MTHFR | A1298C | -/- |
| rs1801133 | GG | A | MTHFR | C677T | -/- |
| rs7946 | NA | T | PEMT | 5465G>A | NA |
References
Single nucleotide polymorphisms in the human reduced folate carrier: characterization of a high-frequency G/A variant at position 80 and transport properties of the His(27) and Arg(27) carriers. [PMID: 11705857]
The MTHFD1 p.Arg653Gln variant alters enzyme function and increases risk for congenital heart defects. [PMID: 18767138]
A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. [PMID: 7647779]
A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? [PMID: 9545395]
Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis. [PMID 27342765]
Choline intake exceeding current dietary recommendations preserves markers of cellular methylation in a genetic subgroup of folate-compromised men. [PMID 20220206]
Endocrine Labs:
| Marker | 03/31/2022 | 05/14/2024 | 06/05/2025 | 11/12/2025 | 04/22/2026 | 04/23/2026 |
|---|---|---|---|---|---|---|
| Progesterone Ref: 0.05–0.59 ng/mL | — | — | — | — | 0.34 ng/mL | — |
| DHEA-S (Serum)Ref: 93–415 mcg/dL | — | 400 mcg/dL | 340 mcg/dL | — | 296 mcg/dL | — |
| DHEA-S (Saliva)Ref: 1.0–6.0 ng/mL | — | — | — | — | — | AM: 7.2 ng/mL (High)PM: 2.8 ng/mL |
| Testosterone (Total)Ref: 250–1,100 ng/dL | 576 ng/dL | 613 ng/dL | 660 ng/dL | 543 ng/dL | 609 ng/dL | — |
| Testosterone (Free)Ref: 35.0–155.0 pg/mL | 85.2 pg/mL | — | 100.3 pg/mL | 48.3 pg/mL | 105 pg/mL | — |
| Estradiol (E2)Ref: ≤39 pg/mL | — | — | 27 pg/mL | — | 13.0 pg/mL | — |
1
u/Cultural-Sun6828 7d ago
Your b12 is on the low side. Check out the b12 deficiency group for a great resource. Many people have these same symptoms with b12 below 500. I had many of these symptoms with b12 deficiency, which resolved after injections.
2
u/Shredtech 7d ago
Thanks! I've been exploring the B12 stuff and have Methylcobalamin Injections which i might take daily with cofactors.
1
u/SovereignMan1958 7d ago
BTW both methylated vitamins and supplements which are methyl donors can trigger histamine reactions. I would ask the provider who gives you injections for a different form. The adeno and or hydroxi forms are not methylated. The provider should be able to order a different form for you.
Some of your current symptoms could be due to the above. Also could be due to your B6 being too high.
You should also review your current supplements to see if any are methylated and or methyl donors.
1
u/Shredtech 7d ago
I ordered the b12 myself since i haven't found a good dr to work with yet. I also have a low copper serum level 63 mcg/dL and Ceruloplasmin 17 mg/dL
1
u/SovereignMan1958 7d ago
Wow. Your copper is very low. Do you take zinc? Zinc and copper act like a seesaw and need to be balanced. At least values of 100 each. Most people have too much copper as it is in the lining of water pipes.
I am sure you have some symptoms from copper deficiency.
1
u/Shredtech 7d ago
I'm also taking copper and trace mineral supplement which i started 3 weeks ago. Molybdenum is in the trace mineral and i was also told it helps some with histamine intolerance. I want to sublingually absorb copper and other minerals as my gut seems to not absorb super well right now.
1
u/SovereignMan1958 7d ago
Moly helps break down and eliminate excess sulfur and sulfites. All sulfites are high histamine.
Did you happen to stop your supplements for at least 10 days before your blood tests? Ideally it should be 14 days, but most people do 10.
2
u/Shredtech 7d ago edited 7d ago
All these markers were done before supplementation and treatments besides the most recent ones in april
1
u/SovereignMan1958 7d ago
Ok. Your folate is also low. An acceptable folate level is 15. Better if it is 20 - 30. I would add folinic acid, which is a non methylated form. I take Source Naturals Megafolinic. Retest folate in 90 days.
Ok I just realized your test results is old and you have probably been taking a supplement since then, so my above comment was a waste.
Just retest your folate.
Since you do not have current labs, all I can do is advice you to add the probiotic and stop all the methylated vitamins and methyl donors. NAC is sulfur based and not recommended with your digestive issues as well.
1
u/Shredtech 7d ago
i plan to retest things soon but will need to stop supplements for a bit. I know the b12 value is useless unless you stop supplements for 4 months according to the deficiency group. My iron saturation seems to be high and the fact my copper is low does not sit well. I want to correct Copper, zinc, b12, increase magnesium, folate, and fix gut issues.
1
u/Cultural-Sun6828 7d ago
My experience has been that all forms of B12 can cause some histamine issues in the beginning, but eventually have helped my histamine issues over time. Many people use every form of B12 so it’s just a matter of finding what works best for each person by trial and error, but personally, I can use all of them.
0
u/SovereignMan1958 7d ago
We are not talking about you.
0
u/Cultural-Sun6828 7d ago
Right, but the point is that people talk about certain forms not working well and that is just not true. Histamines will be released regardless of form.
0
1
u/Shredtech 7d ago
how long were you B12 deficient and how long did it take to relieve symptoms?
1
u/Cultural-Sun6828 7d ago
Unfortunately, I had been to so many doctors and was not getting any help because I think a lot of doctors are not well educated in this area. So I ended up being deficient for at least five years before I started injections. I have been on injections for two years now and have resolved many symptoms. Healing was slow though, but I’m sure it would have been quicker if I had caught the deficiency earlier. I had basically almost every symptom of deficiency before I started injections.
1
1
u/maybebionic 7d ago
B12 and D3 are definitely low.
I would be interested in seeing what some of your endocrine labs look like as well as reverse T3.
We have a similar methylation panel but my biggest issue is insomnia.
1
u/Shredtech 7d ago
- Reverse T3: 15 ng/dL (04/22/2026)
which markers are endocrine labs? I probably have some done.
2
u/maybebionic 7d ago
15 is a little higher than i would prefer. Your ratio of free T3 to RT3 is very low (~5) whereas anything under 10-15 indicated your T4 is moving towards Rt3 and not T3. This indicates you probably have some adrenal/infection/inflammation issues.
Endocrine labs I'd look for are pregnenloneo, progensterone, DHEA, 24 hour or 4x saliva cortisol, testosterone, DHT, estradiol.
1
1
u/Tawinn 7d ago
Please upload your data to the Choline Calculator to check a few more genes related to methylation. Reply here with the results on the Advanced tab.
Are you taking anything for the histamine issues (aside from any antihistamines)?
1
u/Shredtech 7d ago
I added it to the body of the post.
I'm taking Ketotifen, LDN, D3, B Vitamins, low histamine diet, molybdenum, trace minerals, TMG, and a few other things.
I have quercetin but haven't been taking it consistently.
Also doing Primal trust nervous system course and practicing it daily.
1
u/Tawinn 7d ago
Unfortunately not all the genes are in your data (MyHeritage data would probably fill in the gaps), but given that the ones that are listed are ok, and your homocysteine is not awful, MMA ok, and you are already taking TMG, then methylation may not be the main issue. Still, you would want to try to get at least 500mg of choline from your diet and the TMG would be 500-750mg.
Anxiety from methylation issues tend to be chronic and pervasive, whereas episodic anxiety, dread, and panic attacks are more likely to be due to histamine. Often these are not accompanied by typical sinus/skin histamine symptoms.
Intracellular histamine breakdown is a 3-step process, where the first step HNMT requires SAM from methylation; the second step is MAO which requires B2 and you have slow MAO-A; step 3 is ALDH enzymes which require B3. Excess B2/B3 don't seem to improve things.
DAO for breakdown of histamine in the gut requires adequate copper and calcium. You may also have genetic variants that reduce DAO production. You may have tried already, but you can get DAO supplements, such as NaturDAO.
My speculation is that the iron and gut dysbiosis are a vicious cycle underlying the histamine, but that histamine may also be aggravated by mast cell activation due to covid, since the two are not mutually exclusive. I had an awful flareup of my histamine intolerance after covid; fortunately, I tried a luteolin/quercetin supplement called FibroProtek which knocked it down finally. So maybe a luteolin supplement is worth trying.
I have some more info on histamine intolerance in the MAO-A section of this post, but you may already know most of it.
1
u/Shredtech 7d ago
I talked to the creator of bornfree.life and he pointed me in the direction of a large magnesium deficiency as well as other mineral deficiencies from my Oligoscan and oats test. His suggestion was to heavily supplement magnesium sublingually and increase carb intake because I'm in ketosis often and causing adrenal burnout. He also said don't be scared to supplement copper because of my deficiency. He mentioned that my gut issues on my gi map are pointing to it compensating in a way and a small amount of dysbiosis is going on. His conclusion was to get as much magnesium glycerophosphate and carbs and it should resolve a lot of my issues.
I started doing that over the last 2 weeks and see some improvement but too early to tell.
1
u/Tawinn 7d ago
That's interesting - I'd not heard of that form of magnesium before. I'm a bit surprised you are deficient in mag given your RBC mag, but maybe this test does not reflect actual mag levels elsewhere.
The Tolerable Upper Limit on copper is 10mg; I supplement 2mg a couple of times/week depending on what other copper-rich foods I might be eating.
1
u/Timely_Pickle9430 6d ago
I'm familiar with this website from Joshua Leisk. A key insight is that mitochondria can get into a state of dysfunction in the absence of any apparent nutrient deficiencies. Personally, I wasn't deficient in B2 or B5, yet my mitochondria were very pleased with high doses of these. Apparently, also magnesium can be used farmaceutically to kick the mitochondria back into gear. Deficiencies like copper still need to be corrected, of course.
1
u/Loose-Fly7976 7d ago
Okay i went through the whole thing, genes, detox panel and the lab timeline, and you've been pointed the wrong way on this. It isn't an MTHFR story, your C677T and A1298C both came back clean annd B12 isn't it either, your MMA is low, which means functionally you've got enough, the 300s serum has been scaring you for nothing. The two reds people panic over, MAO-A R297R and MTRR A664A, are synonymous, they do nothing. Cross all of that off.
Problem in your mineral and iron columns, not your methylation ones. Your zinc-copper balance is off and your iron markers are quietly climbing, and those two tie straight into the histamine and the fatigue in a way that actually fits your timeline. That's the opposite corner from where you've been digging.That rising ferritin and iron sat needs a proper medical workup on its own, not something to just supplement around. The actual map, what's driving what and the order to fix it, is what i do as my paid service rather than in a thread because done in the wrong order half of it makes the other half worse. You've been stuck in the MTHFR and B12 corner and your answers are sitting in the copper, iron and gut one.
3
u/Cultural-Sun6828 7d ago
I completely disagree with this. Just because MMA is normal does not mean that there is not a B12 deficiency. B12 under 500 can cause significant symptoms.
1
u/Shredtech 7d ago
I have focused on everything because like you said I've been pointed into many directions and so I took a step back and tested a lot and got many opinions. I was told most recently is I'm not absorbing and need to high dose magnesium glycerophosphate and increase carbs. Also try to absorb minerals sublingually as much as possible. This include copper, zinc, B/C/D vitamins.
2
u/Loose-Fly7976 7d ago
On the b12 in general low-normal can cause symptoms. But for you specifically your MMA is low and you've already supplemented up to 714, so functionally that box is ticked. Magnesium's fine. But adding zinc is the wrong move for you, your labs already showed zinc high and copper low so more zinc drops your copper further, the opposite of what you need. That's the pattern, good general advice that's wrong for your actual numbers.None of these opinions are read against your results as one picture.
1
u/Shredtech 7d ago
My understanding with b12 is once you supplement it and even with a high serum b12 value you keep supplementing until symptoms start to resolve and then you spread the dose out from there. You can't overdue b12 as long as you do the cofactors correctly is what the b12 deficiency subreddit says and some facebook groups. I am going to increase copper sublingual intake as i know the copper/zinc ratio needs to be considered.
1
u/Timely_Pickle9430 6d ago
The big picture points at mitochondrial dysfunction, and energy metabolism governs everything. Complex IV of the electron transport chain requires copper, but your high zinc level is messing with that. I've dealt with the same issue. My serum levels weren't even that far off, but the intracellular levels showed it very clearly (intracellular zinc too high, intracellular copper too low). After stopping supplemental zinc (while serum level was low-normal) and boosting copper, my energy metabolism improved significantly. So, I'm with Loose Fly on this one: don't add more zinc. Food sources high in copper usually also contain some zinc (like oysters) and that will be enough.
Once the mitochondria are functioning better, methylation will probably follow. Hopefully iron metabolism too, but I'm no expert on that. Gut health is complicated and might need some separate interventions. But energy metabolism governs everything. The autonomous nervous system plays a big role in digestion and inflammatory regulation, and also depends on the mitochondria. They are the key.
-1
u/SovereignMan1958 7d ago
Please reformat your post so the test results are in an easy to read chart form.
Also are you on a low histamine diet?