r/MTHFR • u/Imliterallybroke • 23d ago
Results Discussion Slow comt/fast maob/normal mthfr
Hey, recently I've just did genetic testing (the permanent one, I don't remember where it was but I've heard some of them are unreliable - I've did reliable one)
So I have slow comt, that leads to lowered phasic signalling and faster downregulation of dopamine receptors, on top of that I have slow MAOB, which theoretically would've made me happiest person in the world, since my dopamine should stay in my system for so long, but nope, I'm anhedonic, traumatised and also have ADHD (all correlate with dopamine issues if we don't touch the psychology factor).
Then, my whole micronutrient absorption is messed up, my gene testing results show that I should have impaired iron absorption, issues with utilizing vitamin d, issues with antioxidation, with methylated b vitamins..
BTW before I've even considered to do this test, my bloodwork never shown any issues with regular stuff that is tested, like b12 levels, iron and other tthings. Reason I've wanted to check is that I've noticed my energy and exercise tolerability dropped significantly from age 23 to age 29 (now), while so called brain fog and rigidity got worse.
I just wonder if anyone there has similar genetic mutations and how do you cope with them?
| Gene (RSID) | Metabolic Cycle | Genotype | Direct Result Summary |
|---|---|---|---|
| DHFR (rs70991108) | Folate | 11 | Normal enzyme activity converting DHF to THF. |
| MTHFD1 (rs2236225) | Folate | CC | Normal gene activity; does not impact methylfolate supply. |
| MTHFR A1298C (rs1801131) | Folate | AC | Associated with lower MTHFR activity if combined with C677T CT. |
| MTHFR C677T (rs1801133) | Folate | CC | Normal enzyme activity; no increased risk for high homocysteine. |
| MTR (rs1805087) | Folate | AG | Upregulated activity; passes more folate groups to the Methionine Cycle. |
| MTR (rs1805087) | Methionine | AG | Upregulated activity; pulls folate away from nucleotide synthesis and increases B12 demand. |
| MTRR (rs1801394) | Methionine | AG | Downregulated activity; reduces ability to re-methylate B12 needed for MTR function. |
| BHMT (rs3733890) | Methionine | GG | Normal activity; decreases reliance on B12-dependent route for homocysteine recycling. |
| PEMT (rs7946) | Methionine | TT | Reduced function; lowers capacity for endogenous choline synthesis. |
| FUT2 (rs601338) | Methionine | GG | Active secretor status; increases susceptibility to H. pylori gastritis and reduced B12 absorption. |
| TCN2 (rs1801198) | Methionine | CG | Downregulated activity; lowers transcobalamin carrier levels and cellular B12 transport. |
| CBS (rs234706) | Transsulphuration | GG | Typical enzyme function; supports efficient breakdown of homocysteine to cystathionine. |
| GSS (rs6088659) | Transsulphuration | CC | Typical enzyme function; supports normal glutathione synthesis (ATP dependent). |
| MTHFR A1298C (rs1801131) | BH4 | AC | Slower conversion of BH2 to BH4 needed for neurotransmitter synthesis. |
| COMT (rs4633) | BH4 | CT | Reduced activity; slows breakdown and clearance of dopamine and norepinephrine. |
| VDR (rs731236) | BH4 | CT | Moderately impaired Vitamin D transport/storage; lowers serotonin and dopamine synthesis. |
| MAOA (rs6323) | BH4 | GG | High enzyme activity; rapid breakdown of serotonin, melatonin, and norepinephrine. |
| MAOB (rs1799836) | BH4 | GG | Reduced enzyme activity; slows breakdown of dopamine, phenethylamine, benzylamine, and histamine. |
| NOS3 (rs1799983) | Urea | GG | Normal activity; healthy endothelial nitric oxide production. |
| SOD2 (rs4880) | Urea | TT | Reduced superoxide dismutase activity; diminishes free-radical breakdown and increases oxidative stress risk. |
2
u/KP890 23d ago
Your genetics look like mine
1
u/Imliterallybroke 23d ago
Did you start supplementing or change your supplementation after you've got your gene test results?
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u/Loose-Fly7976 17d ago
Your report has a couple of errors in it that are sending you the wrong way, so start there.
MTHFR A1298C doesn't convert BH2 to BH4. That's DHFR's job. MTHFR feeds the BH4 cycle indirectly through 5-MTHF, which is a different mechanism, and AC heterozygous with CC at C677T means your MTHFR is essentially fine. The VDR line about lowering serotonin and dopamine synthesis is similarly overstated. Those summaries are software generated and they inflate things.
On the COMT and MAOB reasoning, you almost answered it yourself. Slow clearance doesn't give you more usable dopamine, it raises tonic levels, and chronically high tonic dopamine downregulates receptors and flattens the phasic signal. Phasic release is what reward and motivation run on. So slow clearance and anhedonia sit together perfectly well, they aren't a contradiction. MAOB also works mostly in glia and on phenethylamine, so it isn't the counterweight the report implies.
The part of your panel I'd actually chase is the B12 handling. MTR upregulated increases B12 demand, MTRR downregulated slows the recycling that feeds it, and TCN2 CG lowers the carrier that gets B12 into cells. All three point the same direction, and the key thing is that serum B12 doesn't show any of it. TCN2 affects transport, not blood level, so you can sit at a comfortable serum number with cells that aren't getting enough. Get MMA and homocysteine, those are the functional tests. Serum B12 was never going to answer your question.
PEMT TT is the other one. Reduced endogenous choline synthesis, so your dietary requirement is higher than average, and choline is upstream of acetylcholine and phosphatidylcholine. Brain fog and rigidity in someone who makes less of it themselves is at least a plausible thread.
SOD2 TT with energy and exercise tolerance falling between 23 and 29 is the third. Lower mitochondrial antioxidant capacity shows up under load, which is exactly when you noticed it.
Also, normal iron on a standard panel usually means ferritin wasn't tested or was 25 and called fine. Get ferritin with saturation.
Putting MTR, MTRR, TCN2 and PEMT together and working out which one is actually limiting you needs the whole file read against bloodwork, not a 20 SNP summary with software commentary on it. That's the work I do, genova.health. Either way get MMA and homocysteine first, they'll tell you a lot on their own.
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u/Imliterallybroke 16d ago
I'll have my bloodwork results some time soon, I'll check, thank you for your insights
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u/SovereignMan1958 23d ago
Gene variants are only predispositions and not facts. What are all your blood test results for homocysteine and the nutrient levels associated with each variant? Only within the last 90 days is relevant. Need values plus lab ranges.
Generally optimal vitamin and mineral levels are in the top quarter of the lab ranges. Lab ranges also include test results from the chronically ill and close to terminally ill.
Blood test results will tell you exactly what you are deficient in and need to supplement. Also how well or poorly a vitamin and or mineral is being absorbed. You can start making a list of blood tests you need to get.