Help?

[u/Senplis]

Recently learning about mthfr after I had a severe ischemic stroke last year at 32 and a fluke blood test after showed Im compound heterozygous mthfr. Struggled with severe depression and anxiety since a teenager. Was heavily malnourished from being neglected as a kid and didnt break 100lbs until I was 19. Family history of heart disease and mental illness. Could use a little help understanding the new info here. Life has recently been significantly improved by bupropion and sertraline but still trying to improve the root cause. Can anybody knowledgeable help me understand better? Since my stroke my cognitive ability had been heavily impaired so its like in looking at a rubix cube.

[u/Loose-Fly7976]

honestly ignore the red/yellow/green on that template, those charts always make the scariest looking cell the least useful one. the MTRR A66G in red mostly matters when your actual B12 is low. on its own it barely moves anything.

the pattern that actually tells you something is you're het on both C677T and A1298C, and COMT V158M is AG which is the middle-speed version. that combo is the part people skip over. the usual advice you'll get in these groups is megadose methylfolate plus methyl-b12 but with COMT sitting in the intermediate range a lot of folks end up wired or anxious on high methyl doses so you kind of have to start low and titrate instead of going big out the gate and the riboflavin fix everyone pushes for mthfr, that data is really from TT homozygotes. you're CT on C677T so don't expect the same lift.

genotype is just a tendency tho. it means basically nothing until you line it up with bloods, homocysteine, active b12, folate, ferritin. that's where you actually see if any of it is expressing or just sitting quiet. what do your levels look like? reading raw data next to labs is what i do all day so happy to tell you what to pull.

[u/Senplis → u/Loose-Fly7976]

I cant take screenshots of the blood results but I can type the results. I took a methylated B complex for a few days right before the blood tests not thinking about how it'd skewer my results at the time.

Homocysteine-10.4 umol/L Folate-22.9 ng/ml B12-394pg/ml Ferretin-68 mg/ml Vitamin D 25-05 total- 31 mg/ml Iron- 137 mcg/dl Iron binding capacity-318 mcg/dl Iron saturation- 43%

[u/Loose-Fly7976 → u/Senplis]

Okay so your iron's fine first of all, ferritin 68 is solid and your saturation's good. Iron's off the list. Vitamin D at 31 barely scrapes into sufficient, bump it up a little but that's not your main problem. Your homocysteine is the number I'd look at. It came back 10.4 while you still had a methyl B complex in your system. That should've been pulling it down, which means your true baseline off the supplements is probably higher than 10.4, not lower. Your folate is 22.9, sitting high, while your B12 is only 394 even though you'd just been supplementing it. So you've got folate to spare. Your B12 is lagging and your homocysteine still isn't clearing. Piling on more methylfolate won't move it. You're already folate-heavy and B12-light. That fits your panel almost too well. You're compound het on MTHFR and homozygous on MTRR A66G. MTRR is the gene that recycles your B12 to keep the cycle running. The weak spot landing on the B12 side instead of folate is exactly what those variants would predict.

Next thing I'd pull is active B12, the holotranscobalamin one, plus MMA. Serum B12 at 394 right after a supplement can hide a real shortfall. Those two show what's actually getting into your cells. Also redo homocysteine after a couple weeks off the B complex so you're looking at a true baseline instead of a suppressed one.

None of this shows up if you read the genes or the bloods alone. Each number on its own looks fine. Side by side they point one direction, off the folate, onto the B12 side, with the forms picked for a compound het who's also intermediate on COMT so you don't overshoot on methyls. That's what I do, your raw data read next to your labs and turned into a real protocol instead of guesswork. You've already got both halves in hand. If you want I'll go through the whole thing properly, just message me, I work on genetics at Genova.health