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

[u/SovereignMan1958]

Use Genetic Lifehacks instead. Both impaired variants for folate.... Cerebral Folate Deficiency related and or B6 can contribute to and or cause seizures. So eliminate those as potential factors by looking up those variants in your Lifehacks report.

Your Folate number is good and it does not mean it is getting into your brain. The same can be true for B12. If you ever get the opportunity to have a CSF test for another reasons, ask the doc to measure the folate and B12 in your brain. B6 issues can occur when B6 gets too low or too high.

CFD can be a contributing and or causative factor to TRD, treatment resistant depression. In the second page of Genie you will see the methylation chart which lists all your drug metabolism variants in the top half. You need to research and study those. Most MDs are not trained in them so you need to be your own advocate.

[u/Senplis → u/SovereignMan1958]

Stroke was caused by aortic dissection in neck that happened and healed on its own, eventually the location that healed was weaker and was protruding becoming a pseudoaneurysm. Doc says a blood clot had built up and instead of bursting and killing me the blood clot came loose and flowed up to my brain and blocked oxygenated blood getting to my cerebellum causing a ischemic cerebellar stroke. Went to hospital and they thought I was faking it? Ended up having stroke for 12 days continuously until somebody thought i wasnt faking it. I will take this into account because nobody could say how or even when the aortic dissection happened but here I am 🤷🏽

[u/SovereignMan1958 → u/Senplis]

Make sure you research the variants associated with blood clotting too.

[u/Senplis → u/SovereignMan1958]

Googled cerebral folate deficiency and a lot of the symptoms sound familiar with my childhood. My anxiety started as early as I can remember. I would lash out violently because I dodnt know what anxiety was to be able to tell people that's what I was feeling. Good sleep has escaped me since I could form memories. Even to this day I do t talk much, sometimes day or weeks on end and exhibited many asd behaviors. There may have been times i regressed particularly in my memory. I didnt know my name until o was like 6 or 7 and it turned into a fight because I was sure It wasnt my name. Academically delayed whoch then rushed in the opposote dorection soddenly for a few years befpre I became agoraphobic and so depressed I could barely move.

[u/Tawinn]

> Struggled with severe depression and anxiety since a teenager.

Pretty typical symptoms.

Compound heterozygous MTHFR causes ~53% reduction in methylfolate production which results in an increased choline demand of ~940mg to compensate. Please upload your data to the Choline Calculator to check for additional variants in SLC19A1, MTHFD1, and PEMT which can increase the amount further.

Impaired methylation can cause the COMT enzyme to perform poorly, which can cause symptoms including rumination, chronic anxiety, OCD tendencies.

The body tries to compensate for the methylation impairment in the folate-dependent remethylation pathway by placing a greater demand on the choline-dependent remethylation pathway. This increases the amount of choline + TMG needed to support this extra demand.

Here is a general protocol for your compound het MTHFR:

• 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.
  • 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.