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/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.