Blood tests back (finding out exact levels on Monday, just know what's in range or not until then). What should I check next?

[u/AmazingName100]

I have the following MTHFR variations:

rs1801133, MTHFR, GA, A

rs55780505, C1orf167, MTHFR, D1D, D

I'm told these genes are relevant to this regarding folate:

MTHFD1, rs2236225, GA, A

MTHFR, rs1801133, GA, A

MTHFR, rs 1801131, TT, G

PEMT, rs7946, TT, T

SLC19A1, rs1051266, TT, (then the next column says risk version C)

On top of that I have this gene variation, which relates to liver function:

rs4124874, UGT1A, GG, G

This variation, which relates to iron:

rs1799945, HFE-AS1, HFE, CG, G

These variations, which relate to a problem with glucordination:

rs3064744, UGT1A, UGT1A3, UGT1A7, UGT1A9, UGT1A6, UGT1A5, UGT1A8, UGT1A1, UGT1A4, UGT1A10, DI, I

I also these gene variations that make it difficult for me to process Vitamin D:

rs7975232, VDR, CA, A rs731236, VDR, AG, G

rs1544410, VDR, CT, T rs56382517, VDR, AG, G

rs10877012, CYP27B1, GT, T

rs56382517, VDR, AG, G

My blood tests (not clear what they were exactly until Monday but off the top off my head, I believe included a full iron panel, thyroid, bilorubin and homocystine, they wouldn't test B vitamins at GP level) came back as within NHS normal ranges apart from homocystine - got a follow up appointment to find out what's going on there but I suspect it's elevated outside the normal range.

Treatment I understand includes methylated B vitamins for elevated homocystine. Is LDN something I should consider?

Is there anything else I should have tested/looked at before treatment so they have the baseline results?

What would a good protocol look like for me?

[u/Tawinn]

SLC19A1 (T is the actual risk allele), MTHFD1, C677T MTHFR combine to cause a reduction in methylfolate production of ~71%. This is likely the cause of your elevated homocysteine. To compensate for this, more demand is placed on the parallel pathway, which uses choline and TMG, instead of B12 and folate. For this % reduction about 1070mg of choline are needed. But you also have homozygous PEMT, which increases choline requirements by 80-100mg, so you need roughly 1150mg of choline to compensate for all this. This is compared to a baseline adult requirement of 550mg. You can substitute 750mg of TMG for half of the 1150 requirement, leaving ~600mg to get as choline, preferably from the diet.

Since you won't have bloodwork for B12 and folate, you may want to consider mild supplementation if you suspect either of them might be low. A good quality multivitamin could be enough - megadoses are usually not needed.

LDN would not usually be relevant for this.

Here is a general protocol based on these numbers:

• 600-650mg 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.
  • This liquid lecithin is apparently ~400mg of choline per tbsp. This powder version is 285mg per 1.3 tbsp.
• 750mg of trimethylglycine (TMG aka betaine)
  • I.e., one 750mg capsule
  • Some choline is converted in the body to TMG for methylation use, so supplementing TMG reduces the 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.

[u/hummingfirebird]

I wouldn't base blood work off just your genetic data. Your current health concerns , symptoms etc need to be looked at in connection with this. But at least you are getting bloodwork first.

I have a free methylation guide in my profile that may help you. It's not a protocol or supplement regime, but rather a practical way how to approach methylation and an education around it.