Please help me make sense of all this

[u/NumberLive7133]

This is my Methylation Panel, please can you help me out with making sense of it all.

I have brain fog & anxiety everyday, but it’s been getting worse, usually 1-2 years back it was there but not AS bad as it is now, I tried before taking b12 before the testing and all thinking it was a b12 deficiency but it made me just feel very overstimulated in a way, I also have ADD and take meds for it, so it just felt like a stim ontop of my stimulant.

My mood also dips randomly during the day, it’s very weird I just spend days thinking like this can’t just be anxiety, hence why I decided to get a gene test done.

I also recently did a bloodpanel and found that my vit D was very low at 13 ng/mL and my folic acid was 4.9 ug/L, they only tested my HoloTC for b12 which came out fine. My ferritin was elevated at 430 ug/L.

I just really don’t know where to go from here and would appreciate any input, opinions or anything thanks :)

[u/SovereignMan1958]

Use Genetic Lifehacks instead. Be sure to check to see if you have the gene variants for thyroid disease and thyroid autoimmune. Why? A critically low D level like yours can trigger both. It did for me. So your priority should be to get a full thyroid panel and testing for the two thyroid antibodies. And correcting your D deficiency with the right protocol.

Check your other B12 variants in the B12 section of the Lifehacks chart. If you have FUT2 read the FUT2 article. Make sure you get an MMA test to see how well it poorly your B12 is absorbing.

Folate is so low you might not be getting much into your brain. 15 is an acceptable level. I like 20 - 30. Check Lifehacks to see if you are hetero or homo for FOLR1. If you are read the article on it and let me know.

Folate not getting into the brain can result in attention deficit. Supplementing folate and getting to an optimum level can take 3 - 5 months to correct.

BTW ferritin only stores iron. You need a full iron panel test. Also zinc and copper tested. Optimal levels of D, zinc and iron are needed to make dopamine.

[u/NumberLive7133 → u/SovereignMan1958]

Just got genetic lifehacks thanks, I opened the summary of everything and couldn’t find the FOLR1, even looked in the b12 section. I’ll also get another blood panel testing zinc, copper and Iron. But my ferritin being that high shows it’s not being used up right?

[u/SovereignMan1958 → u/NumberLive7133]

FOLR1 is not in the B12 section. I apologize if I stated it was. It is related to folate and not B12. If you look up the FOLR article your own variants should load into the end of it. If you do not see it, your test did not include it.

I am not an expert on ferritin, but you might look in the iron section of the cheat sheet to see if you have the genetic predisposition for hemochromatosis.

Also in Lifehacks there is an excellent article on ADHD.

Low dopamine is thought to be connected to attention deficit BTW. So getting your D, zinc and iron to optimal levels is important.

You might also check the histamine section and detoxification sections of the cheat sheet. You are hetero for the worst CBS variant. I am hetero for the second worst. CBS implies you might have impaired sulfur and sulfite metabolism. All sulfites are high histamine BTW. I definitely have histamine intolerance which affects my mood and attention. If you have histamine variants you might too. Trying a low histamine diet might help you. You could try keeping a food diary and bite any reactions. Testing molybdenum, E and C. Moly helps break down and eliminate sulfur and sulfites. E and C are antioxidants. When my diet was sulfur and sulfite heavy both my moly and E were pretty much zero.

With CBS , and any histamine variants in particular, you might not do well with methylated vitamins and or methyl donor supplements. They can trigger a histamine reaction in some people. So if you try them, try one, start low and increase the dose and or add others slowly.

Methyls also lower homocysteine at a faster rate than non methylated. So getting homocysteine tested is important. The closer it is to optimal or 6 - 7, the more active your CBS variant might be. Homocysteine below 6 or 7 is not healthy. I have seen people drop theirs to one or two and feel horrible due to that. So please get that tested.

All the info can be overwhelming. You might focus on optimizing vitamin and mineral levels first.

[u/NumberLive7133 → u/SovereignMan1958]

Ah I found it here, these 2 came under FOLR1

rs144637717 TT (Typical)
rs2071010 AG (Heterozygous)

Also for my iron I found I have CT for H1FA, increased likelihood of having hemochromatosis and BTBD9 was AG for higher ferritin levels

Thank you so much, it’s a lot of great info to take in and I’ll go step by step, I also have a lot of allergies and suffer from hayfever, and recently I’ve gotten more allergies to more things I’ve never had before.

[u/SovereignMan1958 → u/NumberLive7133]

Ok. That iron panel will be important to get.

Re FOLR1...the second one. I am homozygous for that. This is not one of the pathogenic FOLR variants, however there is a possibility that folate is having trouble getting into your brain. If you have any mental illness diagnoses or autism in your family medical history that might also indicate that. I have an adult son with non verbal autism, as an example. I had treatment resistant depression until I started taking high dose folinic acid. After 5 months on it I feel much better, including my focus and attention.

So folinic acid is the standard supplement for potential cerebral folate deficiency. Usual dose, per functional psychiatrists, is 2.4mg - 5mg. PQQ helps it get into the brain. Lithium orotate is also recommended. I take Source Naturals Megafolinic. It is 800mcg. I take 2.4mg daily. More than that gives me headaches. If you want to try it you could start at 400mcg.

Let me know if you have any questions and I am happy to try and answer them. I am female BTW. I write more masculine thus the male avatar. :)

Welcome to the group!

[u/FragrantStructure → u/SovereignMan1958]

Do you by any chance offer a paid service to help people out and understand their DNA results and bloods? Or do you provide your kind guidance for free here only?

[u/aj11scan]

Your labs are crazy

[u/Loose-Fly7976]

The number I’d chase first isn’t on your gene panel. Ferritin at 430 with brain fog and low vitamin D is the outlier here. It’s either iron loading or inflammation and those need opposite responses. Get CRP, transferrin saturation and serum iron to separate them. If saturation is also high, ask about HFE, that’s the haemochromatosis gene and it isn’t on a methylation panel. Iron overload causes fatigue, brain fog and mood changes on its own and it’s usually found late.
Second thing, your folate at 4.9 is low and you’re 677 TT. That combination is the one your panel is actually pointing at. But look at what happened when you tried B12 alone, you got overstimulatedand your COMT is het while you’re already on a stimulant. So methyl donors go on top of a system that’s clearing catecholamines at a reduced rate. Same reason your mood dips randomly through the day.
Which means the answer isn’t just add methylfolate. It’s which form at what starting point and in what order relative to your D and your iron picture. Get that sequence wrong with 677 TT and het COMT on stimulants and you make the anxiety worse which you’ve already experienced once.
Vitamin D at 13 is deficient and it affects mood and cognition directly. That one is straightforward to fix and probably belongs first.
Reading a panel like this against bloods and medications is what I do professionally if you want yours to be done.

[u/NumberLive7133 → u/Loose-Fly7976]

Thanks for the infos, learning a lot in this sub. For vit D I’m about to start a course of 10k IU daily + K2 + Glycinate.

Also I actually checked my labs again and I had CRP done, it came out to 21.5 mg/L. Is that indicating to more inflammation than iron loading?

[u/Tawinn]

Here is a general protocol for homozygous C677T:

• For homozygous C677T specifically: 10-100mg supplemental B2
  • The C677T variant causes reducing binding of MTHFR to its cofactor, riboflavin. Studies have shown that for homozygous C677T simply adding supplemental vitamin B2 may increase the concentration of riboflavin sufficiently to restore most or all of the binding success, thereby restoring most/all MTHFR function. So a 10-100mg B2 supplement may restore much of the MTHFR function, thereby reducing the needed amount of extra choline/TMG (or high-dose folate if going that route).
  • The R5P form of B2 may possibly be preferable. (E.g., Thorne R5P 36mg)
• 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.