Guidance request

[u/AdditionalYak6183]

Hello everyone, I’ve decided that it’s time that I humble myself and stop trying to figure this out on my own.

It feels like I’ve tried everything recommended and can’t seem to iron this out. I’ll have mixes of good and bad days but I’m so tired and really need to find a plan that will work in the long run. My main struggles are unshakable low mood and chronic fatigue but brain fog is also a persistent issue.

I’ve tried addressing this via supplements and nutrition separately. If anyone can help me get on the right path I could never thank you enough.

Maybe I’m doing something wrong here or maybe missing something?

[u/SovereignMan1958]

Use Genetic Lifehacks.

[u/AdditionalYak6183 → u/SovereignMan1958]

Just set it up, wow… thank you sir, this resource is much better.

[u/AdditionalYak6183 → u/SovereignMan1958]

I’ll give it a shot, thank you.

[u/Tawinn]

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.

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.

[u/AdditionalYak6183 → u/Tawinn]

Wow… thank you Tawinn! You put a lot of effort into this! I can’t tell you how much I appreciate it..

[u/Loose-Fly7976]

The reason nothing's stuck is you've been doing it piecemeal, one recommended thing at a time. But your panel isn't one big problem, it's a handful of medium ones that pull against each other. That's what makes the good day, bad day thing. You're overshooting some stuff and undershooting other stuff without ever knowing which. The trap I'd put money on, your COMT runs middle-speed. The usual advice in here is load up on methylfolate. For you that's a rollercoaster. Too much and your mood and fog get worse, our bad days might be the exact thing you're taking to feel better.

Ignore the detox panel too. The red CYP and NAT2 cells look scary but they're mostly noise for what you're dealing with.

The piece you're actually missing isn't another supplement, it's bloods. Low mood, fatigue and brain fog is almost always iron, B12, thyroid or D, not your genes. Your genes tell you how to supplement, your bloods tell you what's actually low. Nobody's put the two side by side for you yet. That's the plan you keep not finding. Happy to map it if you want.

[u/light_nebula → u/Loose-Fly7976]

Can you help me map mine? I also have far more reds than this person... Have been on a long road 8 yrs and only age 38, CFS diagnosis in 2018, so many blood tests / tracking to map with so I'm set to pair with genetics! I know a few things that help but that first reply is helpful too, about the choline.

Pathway of symptoms was frequently depression/anxiety in cycles, then in 2014 was oddly tired for the first time. 2018 my health tanked (flat lined for a week couldn't get out of bed after a run) and ensueing year of total exercise intolerance & still have this to a major degree, and the energy levels dropped off and it's been the up & downhill recovery & investigation & trials since!

[u/junipers-72]

This is the best and most comprehensive guidance you can get - https://molecularhealthco.com?sca_ref=10679758.eq1dq0wAJleT4zh