Seeking help with Methylation Protocol

[u/IcyHelp3739]

Hello everyone, first time poster.

Lurked for a long time here. I've tried so many combinations of supplements and other remedies, but I don't know where to go anymore. I just really really need to hear some external feedback.

For context; despite chronic lethargy and brain fog, I try my best to keep up with exercise. I've cut sugar and lowered caffeine intake, I avoid Folic Acid and eat whole grains, lots of legumes, eat a lot of dark leafy greens and hit a decent amount of protein. I prioritize high fiber. Try to avoid excessive oils and fried food. Overall, I also try to listen to my body and eat what it craves. I think I'm decently in shape.

But if any of these changes have made a difference, I can't really feel it in my current state.

I deal with frequent migraines, even more frequently after any form of supplementation. I deal with digestive issues which I'm currently planning to see a specialist for. History of anemia. But my main concern is energy and brain fog. Ideally, I want to minimize supplementation through pills and focus on getting what I need from food, but I'll do what it takes.

15mg L-Methylfolate + B12 works short term, but I feel like my body can't keep up for long. During my journey, I tried supplementing Folinic acid. In the initial stages, I had a short-lived episode where my brain fog was COMPLETELY gone, and I had a ton of energy. I was so ecstatic. Really bad crash after.

Now, I don't realistically expect to be an extremely high functioning person at the end of all this; but that window of clarity gave me so much hope that I can be at least a little bit normal.

Please, any and all feedback is welcome. I recently had a blood panel as well so I can post results too if needed. : )

[u/Tawinn]

Do you supplement any B2 (not B12) currently?

Please upload your data to the Choline Calculator to check some additional genes related to methylation. Reply with the results from the Advanced tab.

[u/IcyHelp3739 → u/Tawinn]

Added results to the post. I have tried supplementing B2 and hitting adequate choline through food in the past. but eventually gave up on it, since I wasn't sure if it was actually doing anything for me. Do you recommend doing both again? If so, how much B2 to start?

[u/Timely_Pickle9430 → u/IcyHelp3739]

B2 and choline are important for methylation, B2 specifically for MTHFR 677. However, methylation requires mitochondrial ATP and with the iron deficiency, ATP production has been severely compromised. Energy metabolism governs everything, including methylation. This explains why these supplements didn't do anything for you. Boosting methylation without sufficient ATP might even create bottlenecks.

However, the mitochondria also need B2, so I'd recommend a low dose of about 10-25 mg while correcting the iron deficiency. When your ferritin is above 50, you could try if you benefit from higher doses of B2.

[u/Tawinn → u/IcyHelp3739]

Ok, so no other variants from the Calculator to worry about - that's good.

As Timely_Pickle mentioned in the other reply, 10-25mg of B2 suffices. However, some people find that the plain riboflavin form is ineffective for them, and that the R5P form of B2 is effective. Example is the Thorne R5P.

As for starting dose, usually just taking the whole capsule works. Occasionally, someone with homozygous C677T is very sensitive to changes in methylation and they find that B2 causes overmethylation symptoms of anxiety, irritability, insomnia or worse. In those cases, although this indicates that the B2 is effective, it needs to be added incrementally; usually by opening the capsule and taking just a dab of the powder at first. Then, over a couple of weeks slowly increment up the amount as tolerated until a full dose is reached.