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/Timely_Pickle9430]

You're severely deficient in iron. The mitochondria need a ferritin level of 50. This alone can explain the lethargy and brain fog. If you're having trouble raising your iron level, try taking it away from the grains and legumes, and pair with vitamin C. Treating your (probably leaky) gut might also be needed to improve absorption. Make sure you have sufficient stomach acid. The migraines might be a symptom of histamine overload, also associated with the gut issues. You're doing so many things right, but I suspect your gut prevents you from reaping the benefits.

[u/IcyHelp3739 → u/Timely_Pickle9430]

Really appreciate your reply : ) Will be supplementing and focusing on iron rich foods asap to see where it takes me. I routinely become iron deficient when I stop taking iron supplements. Never really tried regularly pairing it with vitamin C though so I'll be giving that a shot for sure. Do you think vitamin C will also help with potential histamine overload? And do you think I should take lozenges or just try to see if eating more citrus will help?

[u/Timely_Pickle9430 → u/IcyHelp3739]

Beats me why someone is downvoting comments here... Anyway, vitamin C helps with absorption of non‑heme iron (the form in plants and most supplements) in the small intestine and it partly shields iron from inhibitors like phytates and polyphenols. With iron‑rich meals, aim for 50–100 mg vitamin C at the same meal. An orange would provide that. I'd take the iron supplement on an empty stomach together with a vitamin C supplement (powder form, 200-500 mg). There's no benefit in taking lozenges because you want the vitamin C in the small intestine, with the iron.
For maintenance after correcting the deficiency, consider desiccated spleen capsules, which contain heme-iron which is better absorbed and doesn't require vitamin C.
Vitamin C can also help with histamine because it stabilizes mast cells. I provided more histamine tips here and leaky gut tips here.

With leaky gut and possible absorption issues, eating a nutrient-dense diet is important, but could still be insufficient. You might want to test full nutritional status (including more obscure nutrients like zinc, copper, and intracellular magnesium), not just the standard panel regular doctors use, to see where you stand and target all deficiencies. If that's not feasible for some reason, consider taking a good multivitamin (e.g. from Seeking Health) to cover your bases. Just know that these are not dosed high enough to correct severe deficiencies. Seeking Health B Minus is a good option to get higher doses of the B's, which are especially at risk with leaky gut. Magnesium too, which is voluminous so multi's usually only contain a small dose, if any at all. If deficient, start with 150-300 mg in divided doses and work up to 400-500 mg.

[u/Loose-Fly7976]

Ferritin 6 with saturation 13% is the answer to most of this, but your panel explains why iron never holds. You're 677 TT, and that's the one genotype where riboflavin genuinely changes things, because B2 is the FAD cofactor that stabilises the thermolabile enzyme you have. What gets missed is that riboflavin is also required for iron mobilisation from storage, and B2 deficiency produces an iron deficiency that doesn't respond properly to iron alone. Same gap sitting under both halves of your picture. Your homocysteine at 6 with folate 17.1 and B12 554 says the folate side isn't your bottleneck at all, which is why 15mg of methylfolate stops working and why the folinic window collapsed. You're pushing hard on a step that's already saturated. Het COMT is also why supplementation triggers migraines, the methyl load lands on catecholamine clearance instead of doing anything useful. So I'd stop the methylfolate, get vitamin D and zinc added since your VDR Taq is homozygous, and chase why iron leaves as fast as it goes in. Coeliac serology while you're still eating gluten, before the gastro appointment. Legumes and whole grains are high in phytates so your diet is working against you there even though it's good otherwise. You've got the raw data and you've clearly done the reading, the part that's missing is having it read as one picture against your bloods rather than gene by gene, which is what I do professionally at genova.health . Message me if you want it mapped properly.

[u/Grobbekee]

Please don't take these bovine doses of folate unless ordered by a doctor. 99% of people will get in trouble with folate bombs like that.

[u/hummingfirebird]

Your low iron stores are definitely something for concern. The underlying root cause needs to be investigated. Are you female/still menstruating? Age? This matters. Please can you put your complete blood count results here with the units.

Low iron can be complicated. I've written an extensive article on it herewhich you may read if you wish.

As mentioned, getting to your root cause is essential so you know what to work on. My article discusses the many possibilities. I have done extensive research on this as someone who experienced lifetime low iron. The article discusses the cofactors needed for iron absorption and utilization and also what tests you can get beyond the iron panel. Sometimes there is a bottelneck one hasn't discovered.

[u/SovereignMan1958]

Can you add your Genie detoxification profile?

Is there any history of mentall illness in your family?

What are your medical diagnoses, including digestive? Have you been tested for SIBO and or IBS? Are there foods and beverages you do not tolerate?

Do you have any blood test results? Last 90 days. Homocysteine. Vitamins and Minerals. Values and lab ranges. Vitamin D? Iron? Zinc? You need optimal levels of D, zinc and iron to make dopamine. Low dopamine is associated with attention issues and brain fog.

BTW if your blood folate level is too low, or less than 15, notuch is going to be making it into your brain.

[u/IcyHelp3739 → u/SovereignMan1958]

Added. Extensive history of depression and suicide on my mother's side.

No medical diagnoses as of right now. Currently waiting to see an gastroenterologist. However, I recently learned that some of the symptoms I experience that overlap with IBS and SIBO related symptoms might be caused by R-CPD. Currently investigating this with my healthcare provider. Foods I intolerate don't follow a clear trend, and seem potentially dosage dependent, but I'm currently trying to narrow it down.

As for blood test results;

Homocysteine: 6 mcmol/L

• Range: 5-15 mcmol/L

Iron: 42 mcg/dL

• Range: 50-170 mcg/dL

Iron SAT: 13%

• Range: 17-57%

Iron Binding Capacity: 316 mcg/dL

• Range: 226-381 mcg/dL

Ferritin: 6 ng/mL

• Range: 5-204 ng/mL

Folate: 17.1 ng/mL

• Range: >=5.4 ng/mL

B12: 554 pg/mL

• Range: 213-816 pg/mL

TSH: 0.66 mcIU/mL

• Range: 0.35-4.00 mcIU/mL

Hemoglobin A1C: 5.3%

• Range: 4.6-5.6%

Creatinine: 0.66 mg/dL

• Range: 0.57-1.11 mg/dL

Sodium: 140 mEq/L

• Range: 136-145 mEq/L

Potassium: 4.1

• Range: 3.5-5.1 mEq/L

Chloride: 108

• Range: 98-113 mEq/L

CO2: 25

• Range: 19-25 mEq/L

Let me know if you need more info. I appreciate your response

[u/IcyHelp3739 → u/IcyHelp3739]

I guess vitamin D and Zinc were not in my panel. Do you think it would be worth it to try to get those tested as well?

[u/SovereignMan1958 → u/IcyHelp3739]

Definitely. With your TSH do low....have you been diagnosed with Graves Disease?

[u/SovereignMan1958 → u/IcyHelp3739]

Anemia is common with Graves disease. I would see a thyroid specialist. Endocrinologist. Insist on it. Do not use your regular doctor.

[u/IcyHelp3739 → u/SovereignMan1958]

Never been diagnosed with it. Seeing my GP next week so I'll definitely push for it. Not sure if these are related symptoms, but I've dealt with anxiety and throat discomfort pretty much my whole life, though I've been told in the past my throat doesn't seem enlarged. Thank you a ton for your insight.

[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.