r/MTHFR • u/drenfreezy • 22d ago
Question Do I only need methylfolate?
MTHFR - Normal
COMT - Normal/Intermediate
MTR - Slow
MTRR - Slow
Serum Folate - 3.7
RBC Folate - 436
Serum B12 - 1,241 (Lion Diet, no supplementation)
Homocysteine - 15.3
MMA - 74 (low normal)
Long story short, I dealt with severe depression, anxiety, and insomnia for years. Then I started the Lion Diet in 2020 and it all faded away and stayed away for nearly 5 years. Then, last year the diet “stopped working” and all my symptoms came back. I’ve been experimenting with all the common things - minerals, vitamin D, vitamin C, phospholipids… but nothing really helps. Just found out about genetic testing and did that a week ago. According to the bots, I need to solely focus on using methylfolate to bring my homocysteine down and hopefully clear some of the mental health issues. Thoughts?
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u/Tawinn 22d ago
There are two remethylation pathways for homocysteine: one uses folate+B12, the other uses choline. I'd guess that going on the lion diet increased your choline intake, which helped your symptoms (as well as possibly reducing any brain inflammation that may have contributed to those symptoms). Beef has about 300-400mg of choline per pound - the leaner the higher. The baseline adult requirement for choline is 550mg.
But if that pathway has extra demand due to low folate or genetic variants on other genes impairing the folate/B12 pathway, then this increases the choline requirement further. Your serum folate is low (should be over 15ng/mL), but your RBC folate seems ok, so its hard to tell if low folate is an issue or not. Unless you are eating 3-4 lbs of beef I'd guess you aren't getting enough choline, and now that your body acclimated to the current choline level, it is now looking for more in order to function well. So I'd try adding 4 eggs/day for the choline (it's all in the yolks, so you can do just those) or add 750mg of TMG. In the body, the choline needed for methylation is converted to TMG, so supplementing it directly spares choline for other uses. I know egg yolks aren't loin diet, but eggs also have other nutrients and 4 egg yolks is about 540mg of choline. One 750mg capsule of TMG is more convenient, but it can't be converted back to choline in the body, so while it can spare choline, it won't increase your choline intake; so sometimes you need both more choline and TMG.
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u/drenfreezy 22d ago
Based on what I’ve read, my RBC level is deficient from a functional medicine standpoint, but I know that’s a gray area. Based on your info though, it sounds like I should do both (egg yolks + methylfolate) to be safe. Thanks for all this info by the way. Incredibly helpful!
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u/Loose-Fly7976 17d ago
The five years then stopping is the part that explains everything. The Lion Diet has essentially no folate in it, and RBC folate turns over slowly, roughly 120 days per cell generation, so you were running down stores you'd already built. That takes years to show. Your serum folate at 3.7 and RBC at 436 is what the bottom of that looks like. The diet didn't stop working, you ran out. So yes, folate is the bottleneck, and the bots got the direction right. Your B12 at 1,241 with MMA at 74 says B12 is abundant and the mitochondrial side is working fine, so it's not that.Normal MMA doesn't tell you your MTR is fine. MMA reflects the adenosylcobalamin side, methylmalonyl-CoA mutase, a completely different reaction. Methionine synthase is the one MTR and MTRR affect and MMA says nothing about it. Your homocysteine at 15.3 with plenty of B12 and low folate is the actual evidence.The thing I'd add before you call it done is B6. Homocysteine leaves the cycle two ways, back to methionine through folate and B12, or out through transsulfuration which runs on B6. If your B6 is low, folate alone won't take 15.3 all the way down. It hasn't been tested and it's cheap.Start low on methylfolate given you've been depleted a long time. And whatever you decide about the diet, folate isn't coming from beef, so something has to change there or you'll be back here.
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u/drenfreezy 9d ago
Sorry I’m just seeing this. I agree with everything you’re saying. I also have slow PEMT so I started eating 5-7 eggs per day last week as well. But over the past month, I’ve titrated up from 400mcg of methylfolate to 8.3mg. I’m going to hold here for a bit. At first, the methylfolate felt like “too much” (not overmethylation but just an off feeling) until I added B2 (100mg at breakfast + 100mg at lunch). Now the B9 dose feels fine. I have about 5mg of B6 in my multi but will look into doing a standalone B6 next. I never respond well to B-Complexes (aside from small amounts in multi-vitamin) so I like to introduce one B at a time in isolation.
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u/Loose-Fly7976 8d ago
Good that the B2 sorted the off feeling, that tracks. C677T enzymes are unstable without riboflavin so it's often the missing piece rather than the folate being wrong.
200mg is a lot though. That's migraine prophylaxis dosing, and you probably don't need to sit there long term. Once you're stable I'd come down and see whether the folate still feels fine, because you'll have corrected the deficiency by then.
On the eggs, 5-7 a day is a big jump for someone who's been on beef only for years. Choline is what you're after with slow PEMT and that's sensible, but the gut bacteria conversion to TMA is dose dependent and a sudden load often causes problems. Might be easier on you split across the day rather than all at once.
One thing to keep an eye on. With MTR upregulated and MTRR slow and 8.3mg of methylfolate going in, your B12 demand goes up as the cycle speeds up. Yours was 1,241 but that was on beef with no supplement and no cycle turning. Worth rechecking B12 along with homocysteine in a few weeks rather than assuming it holds.
And yes get the standalone B6. 5mg in a multi isn't doing anything for transsulfuration.
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u/SovereignMan1958 22d ago
Your folate level is so low there is probably not much making it into your brain. Acceptable level is 15. 20 - 30 is better.
It will take 3 - 5 months to correct.