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What could be causing such a high need for Methylfolate?

Messages
87
Couple of years ago I started trying to get my methylation cycle working properly (undermethylator). I was still learning and didn't have all the pieces, but continually working my way up I got to where I could take 40mg of Solgar Metafolin a day with negligible effect.

After months of doing this with little to no effect I started adding ALCAR (fumarate doesn't really work for me) to the Metafolin, Methyl B12 and Active B12 I was taking and that last addition set me off a 5 month ride of overmethylation before fully realizing what was going on and how to reign it in with niacin.

Since starting folate again 3 months ago I am having a similar issue again with a need for really high doses of Metafolin, 10mg at a time is where I start to feel some neurological brightening, but nothing spectacular.

I take Jarrow Methyl B12, Source Naturals Active B12, ALCAR and TMG specifically to promote methylation, but my dose of folate is still 30-40mg a day which is far higher than I'd prefer for the response I'm getting. Oddly I am not really having any real need for additional potassium.

I also recently stopped taking vitamin B1/B2 because I saw a comment from @Freddd that they may increase the need for folate. I do need a pretty sizable amount of B6 (1000mg time released + 100mg P5P a day), don't really know why I need that much but my parents and brother both need the same .

When I was overmethylating, once I started I didn't really need much if any additional folate to keep the problem going for 5 months. So it's weird to still undermethylate at 30-40mg of Metafolin a day.

Any idea what if anything I am missing that could be driving such a high folate need relative to the minimal response I am getting?
 
Messages
10
I have a similar issue regarding folate requirement and was planning to start a new topic when I read yours. So I will post my situation here and perhaps someone will be able to help both of us. Hopefully you don’t think I am hijacking your thread.

Overall I have made great progress following the Freddd protocol. I generally have significantly more energy, less anxiety and brain fog and improved IBS and many other symptoms.

However it has had its sharp ups and downs and over time I have seemed to require up to as much as 30mg Folate or more to stave off deficiency symptoms. In the early days I could feel great on 3.2mg of folate and then later on 6.4mg or 9.6mg and ultimately more was required. This increased requirement seems to have been somewhat linked to starting and ramping up LCF over time.

I certainly seem to have a big benefit from LCF and it has a big positive impact on my energy and anxiety and also seems to reduce inflammation and also bloating. These benefits seem to be lost if I stop for 1 or 2 days. However the benefit from LCF seems to be usually followed by a crash after a few days where my symptoms go the opposite way and I usually require pausing the LCF and ingesting large amounts of folate. But also what really helps a lot is taking large doses of Sam-E and my symptoms are quickly improved as long as I am taking Folate throughout the day also and pausing LCF. Paradoxically my healing soon seems to stop until I subsequently resume LCF.

So I am wondering if anyone has any ideas why I might be always in this cycle where LCF seems to be critically required but then it seems to cause a crash and if it is leading to my folate requirement being extremely high? I have been taking LCF for at least 2 years at varying doses so I would have thought any initial symptoms should be well past.

Is the fact that Sam-E helps so much a clue to something?

At the moment I am taking all the co-factors including B vitamins (being careful to stay under the B1/B2/B3 levels that Freddd has recommended) and also taking approx 4g potassium a day. I am also taking significant levels of B12 transdermally which seems to be working very well in general compared to the sublingual. I have been erring on the side of too much and taking 10mg of estimated absorbed mb12 and adb12 respectively. I also take TMG and D-Ribose.

Would really appreciate if anyone has any ideas about this.
 
Messages
87
However it has had its sharp ups and downs and over time I have seemed to require up to as much as 30mg Folate or more to stave off deficiency symptoms. In the early days I could feel great on 3.2mg of folate and then later on 6.4mg or 9.6mg and ultimately more was required. This increased requirement seems to have been somewhat linked to starting and ramping up LCF over time.

Interesting that you say that because I noticed the same thing. It takes 30mg of folate for me to get a similar feeling to what I had at the beginning with 3.2mg.

One second while I climb out on a limb :) ... If I had to guess we are likely not so much deficient in folate, but more likely an activator of folate because we're getting progressively less impact from the folate we are taking. Which would be the case if there was a deficiency in something necessary for folate to be efficiently utilized.
 
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10
Do you find the ALCAR made a big difference to your folate requirement? In my case I feel like the LCF is the biggest thing that has caused my folate requirement to go so high yet perversely I seem to require it - which seems to be leading to this cycle.

Did you find a similar link with ALCAR or you think it’s something different?

Regarding a deficiency of something else that certainly seems to be a possibility however unfortunately I can’t think of a cofactor that has been mentioned anywhere that I am not already taking!
 
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87
Do you find the ALCAR made a big difference to your folate requirement?
I already had the problem before I started adding the ALCAR, so I don't think that was the driver.

Odd as it sounds ... I am beginning to the think the issue is somewhere in the B6.
 

Eastman

Senior Member
Messages
526
I also recently stopped taking vitamin B1/B2 because I saw a comment from @Freddd that they may increase the need for folate.

Freddd thinks B1 and B2 increase folate usage (see here and here).

It is possible your cells are not fully using the folate you are taking, in which case B1 may actually be helpful as it appears to increase uptake (see here). Also, several members have reported an increased need for B1 after being on the methylation protocol for a while, so it may be something to monitor anyway.

As for B2, it is a cofactor for the MTHFR enzyme and therefore helps recycle methylfolate. It may actually lower folate need. See also this thread.
 
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Interesting. I have also been very careful about making sure I do not take too much B1/B2/B3 etc and have actually reduced my b-complex to a quarter of what I used to take. Seems like there’s a chance that has been the problem.

Seems no harm in increasing my B-complex immediately and monitoring any changes.

Thanks very much for your comments!
 
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10
So very interesting development. For the last 2 days I tripled my b-complex by taking 3 per day instead of 1 per day. I didn’t change anything else in the protocol at all (continued on 30mg Folate).

I really did feel like I was feeling a lot better especially by the morning of the 2nd day. However by the 2nd evening and my 3rd does on B-complex I developed an EXCRUCIATING headache. No other symptoms came along with this other than a desire to vomit (potentially from the pain?). This can only be down to the b-complex as I didn’t change a single other thing I was doing! I crawled around the room and made up a bunch of potassium citrate solution and the headache had subsided within a few hours and I miraculously fell asleep and the next morning I felt fine again (very very faint headache but almost unnoticeable).

I found this whole thing incredible - such a harsh reaction from just 2 more b-complex doses! Based on reading various views on the forums I figure there are only 2 hypothesis ... either the extra B vitamins have sharply elevated my folate activation and all of a sudden 30mg is WAY too much and this reaction has helped me heal but drained me of potassium at the same time. Or alternatively the extra B vitamins have caused an insatiable need for Potassium but not doing anything productive.

Would love to hear people’s thoughts. For the record I am using Thorne B1 complex #12. https://www.thorne.com/products/dp/b-complex-12

p.s. is it unusual to have low potassium symptoms that only involve an excruciating headache and no change in heart beat or muscle cramps? I have had this a couple of times before (a long time ago) as I ranked up the methylation supplements. It usually seemed to be treated by higher potassium but just wondering if this is definitely potassium deficiency or could be something else.
 
Messages
87
However by the 2nd evening and my 3rd does on B-complex I developed an EXCRUCIATING headache.
I recently cut out all of my Pyridoxine HCl form of B6 after finding out that form inhibits P5P receptors and stuck with the 100mg of P5P I was taking, I had the exact same response ...massive headache, but only lasted one day.

Based on reading various views on the forums I figure there are only 2 hypothesis ... either the extra B vitamins have sharply elevated my folate activation and all of a sudden 30mg is WAY too much and this reaction has helped me heal but drained me of potassium at the same time.
I'd suggest your first hypothesis is likely the correct one, but I am finding that the removal of the non active forms of B-vitamins are, as if not more, important then just increasing overall b-vitamin amounts.
I have some active B2 coming in today so I'll report back my findings in relation to necessary folate supplementation.
 
Messages
10
I recently cut out all of my Pyridoxine HCl form of B6 after finding out that form inhibits P5P receptors and stuck with the 100mg of P5P I was taking, I had the exact same response ...massive headache, but only lasted one day.

What was your course of action? Did you reduce your Folate dose or just continue with the high level of folate intake?