Methylation & A1298C? What has your experience been?

[Avengers26]

While it's true that Genetic SNP's mutations might not mean much by themselves, but I have come across a lot of conflicting info about the A1298C mutation & the need for Methyl Folate? I am homozygous A1298C & I don't do well with MTHF beyond a certain point (800 mcg/ day) or for that matter any of the "methyl" rich supplements like P5P.

I have also heard & read about the need for biopterin with this mutation. I have never supplemented it but I have tried to increase it naturally. I am not sure how effective is the strategy to increase it naturally.

What has your experience been with Methylation supplements if you have A1298C mutation?

 

[PennyIA]

I tolerate very high doses of methylfolate; but that was after many years of taking folic acid and b6 and getting more and more ill ... I did test positive for b6 toxicity and feel (though no proof, of course) that I really was needing the methyld folate to clear out the toxins built up in my system.

I've tried taking P5P for the b6 deficiency; but it seems like I don't tolerate it well either.

 

[Critterina]

I tolerate folic acid and methylfolate, but apparently not folinic acid. I tolerate P5P (50-100 mg); 50 mg reduced my Vitamin B6 deficiency in a way the pyridoxine hydrochloride did not. I live for my methylB12 - 5 mg twice a day, but I could eat them like candy. I tried BH4, but not consistently and with no noticeable effect, except for the severe lightening of my wallet.

1 mg methylfolate, 50 mg R5P, 10 mg methylcobalamin, and an active B complex (Answers from Nature) all seem to be important to me. I was also using 5 mg Li orotate, to good effect, until it started making me sleepy after I took it with breakfast. I switched it to bedtime (a good time to be sleepy) but I think it caused problem-solving dreams. I have enough of that without imaginary people needing me to solve their problems too, so I quit it for now.

 

[alicec]

I am homozygous A1298C & I don't do well with MTHF beyond a certain point

The two aren't necessarily connected. There could be many reasons for sensitivity to these supplements. The snp causes a minor slowing of enzyme activity, something which could be overcome with modest doses of methylfolate.

I have also heard & read about the need for biopterin with this mutation.

This is part of the mythology created by Yasko. The enzyme does not run in reverse and somehow recycle BH4. Yasko misunderstood a laboratory experiment where the enzyme was forced into reverse under different conditions. The snp simply affects the capacity of the enzyme to make methylfolate.

There could be an indirect link since methylfolate is a peroxynitrile scavenger and removal of the latter might help to prevent oxidation of BH4.

 

[Critterina]

The enzyme does not run in reverse and somehow recycle BH4.

Would you please supply the reference for this - what research Yasko misread, so that I can understand what is going on? Thank you!

 

[ahmo]

I got up to 30mg Mfolate, before I understood that my vegetable intake was blocking it, with the veg form of folinic. In addition to quitting green veg, I also began taking folate sublingually (actually along gum line) which reduced my needs by 50%. Dudring the last 6 months, several interventions have reduced my needs. I'm currently taking 2mg folate, about the same of MB12. Presumably my efforts at eliminating peroxynitrite, decreasing oxidative stress, is also helping BH4 levels. It's at the center of Martin Pall's explanations of nitric oxide cycle. (links in my sig.)

 

[alicec]

Would you please supply the reference for this - what research Yasko misread, so that I can understand what is going on? Thank you!

A long time ago I accepted Yasko's claims about MTHFR snps at face value but was puzzled by her notion that the A1298C snp affected the reverse reaction while C677T affected the forward reaction of the enzyme. When I went searching I could find nothing whatsoever to support the claim.

I then searched for information on the reverse reaction and again could find nothing to suggest that this actually happens, apart from the in vitro study referred to by Yasko, which was using a different combination of substrates and products. In other words this was an artificial construct designed to study an aspect of enzyme activity but it did not translate to what is going on in vivo.

This is the same sort of mistake she made with her claims about CBS enzyme activity.

When I went searching this morning for this original paper I was reminded that there has already been an excellent discussion of this on PR with links to this paper, so rather than go through it all again I'll just link to these posts by @nandixon.

here and here

 

[xena]

i have one mutation at a1298c; i use between 15-20 mg mthf, more if i am taking sam-e, along w/ 10 mg methyl b12 injected daily
i've never tried folinic acid but don't seem to have a problem with normal intake from food
oh and i have improved about 20/30% percent after 4 months of this
improved sleep, digestion, energy. brain fog improved at first and now is stuck- i suspect due to some vitamin deficiency. brain fog has improved slightly with choline supplementation (500 mg citicoline, 2x/day)

 

[Gondwanaland]

I tolerate folic acid and methylfolate, but apparently not folinic acid.

I probably asked you before, but what symptoms do you experience with folinic?

 

[Critterina]

I probably asked you before, but what symptoms do you experience with folinic?

It's as close as I've come to narcolepsy. I just couldn't stay awake starting about 20 minutes after I took it. Plus increased general unhappiness (moving toward depression).

 

[dannybex]

I tolerate very high doses of methylfolate; but that was after many years of taking folic acid and b6 and getting more and more ill ... I did test positive for b6 toxicity and feel (though no proof, of course) that I really was needing the methyld folate to clear out the toxins built up in my system.

I've tried taking P5P for the b6 deficiency; but it seems like I don't tolerate it well either.

I think you're on to something Penny. Check out the study at the bottom of the page on this thread:

http://forums.phoenixrising.me/inde...b6-and-feeling-funny-help-please.34126/page-2

Edit: Tagging @alicec for her opinion as well. And anyone else's of course.

 

[dannybex]

It's as close as I've come to narcolepsy. I just couldn't stay awake starting about 20 minutes after I took it. Plus increased general unhappiness (moving toward depression).

It makes me reeeeeaaaally sleepy as well. That's a good thing to a certain extent, but when one's radio alarm is set pretty loud and I sleep a half-hour through it, then, maybe that's a sign to back off. Or balance it w/more b12. I'm also wondering if it makes me weaker, but I don't think so. It's probably a lack of b12. I take maybe 1/2 5000 mcg 'Natural Factors' methylcobalamin every other day or so, and it dissolves really fast too.

Also interesting re the depression. I've certainly been more depressed, but I attribute that to still losing muscle, and thus being less and less able to walk, even within my apartment.

 

[Gondwanaland]

Edit: Tagging @alicec for her opinion as well. And anyone else's of course.

She won't be notified through post editing
Must write a new post to do that
@alicec

 

[alicec]

Edit: Tagging @alicec for her opinion as well. And anyone else's of course

Sorry @dannybex I don't really have an opinion. I wasn't aware that B6 toxicity could develop at very low doses though of course I realise that B6 is problematic for many people for various reasons.