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Low Folate Symptoms/Paradoxical Folate Deficiency

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
Thanks, Valentijn.
The SHMT is a bit of a "?", but since it has been studied and the increased risk only shown when combined with another SNP, it's pretty unlikely that it does anything on its own. Plus it is a "synonymous substitution", which means the + version doesn't result in a structural change to the protein created by the gene - which means it would be very hard for this SNP to have much of an impact.
Well, that's surprising to me based on my reaction when I added folinic acid to my regimen, but I made a lot of changes at once, so perhaps I need to isolate the change and try again. Hmmm, how would it complicate things for an MTHFR C677T mutation then, I wonder? If it's not depriving it of substrate, (which would affect more than C677T people), what could it be doing?

I'm not sure about the COMT discussion. Maybe you mean http://forums.phoenixrising.me/index.php?threads/interesting-comt-variations.24672/ where I have other COMT variations listed? It's possible that the additional COMT variations are having an additional impact to the ones listed by Yasko and GeneticGenie.
Thanks. That was a good one, but that wasn't it. Maybe I confused or conflated something.
 
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15,786
Hmmm, how would it complicate things for an MTHFR C677T mutation then, I wonder? If it's not depriving it of substrate, (which would affect more than C677T people), what could it be doing?
No idea, and I don't think the papers I saw really speculated about it - or I just wasn't interested in the "why" so skimmed over it :rolleyes:
 

aaron_c

Senior Member
Messages
691
@adreno

I don't believe in "paradoxical folate deficiency". It seems more likely to me that you need something else. In my case, when I increase MB12 and methylfolate, I vastly increase my need for B2, zinc and potassium. Same like Crux, I felt wonderful for a few days, then suddenly felt terrible. After I added in more B2 I felt better again.

I know this is an old thread, but...

Somewhere on the forums I came across this article. It indicates that B2 is a cofactor for MTHFR, and that the C677T mutation causes B2 to bind poorly. Meaning that maybe the extra B2 helped you make more 5-MTHF, allowing you to get out of the--I think this was the "donut hole?"

And since it's been so long, how are you doing with the methylcobalamin and all that? And how much did you take of mB12 and B2?

Thanks!
 

adreno

PR activist
Messages
4,841
Actually, at this point I take only a B complex (Thorne) and 800mcg methylfolate. That's it. I am doing okay, and I don't seem to feel better on the higher doses.
 

aaron_c

Senior Member
Messages
691
@adreno
When you ramped up the B12, what symptoms did extra B2 (and potassium and zinc, if you took them all together) alleviate?
 

brenda

Senior Member
Messages
2,266
Location
UK
Methylb12 gives me worsening insomnia but b2 helps. All b vitamins use up b2. Sorry no time to give evidence. You could look up the l love b2 thread.
 
Messages
65
I think the debate about folic acid is due to it using the same (transportation?) mechanisms that folate does, hence blocking them? I don't recall exactly, but there are definitely studies showing that folic acid supplementation does not help some people with folate deficiency issues: about 10%, if I recall correctly. I think the theory about folic acid interfering with folate, however, is much more hypothetical.

From what I've read, SHMT has only been shown to worsen the effects of problems caused by MTHFR C677T, and that's only when the SHMT is +/+ (AA). Hence it probably has little or no effect on its own. Though I haven't had a complete re-read of the research yet, so it's possible I missed something the first time around.

For what it's worth, I'm SHMT +/- and MTHFR C677T, and my blood profile is:

Folinic acid: 8.3 nmol/l (ref: 1.2-11.7 nmol/l)
5-MTHF: 16.4 nmol/l (ref: 8.4-72.6 nmol/l).

Also, THF: 0.48 nmol/l (ref: 0.6-6.8 nmol/l)

Amy Yasko says: "Based on the research of Dr. Patrick Stover, I’ve concluded that the SHMT mutation often shifts the methylation cycle away from both the long and short routes through the methylation cycle into a side reaction that leads to the production of thymidine ..." Clearly, I'm privileging conversion of 5,10-methylene-THF to pyrimidine/DNA, as shown by my reservoir of folinic acid (my 10-formyl-THF is also high), but showing problems getting back to 5-MTHF. Throw in potential problems with MTHFRS, and you can see that taking folinic acid is unlikely to be helpful. Yet, Amy Yasko recommends supplementing with folinic acid, since this will regulate SHMT activity, and promote methylation. I can only assume this means that taking folinic acid inhibits the portion of SHMT that converts 5,10-methylene-THF to folinic acid through negative feedback, thereby promoting the conversion of 5,10-methylene-THF to 5-MTHF, whilst maintaining levels of folinic acid through supplementation for DNA synthesis. This will, in turn, bring THF up. That would be the system "in balance".

Quite why a mutation in the SHMT gene should maintain conversion of THF to 5,10-methylene-THF but cause "shunting" of 5,10-methylene-THF to folinic acid, I don't know. One argument is that infection can cause high chain ferritin, which increases SHMT activity and pyrimidine synthesis. Taking apolactoferrin would presumably help regulate SHMT activity. I wonder how many people who can't tolerate folinic acid, as well as potentially having clues in the relevant MTHFRS gene, have infections that habour iron.
 
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15,786
@Leon - I generally stop reading after "Yasko says...". She's not a source of scientific research, and really has proven herself to be untrustworthy when it comes to her interpretations of research.
 
Messages
65
@Valentijn - I'm not one of her patients, but if you'd care to share, I'd be interested in knowing why in particular the hard line? By the by, I've read about the iron asociation elsewhere.
 
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@Valentijn - I'm not one of her patients, but if you'd care to share, I'd be interested in knowing why in particular the hard line?
Because she can't tell the difference between half a gene being removed from a lab yeast and the effects of a very minor change in a single SNP which doesn't even result in a mutation in the encoded protein.

She either can't understand research, or she's willing to spin it wildly to support the sale of her products.
 
Messages
65
I must admit that you're post about the COMT gene did get me reflecting that the notion of up- and down-regulation is potentially misleading when structural changes might not take place in the gene, aka Yasko and others.
 

boo85

Senior Member
Messages
178
I took B12 for about a year on and off, first it was cobalamin (the most common kind), and then a mixture of B12 injections (hydroxy) and cobalamin, then a mixture of methylB12 tablets and injections. I took B12 for the longest time without taking methylfolate with it. Methylfolate seems to have helped a lot.

My question is...

at this point, would I be too high in B12 that I need to take large doses of methylfolate in order to even it out?

Does the high B12 get kept in storage until it has enough methylfolate so it can be used?

What happens when one takes B12 for a long time without the folate?

Thank you! :):):)
 

dannybex

Senior Member
Messages
3,561
Location
Seattle
I basically felt like shite. I also had angular chelitis at some point.

Fred always lists angular chelitis as one of the main symptoms of folate deficiency, but it's actually more connected to riboflavin def. Your improvement w/riboflavin confirms this, at least in your case.
 

sregan

Senior Member
Messages
703
Location
Southeast
I don't think you need to "even" anything out. If you are feeling good on high B12 then that's good. Adding MFolate if it helps you then maybe add a little more and see if it helps you more. How much are you taking now?

Taking too much might deplete your B12 and potentially get you in a Methyl-Trap position. Also if you are taking Mfolate you might need to start supplementing Potassium if you are taking a lot. Possibly Magnesium also.

According to Wiki the half life is:

Approximately 6 days
(400 days in the liver)

Not sure how much the liver will hold. But B-vitamins are water soluable which means a short half life.