MTHFR gene : Does anyone else have... - Pernicious Anaemi...

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MTHFR gene

CW12
CW12
34 Replies

Does anyone else have MTHFR gene mutation? How does it affect your PA treatment? And Diet? Any suggestions for managing PA and MTHFR

34 Replies
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fbirder

Yes. just about everybody has a mutation in the MTHFR gene - b12science.com/B12Science/D...

It shouldn't affect the way that PA is treated. Some places on the Interwebs will try to tell you that anybody with a MTHFR mutation needs to take methylcobalamin. That is wrong - b12science.com/B12Science/D...

Some people with a specific mutation (homozygous for C677T) might find it beneficial to supplement with methylfolate (400 mcg a day) instead of folic acid. Most people will find there is no advantage in paying ten times the price.

The best suggestion comes from the genetic testing company 23andMe - blog.23andme.com/health-tra...

"Based on the existing data, scientists at 23andMe have concluded that people should not interpret their genotypes at the common MTHFR variants as having an effect on their health"

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CW12
CW12
in reply to fbirder

Thank you! I think I have a problem processing folic acid and B6 as both were high.wondering if they are just swirling around in my blood . My b12 was low. I was taking a folic acid supplement at the time it was >20. I stopped taking it. Not sure of the right thing to do.

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fbirder
fbirder
in reply to CW12

Low B12 can cause the symptoms of low folate, despite high blood levels of folate. It's called the folate trap and is explained here - b12science.com/B12Science/D...

The problem results in most of the folate in the body getting trapped as methylfolate. MTHFR mutations cannot affect this at all.

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CW12
CW12
in reply to fbirder

What do you do to resolve this

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fbirder
fbirder
in reply to CW12

Ensure your B12 levels aren't too low.

Your body needs enough B12 to convert methylfolate into other forms of folate (which are important for DNA synthesis). If you don't have enough B12 then all of the folate in your body ends up trapped as useless methylfolate. If you keep supplementing with folate (any sort, including folic acid) then folate levels will rise, but symptoms will still be present.

The way to stop it is to have enough B12 for the body to convert methylfolate to other forms of folate.

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CW12
CW12
in reply to fbirder

Thank you!!

I am 3months into PA treatment. I get injections once a month. Now twice a month starting this month...I asked for the increase. But up until this point they have been a month apart. Neurological symptoms improve but were coming back. My starting level was 230. I am now at 630 with folate >20

What supplements should I take?

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CW12
CW12
in reply to CW12

My multivitamin has folate so was wondering if I should switch to one without folate

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Gambit62
Gambit62Administrator
in reply to CW12

depends on how much 'folate'/folic acid is in the supplement. Does >1000mcg per day can cause problems. If you meant that you were thinking of switching to a methylated folate it may help but it is also more expensive.

I do use a methylfolate supplement as I find this has helped resolve issues with pain in the ankles but that is me and things could be different for you.

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CW12
CW12
in reply to Gambit62

I would gladly pay extra. But was wondering if I should stop folate supplement all together because my level was >20 on my last blood test

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Gambit62
Gambit62Administrator
in reply to CW12

>20 means that the amount in your blood is above the level that can be reliably measured by the test. If you have a B12 absorption problem then its likely that you will also have/develop a folate absoption problem as well.

You could stop the B9 supplementation and see what that does for you but there isn't anything specifically untoward in the blood test level and it may well have changed since the blood test - particularly if you are now receiving B12 injections.

Folate levels are very variable. The thing really is to avoid very high supplementation unless prescribed by a GP. If the supplement is significantly above 400mcg then cut back ... and see if getting folate from your diet is sufficient.

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CW12
CW12
in reply to Gambit62

Thanks so much. Excellent advice!

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Barbaraj
Barbaraj
in reply to CW12

It's fine as long as it isnt in the form of folic acid.

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fbirder
fbirder
in reply to CW12

If your B12 is that high it's very unlikely you will be experiencing the folate trap. It really does need quite low amounts of B12.

I would stick with 400 mcg of folic acid, or methylfolate, a day.

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Barbaraj
Barbaraj
in reply to CW12

If you have a mutation in the MTHFR gene then folic acid is a big no no for you. Because this mutation means there is significantly reduced capacity in the methyltetrahydrate reductase enzyme so the synthetic folic acid will sit on the folate receptors of every cell in your body as it is unable to progress any further due to lack of this enzyme thereby blocking those receptors from up taking even natural folate from fruit & green vegetables etc. Far wiser to take methylfolate

which is immediately biologically available. I have postulated that the increased incidence of tongue tie which is a mid line defect in new borns is due to mothers who have MTHFR taking folic acid in pregnancy rather than methylfolate thereby adversely affecting their methylation cycle.

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fbirder
fbirder
in reply to Barbaraj

.If everybody with a MTHFR mutation were harmed by taking folic acid then 99.9% of people would have problems with folic acid (that's how many people have at least one MTHFR mutation).

Synthetic folic acid will not 'sit on the folate receptors'. Folate transporter proteins respond equally to all forms of folate.

Folic acid will be able to progress further. It will be easily converted to dihydrofolate (by the enzyme dihydrofolate reductase) which will be converted to tetrahydrofolate (also by dihydrofolate reductase) which will be converted to methylenetetrahydrofolate (by the enzyme serine hydroxymethyltransferase) which will be converted to methyltetrahydrofolate by the enzyme MTHFR.

So it should be obvious that, if MTHFR isn't working properly it will be methylenetetrahydrofolate that cannot progress any further and would 'sit on the folate receptors' if such a thing existed.

But even so, there should still be no need for methylfolate because the, even with the worst MTHFR mutation (homozygous for C677T) the MTHFR enzyme still does work. It just doesn't work as efficiently. Luckily, the body has a way to compensate - it just makes more of the MTHFR enzyme. Simples.

Methylfolate isn't the natural form of folate. It is a natural form of folate. Most of the folate in food is tetrahydrofolate.

Folate in food is not 'immediately bioavailable' in fact it is less bioavailable than folic acid. That's because folate in food comes attached to several molecules of glutamic acid. Before the folate can be absorbed these glutamate molecules must be chopped off by pancreatic enzymes. These can be quite inefficient, especially in people with some absorption problems).

You postulation isn't backed up by the evidence - ncbi.nlm.nih.gov/pmc/articl...

"Importantly, folic acid supplementation in women with the TT MTHFR genotype has been shown to increase folate status above that which is considered maximally protective for NTDs (9). Furthermore, women with vitamin B-12 deficiency have diminished ability to metabolize 5-methyltetrahydrofolate, which may make it less effective in preventing NTDs than folic acid. "

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CW12
CW12
in reply to fbirder

Thank you for your interesting response. It gave me a lot to think about. Are you a Dr./scientist? You seem very well informed. There is a lot of information out there about folate receptors. So I can see how people are confused. I also read to stay away from folate supplementation . But not feeling great doing so. Also just had a b12 injection and did not feel great after it... probably because I’m not taking folate. I will start again with a low dose.

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fbirder
fbirder
in reply to CW12

I spent 33.3 years as a biochemist. I've spent almost 4.5 years investigating everything about B12, folate and (because I am homozygous C677T) MTHFR.

Yes, I'd forgotten about transport receptor proteins for folate. They respond to all folates in exactly the same way. folic acid cannot 'sit on them'. Thanks.

People with absorption problems can have difficulty absorbing folate, especially folate in foods. Folic acid has a higher bioavailability, even in people without an absorption problem.

Women of childbearing potential are advised to take 400 mcg of folic acid a day. I can think of no reason why everybody at risk of a folate deficiency (a known absorption problem or a poor diet) shouldn't also follow that advise.

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CW12
CW12
in reply to fbirder

Thank you so much. Clearly you are qualified to give advice! Much appreciated

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Barbaraj
Barbaraj
in reply to fbirder
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Barbaraj
Barbaraj
in reply to fbirder

The statistics you quote of the percentage of people who have either a homozygous or heterozygous mutation in the mthfr gene is wrong! Up to 50% are affected. These people can't 'simply make" more methylenetetrahydrofolate reductase as they have a much reduced capacity to do so.

Folic acid in foods is banned in Scandinavian countries - governments don't implement such laws for no reason.

webmd.com/cancer/news/20091...

breastcancerconqueror.com/t...

Btw - I was trying to be helpful not looking for an argument in cyberspace.

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fbirder
fbirder
in reply to Barbaraj

You are not being helpful posting totally wrong information. You are being the opposite.

Up to 50% have a mutation in MTHFR at one location - rs1801133 - snpedia.com/index.php/Rs180...

Over 50% have a mutation at another location - rs4846049 - snpedia.com/index.php/Rs484...

Over 50% have a mutation at another location - rs1476413 - snpedia.com/index.php/Rs147...

Half of those without the rs1801133 will have a mutation in rs4846049. Half will not. So only 25% will not have a mutation in either location.

But half of those 25% will have a mutation at rs1476413 . So only 12.5% will not have a mutation at any of those three locations.

There are another dozen listed locations where mutations are known

Almost everybody has a MTHFR mutation. Those clickbait websites you are relying on are lying or they are mistaken

Folic acid in foods is not banned in Scandinavian countries - it is voluntary.

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Barbaraj
Barbaraj
in reply to fbirder

Are you referring to the many mthfr genes? I am referring to MTHFR C677T & MTHFR A1298C. I prefer to look at the science & my observation of effects of compromised methylation pathways in those in my reality.

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fbirder
fbirder
in reply to Barbaraj

Yes, C677T and A1298C are two of the possible mutations. But only two. There are many more. At least 14 more according to Promethease. SNPedia lists 83 of them - snpedia.com/index.php?title...

If you were interested in the science then you would look at what real scientists say.

Here's what one of the biggest gene testing companies in the world says about MTHFR - blog.23andme.com/health-tra...

Based on the existing data, scientists at 23andMe have concluded that people should not interpret their genotypes at the common MTHFR variants as having an effect on their health. In order for a connection between a genetic variant and a health condition to be considered real and clinically meaningful, well-run scientific studies need to show convincing and consistent evidence for that association. As statements from multiple scientific and medical organizations indicate,[14] [15] that is currently not the case for the common MTHFR variants.

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Colorado76
Colorado76
in reply to fbirder

Just watched the YouTube video you posted, WOW just fascinating! Thank you for posting.

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Barbaraj
Barbaraj
in reply to fbirder

No they don't - up to 40% do

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fbirder
fbirder
in reply to Barbaraj

Please stop reading garbage websites.

99.9% of people have a MTHFR mutation. Here is the maths - b12science.com/B12Science/D...

If you can find something wrong with that then please tell me. If not....

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Sanders1
Sanders1
in reply to fbirder

@ fbirder...I would like to pick your brain regarding MTHFR C677T and high serum B12...if that's ok? Also could you tell me who runs the website b12science.com? I was trying to find more info on this. My serum levels are >1999 without supplementing. However my naturopath ran a micronutrients panel from spectra cell labs which shows my B12 deficient at 14%. My HoloTC is also high without supplementing. BUT I have all symptoms of deficiency...severe muscle weakness, small fiber neuropathy, severe memory loss and cognition, numbness over my whole body, burning on the tops of my hands etc. When I inject (hydroxy) I get massive fatigue and start to have edema swelling of mid section and legs. I have had a medical professor from UC Davis tell me that my transport receptor could be damaged. I have MTRR, MTR, TCN1, TCN3. I once had a genetic naturopath tell me not to add methyl B12 or methyl folate for 9 mos to 1 year before fixing other mutations due to not having enough glutathione to support B12. Do you know anything about this? Is glutathione needed for B12? I know I need B12 but it makes me feel horrible...could it be trapping?? No one seems to know how to help me and I am desperate as I am declining by the day.

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fbirder
fbirder
in reply to Sanders1

Chuck the naturopath.

What are your MMA and hCys results?

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Sanders1
Sanders1
in reply to fbirder

Yes I've seen 3 naturopaths on this issue and a neurologist and 3 different hematologists. They are all stumped. MMA & homocystein are normal. One time my UIBC was low.

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fbirder
fbirder
in reply to Sanders1

naturopathicdiaries.com/ Confessions of a Naturopath.

If MMA and hCys are both normal then there is no problem with getting B12 into your cells. So nothing wrong with transporter proteins. It also means there's nothing wrong with the other genes you mention. It also means there's nothing wrong with the conversion of B12 into cob(II)alamin - which is what glutathione is important for.

If you were not getting the right type of cobalamin to the right place in the cells, or if were not doing a proper job there, then hCys and/or MMA would be raised.

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Sanders1
Sanders1
in reply to fbirder

sorry fbirder I have to disagree with you on the opinion of naturopath's. They are the only ones that have gotten me this far with my multiple diagnosis. Western Doc's in the USA just wanted to push pills and not get to the root of the problem. One of my tests says that my lymphocytes are extremely deficient in B12 and I have all of the symptoms of a B12 deficiency. I will keep searching but thank you for your time replying to me..I really appreciate it.

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fbirder
fbirder
in reply to Sanders1

Your lymphocytes are 'extremely deficient in B12'!

And you give money to these people!

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Sanders1
Sanders1
in reply to fbirder

I sure do. And I have no regrets. There are some things we just don't know yet. I am going to keep searching.

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Sanders1
Sanders1
in reply to fbirder

Oops sorry I meant my B12 unsaturated binding capacity was low.

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