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Pernicious Anaemia Society
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B12/MTHFR

my wife is poorly having all symptoms of B12 deficiency. Unfortunately GP is not helpful, she seems oblivious to this problem, that's very worrying. I provided GP with many papers including stuff produced by pernicious anaemia society, haematology committee, Sally Pachaloc etc also the video by Sally Pacholoc regarding B12 David Carr etc. All this includes many references that blood tests are not reliable and that symptoms are the best guide. Disappointingly GP done a blood test, results were in reference range, GP said there's nothing wrong with her B12, despite confirming he watched the video. So my wife is supplementing with methyicobalamin SI every other day. My wife has serious peripheral neuropathy, no balance, unable to walk, extremely exhausted, energy completely gone, I still have hope even though she has suffered with serious neurological problems for some time.

She has MTHFR mutation C677T plus 4 homozygous and 9 heterozygous mutations. these methylation profile results appear to me she has an inborn with B12 she has difficulties taking B12 up, she looses it to quick, and also can be depleted by ACAT1-02 (this is as I understand)

She is not improving by SI B12 does the above indicate because of the length of time with neuropathy etc, she would need her doses of B12 or is she in need of other vitamins to help absorb B12, any thoughts would be appreciated as my love is so poorly, thankyou.

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Sounds awful. Has your wife had a mri scan suggested and to take all bloods done. I don't understand if levels of B12 are even borderline (you didn't state what they are) Her symptoms are enough to treat? Has she been given anything to help?

I don't understand the results she does have to comment.

There is lots of information on here.

I'm still waiting for B12 injections to help so if she does get them it's not a quick fix but vital to stop further neurological /nerve damage.

See another doctor? Hope she gets some understanding from a medic very soon for the right treatment. Take care

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MTHFR mutations have no bearing at all on absorption of B12. Taking methylcobalamin supplements, in any form, will be of no help at all.

Only one type of MTHFR mutation (homozygous C677T) has been shown to have any possibility of significant effects. If one does suffer from this then the symptoms are those of a folate deficiency. They can be alleviated by taking methylfolate as a supplement. This post explains why... healthunlocked.com/pasoc/po...

Has your wife seen a neurologist? There are a lot of different causes of peripheral neuropathy. Mine started just after my PA diagnosis and it was the neurologists who determined that it’s not because of my PA (the timing was really wrong).

Some people have a bad reaction to methylcobalamin. Hydroxocobalamin or cyanocobalamin are just as good, if not better. onlinelibrary.wiley.com/doi...

I would get to see a neurologist and swap the methylcobalamin for one of the better forms ASAP.

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45hillbilly I would echo fbirder's suggestion to swap the methylcobalamin for another form. I prefer to use hydroxocobalamin.

There are some writers who make a passionate and persuasive case to use methylcobalamin but their ideas are not mainstream and it does not suit everyone.

Genuine genetic B12 conditions are extremely rare but they do occur. Some genetic conditions (I do *not* mean MTHFR problems) respond weakly to additional B12 but it would be unusual to make a diagnosis from genetic tests alone.

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Hi,

Link about "What to do next" if B12 deficiency suspected.

b12deficiency.info/what-to-...

Was your wife tested for PA (Pernicious Anaemia)?

In UK, Intrinsic Factor Antibody (IFA) test is recommended as diagnostic test for PA although it's not always reliable. People can still have PA even if result of IFA test is negative. IFA test can give a false positive if blood is taken close to B12 injection or B12 supplements.

Have you considered joining and talking to PAS?

PAS (Pernicious Anaemia Society)

Based in Wales, UK.

pernicious-anaemia-society....

PAS tel no +44 (0)1656 769717 answerphone

B12 Deficiency Info website

b12deficiency.info/

B12 Deficiency Symptoms

pernicious-anaemia-society....

b12deficiency.info/signs-an...

Risk Factors for PA and B12 Deficiency

pernicious-anaemia-society....

b12deficiency.info/what-are...

b12deficiency.info/who-is-a...

Has she been tested for Coeliac disease?

NICE guidelines Coeliac Disease (2015 version)

nice.org.uk/guidance/ng20/c...

Tested for H Pylori?

patient.info/health/dyspeps...

Exposure to Nitrous Oxide?

Nitrous Oxide

gov.uk/drug-safety-update/n...

Tested for internal parasites eg fish tapeworm?

patient.info/doctor/cestode...

My understanding of current UK B12 guidelines is that if someone is symptomatic for B12 deficiency they should be treated even if B12 is within range.

UK B12 documents

BSH Cobalamin and Folate Guidelines

b-s-h.org.uk/guidelines/gui...

Flowchart from BSH Cobalamin and Folate Guidelines

stichtingb12tekort.nl/weten...

BMJ B12 article

bmj.com/content/349/bmj.g5226

BNF

bnf.nice.org.uk/drug/hydrox...

NICE CKS

cks.nice.org.uk/anaemia-b12...

"results were in reference range"

Have you seen actual results? I learnt not to trust what I was told about results unless I had a copy in my hand.

Has she got results for B12, folate, ferritin or other iron results, full blood count (FBC)?

Blood tests

b12deficiency.info/b12-test...

Macrocytosis

patient.info/doctor/macrocy...

Full Blood Count and Blood Film

labtestsonline.org.uk/tests...

patient.info/doctor/periphe...

Folate Deficiency

patient.info/doctor/folate-...

Iron Studies

labtestsonline.org.uk/tests...

B12 books I found useful

"What You Need to Know About Pernicious Anaemia and B12 Deficiency" by Martyn Hooper

Martyn Hooper is the chair of PAS (Pernicious Anaemia Society). Book is up to date with most UK b12 guidelines.

"Living with Pernicious Anaemia and Vitamin B12 Deficiency" by Martyn Hooper

Has several case studies.

"Could it Be B12?: An Epidemic of Misdiagnoses" by Sally Pacholok and JJ. Stuart (USA authors)

Very comprehensive with lots of case studies.

Unhappy with Treatment (UK info)?

Letters to GPs about B12 deficiency

b12deficiency.info/b12-writ...

Point 5 in above link is about being symptomatic for B12 deficiency with an in range B12 result.

CAB NHS Complaints

citizensadvice.org.uk/healt...

HDA patient care trust

UK charity that offers free second opinions on medical diagnoses and medical treatment.

hdapatientcaretrust.com/

More B12 info in pinned posts on this forum.

I am not medically trained.

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There are broadly 3 steps in metabolising B12

a) absorbing B12 from your food and getting it into your blood

b) transferring it from your blood to cells

c) using B12 in various processes in your cells.

PA is a condition that affects the efficiency of step a)

The genetic variants known to affect step b) are rare and lead to developmental problems early in life. This doesn't mean that there aren't other variants that can affect step b) but they haven't been identified and how they work isn't understood. It is the case that this step seems to become inefficient in significant numbers of people who have raised serum B12 levels but what exactly is going on is a long way from being understood.

There are genetic variants that affect how B12 is processed in step c) but, as fbirder says, MTHFR is not one of them (though there may be a minor secondary effect as a result of the way it affects the procesing of folate).

As far as I can see ACAT1 mutations don't have a direct impact on B12.

ghr.nlm.nih.gov/gene/ACAT1

ghr.nlm.nih.gov/condition/b... (see comments under 'causes' and 'inheritance patterns'

To be effective it would appear that you need 2 copies of variants on this gene and it manifests very early in life as a result of the increased risk of ketoacidosis. B12 is involved in the process that is affected by this gene meaning that ketoacidosis is also a potential symptom of B12 deficiency, but these are separate things that can lead to ketoacidosis. The most common cause of ketoacidosis is badly controlled diabetes.

What exactly were your wife's results? Did she have previous B12 results that showed significantly higher levels? Have her symptoms improved since starting the injections?

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Hi,

One of my doctors told me that I should be taking vit D also as this is required for the b12 to work properly. It’s worth a try.

Hope she feels better soon.

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How wonderful to be so involved with your wife’s care. B12 needs folic acid to convert. If she is self injecting every other day, she needs 5mg of folic acid every day. Folic acidnis best taken about an hour before B12 injections. In addition, a B-complex needs to be administered for 4 months then off for 2 months (repeat). Ferritin levels need to be optimal, too. How is her thyroid? A thorough check needs to be done. Keep us posted! 😊

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Kaoz - 5mg of folic acid is a very high dose. It is the dose that is used to treat a folate deficiency. some of the processes that B12 is used for also need folate to work.

The best source of folate is diet. If you have a B12 absorption problem that can also affect folate and iron and you may need to supplement.

Ferritin is only one measure of iron - and although it is a good general indicator you really need a full iron panel to establish iron deficiency.

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Self injecting B12 every other day depletes folate. I know as I have had a terrible crash. 5mg folic acid along with B-complex to keep all B’s in check was recommended to me. I now feel so much better. I understand that supplementing with one B can skew other B levels.

Full blood count is required, but ferritin is often left out of the panel (as is folate when measuring B12), and is important for absorption.

Here’s to good health and healing...

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No. Injecting B12 every day doesn't increase the need for folate. Just like filling your car's oil reservoir every day means you need to put in more petrol.

Many of us inject B12 frequently. Almost all of us know that huge doses of folate aren't needed, don't take them and suffer no consequences.

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fbirder, thank you for your reply. Personally, I have experienced a folate crash as a result of injecting hydroxocobalamin every alternate day; not fun with symptoms similar to B12 deficiency. Folate is an important co-factor necessary for B12 absorption. Without adequate folate, B12 will not be properly absorbed. Vitamin D needs K2 and magnesium to be properly absorbed. Iron needs Vitamin C, etc. Research shows that overloading in one vitamin or mineral will create an imbalance of others. However, if you feel fine with your protocol, that is great. It is important that the most accurate information based on scientific research is given to people, especially those who are seeking good health. I wish you good health, as well.

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No. Folate plays no part at all in the absorption of B12.

Nor does iron need vitamin C. The absorption of iron is made easier in the presence of vitmain C, but other chelating agents, like citric acid, do the exact same thing. Indeed, haem iron is absorbed much better than any other form of iron as it’s already chelated.

If you have research that shows that overloading with B12 increases the requirement of folate if love to read it (as long as it’s real research, published in a real scientific journal).

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Ok, fbirder, I’ll point you to the research articles that I have found. I ask that you respectfully do the same. A caveat I will add regarding folate is that if you can keep serum folate levels in the upper 3rd of the range, supplementation is not necessary.

Please look at this following research article:

“The influence of serum folate on urinary excretion of Vitamin B12.”

Authors: Eric Van Royen, Pierre Blockx, Fritz Molter

And this article:

“Diagnosis and Treatment of Vitamin B12 Deficiency—An update”

Authors: AM Hvas and E Nexo

In addition, frequently checking iron levels is equally important as B12 supplementation draws on iron due to the increased red blood cell production.

I feel very strongly that the right information must be shared to others in order to heal properly. Through my illness, I have completed an enormous amount of research in order to learn and heal. I look forward to reading the scientific articles you find that state the contrary. The same conditions apply to your articles.

Plus, what is the big deal about taking 5mg of folic acid, anyway? Your body excretes what is unused. It’s the same with B12.

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Your first reference explains how low folate can increase the elimination of B12. It definitely doesn’t even hint that high dose B12 can increase folate demand.

Nor does your second reference.

I have no references to say that high dose B12 doesn’t increase folate requirements. That’s because real scientists don’t publish studies on things that have negative results, specially when those negative results are exactly what would be expected by anybody who understands the underlying biochemistry. Nobody has published proof that drinking three drops of elderflower cordial daily can increase the body’s requirements for molybdenum.

Increased red cell production only happens for the first few weeks after treatment for megaloblastic anaemia starts. After that it is not a reason for checking iron levels. bloodjournal.org/content/bl...

I’m surprised your research hasn’t picked up that megadoses of folate may not be safe. jamanetwork.com/journals/ja...

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Obviously your mind is made up regarding folic acid as a co-factor and I am wasting my time producing research articles to which you do not have any to counter argue with the exception of your opinions. I could elaborate about the unwillingness to to be receptive, but this discussion does raise an excellent point. Our symptoms should lead treatment. My experience of alternate day B12 hydro injections without the folic acid co-factor lead me to feel worse with many B12 deficiency like symptoms reoccurring. Taking 5mg of folic acid daily as I continue to do my alternate day B12 injections has made me feel 100 times better. I also monitor my full iron levels. I am surprised that you did not mention treating symptoms and are focused solely on research.

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I would love if someone could provide evidence that vitamin D requires K2. I keep seeing this but it's always anecdotal.

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Thanks for posting this Curlygal - confirms the sauerkraut I take is , not only good for my gut but also, good for my bones and heart 🤗

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I want to try eating sauerkraut again, but I'm worried as my stomach is very very sensitive at the moment and I'm on a bland diet. Would it be ok do you think?

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I can only speak from my own experience of having a very sensitive digestive system for years, together with migraine with aura (linked with leaky valve/PFO) triggered only yesterday, by realising I inadvertently ate chocolate, cheese and tomato on the same day - doh!

A gluten free diet and eating daily dollops of sauerkraut (Biona organic from health food shop) made an amazing difference in relieving the constant digestive issues and I now have perfect poo 😳😀

I don't know if this helps Curlygal. I suppose you could buy a small jar and try introducing it gradually. A lot of people make their own, which is ideal.

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Vitamin K2 and the Calcium Paradox: How a Little-Known Vitamin Could Save Your Life

Kate Rheaume-Bleue (Author)

amazon.co.uk/Vitamin-K2-Cal...

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Kaoz_83 I am intrigued to know what you mean by "folate crash" and how it is caused.

I haven't heard that phrase before but it sounds as if it may describe what I epxerience when I take toomuch B12 and get worsened symptoms of B12 deficieny.

I appeciate B12's role is to assist in the transfer of methyl groups obtained from folate but where does the crash fit in?

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The “folate crash” I described was a result of doing alternate day B12 injections and regressing significantly with B12 like symptoms. Once I began taking folic acid with my injections, my symptoms improved as did my overall well being. Hope this makes sense! 😊

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Im no expert but I read that high folate gives a false positive on a b12 test. I read that folate binds to the cells in competition with b12 like a key that fits in a lock but doesnt turn.

If the cells are full of folate a blood test thinks that is actually B12.

I also read that since the powers that be recommended pregnant women fill up on folate and baby milk etc is fortified there is potentially an invisible B12 deficiency epidemic

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I’ve never heard of high folate affecting a B12 test. The ones they use currently are extremely specific to the B12 molecule’s shape. And folate has a totally different shape.

Folate doesn’t bind to cells. Nor does B12.

High levels of folate can mask one symptom of a B12 deficiency (macrocytic anaemia). It cannot make somebody deficient.

If you are already B12 deficient, and you take lots of folate, and if your doctor ignores all of the other symptoms of a B12 deficiency, and if your doctor thinks that you can’t be B12 deficient if you don’t have macrocytic anaemia. Only then can the B12 deficiency go undetected. That’s a hell of a lot of ifs. Definitely not enough for an epidemic.

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I wonder what they were saying on the podcast i listened to then. It was more likey Folic acid so I probably got that bit wrong.

From my recollection the speakers were in the cutting edge. I may have mis remembered some details

I shall try to find it again as it was fascinating.

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The basic message was that by topping up Folic acid a generation who are low in B12 were being missed as bloods were coming back within the normal range. People were symptomatic but B12 deficiency was ruled out

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No. That cannot be correct. No amount of folic acid can affect the results of a serum B12 test.

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Well, I'm not actually trying to be right! As I said, it was fascinating. If I manage to track it down again I will share the narritive

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It sounds like it may refer to macrocytosis. If a doctor will only test for B12 deficiency in the presence of macrocytosis then it could be said that folic acid "masks" the deficiency, if the doctor thinks it's impossible to be B12 deficient without it. To be fair, there are plenty of doctors that stupid!

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Yeah that could well be it. Thanks for posting. Ohh yes they could. I can't believe some of the one sided conversations they have had at me lol

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Thank you all for your wonderful comments and time spending writing this, I do love my wife dearly and I always find hope. Because I am caring for my wife full time it is difficult to find time replying to you all, but I really do need all the help and advise I can get it's really important to me I just want my wife to get better, I'm not used to social media I do rely on someone to help me with it as well so apologies if my replies are slow.

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I do so sympathise 45hillbilly, as many of us on the forum have had this problem and it seems utterly inhumane not to treat such serious symptoms when treatment is so cheap and simple. You are doing wonderfully well though to have researched this to support your wife.

You probably already know that B12 symptoms are very subtle and creep up slowly over the years so, by the time neurological symptoms are recognised, it can take some while to see an improvement.

Personally, I find taking a really good multivitamin and mineral supplement has really helped. 'Wellwoman 70'' is one that also contains other B vitamins to work synergistically with B12 and, if iron needed, 'Floradix' or 'Gentle Iron' helps fatigue (although it may take a while to work) - all of these are usually easily available at local supermarket.

Some links that may interest you:

drhyman.com/blog/2011/02/08...

ncbi.nlm.nih.gov/pmc/articl...

Very best wishes to you and your wife for a steady improvement soon.

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