Help understanding B12 deficiency

[CSMMUM]

Hi, I was hoping you guys could help me answer a question…. I have been taking B12 for a long time and I am just above the threshold for B12 deficiency. I have been advised to ask about Pernicious Anaemia and ask people who know. I have also been suggested to stop taking my B12 for five months to confirm. I just wanted to ask if I could increase my B12 and it eventually looks good in range would there be any need to get a diagnosis/ treatment? Could I manage it with supplements alone? Many thanks

[Gambit62 Administrator]

This forum is actually about a particular B12 absorption problem, an autoimmune gastritis which which attacks the mechanism you use to absorb B12 from your diet. This is the main cause of non dietary B12 deficiency.The body stores B12 in large quantities in the liver and releases these in bile to be reabsorbed into the blood stream in the gut. This store can last for several years.

If you have an absorption problem it is a double whammy because it not only means that you can't absorb B12 from your diet but also that you can't reabsorb any B12 released from your liver.

People vary a lot in how much B12 they need which is why the range for B12 is so large, and the way the 'normal range' is determined means that there will be some people who naturally sit above the top and also below the bottom.

This means that using a serum based B12 test to determine if someone is B12 deficient is quite difficult - particularly if you only have one test result. Examination of clinical symptoms is extremely important in diagnosis as a result but as the symptoms overlap with a number of other conditions - including thyroid conditions - the use of symptoms can also be difficult. Monitoring serum B12 levels over time can be a good way of spotting an absorption problem because you will see the drop in levels as the absorption problem starts to bite.

Being low in range doesn't necessarily mean you are deficient - it could be that that is just your natural point in the range. I know there is quite frequent mention of needing levels at the top of the range on the thyroid panel but this is confusing the situation after diagnosis of a serum B12 absorption problem and once treatment has begun with the situation of someone who doesn't actually have an absorption problem. It is also making a logical error of assuming that what is true of the average person must be true of all individuals. Individuals do vary.

Having a thyroid condition - particularly if it is auto-immune - does increase the chances of also developing PA but, again, that doesn't mean that all people with thyroid conditions will have PA or another B12 absorption problem.

Supplementing with high dose oral can confuse the interpretation of serum B12 levels again as a drop could just be the result of levels returning to normal for the individual, rather than a true indication of an absorption problem. It can take a long time for levels to fall back to the individuals normal point.

High dose oral can be an effective treatment for some people with B12 absorption problems because it relies on a secondary absorption method - passive absorption - which means very small amounts of the dose is absorbed but a very small amount of a very large amount may be enough to meet normal requirements. However, it will be a very slow way of correcting a deficiency.

Sorry - no direct answer to your question but hope that this helps you understand better the limitations and problems of drawing conclusions from serum B12 tests.

[CSMMUM in reply to Gambit62]

Hi Gambit62, that helps a lot thank you. 🙂

[Nackapan]

It does depend on your actual symptoms. An Intrinsic factor antibody test is helpful.

It positive you have PA.

If negative its not ruled out.

It's useful to know your serum b12 .

A baseline for you personally.

Some just need top ups orally with b12 tablets to top up their diet to stay well.

Other with PA or an absorption problem usually rely on b12 Injections .

Go by symptoms .

[CSMMUM in reply to Nackapan]

Hi Hackapan, ok and thanks. Hypothyroidism has similar symptoms, I think I’m fully medicated as far as Hashi’s go so was hoping I could rule this out too. I just ordered Superdrug Intrinsic factor antibody test (cheaper than Medichecks) and see what it comes up with. I also have Polycystic ovarian syndrome another autoimmune issue so fingers crossed it comes back negative.

[Nackapan in reply to CSMMUM]

If it is negative remember it doesn't rule out PA .Good you are getting ift done.

Hoping if negative is negative with what else you have to deal with.

[CSMMUM in reply to Nackapan]

Hi Nackapan,I went through some of my old results and it does look like the numbers are slowly increasing…10/11/21 310 (200-910) 15.49%

23/11/21 77.2 (37.5-188) 26.38%

7/2/22 76 (37.5-150) 34.22%

so very unlikely to be PA, was hoping to find a reason for symptoms but at least I can rule this out. Thanks for all your help.

[Sleepybunny in reply to CSMMUM]

Hi,

If you know the units of measurement, it's helpful to include them as it makes it easier to interpret the results eg ng/L or pmol/L or other units.

10/11/21 310 (200-910)

23/11/21 77.2 (37.5-188)

7/2/22 76 (37.5-150)

Was the result from 10/11/21 for serum (Total) B12

and the other two results for Active B12 (Holotranscobalamin)?

The ranges look very different.

[CSMMUM in reply to Sleepybunny]

Hi Sleepybunny,Great username, describes me down to a tee. Yes the results are for Serum and Active results as below…

10/11/21 310 (200-910) ng/L Serum B12 NHS,

23/11/21 77.2 (37.5-188) pmol/L Active B12 Medichecks,

7/2/22 76 (37.5-150) pmol/L Active B12 Medichecks.

I live in the London and thank you for all the info supplied below, will have a good read. Yes I have symptoms of both Hashimoto’s and B12 deficiency but they can overlap so hard to know if it’s just hypothyroidism that isn’t responding well to medication. It was one of the Thyroid UK members that recommend me to ask this group for advice. Thanks again for the info, I’ll look to see if anything jumps out/ fits. 👍

[Sleepybunny in reply to CSMMUM]

Hi,

I had severe B12 deficiency symptoms including neurological symptoms with most of my serum (total) B12 results well within normal range , most between 300 - 500 ng/L.

From personal experience can be very difficult to get GPs to take the possibility of B12 deficiency seriously if serum B12 is normal range.

[CSMMUM in reply to Sleepybunny]

Hi Sleepybunny, oh ok, did you test positive for IFA test, or was your diagnosis based on symptoms only? I’m beginning to realise it’s not that straightforward to confirm. 😅

[Sleepybunny in reply to CSMMUM]

Hi,

IFA test result was negative and I don't have a confirmed PA diagnosis despite years of typical symptoms and one serum B12 result that was well below range.

I was not referred to a haematologist, which I should have been ... with a below range B12 result and many neurological symptoms.

Have you been referred to any specialists?

If neuro symptoms present and B12 deficiency diagnosed or suspected, I would expect you to be referred to a

1) neurologist

2) a haematologist

If GP won't refer to a haematologist ( referrals cost money) worth asking them to write to a local haematologist asking for advice on treatment.

If gut symptoms present

3) a gastro enterologist

UK link about when to refer patient with B12 deficiency to haematologist and gastro - enterologist

cks.nice.org.uk/topics/anae...

UK link about referrals to neurology services

NICE guidelines neurological referrals

nice.org.uk/guidance/NG127

Try to find out if your CCG (Clinical Commissioning Group)or Health Board had guidelines on when to refer. Search on their website or submit a FOI (Freedom of Information) request to them asking for referral guidelines.

If you think you need a referral, might be worth putting request into brief, polite letter to GP as harder for them to ignore it. GP surgeries are under financial constraints so you may need to make a really good case for a referral.

Try to include evidence that backs up any referral request eg extracts from NICE guidelines, extracts from CCGs or Health Boards guidelines, other UK medical documents, symptoms list etc but keep it short.

One thing I did learn is that there is plenty of ignorance about B12 deficiency among specialist doctors. Make sure you are well prepared for any appointments.

Seeing a specialist is no guarantee of better treatment although I hope you get a good one if you get any referrals.

NHS refused to treat me when my symptoms were at their worst despite me fighting really hard to get treatment and I had to resort to treating myself to avoid permanent dementia and permanent spinal damage, I already had dementia type symptoms and spinal symptoms.

It's still possible to have PA even if IFA and PCA test results are negative.

Coeliac test (tTG IgA ) was negative but I was not referred to a gastro enterologist despite symptoms consistent with coeliac disease which I should have been and I don't think I had other tests that can help to diagnose coeliac disease.

I think it's possible that I have Antibody Negative PA although I suspect that there might be a rarer unknown genetic problem with how B12 is metabolised in my body.

The other suspicion I have is that I may have had lots of temporary causes of B12 deficiency when symptoms were at their worst eg nitrous oxide during operations, dietary intolerances, medicines that affected B12 levels plus other causes which led to nerve damage and the B12 I take now alleviates the symptoms of nerve damage.

What I do know is that my many symptoms start to return within a few days of a b12 injection so I need far more than NHS recommends.

Flowchart below discusses diagnosis of Antibody Negative PA.

stichtingb12tekort.nl/engli...

Testing for PA

pernicious-anaemia-society....

PA tests

Intrinsic Factor Antibody (IFA) test

labtestsonline.org/tests/in...

Parietal Cell Antibody (PCA) test

labtestsonline.org/tests/pa...

PCA is not recommended as a diagnostic test for PA in UK.

It is still possible to have PA with a negative result in IFA or PCA test.

About 50% of people with PA test negative on IFA test.

About 10% of people with PA test negative on PCA test.

Gastrin test

labtestsonline.org.uk/tests...

I came across an article recently that suggested a pepsinogen test could help to diagnose PA.

It's hard to compare a serum (Total ) b12 result with Active B12 results as it's not known what portion of the serum (Total) B12 was active B12.

Do you have any older results for serum B12 that you can compare the result from 10/11/21 with?

10/11/21 310 (200-910) ng/L Serum B12 NHS,

That leaves you with two Active B12 results to compare, which are very similar although the ref range for the two tests is different (37.5 - 188) and (37.5 - 150) pmol/L.

23/11/21 77.2 (37.5-188) pmol/L Active B12 Medichecks,

7/2/22 76 (37.5-150) pmol/L Active B12 Medichecks.

Have you considered having a MMA test and Homocysteine tests which can be helpful in diagnosing B12 deficiency when serum B12 result is normal range?

Links about MMA and Homocysteine

MMA

labtestsonline.org.uk/tests...

Homocysteine

labtestsonline.org.uk/tests...

Article about MMA

stichtingb12tekort.nl/engli...

If you look at the flowchart I linked to in this reply, on the right side of flowchart it suggests that doctors should consider continuing B12 treatment in those who have shown an objective response (meaning symptoms have improved) even if tests such as MMA/Homocysteine/Active B12 are normal range.

If your symptoms are consistent with B12 deficiency but serum B12 is within range, have you considered asking GP for a trial of B12 injections?

Once you start to inject/supplement B12, results of MMA/Homocysteine/Active B12 /serum b12 are likely to be affected.

"I’m beginning to realise it’s not that straightforward to confirm."

You are so right about that.

PAS (Pernicious Anaemia Society) did a survey a few years ago and found that a large proportion waited many years for a diagnosis.... and of course sadly some people never get a diagnosis.

pernicious-anaemia-society....

I suggest you think about joining PAS if you suspect that you have PA.

You do not have to have a confirmed diagnosis of PA to join PAS.

PAS membership

pernicious-anaemia-society....

Is there a family history of PA and B12 deficiency, as this may be useful for your GP/specialist to know.

[CSMMUM in reply to Sleepybunny]

Hi Sleepybunny,

no I haven't been referred to any specialists as I haven't approached GP as I had so many issues with my Thyroid that after a change in GP and the same response/ feedback I just gave up on getting anywhere with them and found Thyroid UK forum. If I hadn't I would still be suffering debilitating symptoms, while they have improved I still don't feel well.

I started taking B Complex over five years ago because I felt tired and have been iron anemic forever. I unfortunately don't have any previous B12 Serum levels to compare to, I just assumed after taking B Complex for so long that the numbers would have risen more. I take Thorne Basic B Complex and plan to add Jarrow Methylcobalamin B12, 1000mcg too.

My symptoms are fatigue (have to have naps during the day just soooo tired all the time), can get breathless on dog walks, have tinnitus, get spinning sensations, brain fog, upper spine and arm pains (under a physio for that), pins and needled/ numbness in fingers. As I seem to be pretty much on top of Hashimoto's so thought I should start looking elsewhere as symptoms are very similar. I'm hoping to rule out PA.

[Sleepybunny in reply to CSMMUM]

The symptoms you describe can be found on the lists of symptoms of B12 deficiency I included in one of my replies. Have a look if you have time.

Tinnitus, spinning sensations, brain fog, spine pain, pins and needles, numbness would all usually be considered as neurological.

Do you have other neuro symptoms?

I suggest you push for a referral to a neurologist.

NHS link below about B vitamins.

nhs.uk/conditions/vitamins-...

I think PA should be on your GPs radar as you already have auto immune conditions diagnosed and having one increases the chances of developing another one. PA is an auto immune condition. Coeliac disease is another auto immune condition that can lead to B12 deficiency.

Do you have any blood relatives with a PA diagnosis or B12 deficiency diagnosis?

PA can run in families.

Some people on this forum do manage their PA or B12 deficiency by using oral supplements but others, including myself, report that oral B12 is ineffective.

The risk of B12 deficiency causing permanent neuro damage including damage to spinal cord is likely to be increased if B12 treatment is denied, delayed or inadequate.

Blog post from Martyn Hooper's blog, mentions SACD, sub acute combined degeneration of the spinal cord.

martynhooper.com/2010/09/21...

"I'm hoping to rule out PA."

It's quite tricky to rule out PA.

If IFA test is negative a patient might have Antibody Negative PA.

See link to PAS article on "Testing for PA".

Does your GP know that you have been supplementing with a B vitamin supplement?

[CSMMUM in reply to Sleepybunny]

Hi Sleepybunny,

Not that I know of but a lot of autoimmune disorders on both sides of family. I also have Polycystic Ovarian Syndrome (which I discovered when I was refused insurance!??), they didn't think to tell me even when I couldn't conceive. I will try my GP but don't hold out much hope, just a bit disillusioned by the medical profession and having to educate them on their own guidelines.

🤪

[Sleepybunny]

Hi,

I've assumed you're in UK.

It's helpful to know which country someone is in as patterns of treatment and type of B12 used can vary between countries.

UK guidelines indicate that people who have the symptoms of B12 deficiency should be treated even if their serum B12 result is within normal range.

Do you have symptoms consistent with B12 deficiency?

There's a lot of info here so you may want to take a week or so to sift through it.

Some links I post may have details that could be upsetting.

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

b12deficiency.info/what-to-...

Have a look at symptoms lists below.

Symptoms of B12 Deficiency

pernicious-anaemia-society....

b12deficiency.info/signs-an...

b12d.org/admin/healthcheck/...

Next link mentions symptoms of B12 deficiency and folate deficiency

cks.nice.org.uk/topics/anae...

Symptoms list (from B12 Institute Netherlands)

b12-institute.nl/en/symptom...

Symptoms of Peripheral Neuropathy (damage to peripheral nerves)

nhs.uk/conditions/periphera...

Peripheral neuropathy can be associated with B12 deficiency and sometimes with folate deficiency.

Neurological Consequences of B12 Deficiency

PAS news item

pernicious-anaemia-society....

PAS article about SACD, sub acute combined degeneration of the spinal cord

pernicious-anaemia-society....

Risk Factors for PA and B12 Deficiency

pernicious-anaemia-society....

b12deficiency.info/what-are...

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

If you suspect PA, I suggest you consider joining and talking to PAS.

PAS (Pernicious Anaemia Society)

Based in Wales, UK.

pernicious-anaemia-society....

There is a helpline number that PAS members can ring.

Testing for PA

pernicious-anaemia-society....

PAS website has lots of useful leaflets/articles about PA and a page for health professionals that your GP may find useful.

pernicious-anaemia-society....

pernicious-anaemia-society....

UK B12 documents

NHS article about B12 deficiency (simply written, lacks detail in my opinion)

nhs.uk/conditions/vitamin-b...

BSH Cobalamin and Folate Guidelines (detailed, aimed at health professionals)

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

Summary of BSH Cobalamin and Folate Guidelines

pernicious-anaemia-society....

Diagnostic flowchart from BSH Cobalamin and Folate Guidelines which mentions Antibody Negative PA.

stichtingb12tekort.nl/engli...

BMJ B12 article

bmj.com/content/349/bmj.g5226

Emphasises need to treat patients who are symptomatic even if their B12 level is within range.

BNF Hydroxocobalamin

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

NICE CKS B12 deficiency and folate deficiency

cks.nice.org.uk/topics/anae...

There are currently new NICE guidelines in development for Pernicious Anaemia and B12 deficiency. These should be published next year.

nice.org.uk/guidance/indeve...

If you click on "project documents" then on "consultation comments and responses" it gives a good insight into current issues around diagnosis and treatment (over 40 pages of info).

Have you been tested for coeliac disease?

Guidelines below suggest anyone with unexplained B12, folate or iron deficiency should be tested for coeliac.

NICE guidelines Coeliac Disease

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

UK local B12 deficiency guidelines

Each CCG (Clinical Commissioning Board/Health Board/NHS hospital trust in UK is likely to have its own local guidelines on treatment/diagnosis of B12 deficiency. Might be worth tracking down the local guidelines for your area of UK and comparing the info in them with BNF, BSH and NICE CKS links.

Some local guidelines have been posted on forum so try a search of forum posts using terms "local guidelines" or try an internet search using "name of CCG/Health Board B12 deficiency guidelines" or submit a FOI (Freedom of Information) request to CCG/Health board asking for access to or a copy of local B12 deficiency guidelines.

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 serum B12 result and it mentions functional B12 deficiency, where there is plenty of b12 in the blood but it's not getting to where it's needed in the cells.

Two useful B12 books

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

Martyn Hooper is the chair of PAS (Pernicious Anaemia Society).

BNF treatment info (UK) is out of date in above book. See BNF hydroxocobalamin link.

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

Very comprehensive with lots of case studies.

Films about PA and B12 deficiency

PAS conferences

pernicious-anaemia-society....

Films about b12 deficiency

b12deficiency.info/films/

B12 article from Mayo Clinic in US

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

Table 1 in above article is about frequent misconceptions about B12 deficiency that health professionals may have.

Links to forum threads where I left detailed replies with lots of B12 deficiency info eg causes and symptoms, more UK B12 documents, B12 books, B12 websites and B12 articles and a few hints on dealing with unhelpful GPs.

Some of the info will be specific to UK.

healthunlocked.com/pasoc/po...

healthunlocked.com/pasoc/po...

healthunlocked.com/pasoc/po...

I am not medically trained

[Sleepybunny]

Hi again,

"I have been taking B12 for a long time "

Sorry...I missed your comment above when I read your post.

What made you start taking B12 supplements in the first place?

Did you have a very low B12 result at some point?

What strength B12 are you taking?

Is it low strength eg 50 mcg (this is sometimes recommended by UK doctors for dietary B12 deficiency) or high strength eg 1000 mcg or stronger?

My understanding is that severe dietary B12 deficiency should be treated with B12 injections.

[CSMMUM in reply to Sleepybunny]

Hi Sleepbunny,

I take Thorne Basic B complex and it has 400mcg of B12 but as said above I am planning on adding Jarrow Methylcobalamin B12, 1000mcg on top.

😊