Pernicious Anaemia Society
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Can I rule out PA now?

Hi

Advice appreciated please. My understanding is taking multivit with b12 in might affect the blood results but would not affect the urine MMA? Is that right? I'm on a slow, expensive mission to resolve amongst other things my chronic fatigue

My B12 serum was norm

My active b12 was high

And

my 24 hour urine

Methylmalonic acid/creatinine 1.0 mg/g crea (range < 3.7 )

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It would help to know what your results for both active and serum B12 were - though looking back through your past posts it looked as if serum B12 was also quite well into range in September - has it now fallen? if so then that would be suggestive of an absorption problem.

How are your Vitamin D levels now.

MMA would seem to rule out B12.

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Hi tiredBFmum.

The blood tests you’ve had can't rule out PA...and if you've been taking B12 supplements (especially high dose ones) then the tests can't rule out B12 deficiency either (since supplements skew B12 levels by raising them and lower MMA levels).

The test for pernicious anaemia is called the IF antibody test. A positive result is 95% accurate so a positive result indicates that PA is present. However, 40%-60% of those with PA test negative for IF antibodies, so you can test negative and still have PA.

Have you had the IF antibody test? Here's some information about the IF and MMA tests:

stichtingb12tekort.nl/weten... (B12 Deficiency and Intrinsic Factor – Can Be Negative and Still Have PA)

stichtingb12tekort.nl/weten... (Methylmalonic Acid – MMA)

However, Pernicious anaemia is not the only one cause of B12 deficiency - there are many others (IBS, Crohn’s disease, Coeliac disease, helibactor infection, certain medications, gastric or interstitial surgery, tapeworm...to name but a few.

B12 deficiency, whether caused by PA or some other cause is quite tricky to diagnose sometimes...especially if B12 supplements have already been taken. There is no gold standard test and all guidelines state that the full,clinical,picture should be considered - this means that your GP should look at symptoms, and not just blood test results.

Here's more information might help, including details of some of the common symptoms of PA / B12 deficency (not an exhaustive list), the BSCH Cobalamin and Folate deficiency treatment guidelines, information about B12 testing, and some of the common mistakes they GP's make:

b12researchgroup.wordpress.... (Serious Caution Note about the use of Oral and Sublingual B12 Supplements)

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

(BNF B12 Deficiency: Hydroxocobalamin Treatment Regimes)

pernicious-anaemia-society.... (PAS Symptom Checklist)

stichtingb12tekort.nl/weten... (BSH B12 Deficiency / PA Diagnostic Flowchart)

onlinelibrary.wiley.com/doi... in Haematology (BSH) Guidelines: Treatment of B12 Deficiency and Folate Disorders)

onlinelibrary.wiley.com/doi... (UKNEQAS B12 Treatment Alert, Neurological Symptoms and Risk of Subacute Combined Degeneration of the Spinal Cord – Immediate Treatment with B12 Injections)

stichtingb12tekort.nl/weten... (Problems with Serum B12 Test)

stichtingb12tekort.nl/weten... (Testing B12 During Treatment)

stichtingb12tekort.nl/weten... (Misconceptions About B12 Deficiency – Good to Know Before Seeing GP)

stichtingb12tekort.nl/weten... (B12 Treatment Safety / Long Term Treatment for neurological symptoms)

bloodjournal.org/content/bl... (Haematologist B12 Treatment Review March 2017 – Includes Advice No Reason to Advise Against Self-Injection/More Frequent B12 Injections)

stichtingb12tekort.nl/weten... (B12 Deficiency and Neuropsychiatric Symptoms)

gov.uk/drug-safety-update/n... (Low B12 - Nitrous Oxide Contraindications)

ncbi.nlm.nih.gov/books/NBK2... (Gastric Autoimmunity: Heliobactor Pylori)

If you read the third and forth pinned posts (to the right of this page or at the bottom if on a phone) there is more information about PA and B12 deficiency...might help in discussions with your GP. Also worth checking out the Pernicious Anaemia Society website if you are still concerned then PA may be an issue.

Incidentally, I note that you've also been posting on the thyroid forum...did you get the thyroid antibody tests suggested? Asking because there are many cross-over symptoms between hypothyroidism (and Hashimoto's) and B12 deficiency, so it would be good to rule out thyroid as a problem.

Indeed, there are many symptoms of B12 deficiency which can also be symptoms of other conditions (i.e. diabetes, autoimmune conditions etc.), so hope,your GP,is working with you to rule,out other potential reasons for your health issues.

Hope you find some answers soon.

Good luck 👍

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Foggyme

Thanks thats a lot to read.

I've skimmed a lot of it but can't see how long I have to stop the multivits for before retesting.

And by the looks of it, I should then do the MMA test because the others can be falsely normal??

Thyroid antibodies fine I think:

THYROGLOBULIN ANTIBODY <10 IU/mL 0.00 -115.00

THYROID PEROXIDASE ANTIBODIES 12.9 IU/mL 0.00 -34.00

Going to the GP is stressful to say the least. She thinks i'm depressed with IBS and hypochrondria. I have at least got a gynae, gastro and endocrinolgist referral in the pipeline but those will take months I expect. 24 week waiting lists.

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Hi tiredBFmum.

It's not so much that the serum B12 and active B12 are falsely normal, it's more the case that you've taken B12 supplements and this may have raised your B12 levels above a previous level which may have indicated a B12 deficiency.

In other words, the supplements may have raised your serum B12 levels so that they are within the normal reference range but not Provided enough B12 to effectively treat a B 12 deficiency (if one previously existed).

Now that you have taken B12 supplements, there's no way of knowing if this was the case, and it will be very difficult to get a GP to consider B12 deficiency as a potential cause for your symptoms (because GP's place to much emphasis on blood tests and not enough on symptoms).

Once B12 supplements have been taken it can take three or even up to six months for B12 levels to drop to pre-supplement levels (applies to serum B12,active B12 and MMA).

Don't think there's much value in doing another MMA test right now, since this may also have been effected by the B12 supplements - the 'normal' result rules out functional B12 deficiency, where the cells don't process B12 properly (the result would still have been high despite taking B12 supplements, if there was a problem with functional B12 deficiency).

Unfortunately, because you've already taken B12 supplements, this really 'clouds' the diagnostic picture where B12 deficiency is concerned. However...

Note that you have been diagnosed with IBS and this is one potential known cause of B12 deficiency - so this should be a red flag to your GP (absorption issues are common in the presence of IBS - this could be a potential cause of your previous ferritin and vitamin D deficiencies - so makes B12 deficiency more likely).

Your GP may not be aware that B12 deficiency can exist where B12 levels appear normal - especially after supplementation has taken place.

Here's what the BMJ says:

Summary of key recommendations

1. The clinical picture is the most important factor in assessing the significance of test results assessing cobalamin status because there is no ‘gold standard’ test to define deficiency.

2. Serum cobalamin currently remains the first-line test, with additional second-line plasma methylmalonic acid to help clarify uncertainties of underlying biochemical/functional deficiencies. Serum holotranscobalamin has the potential as a first-line test, but an indeterminate ‘grey area’ may still exist. Plasma homocysteine may be helpful as a second-line test, but is less specific than methylmalonic acid. The availability of these second-line tests is currently limited.

3. Definitive cut-off points to define clinical and subclinical deficiency states are not possible, given the variety of methodologies used and technical issues, and local reference ranges should be established.

4. In the presence of discordance between the test result and strong clinical features of deficiency, treatment should not be delayed to avoid neurological impairment.

bmj.com/content/349/bmj.g5226

Might be a good idea to print and read through the evidence in the links above, highlight what's relevant to your case, then take to,discuss with your GP again.

Sometimes putting a B12 treatment appeal in writing (including evidence from the above) works well since the evidence becomes part of your medical record so the GP has to read it...and would then be aware of a) treatment according to the guidelines and b) accountability issues.

If you have neurological symptoms point your doctor to the fact that untreated or undertreated B12 deficiency can cause a potential irreversible neurolgical condition called subacute degeneration of the spinal cord - which can occur even if B12 levels are within normal range. Print and show your GP this UKNEQAS Treatment Alert:

onlinelibrary.wiley.com/doi... (UKNEQAS B12 Treatment Alert, Neurological Symptoms and Risk of Subacute Combined Degeneration of the Spinal Cord – Immediate Treatment with B12 Injections)

I’m not suggesting that you have this, it’s just that many GPs have not heard of it and it might sharpen their minds a little.

No idea if B12 deficiency is what's occurring in your case but the only way to rule it out is to try a therapeutic trial of B12 injections (the neurolgical regime if you have neuro symptoms). If it is a B12 issue, then a positive response to injections would indicate this and injections should be continued...though you're probably going to have to work hard to help your GP to see/accept this.

Good luck 👍

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Thanks Foggyme

I have tried to read a lot of that but couldnt see very much on whether I should have the intrinsic antibody test when I have already had some B12 in my multivits? I have never had that test.

The only bit I saw was 'BE AWARE – taking supplements that contain B12 will affect any tests ordered by your doctor to assess your B12 status. You should not take any supplement before having your B12 assessed and/or having the test to find out if you have the Intrinsic Factor Antibody.' on pernicious-anaemia-society....

I presume that is true but I guess I dont understand why the antibody would disappear if consuming some B12?

If it is worthwhile to have it still, would it be this test? medichecks.com/tests/intrin...

I have rung the PA website and the man was very blunt - he said supplements could take 2 years to leave system and the intrinsic antibody test is pointless. I understand it has very low sensitivity but 95% specificity.

I understand that trialling b12 injections is a possibility in an ideal world but in reality the GP is not going to do this without some more evidence eg blood test results.

Interestingly my fatigue, weakness and dizziness has increased after having entonox (gas and air) on Monday for a sigmoidoscopy (results clear but had due to severe IBS pain). I have had to take today off work as I tripped over and feel "all over the place" /foggy brained today. But maybe something else is going on like about to start period or something.

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