B12 deficiency but negative IF and PC antibody tests?

[MarvelousWays]

Hi All

I'll try and keep this brief!

Last year I experienced a severe dperessive episode. This has been treated with antidepressants and generally is much improved. However, since then I also delveloped a whole host of other symptoms and have honestly felt more unwell than I have ever done in my life, honestly some days Ive felt as if Im dying - and I know this sounds V dramatic! (I'm 51 and was previously fit and well with no other health conditions)my symptoms included:

Exhaustion/fatigue really, really severe

Muscle weakness and random twitching

always cold, especially feet to the point of them being painful

dizziness, really badly

breathless on minimal exertion eg going upstaris (used to run half marathons!)

horrendous brain fog

nausea

reduced apetite

clumsiness eg walking into wall, tripping off the kerb etc

hair falling out

fast heart rate & palpitations

In Feb my GP finally did some boods and for the first time ever included ferritin, folate and B12.

My ferritin was 9, folate 4.5 and B12 was 263. I also had a rasied MCV at 99.8 (although not anaemic as HB level was fine)

Initially GP signed all off as "normal, no further action" ! I managed to argue the ferritin and get some ferrous sulphate tablets. I did lots of further research and ended up having a private consulation with Dr Klein - he said I was obviously severely iron deficient - which would be contibuting to my symptoms, but given my symptoms he also strongly suspected B12 deficiency and recomended an iron infusion and starting B12 injections. I went down to Cambridge for the infusion and started injections 1 week ago. All good so far (apart from being totally let down by the NHS but that's for another day!)

Meanwhile I had sent off a medichecks MMA blood test (although Dr Klein was happy to treat without, I just wanted to know what it was!) and it has come back raised at 48.

In the meantime I had somehow managed to pursaude my GP to do Intrinsic factor and parietal cell antoibody tests - and here's where Im confused - both have come back negative. Does this mean that the cause of B12 deficiency is defintiely not atrophic gastiritis? So this isn't PA? I know IF test isnt reliable and can be negative, but can a negative PC test conclusively rule this out? Is there any point ever redoing that test? WHat other possible causes should I be considering?

In terms of treatement I know it doesnt much matter, I am now SI and have all the stuff to carry on doing so , but would like if I can to understand a bit more about why this has happened. (I'm not vegetarian and eat a good balanced diet)I have been so unwell and have got absolutely no where with my GPs so have bascially been figuring this all out on my own!

Thanks for your thoughts.

[J972]

I’d say wait and see what effect the injections have. Also, have you had your morning cortisol level checked?

[MarvelousWays in reply to J972]

yes, will see if they help or not.

re cortisol....After going back and forwards to GP since Jan they have actually just finally suggested checking my monring cortisol and Im booked in on tuesday for that. I do now have suspicions about low cortisol as I've also lost a lot of wieght unintentionally.... However, I'm on HRT (patches) and the recomendaiton is to be off all oestrogen containing meds incl HRT for 6 weeks before cortisol tests....except GP didnt tell me that initially, and now is not totally sure whether that applies to transdermal HRT or just oral, so has siad have the test anyway, but it may not be reliable....so basically may need repeating after Ive been off hrt for 6 weeks.....Its never ending 🤣

[J972 in reply to MarvelousWays]

The research about the effects of transdermal oestrogen is lacking but there’s thought to be a causal link, at least anecdotally. So, yes, the result may be unreliable. I’m scheduled to have a synacthen test next month and the paperwork accompanying the appointment was….what’s the word?….pathetic. Zero mention of withholding HRT prior to testing, oral or otherwise. Very poor.

Good luck with the injections, it is such a minefield and there’s a huge amount of overlap between symptoms of different conditions/deficiencies.

[bflare]

I cannot really offer much advice but a lot of what you’ve said is almost identical to what I’ve experienced even down to your B12 / MMA levels and negative Intrinsic factor and parietal cell antibody tests. My GP is useless and has prescribed me 150mcg oral tablets! I’m considering a consultation with Dr Klein. However, I don’t really have any symptoms so it’s making me a bit hesitant to seek further treatment.

[Nackapan in reply to bflare]

Yes I too would be wary if no symptoms.

Having blood tests to monitor or compare alongside a symptom/ wellness diary useful.

[oilbeetle]

My symptoms were less severe than yours but ticked a lot of the same boxes. Also negative on the antibodies. I'm still having tests as GP seems confused. However, B12 injections, iron etc. definately helping. Not perefect at all, but I can work and function. I would keep an open mind on being antibody negative and still being severely b12 deficient. Try and see what helps.

[Caradoc1a]

My B12 was 344 and I had lots of similar symptoms. I'm negative for IFAB and GP says she can't order PCAB tests. Got to be a gastro referral but won't make one. Negative for coeliac and H-Pylori. I SI EOD. The cause may be getting older but could also be AIG, maybe I'll never know.

[Orchard33]

From your ferritin number alone your symptoms are to be expected. I took haem iron in higher doses for six months and 2/3 times a week now as maintenance (20mg). I've now found that I no longer have to SI EOD as my iron level increases and is maintained. I SI'd EOD for 2 years. And now, because I've concluded that my body was kept going by adrenalin for possibly 7 years as B12 and iron declined, I'm now taking an adrenal cortex supplement (bovine) to help my adrenals recover and my body as a whole in its recovery process. I also take the recommended cofactors. I am not medically trained, just a hardened PA sufferer. The only medical attention I receive now is from a private haematologist who has monitored my anaemia/low ferritin for the past year and who supervised a private ferritin infusion last February. At the beginning I had a negative IFAB result but my GP treated me as PA because my B12 was so low at 90. She invoked a two monthly injection regime. Woefully inadequate, of course. Hope this helps.

[Nackapan in reply to Orchard33]

Glad to hear you've made good improvements. How many years in ?

I too started with low b12 106ng/ml( 200-900)

Low folate

Low vitD

Ferritin dropped to 29 which was Low enough for my hair to start falling put out Breathless. And Palpitations.

Nothing else was found to treat on no other medications.

Was given loading doses of b12 Injections .

A brain MRI because of symptoms.

I was then supposed to wait 3 months for next b12 injection.

I lasted 5 weeks taking high dose b12 sublingual sprays that dud nothing.

I managed to get on EOD via G.p and neurologist and was left to decide when to change this routine witb 'encouragement ' to get to 2 monthly .

My aim was monthly. ??no reason other than hopeful that would be enough .

Indoctrinated probably.

5months EOD

Then 2 a week

Then weekly

Then every 10 days

Then 2 weekly

Was on 2 weekly b12 injections for 2 years

My aim changed to whatever frequency kept me as well as possible.

Tricky as was suffering migraines of varying degrees which were much worse day after a B12 injection ???

Then everyone at threatened getting their B12 witb the pandemic .

Mine actually were never stopped despite the threats .

At this stage I bought my own as well though .

6+ years on with many reviews/ challenges I've kept a 2 week NHS b12 prescription.

Mostly injected at home sc.

Two neurologists stated ' to continuev'

1 haematologist.

Advice was no harm with 2 weekly b12 injections.

Never found the cause .

Nothing else found to treat

On no other medications.

Have regular bloods

as Need Low iron supplements ( never before)

Also take vitvD 1-3000i.u) daily with K2

Also take a multivit every other day.

With 200mcg folic acid in it .

Extra vit c in the winter .

And an eye vit complex on days no multivit.

All guess work.

But do get bloods 6 monthly.

Werd 3/4" monthly for yesrs ( NHS )

Took years to get some normality back .

Left with a vestibular disorder and fatigue .

It's management now with a strong will to 'get on '

Hope this helps too MarvelousWays

[Orchard33 in reply to Nackapan]

Diagnosed Christmas 2021. Began EOD late 2022 after 2/3 monthly inevitably proved hugely inadequate. Iron/ferritin realization early 2024 when I hit a recovery ceiling. No action taken by GP except the referral letter. My GP said, your ferritin and iron are within normal levels. I said, I want optimal not minimal. She was silent but wrote the letter.We follow our hunches and listen to our bodies. It's how we adapt to live with this condition and manage it in the best way possible. I'm now slowly coming to terms with the new reality: I have what in any other era would have been a fatal condition. Now it can be managed but my body will never work properly again especially as I age.

[MarvelousWays]

Thanks for all the replies. It is so frustrating the lack of knowledge/help/care available from the NHS. I am 51 and have never needed anything really from my GP before all this. Now I am having to access almost everything I need privately at significant cost. (iron infusion, private consultations, private blood tests, buying own self injection supplies etc) I have even worked for the NHS for nearly 30 years, and I'm sure the stress of my current job has contributed to my body basically starting to fall apart! Still, I am thankful I am now at least on some treatment. I am Hopeful I'll start to feel the benefits soon, fingers crossed.

[Bellabab]

Diabetes type two has similar symptoms so it would help to rule this out with an HbA1 C test of your blood. This gives the average level of glucose in the blood for the last 3 months, I have type 2 and PA. Type 2 flared up last year and I now have it under control with a careful diet.

[MarvelousWays in reply to Bellabab]

My HbA1c has been checked a couple of times and has been well within range, so not that for me. Thanks for the suggestion though.

[Showgem]

I’m pleased you are now being treated as low ferritin is very debilitating. Hopefully the iron and b12 will soon be helping with your energy levels and other symptoms.

Unless I have iron supplementation my ferritin will drop right down to >4 or 5. I have difficulty absorbing iron and sometimes I have iron infusions. I used to have iron injections at my previous GP surgery but they no longer do them here.

Very lightly cooked liver is an excellent source of iron and also b12 if you can eat enough of it.

[Sea-blue]

Hi Marvelous ways. Sorry you're going through this. Well my second IF test came back positive so it can happen . Although advice is not to have one after getting treatment for B12 deficiency. It can skew results . Hope you continue to improve. Most of us on here had to take matters into our own hands because the NHS is woefully uneducated about it.

[Sleepybunny]

Hi,

Welcome to the forum.

I've assumed you're in UK.

"managed to pursaude my GP to do Intrinsic factor and parietal cell antoibody tests - and here's where Im confused - both have come back negative"

About half of people with PA test negative or normal range on IFAb test.

Some people with PA get a negative result in PCAb test (can't remember %).

Parietal cells produce intrinsic factor which is needed for absorption of B12.

Over time, parietal cells are lost from the gut in PA.

A person who's had PA for a long time, might have few or even no parietal cells left therefore little or no intrinsic factor produced and in turn IFAb and PCAb tests might be negative.

Thread about tests for PA and B12 deficiency

(Mentions other tests besides IFAb and PCAb)

healthunlocked.com/pasoc/po...

There are many other potential causes of B12 deficiency besides PA.

Here's a few

diet, coeliac disease, other gut conditions eg crohn's disease, some drugs/medicines eg metformin a diabetes drug, PPI drugs etc, excess alcohol, damage to terminal ileum (part of gut where B12 is absorbed), internal parasites eg fish tapeworm.

See websites below for more causes/risk factors.

PAS (Pernicious Anaemia Society)

Have you considered joining PAS?

pernicious-anaemia-society....

PAS membership is separate to membership of this forum. You do not need a PA diagnosis to join PAS.

PAS website has useful leaflets, a list of PAS support groups, a page for health professionals, webinars on aspects of PA/B12 deficiency and lots of other useful info.

Other UK B12 websites

B12info.com

b12info.com/

Run by a UK campaigner on B12 deficiency issues.

Lots of useful info and interesting blog.

The B12 Society

theb12society.com/

Has useful lists of symptoms and causes.

B12d.org

b12d.org/event/

Has online talks about B12 deficiency and monthly coffee mornings near Durham.

I can post a lot more info just ask in a reply if you want me to.

[MarvelousWays in reply to Sleepybunny]

Thanks Sleepbunny.

I did actually join the PA society - but had forgotten I did (brain fog!) I have looked at lots of the info on there but will go back and browse more thoroughly.

I had a negative antibody test for coeliac - although I wasnt eating a lot of gluten when test was done so may not be totally reliable. I have limited gluten for a few years as it does tend to give me some GI symptoms. My diet is pretty good and varied - not vegetarian so I dont think it's diet related. They also did a FIT test to check for any lower GI bleeding from eg crohns which was negative. No meds which may be causing it.

I did ask for referral to gastro - GP declined.

In some ways it doesnt really matter as I plan to continue SI and will source my own B12

Im just so tired and worn down dont have the energy to keep fighting with GPs!

[Sleepybunny in reply to MarvelousWays]

I had a negative antibody test for coeliac - although I wasnt eating a lot of gluten when test was done so may not be totally reliable."

Usual test for coeliac tTG IgA may be negative in people who

1) have IgA deficiency.

These people will need a different test.

Did you have a Total IgA test (checks if you have IgA deficiency)?

2) were not eating enough gluten before blood tested.

Coeliac UK have a useful article on diagnosis and an online self assessment.

coeliac.org.uk/information-...

isitcoeliacdisease.org.uk/

Search for this UK document if you have time

"NICE guideline Coeliac disease"

Some forum members report benefits from going gluten free even if coeliac tests are negative.

[MarvelousWays in reply to Sleepybunny]

Thanks, yes I've read all those (even helpfully sent my GP the NICE guidelines!!) The thing is I'm just not sure if I can face eating that amount of gluten for 6 weeks to redo the test. Think Im just maybe going to go strictly GF anyway.And not IgA deficient as that was checked.

[boisland]

MarvelousWays: When both antibody testing for PCA & Intrinsic Factor come back negative it does NOT mean the cause of your B12D is NOT associated to Autoimmune Atrophic Gastritis (AIG) , as some patients may have seronegative AIG. The gold standard for determining AIG is via biopsies performed during an EGD, as clinicians rarely find endoscopic changes. AIG only becomes a clinical disease when pathologists diagnose it in gastric biopsies. Please know you do not have to have AIG to have Atrophic Gastritis (meaning antibodies not responsible for the atrophy). Some other causes of B12D due to malabsorption are Celiac, H- Pylori, Crohns, SIBO, Colitis, ileitis & low stomach acid. There are other reasons for B12D due to malabsorption (medications). It is excellent you want to pursue the cause of your deficiency. See how the B12 injections play out, as of right now you want to have enough B12 to do your everyday activities, repair any damage done and prevent further damage. Best to you.

[MarvelousWays in reply to boisland]

thanks boisland

For now Im just happy Ive got some treatment

I asked GP for referral to gastro for endoscopy but they refused.

I suppose in many ways it doesnt really matter as I plan to keep self injecting and will source my own B12. Just seems the easiet option right now!

[boisland in reply to MarvelousWays]

MarvelousWays - I would agree to self-injecting your own B12 as the treatment for B12D is the "same" regardless of origin. However long term, I would pursue an EGD as low iron is a common condition of PA/B12D as the low stomach acid (caused by AIG/AG) hinders the absorption of iron as well as preventing the release of free cobalamin from animal proteins. You would want to know if indeed you had AIG/AG as if you did you would need your iron levels monitored for life . Please keep up on your folate levels. Best