Falling b12: Hi, I’m. A bit concerned... - Pernicious Anaemi...

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Falling b12

Hsss7 profile image
32 Replies

Hi, I’m. A bit concerned about falling b12 levels as I thought they we had stores that lasted years.

In June 18 I had a raft of tests that showed

b12 at 159, so right on the bottom of the UK “normal” range.

intrinsic factor antibodies test which came back at 2.7 (0-6)

parietal cell antibodies test that just shows n/a online but I was verbally told all tests ok. (I wonder now if it was actually done).

Possibly relevant are

vit d at 55,

ferretin 13 (highest it’s ever been tested (11-?)

Mcv always mid to high 80’s (80-100),

folate at 6

Anyway dr refused to treat b12 levels despite a host of symptoms. I was also diagnosed type 2 diabetic at this time and have had excellent non medicated control since with low prediabetic hb1ac’s each quarter.

I took melt in the mouth methycobalamin for approx two months then and the next raft of tests in September 18 showed

b12 at 818 a month after supplements were stopped.

vit d at 70

ferretin 13 (11-?)

Mcv always mid to high 80’s (80-100),

folate at 13

The latest tests in March 19 show

b12 at 415

vit d at 64

ferretin 7 (11-?) now on ferrous sulphate

Mcv always mid to high 80’s (80-100),

So I guess my question is why is the b12 now half it’s high level (after supplements) in only 6 months? I eat a lot of meat and dairy products so it’s not diet.

The gp I asked said it’s fine (yes I know the level is ok but it’s fallen a lot in only months) he said b12 is water soluble and we don’t store it (pretty sure the liver does just that) just pee out excess. My takeaway from that comment is he thinks the 818 was higher than my body needs and has peed out the extra. Is this right? In which case why did it absorb it in the first place if it was surplus to requirements. And surely in the month between finishing supplements and the 818 test my body would have had sufficient time to ditch any surplus anyway keeping what it could use/store in the liver?

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32 Replies
fbirder profile image
fbirder

The GP’s thinking sounds reasonable.

Taking the supplements would have raised your B12 to above normal levels if you don’t have an absorption problem. They did, so you probably don’t.

When you stop the B12 supplements your levels will drop back down to normal. A level of 425 is pretty close to normal. If another blood test in six months time, with no supplements, would be the key. If it’s still normal then there is no problem. If it’s back down to the mid 100’s then it needs further investigation.

Many of the symptoms of diabetes overlap with those of a B12 deficiency.

The question is want to know is - why were your levels low initially.

Hsss7 profile image
Hsss7 in reply tofbirder

The supplements were via oral mucosa so bypassed the whole gastric absorption issue, but yes it did raise them. How would I know what “my” normal level is though?

And yes I’d like to know why they got so low in the first place and will be watching to see if they head back there. I just didn’t expect such a large drop in such a short time.

I did feel better after supplements but have no way of knowing if it was that or the control of diabetes that is the reason. I was not especially high on diabetic diagnosis. I am now feeling pretty rubbish again but that’s being put down to ferretin as b12 and hb1ac both good currently. Btw hb levels were/are normal at 134 (120-150) and much was/is in range too.

The gp worried me by saying we don’t store it so I guess that made me doubt the rest of his explanation.

fbirder profile image
fbirder in reply toHsss7

You may have sprayed the B12 into your mouth, but almost all of it was swallowed and absorbed in the gut. The B12 molecule is far too big to cross the buccal membrane. And there is a protein (haptocorrin) in saliva that binds to B12, making it even more difficult to absorb.

Yes, we do store B12 in the liver. But it's not a huge amount. So taking supplements means a huge increase in blood levels for a day or two as B12 in the blood gets distributed to tissues (especially the liver) and also gets eliminated in the urine. After that rapid elimination phase the levels slowly drop until the rate that B12 is getting used up is the same as the rate at which it is coming in.

Hsss7 profile image
Hsss7 in reply tofbirder

It was actually held under the tongue and produced little saliva so it did seem to be absorbed via the mucosa, though I am sure some was swallowed too. All the research I did suggested that methycobalamin can be absorbed via the mucosa which is why I chose this type rather than cyancobalamin in case the gut was the problem.

Whatever route it used, it was definitely absorbed as I went from 159 to 818. And that level was a month after I ceased supplements. By then surely the rapid elimination of whatever wasn’t taken into the liver and other tissues would have occurred?

In which case why in the following months has it dropped so much when I eat plenty of sources of b12? Surely if there were no problems with absorbing it via food it would have remained a lot closer to the 818 level I previously appeared to settle at?

Ultimately all i can do is continue to monitor and if the low levels of last year reoccur despite adequate intake then there’s categorically an issue with absorption as it shouldn’t keep dropping. The tricky thing is getting the dr to monitor it when they see no problem.

fbirder profile image
fbirder in reply toHsss7

This research, which papers were those results in. Because every single scientific study I’ve found says that the amount absorbed from a sublingual dose is the same as that absorbed from an oral dose.

The doses you were taking were probably around 100 times that you would get from food.

If you do have a problem with absorption then you should just carry on using the sublingual spray as that obviously is boosting your levels to way above normal.

Hsss7 profile image
Hsss7 in reply tofbirder

I’m not trying to have an argument here. It was almost a year ago. I have no idea which papers they were. It was not google but genuine peer reviewed articles. I could go look for some now but to be frank I’m not inclined to in order to satisfy your doubt. If absorption is the same by both methods in your studies that implies there are no issues in gastric absorption, if there were then the oral route would not achieve the same results the mucosal route does.

Whatever route it absorbed through it got into my blood. Obviously it was much higher/better absorbed than my food. That’s why I took it, because for whatever reason the amounts in my food were not sufficient to prevent my low levels initially or to maintain the high level I did achieve.

Yes I could continue to take the tablets that dissolve in the mouth (not a spray) but that doesn’t identify what my problem is or if it can be addressed any other way than ongoing supplements.

I appreciate your efforts to help but they are critiquing the methods I supplemented by rather than answering my question of why the levels are falling again post supplements.

Hanneke12 profile image
Hanneke12 in reply toHsss7

fbirder I'm sorry I'm very new at this and no expert at all, but I recall reading in this forum that high serum levels don't necessarily mean high tissue levels and that supplementing should be symptom based, not serum level based? Is that correct? And could that be relevant to Hsss7?

fbirder profile image
fbirder in reply toHanneke12

That's true. But to treat the symptoms one needs to get the B12 into the blood first of all. How you get it into the blood is pretty irrelevant. For those with PA, or an equivalent absorption problem, the only way is to inject the B12. But if people can raise their levels by another route - intranasal, sublingual, skin patches, suppositories, or tablets - then they can use that route.

Hanneke12 profile image
Hanneke12 in reply tofbirder

Thank you for the clarity, fbirder!!

fbirder profile image
fbirder in reply toHsss7

I wasn't criticising the route you used to get B12 into your blood. I was explaining how it got there - which is almost certainly from inside the gut, rather than across the buccal membrane. Any means to get the B12 in there is good.

If everybody could absorb B12 via the buccal route then none of us would need to inject. The fact that we do strongly suggests that we can't absorb a sublingual dose.

The fact that all of the peer-reviewed studies comparing sublingual doses with oral doses show they absorb the same amount strongly suggests it's not absorbed via the buccal route.

If B12 easily crossed mucous membranes with no help then we would all be taking B12 suppositories. Because that would keep it in contact with the membrane for hours instead of minutes (and there would be no haptocorrin to restrict absorption). We don't take suppositories because they don't work (despite people having patented them).

If taking the sublingual tablets raised blood levels to above the upper end of the normal range and reduced my symptoms I would be quite happy.

Hsss7 profile image
Hsss7 in reply tofbirder

Like most thing with the human body there is no one way that works for all. Sublingual doesn’t work for everyone but it appears to have worked for me in some way when suitable food alone wasn’t doing the job. So I know how to fix it for me but I want to understand why my diet isn’t enough? And if it’s ongoing or temporary?

Hsss7 profile image
Hsss7 in reply toHsss7

In the lack of a positive intrinsic test do people whose level repeatedly drops without obvious explanation get a diagnosis of PA generally or just treat according to serum b12 and symptoms without a specific diagnosis ?

I eat plenty of sources and don’t recognise myself in any other at risk categories.

Ashweb901 profile image
Ashweb901 in reply toHsss7

I don’t know the answer to your root question but if your ferritin is 11 that can cause you to feel awful and be very tired. Mine was 20 once and my hair was like straw and I was breathless all the time. Even with supplementation of b12 and iron my RBcells are still macrocytic and now my white cells have decided to be chronically just below the bottom of normal. I keep trying to find answers but I don’t have any yet.

Hsss7 profile image
Hsss7 in reply toAshweb901

Mine have never been above 13. I am not anemic though. I understand that this iron deficiency can have the opposite effect on cell size to low b12 hence resulting in a normal mcv

1healthy1 profile image
1healthy1 in reply toHsss7

Am I understanding that you originally had a low B12 level blood test? And a negative intrinsic test result? Your blood tests didn’t indicate another form of low B12, PA - Megaloblastic Anaemia? It’s the form of PA I have though the intrinsic factor was non conclusive. I don’t recall you mentioning it so I’m presuming you don’t have it?

Hsss7 profile image
Hsss7 in reply to1healthy1

Yes low b12 originally and “normal” IFA of 2.7u/ml. Low ferretin but no anemia noted. See my comment above re mcv.

Hsss7 profile image
Hsss7 in reply tofbirder

Could you point me towards studies that show the buccal or sublingual route doesn’t work in anyone please? Does it make any difference which type of b12 or what the subjects cause of deficiency is?

I’m interested to read about it, potential to save some money if I end up agreeing. Your argument that the same amounts are measured via both routes seems to say to me just that they are equally effective under the conditions and with the subjects tested rather than sublingual is actually swallowed and therefore really oral.

fbirder profile image
fbirder in reply toHsss7

Studies showing no difference between oral and sublingual. Note that none of these were in people with diagnosed PA.

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

liebertpub.com/doi/abs/10.1...

pdfs.semanticscholar.org/2f...

Drugs not absorbed are swallowed: ncbi.nlm.nih.gov/pmc/articl...

What makes a good drug for sublingual administration - journalofpharmaceuticalrese...

"In general, a drug

which has been formulated for sublingual should ideally have a molecular weight of less than 500 (as free base) to facilitate its diffusion"

B12 has a molecular weight of 1344 - far too large to cross the membrane.

Hsss7 profile image
Hsss7 in reply tofbirder

Thanks. I’ll do some reading

Hsss7 profile image
Hsss7 in reply tofbirder

The first and second studies I’ve seen. As you say these are non pa people. If they have no absorption problems then I’d expect both routes to be equally effective. It shows no difference between routes in these people, not that sublingual doesn’t work.

The third is about a vegetarian with no absorption issues who is treated with IM injection not either oral or sublingual so irrelevant to the issue of which of those works best or at all.

The fourth is about absorption rates into the mucosa and then into the systemic circulation, particularly with reference to asenapine, an antipychotic drug. It doesn’t say all the drug is swallowed. It says any remaining does not absorbed is swallowed and makes no assertions about quantities or effect. Again fairly irrelevant to the issue at hand and your summary of it somewhat misleading.

The last does indeed use the words “in general” and “ideally” and “facilitate” when talking about molecular weight. These are not absolutes. It does not say larger molecules cannot cross the membrane. It also lists quite a number of other factors that effect diffusion through the mucosa. The source reference 29 this assertion is taken from is missing from the list of references so I can’t make any comment on the source. My question remain can it cross the membrane despite molar weight, perhaps those other factors enable it to do so.

Overall I’ve still seen nothing that tells me sublingual/buccal b12 inherently fails - I’m living proof it doesn’t as are many others. Nor anything that shows it is actually a disguised oral administration.

Perhaps it doesn’t work for everyone (what does?). Perhaps the cause of deficiency matters, or the type of b12 used? Or some other genetic factor in the subject dictates if or how well it works. Pretty sure I’ll stick with what works with me as I’m sure you do with you.

Genuine thanks for the links to some interesting, although unconvincing to me, studies. I’ve still learnt a fair bit.

fbirder profile image
fbirder in reply toHsss7

The only other main factor is the polarity of the compound. It needs to be water soluble to allow it to dissolve in the saliva, but not so water soluble that it will not dissolve in the lipid layer of the membrane. B12 is very water soluble.

Honestly, if it easily crossed over biological membranes then evolution wouldn't have had to come up with some complex mechanism for its absorption. Indeed, we wouldn't need to consume any B12 at all because we would be able to absorb that made by our own gut bacteria. And the company that patented B12 suppositories would have actually been able to market them.

Ashweb901 profile image
Ashweb901 in reply tofbirder

I also understand that metformin can affect b12 levels but if you’re not taking meds for diabetes then that wouldn’t be a factor.

Hsss7 profile image
Hsss7 in reply toAshweb901

I understand the same but do not take any regular medication and never had metformin.

KS69 profile image
KS69

Personally I'd change doctor... at that initial level they should have put you on injections, albeit the level varies in different areas of the UK (mine treat under 190 as deficiency). Have a look at the B12 groups on fb, taking supplements can skew the result of a blood test but not necessarily make the symptoms disappear. If it works for you symptom wise fair enough but if symptoms are not disappearing (regardless of the level going up) then join a B12 group and see how many others are in the same position.

As for the drop, I'm on very regular injections, however at first, following an injection - two months later I was at 1725 and another two months on and it was at 511, I had to argue the case to get my injections more frequently. Mine drops rapidly, I now have injections every 3 weeks, it is the only way I can function. Even so, if I am too active, I am exhausted after 10 days.

Even meat eaters can have low B12, problem gets worse as we age.

I'd also supplement Vit D (you're near the bottom of the range, I had a lot of bone pain around that level) and folate (aim for 3/4 of the range as needed for B12 to work) and your dr should have had you on iron supplements from the first low test (aim for 80 if you can ever get there!).

I'd also ask them to test TSH as often all these issues seem to go hand in hand.

And again, I would change dr.

Hsss7 profile image
Hsss7 in reply toKS69

Thanks. It’s good to have an idea how fast it can drop if diet doesn’t work to maintain levels and supplements are required. 1700? Wow that sounds a lot. And you personally feel awful at 500? Do you know what’s your base to feel ok? The only uk guidelines I found at the time said 160. I pointed that out at my appointment by all forms of treatment were refused, hence I did it myself for two months immediately after. Levels raised, I also resolved my mild diabetes and for a while felt better. Now I feel worse again b12 down to half what it was .

Ferretin has only ever been low. A previous attempt a couple of years ago of ferrous fumerate only raised it from 6-13 in three months with lots of digestive side effects so bad I stopped. A gastroenterologist appointment checked for cealiacs (negative) refused a transfusion due to the risk of serious complications and discharged me back to the gp blaming my heavy periods. A gynaecologist diagnosed previously adenmyosis and said to wait for menopause (I’m 48 and perimenopausal).

TSH and t4 are being monitored (so far) at my insistence following a hemithyroidectomy for a suspicious lump early last year. It’s luckily was just a cyst but I was made aware that what’s left may be fine for years or give up in exhaustion at any time. T4 has fallen from 10’s it was previous to surgery and initially afterward to 8.6 the last 2 tests. (7.7-15.1) so in range but starting to fall. TSH has doubled from prior to surgery 0.6’s to 1.21 last few. But then perhaps half a thyroid has to work double time to put out the same t4 a whole one does.

I’m aware that all these issues of ferretin b12 thyroid folate and d3 are interlinked and I need to adjust all those I can to optimal levels in order to support the rest.

I can’t switch drs. Our practice has one regular dr when there used to be 6. It’s always locums that regularly change. It’s a two week wait. Appointments can only be booked for that one day 2 weeks ahead with whoever is doing clinic that day. No way of knowing when booking which day to call in (phone calls take 45mins + to be answered) to get the one you want even if they are still there. The only other local practice is getting just as full as people have left ours to go there. For me the main reason not to try that one is this one actually gives me testing equipment and strips for my type 2 diabetes that the other (any virtually any other) won’t as I am purely diet controlled . They are expensive without prescription. Prepayment costs me £10 a month. And any other meds included. Otherwise it’d be £60ish just for strips.

Mild t2 diabetes was diagnosed at the same time at low b12 and immediately taken down to low prediabetic slightly above normal levels by going low carb without any medication. No complications. No symptoms beyond the tiredness all these conditions are typified by.

KS69 profile image
KS69 in reply toHsss7

I wouldn't worry about the levels, 1700 is normal for being on injections, in fact it's probably mostly around 2000 now as it is after an injection. I have to go purely by symptoms and not by the level - the sublingual and sprays did absolutely nothing for me for the fatigue and other symptoms. A lot of people self inject if their drs won't give them injections. Or there are clinics you can pay for injections with no questioning. But worth trying to force your dr to treat you first by taking the guidelines in, writing a letter saying you will held them responsible for not giving them etc etc. They need to be accountable for not following the recommended treatment..

I have all those things: B12, thyroid, D, folate and ferritin and it's only getting them all optimal that is improving my symptoms as well as those to support thyroid ie selenium, zinc, magnesium.

The iron tablets I take are ferrous gluconate, they are supposed to be the easier of the prescribed ones to put up with, I don't find them bad and have been taking them for a few years now, up from 9 to 40-50 ish but I wasn't taking them every day. The magnesium tablets I take counteract the constipation. There are some called Ferric Maltol I think they were for IBD patients but I can't comment on them as I never took them in the end as they contained gelatine.. The Solgar one is a supposed gentle one over the counter but again not tried it. You need to find one that works for you and there are a lot of different types to try.

I can understand re the cost why you don't want to change drs but your current dr is not working with you and not helping you with his outdated ideas on B12. Please do join one of the specific B12 groups (there are some good ones on facebook) and they can provide you with the current latest guidelines on treatment for B12d ie injections if under 200 and the thinking is a level of 1000 or above to resolve issues caused by the long term level of under treated B12 and every other day injections if neuro symptoms.

B12 injections were life changing for me, I'd hate to think of someone not getting that due to their dr. If you still have fatigue you are not being treated properly.

Hsss7 profile image
Hsss7 in reply toKS69

Thank you

Ashweb901 profile image
Ashweb901 in reply toHsss7

Your body is keeping your hematocrit up (making you “not anemic”) at a cost to your iron stores, which are very low. Mine was 20, and with supplementation of iron glycinate I was eventually able to get it up to 50 (no gastro effects with glycinate and I have IBS-C with *epic* constipation due to too many feet of large intestine in one tiny person!).

And yes b12, folate, iron, all work hand-in-hand.

Sleepybunny profile image
Sleepybunny

Hi,

Some links about B12 deficiency that may be of interest.

Symptoms of B12 Deficiency

pernicious-anaemia-society....

b12deficiency.info/signs-an...

b12d.org/admin/healthcheck/... (may need to be B12d.org member)

Risk Factors for PA and B12 Deficiency

pernicious-anaemia-society....

b12deficiency.info/what-are...

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

Have you ever been tested for Coeliac disease and H Pylori infection?

NICE guidelines Coeliac Disease (uk document)

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

Coeliac Blood Tests

coeliac.org.uk/coeliac-dise...

H Pylori

patient.info/digestive-heal...

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).

"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. There is also a paediatric version of this book "Could It Be B12? Paediatric Edition: What Every Parent Needs to Know".

PAS (Pernicious Anaemia Society)

Based in Wales, UK.

pernicious-anaemia-society....

PAS tel no +44 (0)1656 769717 answerphone

PAS support groups in UK

pernicious-anaemia-society....

B12 Deficiency Info website

b12deficiency.info/

UK B12 Blogs

Martyn Hooper's blog about PA

martynhooper.com/

B12 Deficiency Info blog

b12deficiency.info/blog/

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...

If you're in UK, I suggest reading following documents.

UK B12 documents

In UK, patients who have the symptoms of B12 deficiency but an in range B12 result are supposed to be treated.

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...

More B12 info in pinned posts on forum.

I am not medically trained.

Hsss7 profile image
Hsss7 in reply toSleepybunny

Thank you. I’ve seen some links but there are quite a number I haven’t so will do more reading. I had an endoscopy about 4 yrs ago which included a negative h pylori test and no sign of any gastric damage or problems other than the possibility of slow motility. (Possibly a low Hcl issue there but it seems there’s no real test for that available). Just over a year ago I was tested for cealiac and it was negative.

I guess I’ve got as far as finding numerous low levels with no obvious explanations for why they occur, those quite possibly there’s some knock on effect occurring. I’m finding the problem is getting a gp to see the whole picture rather than isolated test results. Perhaps I need to get it all together, along with supporting recommendations and papers and write a letter which should be responded to and placed on my file.

Sleepybunny profile image
Sleepybunny in reply toHsss7

" Just over a year ago I was tested for cealiac and it was negative. "

Which tests did you have for Coeliac disease?

In UK, two tests are recommended but UK GPs sometimes only do the first one.

1) tTG IgA

2) Total IgA

If doctors don't do both tests, I think it's difficult to be sure the patient does not have Coeliac disease.

Total IgA test checks who has IgA deficiency (an immunoglobulin). People with IgA deficiency will not be able to make the antibodies to gluten that tTG IgA test looks for, even if they have Coeliac disease so their results on tTG IgA test will be negative. People with IgA deficiency will need different tests for Coeliac disease.

Were you told by your doctor to eat plenty of gluten in more than one meal a day for several weeks before testing for Coeliac?

One reason for a negative result in tTG IgA test is that patient was not eating much gluten before test and therefore not enough antibodies to gluten were in the blood to show a positive result.

Coeliac disease can also present purely with neurological symptoms and no gut issues. Coeliac disease that presents in this way can be much harder to diagnose and may need different tests.

coeliac.org.uk/coeliac-dise...

"and write a letter which should be responded to and placed on my file."

Unhappy with Treatment (UK info)?

Letters to GPs about B12 deficiency

b12deficiency.info/b12-writ...

Point 1 is about under treatment of B12 deficiency with neuro symptoms.

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

Point 5 mentions Functional B12 deficiency where there is plenty of b12 in blood but it's not getting to where it's needed in the cells.

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/

Do you have any neurological symptoms eg tingling, pins and needles, brainfog, memory problems, balance problems, tinnitus, tremors etc?

Neurological Consequences of B12 Deficiency

PAS news item

pernicious-anaemia-society....

PAS article about SACD, sub acute combined degeneration of the spinal cord, access to PAS members only.

pernicious-anaemia-society.... See Page 2 of articles.

Blog post from Martyn Hooper's blog, mentions SACD

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

B12 Awareness (US website)

b12awareness.org/

Stichting B12 Tekort (Dutch website with English articles)

stichtingb12tekort.nl/weten...

Hsss7 profile image
Hsss7

I can’t find my results now re cealic as it’s not in my online records (done by a specialist -gastroenterologist- and the logging of results done by others outside the surgery is shocking). I remember him asking if I ate gluten but in reality I’ve rarely eaten huge amounts of bread, rice, pasta or cereals but didn’t actively avoid them until last year (very low carb since last June)

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