Pernicious Anaemia or ME - misdiagnosis concerns

[erin]

Very interesting AWNTY, I remember my blood tests and MCV is being always high but no attention payed this. I had severe ulcers in my mouth, specialists gave a spray for this and he was suspecting of Behcet's. But ulcers gone now. Well only few appears every now and then but not massive and not persistent.

 

[arewenearlythereyet]

Very interesting AWNTY, I remember my blood tests and MCV is being always high but no attention payed this. I had severe ulcers in my mouth, specialists gave a spray for this and he was suspecting of Behcet's. But ulcers gone now. Well only few appears every now and then but not massive and not persistent.

Yes I have mouth ulcers most of the time and have done since a teenager (I.e a long time). Since I started tracking these as a symptom recently I've noticed that they go from being nearly completely clear to covering most of my inner cheeks and lips. Since tracking I notice that this tracks in intensity almost exactly with PEM and its associated symptoms of joint and head pain, poor temperature control and partly with cognition (although that's so freaking variable it's difficult to tell). I am sure that this has something to do with folate/B12, although I think this is some sort of deficiency other than PA but with the Pa tests being so unpredictable and the NHS so unhelpful who can tell really.

 

[Alvin]

Yes I have mouth ulcers most of the time and have done since a teenager (I.e a long time). Since I started tracking these as a symptom recently I've noticed that they go from being nearly completely clear to covering most of my inner cheeks and lips. Since tracking I notice that this tracks in intensity almost exactly with PEM and its associated symptoms of joint and head pain, poor temperature control and partly with cognition (although that's so freaking variable it's difficult to tell). I am sure that this has something to do with folate/B12, although I think this is some sort of deficiency other than PA but with the Pa tests being so unpredictable and the NHS so unhelpful who can tell really.

The easy way to tell is to get a bottle of sublingual methylcobalamin, 1000mcg once a day for 6 months will eliminate the problem if it is pernicious anemia. It might keep you awake so take it first thing in the morning (or with breakfast), and most is absorbed in the gut so don't worry about how fast it dissolves under your tongue.
I just chew the tablet and swallow it these days.

 

[arewenearlythereyet]

The easy way to tell is to get a bottle of sublingual methylcobalamin, 1000mcg once a day for 6 months will eliminate the problem if it is pernicious anemia. It might keep you awake so take it first thing in the morning (or with breakfast), and most is absorbed in the gut so don't worry about how fast it dissolves under your tongue.
I just chew the tablet and swallow it these days.

I moved away from the sublinguals a while ago. I currently take 2x2mg ( assuming 80% absorption) of subdermal hydroxy/methyl

Initially I had noticeable effects from a much smaller dose of oral, upped dose to sublingual in 2016 and then transferred to subdermal. It definitely has an effect and the subdermal is less up and down/ slower release than the sublinguals. I've been on this latest dose for over a year now. It's a bit pricey but in the absence of injections it's my best option for convenience and effectiveness ...and the neuropathy is quite severe in hands and feet so I don t want that to get any worse.

I believe the issue partly for me is antagonistic action of the carbamazepine on folate, hence the high dose of folate. It could be I'm ready to drop the b12 down a bit but it's early days on the mouth ulcer monitoring (which is more associated with folate deficiency as oppose to B12) I may play around with the folate b12 balance, but I would like to get my ferritin checked first to see if this has improved.

Of course this is all speculation on my part given a lack of help or interest by my GP.

I guess they only want to prescribe antidepressants, suppositories for piles and dish out antibiotics (I'm not bitter ...much)

 

[Alvin]

I believe the issue partly for me is antagonistic action of the carbamazepine on folate, hence the high dose of folate. It could be I'm ready to drop the b12 down a bit but it's early days on the mouth ulcer monitoring

I know nothing about carbamazepine or its effect on B12/folate so i can't give any advice. That said B12 testing should be orderable by your doc if they will cooperate, though from what i remember to get the actual bound to protein (correct term?) reading you need to stop supplementing for a month or the test reads the supplement level (which is not a bad thing in a way, it would prove its getting into your bloodstream). IIRC you should aim for over 1000 bound to protein result, they accept lower but newer then 1960s research has found higher levels then 300 are necessary.
That said if there is permanent damage from long term low levels then you can't undo all of it and if its not B12 related then the initial improvement is all you can hope for and you need to chase the comorbid cause. Its easy to get stuck on a possible cause because there was some improvement, a trap many fall into. I recall coming across a paper that found K2 was effective at treating to B12 deficiency induced neuropathy As for ulcers i have no information to provide

I guess they only want to prescribe antidepressants, suppositories for piles and dish out antibiotics (I'm not bitter ...much)

I basically agree, finding very good doctors is like winning the lottery, many are good at what they commonly encounter but anything novel is over their heads. There are some great docs out there but finding one is tough if your unlucky and can take a lot of doctor shopping

 

[Seven]

My sister struggles with this, they have her on Iron and b12 shots for live, and she has to be very careful and she does experience extreme fatigue, she does not have PEM, so the difference between us is she rest and is good to go and can exercise (unlike me).

 

[arewenearlythereyet]

I know nothing about carbamazepine or its effect on B12/folate so i can't give any advice. That said B12 testing should be orderable by your doc if they will cooperate, though from what i remember to get the actual bound to protein (correct term?) reading you need to stop supplementing for a month or the test reads the supplement level (which is not a bad thing in a way, it would prove its getting into your bloodstream). IIRC you should aim for over 1000 bound to protein result, they accept lower but newer then 1960s research has found higher levels then 300 are necessary.

I've heard the same regarding therapeutic levels and I think in places like Japan where the lower threshold for serum cobalamin is 500 I would be treated. I think the PA society recommends ditching any serum testing once you start supplementing since even after abstaining for 8 weeks you can still get a false/misleading picture. Homocysteine and MMA tests will be more useful during supplementation apparently but in the UK these are special tests so I may need to pay for these privately.

 

[Alvin]

I've heard the same regarding therapeutic levels and I think in places like Japan where the lower threshold for serum cobalamin is 500 I would be treated. I think the PA society recommends ditching any serum testing once you start supplementing since even after abstaining for 8 weeks you can still get a false/misleading picture. Homocysteine and MMA tests will be more useful during supplementation apparently but in the UK these are special tests so I may need to pay for these privately.

If your concerned about homocysteine add methylfolate 1mg daily to the B12, that should take care of it and be much cheaper then testing.

 

[wastwater]

My friend has both genetic anemia and a diagnosis of ME and had transverse myelitis and hypothyroidism Not otherwise specified that doesn’t need treatment
The transverse myelitis shows there’s probably a fault with immunity but with all that going on I wondered how they were confident in the ME diagnosis or is that a clue the TM

 

[arewenearlythereyet]

If your concerned about homocysteine add methylfolate 1mg daily to the B12, that should take care of it and be much cheaper then testing.

Yes Im already on 1.2mg (3x400mcg) Methylfolate per day. The issue is that the effect is only short lived (3-4 hrs) and some days the total daily dose is enough, other days it clearly isn't. This has changed only recently after being quite stable. The reduced cognitive stuff recently makes me wonder whether a dose change may be needed but I'm reluctant to play about with things after it being stable for so long. I really need to get some ferritin and THS results (free on the NHS) to see if they have improved or worsened just to elliminate these since I started off quite low. Then need to probably redo my OAT. After that I can then start looking at other things. Perhaps I can bring the b12 dose down now after a year of very high? One thing at a time I guess and free stuff first.

 

[large donner]

In my experience the clinical presentation of hypothyroidism is not like ME or PA or vitamin D deficiency. I also suspect that the idea that some patients feel much better on the upper end of the range for B12 is not backed up by any blinded studies.

One of the main problems though is that doctors don't apply any ME criteria when they "diagnose CFS". Neither do they rule out other things and they certainly don't advise follow up in order to get a clearer diagnosis as the illness progresses etc. To most of them if they can get you to say the word fatigue even though you may not have even went there complaining of fatigue they will dump you in the fatigue category.

The problem when assuming x or y presents differently to z so it cant be z is the assumption that the original diagnosis took an accurate account of symptoms, ordered the correct tests and follow up, interpreted the tests correctly and then came up with the right diagnosis.

 

[Alvin]

Yes Im already on 1.2mg (3x400mcg) Methylfolate per day. The issue is that the effect is only short lived (3-4 hrs) and some days the total daily dose is enough, other days it clearly isn't. This has changed only recently after being quite stable. The reduced cognitive stuff recently makes me wonder whether a dose change may be needed but I'm reluctant to play about with things after it being stable for so long. I really need to get some ferritin and THS results (free on the NHS) to see if they have improved or worsened just to elliminate these since I started off quite low. Then need to probably redo my OAT. After that I can then start looking at other things. Perhaps I can bring the b12 dose down now after a year of very high? One thing at a time I guess and free stuff first.

Very strange, to what effect are you referring?
I take B12 and methylfolate because a study had found high homocysteine in the CSF and it lowered it so i tried it and what i found was it fixed my B12 deficiency (i had asked my doctor to check my level which turned out to be low) and it reduced my recently (at the time) worsening headaches. I take 1mg once a day and it works fine with no wearing off, its been about a year so i was thinking of going off the methylfolate when the current bottle runs out to see if the headaches return (i have a feeling they won't), though i plan to keep taking the B12 since i did have an actual deficiency though i might reduce it to once a week

 

[Jonathan Edwards]

One of the main problems though is that doctors don't apply any ME criteria when they "diagnose CFS". Neither do they rule out other things and they certainly don't advise follow up in order to get a clearer diagnosis as the illness progresses etc.

I totally agree that there is likely to be a problem with inadequate investigation of alternative diagnoses and particularly diagnoses that might emerge later and would only come to light on follow up.

What I am not very convinced about is that measuring a B12 level is necessary if the MCV is in the normal range and there are no neurological symptoms. What puzzles me is that those who advocate for more testing point out that the B12 level is actually unreliable and so not diagnostic. So I am not sure how much it helps.

In general in order to make a diagnosis of a problem one needs to have either a reliable indicator on a test or a symptom or sign that is best explained by a test finding (even if not reliable in isolation). One also takes into account indications that the test is not the best explanation, like a normal red cell size.

The problem I see is that if people who present with fatigue and a slightly low B12 level are then given a trial of B12 injections by muddle-headed doctors (of which there are many) then you are pretty stuck with ever making a proper diagnosis and people end up with life long B12 injections for no good reason. In Western countries B12 deficiency is almost always due to pernicious anaemia (or some fairly obvious problem like Crohn's disease) and pernicious anaemia requires a well thought through diagnosis because it is a lifelong problem. If patients with low B12 levels were all referred for specialist haematological assessment then things might work well but my impression is that doctors continue to do what we they did fifty years ago an 'try a bit of B12'. B12 has an excellent placebo effect so nobody knows if B12 deficiency was the cause of the problem or not.

 

[Barry]

B12 has an excellent placebo effect so nobody knows if B12 deficiency was the cause of the problem or not.

This sentence intrigues me. Given that placebo effect is all about perception, why would B12 promote a more potent perceived effect than something else? Is it just that "B12" sounds more convincing? Or is it that the clinical activities that accompany the prescribing of B12 are especially convincing? Or that it achieves some secondary symptom alleviation, and convinces that primary symptoms are also improved? Like I say, I'm intrigued.

 

[Jonathan Edwards]

Given that placebo effect is all about perception, why would B12 promote a more potent perceived effect than something else? Is it just that "B12" sounds more convincing? Or is it that the clinical activities that accompany the prescribing of B12 are especially convincing? Or that it achieves some secondary symptom alleviation, and convinces that primary symptoms are also improved?

I don't think we know exactly why B12 injections have a good placebo effect. However, in the days when B12 was often given pretty much as a deliberate placebo because we did not have much else it was common for people to say they felt better after each injection and not so good just before. This is very unlikely to have been because of a physiological effect of the B12 since the standard regimen keeps people well above adequately topped up all the time.

But in general injections seem to be good placebos. And once a month may be a good rate to keep up the placebo effect. More often would be a bore. Less often and the effect would wear off maybe. It has been suggested that B12 gives people a 'high' a bit like the way steroids definitely do. However, I don't think there is good evidence for this. Steroid highs are pretty convincing, especially as a few of them go as far as making people actually deranged.

 

[ladycatlover]

Can't say I find any placebo effect from B12 injections. Or at least not thus far! Had loading dose last summer, 6 injections alternate days, plus folic acid pills. Since then have had one more injection, 3 months later, and am almost due another. Still on folic acid too.

Nurse practitioners involved, loading dose in local to caravan walk in centre in Wales, later jab at my GPs surgery. All seemed very disappointed that I didn't feel miraculously better. Perhaps part of the placebo effect is from not wanting to disappoint the med professionals involved? Rather like why PACE etc appeared to work.

So far as I understand I don't have PA but just age related reduction in production of intrinsic factor. Better ask next time I go for jab! I do have macrocytosis, for a number of years now. Prob why they finally decided to check B12 and folate. I gather I have to continue treatment for the rest of my life.

 

[Arnie Pye]

It has been suggested that B12 gives people a 'high' a bit like the way steroids definitely do.

This is similar to the comment made by some doctors to people with hypothyroidism on the subject of T3. When some patients had the opportunity to try T3 they started to feel better. The response of some doctors to this news was "Well, heroin makes people feel better too, but we don't prescribe that either." (Sometimes cocaine is suggested, instead of heroin.)

This causes great hilarity all round, and the patient goes away chuckling at the doctor's great sense of humour.

Well, no that isn't really what happens.

It is far more likely that the patient starts crying because they have been so outrageously patronised, diminished, made fun of, and at having their own experience of living in their own body completely dismissed. The doctor then perks up and says they appear to be depressed, do they want some anti-depressants?

 

[Jonathan Edwards]

This is similar to the comment made by some doctors to people with hypothyroidism on the subject of T3. When some patients had the opportunity to try T3 they started to feel better. The response of some doctors to this news was "Well, heroin makes people feel better too, but we don't prescribe that either."

I think it may be the opposite. The doctors who said B12 made people high were the ones who liked to dish it out like smarties because they thought it was good practice (and business) to make people feel nice, even if they did not have B12 deficiency. You seem to be referring to doctors who refuse to dish out T3.