Latest PAS proposed Reserch - Pernicious Anaemi...

Pernicious Anaemia Society

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Latest PAS proposed Reserch

Nackapan
Nackapan

Have just read about a factory making 1000mcg oc cynocobalamin in the UK so quality can be assured.

A larger comprehensive study /reserch if funds are got. To ascertain if b12 tablets can be of any use for PA Or b12 absorbtion issues as well as dietary.

In the current climate yes this is needed for guidance for Gps.

I do hope more is found out on injections too . Why we need different frequencies or different sorts or why we need more b12 once b12 once jections started . Also for the medical world to know so many more are self injecting making' their' problem go away by under treatment of infact withdrawing treatment!!

More reserch on PA treatment and symptoms all round .

40 Replies
oldestnewest

Hi,

Link to PAS news item on this matter.

pernicious-anaemia-society....

Does anyone know why cyano- rather than hydroxo- or even methyl- ?

wedgewood
wedgewood in reply to helvella

It’s the cheapest form of cobalamin , and it works well . It’s the most widely used form in the U.S. Hydroxocobalamin is used in U.K because it’s supposed to stay in the system for longer than Cynocobalamin.

helvella
helvella in reply to wedgewood

I have taken cyano-, hydroxo- and methyl- tablets - and find little obvious difference. Nonetheless, thought that any form of testing and trialling might be better using the same form of B12 so that there could be no concern that the chemical form had an effect rather than the delivery method (and guaranteed potency)? And as that is virtually always hydroxo- in the UK, just looks like the obvious choice.

I have no idea how the bulk ingredient costs differ.

pernicious-anaemia-society....

fbirder
fbirder in reply to helvella

My guess. Because cyanocobalamin is already licensed for use in the UK. Therefore it will be easier to get the trial approved as being safe.

Also, because the trials (Dr Hajo Auwerda's colourful description at the PAS conference) that supposedly showed passive oral absorption all used cyanocobalamin. If this trial were to use hydroxocobalamin they would leave an opening for people to say "Well, obviously it's only cyanocobalamin that is absorbed passively".

Gambit62
Gambit62Administrator in reply to helvella

Helvella, if you look at the article it is the manufacturer who has decided on the type - most likely because cyano is the most stable form and hence the cheapest.

I can't remember where I came across it but my understanding is that hydroxo was selected as preferred treatment in the UK because of the risks to patients with leber's from cyanocobalamin. When it was first introduced the frequency of injections was 1 month so not sure about validity of any arguments about it being selected because injections could be done less frequently (which feeds on false logic about an average result being applicable to everyone as some people actually retain injected cyano longer than they retain hydroxo).

The greater stability of cyano may mean that it will present fewer problems with quality control so would seem to be the logical choice if wanting to develop a pharmaceutical grade product.

helvella
helvella in reply to Gambit62

Yes - I realised it was the company that made the decision. :-)

I did not realise anyone retained cyano- longer than hydroxo-!

One of the reasons I have long wondered about the forms of B12 is that hydroxo- can, and does in the smoke inhalation treatment, take some substances out of circulation. Obviously, depending on what substances it acts on, it could have appreciably different effects. Sometimes, as with smoke, positive.

Gambit62
Gambit62Administrator in reply to helvella

cobalamin has a very strong affinity for the cyanide molecule - which is why hydroxocobalamin is used to treat cyanide poisoning. cyanide is used in curing tobacco in very small quantities.

Many years ago there was a member of the forum who found they got on better with cyanocobalamin rather than hydroxocobalamin and suspected that it was to do with the trace amounts of cyanide. Can't say if that is a real thing but that was what they noticed.

Leber's is a particular genetic sensitivity to cyanide that can result in blindness.

I just hope that they do everything possible to ensure that their test subjects have PA. If it were up to me I'd insist that they all - had a definite B12 deficiency; have hypergastrinaemia, tested positive for IF antibodies.

The test for hypergastrinaemia would exclude people with a false positive for the antibody test. False positive will be a small proportion. But anybody with PA will have autoimmune metaplastic gastric atrophy - they will have no Gastric Parietal Cells, therefore they will have low (or no) stomach acid, therefore they will have high levels of gastrin in their blood.

False positive IFAB tests have been reported in people with high blood levels of B12.

Nackapan
Nackapan in reply to fbirder

Sk why arnt people tested for that? Hypergastrinanaemia? No gastric parietal cells. So a negative test result. I thought that test wasnt used to diagnose PA ?

I get your point toy have to have the right people included on the reserch programme. So many have tried tablets to no effect

I wonder how they will get willing people to get ill on this study?? Or will they collect data from all those people with stopped I jections??

fbirder
fbirder in reply to Nackapan

I've no idea why hypergastrinaemia isn't used as a diagnostic tool more often. There are two main causes - low stomach acid (either through gastritis, H. pylori, or PPIs) or a tumour (a gastrinoma - Zollinger-Ellison syndrome). If your gastrin is high then it's a good idea to get your stomach checked.

The study is unlikely to happen before we have wiped out the covid-excuse. Maybe they can recruit just from Gloucestershire?

To be ethical they wouldn't be allowed to withhold injections from subjects once they started showing severe symptoms. And any participant will be allowed to withdraw from the trial at any time.

Litatamon
Litatamon in reply to fbirder

Off topic but how does an gastroscopy reveal pernicious anemia. The lack of parietal cells can be seen, I am guessing.

The procedure can also uncover H pylori? What else? Evidence of celiac, Crohn's disease, a tapeworm?

Obviously I am trying to ascertain that this test covers/crosses out all the possibilities.

Nackapan
Nackapan in reply to Litatamon

I'm trying to find out the same.

I tested negative for parietal cell antibodies.not tested for the intrinsic antybody i cant absorb tablets though in enough quantity anyhow to make any difference.

A blood test shows maybe celiac disease and only if that positive does it go on to an endoscopy.

My daughter had an endoscopy and it revealed nothing. She had megobalastic anaemia and a serum b12 of 6o something and very low ferritin and folate. ???

I'm pretty confused right now.

H pylori can be tested from a faecal sample.

Litatamon
Litatamon in reply to Nackapan

"My daughter had an endoscopy and it revealed nothing. She had megobalastic anaemia and a serum b12 of 6o something and very low ferritin and folate. ???"

Wow, I don't even understand how nothing can be ascertained from the gastroscopy. Or let me rephrase, I am so surprised- didn't even think that outcome was possible!

Just talking out loud Nackapan, not trying to be condescending - smiling.

Nackapan
Nackapan in reply to Litatamon

Well I didnt either. Obviously a good result. Shd was reluctant to havd if but gastro . Persuaded her.

I suppose its ruling out things?? My mum was persuaded to havd one too. Hers was said okay. At 90 she made mevsmile." Well I'm never having that again. " She usually so compliant and doesnt question enough.

fbirder
fbirder in reply to Litatamon

A gastroscopy will show signs of gastritis. It it is restricted to the two top bits of the stomach (the fundus and corpus) then that's a good sign that it's autoimmune. If it's in the lower bit as well, then it's likely to be H. pylori or too many NSAIDS like ibuprofen.

Mine used to be fundus and corpus only. Then it got much worse, but only at the antrum.

They will take biopsy samples. These will spot any H. pylori that are present. It will also shows signs of metaplasia (where the wrong type of cells are drawing where the gastric parietal cells are supposed to be).

My biopsies also showed up a small Neuroendocrine cancer. I've had that for many years and it's just been sitting there doing nothing. Which is exactly what they tend to do. They just give me a gastroscopy every year to keep an eye on them. I've had two this year because the newbie at the local hospital misinterpreted my tumour's biopsy. Luckily the people at Kings got it right.

They also send the camera into the duodenum where they can spot signs of coeliac's (the inside of the small intestine is smooth - it shouldn't be). They don't go any further than the duodenum, so I don't know if they could spot Crohn's or a tapeworm.

PA is the result of Autoimmune Metaplastic Gastric Atrophy. If you have gastritis, metaplasia and antibodies to IF or gastric parietal cells then you almost certainly have PA.

Nackapan
Nackapan in reply to fbirder

Thank you

Litatamon
Litatamon in reply to fbirder

Thank you. Appreciate it.

mountainice
mountainice in reply to fbirder

Is it uncomfortable, I didn't hear about a referral last August to the gastro, now the doctor says get in touch with them again - I did, and they said not enough information from the GP the first time around and she should re-refer me again, but I am scared of having it done.

Nackapan
Nackapan in reply to mountainice

My daughter had sedation and was fine. She only remembers being rold to swallow and well done! . I was in the hospital. Hed the hospital her throat a little sore but she said it was okay again very quickly. With sedation you have to be collected

My mum didnt have sedation . She has had plenty going up to the bowel without sedation . Its best to get these things done.

You said:-

I just hope that they do everything possible to ensure that their test subjects have PA. If it were up to me I'd insist that they all - had a definite B12 deficiency; have hypergastrinaemia, tested positive for IF antibodies.

Oh dear, I do hope you aren’t suggesting that people who are IFAB negative haven’t really got PA; I thought the BCSH guidelines had knocked that one on the head.

But perhaps you are just thinking that the study should be carried out only on those who have unquestionably got PA, and that the ignorant, both in the medical profession and outside it, might secretly think that the IFAB negative don’t really have PA?

Which is actually a critical reason why those with IFAB negative PA need to be included in any study or trial; to see if there is any difference in how they respond to oral treatment from those who are IFAB positive.

I think there won’t be; but a study could establish this, or the contrary, beyond doubt.

So by all means suggest that whether participants are IFAB negative or not should be recorded, and considered as a factor; but please don’t suggest excluding those of us whose PA, as far as we can tell, affects us no less, and no differently, from the PA of IFAB positive people.

Yes it would be a good thing to include those with absorbtion issues without a PA diagnosis. I'm not volunteering though ad tried enough tablets and sublinguals with no effect to sink a ship. Have never had the IFA test. K was tested for parietal antibodies and it was negative. Hence the Go thinking my deficiency dietary. It clearly isnt as always had a b12 rich diet ncluding meat fish diary ect

I'm now Increasing b12 injections contrary to what my Gp was trying to do and I was hoping would work. I.e less injections with oral supplements. Still not had a symptom free day though and a long way to go.

I'm pleased a pharmaceutical b12 tablet being made . I would like more details when known hoe the study wi take place and with whom.

Any research obviously welcome done in the right way and not used against us.

fbirder
fbirder in reply to Nackapan

But perhaps you are just thinking that the study should be carried out only on those who have unquestionably got PA,

That is exactly what I am saying.

Yes, it is true that people who are IFAB negative can have PA (I am one). But people who are IFAB negative can also not have PA. They may have a B12 deficiency that is caused by a diminished ability to absorb B12 using the IF route. As such, they may show absorption of a small part of an oral dose.

But this study's aim is to see if people with PA can absorb an oral dose. So they need to ensure that their subjects definitely do have PA.

If this study show that people with definite PA cannot absorb oral B12, then a second study can be carried out in those with AbNegPA.

It is a rule when doing scientific experiments that you alter one variable at a time. Otherwise your results can be confusing.

I think we alm building our own cases for reasons of b12 absorbtion problems. They used to say dont worry about the cause the treatment is the same. I In jections for life.

Why we need different frequencies or different sorts or why we need more b12 once b12 once injections started .

Could I just address this please - I have read this before more than once that we may need more jabs the more we have. Does anyone else have experience of this? I am injecting every 10 days - just had a letter from the GP to say -they have cut my monthly jabs I have been on for 5 years to 2-monthly. I am now wondering whether to up injections myself to once a week as stomach problems getting worse and worse. Only get one or two days off from the problems of diarrhoea and I can't really go out on the bad days and I feel unwell a lot of the time, wondering if more frequent injections might help, thought I might try.

Nackapan
Nackapan in reply to mountainice

I dont have the answers to why. I think gambits65 wrote about it

I've been on 2 weekly for a year with a few 3 weekly as put on tablets to see if they could be reduced. It failed.

I'm presently injecting every 6th day. I have a prescription for 2 weekly still. Some done at home. Presently 6 weekly IM. by the nurse as wasnt brave enough to switch to all Sc incase disnt have the sane effect on me. They do.

I'm trying as still waiting for a symptom free hours even.

I still cant read a book. Look at a letter without head and eye pain. TV 20mins tried since February. Weary fatigue ++ Ect .would love a clear pain free head.

So striving for a better functioning life. Like we all are.

On the bed now. I think the heat an enemy too though . Have found any extras like heat or worry or tooth pain sets me right back . The DIY I find very difficult. Same with vitamins to take or not to take!! And iron. I have refused all other drugs offered for over a year now . So b12 is doing the work.

A change in diet might help you ?? Hooe the extra b12 injections help you.

Do angry with the letter you recieved. So how else do they intend to treat you?? Write in . It eilm be scanned on your notes. Gps can prescribe higherfrequencies of b12 injections if deemed in the best interest to their patient.

TC

Nackapan
Nackapan in reply to Nackapan

Sorry gambit62

Gambit62
Gambit62Administrator in reply to mountainice

I've not heard of 'need more jabs the more we have'. I would recommend that people go by symptoms rather than measures that we know just aren't giving the full answer such as normal serum B12 levels'. I am not aware that people then start experiencing symptoms returning more and more frequently. More likely that people might notice a different set of symptoms recurring more frequently as symptoms that have the most impact start to improve.

GPs do have a tendency to treat a disease rather than a patient and forget that people can respond quite differently to the same set of circumstances. They would rather blame it on 'addiction' rather than accept that there isn't one-size fits all for treatments (not unique to B12 absorption problems) and the 'need more jabs the more we have' does sound like an addiction argument.

Have you discussed the problems with diarrhoea (loose movements) with your GP. It may be that there is something else going on in the gut?

mountainice
mountainice in reply to Gambit62

Exactly what I said in my letter to the GP - one size does not fit all when she told me over the phone 'they're following guidelines (meaning the practice). They've got to follow medical evidence, it can't be one rule for one and not for others'. I have the whole transcription of that 'phone call saying 'they are probably following NICE guidelines, kind of NICE guidelines'.

There are no new NICE guidelines.

Yes, I have told them many times about my bowel problems and it is getting worse.

Nackapan
Nackapan in reply to mountainice

It can be one rule for one and not another on clinical need!!

But unfortunately clinical skills are being lost. Slaves to a computer system dictating drug targets and time management targets. I worked within this computer system. I'm told by several ex colleagues little has changed.

I naively thought essential medical details could be accessed at a and e. No often on different systems as choices given to opt in or out by different departments ?? No computer has even got my bloodgroup on.

I think Gps are getting bored weary and not able to use their bright brains enough. The computer works out drug cocktail s No time to discuss a patient with a mentor. Mentors retiring early as burnt out.....Then given conflicting opinions guidance from consultants all the more confusing on b12 issues.

One Gp tries to block anything for me whether b12 I jections referrals ect. I've seen him twice . Once for an unsuccessful Epley Manouvre which I had the 'galk' to say it dudnt work coukd he try again . He woukdnt. Aksi dudnt take the ant sick medication he prescribed as wasnt sick??? That was it . I could have lied saying I'd taken the medication. But on that knowledge he refused to refer me to ENT for not taking it.

I was never rude to him but pride was touched ot something. I also think there is an attitude to women of a certain age treated as hypochondriac or a nuisance that question s things. Despite if records looked at havent been to the Gp in years surely thus should be a red flag. Surely should be listened to .

Stress anxiety alm over used. I wad even questioned about domestic abuse. Obviously my sympto s were not physical my G9 said she was learning from me and liked a challenge. I think she bored with me now as still ill. Covid19 has and is devastating.

Also by some bri g used as an excuse to deny or 'review's essential treatments . My husband got referred to a diabetic hospital specialist without him being g told. Thus was from a Go trawling through notes and we had requested a glucogen injection incase of need to save an ambulance (should always have one in date anyway) This triggered a referral as deemed he hadnt been enough times to the Gp. Specialist rang out of the blue. Agreed what a waste of time and it had been assumed his diabetes out if control wanting this prescription????

So are Doctors being told to review everything to cut costs or what. Something going on. Communication save money. Correct treatment without the need goe complaints to desk with saves money.

Teaching to self inject saves money with review date not to reduce injections but review your health ! Do hope the tria and reserch PAS is working hard on brings results that can help us.

. ....

mountainice
mountainice in reply to Nackapan

You're so right. I've told them I've got plenty to do and 7 grandchildren and hobbies, I don't want to always be thinking about health, but no, I get told I have health anxiety.

Nackapan
Nackapan in reply to mountainice

I was told k was having anxiety attacks!! I was anxious at the time as was very I'll with no diagnosis. I now know a symptom of low b12. But not attacks causing the symptoms. I did try and explain. Not listened to.

🤷‍♀️

mountainice
mountainice in reply to Nackapan

i now believe my hospitalisation in a psychiatric ward for 4 months in 95 and 3 months in 96 was B12 related - won't go into the why's and wherefore's but it makes sense to me now.

Nackapan
Nackapan in reply to mountainice

Yes. Hindsight hey. A fes things have fallen onto place for me too I wonder why b12 isnt checked !! It so should be on a routine blood form. !!

mountainice
mountainice in reply to Nackapan

Definitely should be, but then doctors don't understand it, what hope is there? Well, not many do.

During the consultations I have been having with a neurologist recently about frequent injections of B12 she is well aware of there being a ‘large cohort’ as she puts it of patients self injecting frequently for long periods. She maintains there isn’t a mechanism by which this can have the beneficial effects such patients maintain nor are there any ways of measuring it. She considers it to be a placebo effect. Therefore she is not prepared to support such practices. This is the attitude I have found to be disgraceful, to be so blinkered. For those of us who do get benefit from frequent self injection any study which is done has to address this aspect.

Hopefully the leap onto pills away from injections so many have been ordered to by their GP’s through the Covid19 panic should show how useless such a move actually is for absorbent deficient sufferers. For that to have any hope of success though it will need to be counting everyone so ordered and not just the individual practice numbers. Perhaps that is a project for this forum.

It would be a real boon if cyanocobalamin pills would take the place of frequent jabs especially if they cost no more than we presently pay. It does surprise me though than it could even be a novel question.

Cherylclaire
CherylclaireForum Support

What a rigmarole it is getting any sort of diagnosis, and getting it to stick beyond the first couple of consultants. I have reached the end of a long line now, and am no nearer to an answer. There have been objections raised to my frequent self injecting, but no alternatives offered, and quite often this then becomes their main focus, rather than the ongoing long term symptoms presented. Much has already been ruled out so far (not bowel cancer, not coeliac disease) but nothing yet ruled in.

I had B12 deficiency, and later diagnosed with functional B12 deficiency. Despite consultants finding no reason for this, I believe it is why frequent self injection is having gradual positive results for me.

"Flattened mucosal pattern" in duodenum and "patchy gastric metaplasia" were found from gastroscopy, yet intrinsic factor antibody and parietal cell antibody both negative.

Five years after first going to GP, I still have daily symptoms- although many improvements which can only be due to frequent injections.

Low folate and ferritin took a couple of years to stabilise.

Raised MMA took at least 3 years to bring into range.

Don't know about improvements to vitamin D and osteoporosis of the spine, as I haven't heard from Dexascan: should imagine there's a large waiting list.

So many people left in limbo like this.

As Midnight_Voice pointed out, those not included in trials are unlikely to be included in subsequent treatments. I am very glad that the Pernicious Anaemia Society are involved as issues such as this can at least be discussed as valid proposals for inclusion.

Is the previous PAS research regarding why some people need more injections than others still ongoing ? Let's hope so. The results of the trials seemed so promising.

Thinking that your three generations should be seeing the consultants together as a group, Nackapan !

Ha . Yes They would have their work cut out. I've asked and told them.

They have said my mum its because of her age. Her virtigo headaches no connection. Her IBS no connection. She had had endidcopys looking for bowel cancer. Clear. Better diary free.

My daughter no connection as different set of medical issues b12 being one???B12 deficuency was the cause of her set of medical issues. It was missed it got to the stage if severe megobalastic anaemia severe folate and vit and ferritin deficiency. It caused POTs .

Misdiagnosed as fibromyalgia for years.

My sister because shes a vegetarian but was fine for 35 years. ??Fortunately nipped on the bus with b12 oral supplements from the age of 60. (Result of menopause ..well known risk factor of low stomach acid and less a absorbtion??) Least symptoms and now fine.

Like you say no alternative treatment or explanation offered. Last neurologist who has b12 deficiency was surprised he couldnt conform to 3 monthly b12 injections. He manages on 6 weekly. He condoned my 2 weekly injections at the time and wrote to my Gp. He thinks the delay in my diagnosis caused damage?? He offered propranolol I didnf take.

He also said hed taken an interst. Astounded so little sound reserch. The oral b12 reserch inadequate tk date.

Woukd also be interested ic that reserch into different frequency of b12 injections needed is continuing. Also why higher levels of b12 needed in your blood once on injections which the Gps seem to forget or dont k ow when testing and using numbers

That sounds promising. Thank you for sharing. It would be good to be able to access what we need in the UK.

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