Now here’s a story to ponder – and it’s not an isolated case. A man with Pernicious Anaemia is receiving an injection of B12 every three months (this is the ‘normal’ treatment regimen in the UK). After a month he starts experiencing the symptoms of B12 Deficiency. He gets that strange tiredness, he becomes irritable, he forgets words, his family notice the changes in his personality. He struggles on until the time has come for his injection. So, he makes an appointment to see the practice nurse, arranged to take a morning off work and dutifully turns up at the local health centre where he rolls up his left sleeve to save the nurse’s time.
It’s a Friday. He is summoned into the nurse’s room, take a seat and presents his arm to the nurse. She checks his records and shakes her head.
“You have to have the injection every three months” she says.
“Yes” he replies
“But it’s only 11 weeks and five days”
“But I can’t come on Monday as it’s a bank holiday and you are closed”
“Well you’ll have to come back on Tuesday” says the nurse as she puts the injection back in the fridge.
Think that’s unusual? It’s not, it happens all too frequently. Just like patients who are told that, because their B12 levels are now normal or high (well they would be – after all the injections are supposed to do just that) their injections will now be stopped all together. That happens so often that it is almost normal to get two or three reports every week. And then there’s the case I am dealing with at the moment – a pregnant lady whose injections have been stopped because “you have too much B12 and it will harm the baby”.
Let’s take another scenario – let’s go to the far east. We walk into a shopping centre and are greeted by advertisements for a brand of B12 injection. We go to a supermarket and choose five ampoules of B12 in the form of Methylcobalamin and take them to the checkout. The ampoules are cheap and you hand over a few coins and return home where you take a clean single-use syringe and inject the contents of the ampoule using a small needle – there’s no need to find a vein or a muscle – you just inject the B12 under your skin in the top of your thigh. And then you carry on with your life.
These two situations reveal just how disparate the treatment of Pernicious Anaemia is. And because there is such a variation in how patients’ B12 Deficiency is treated it causes unnecessary suffering (to various degrees), patient frustration and, perhaps more importantly health inequality.
Let’s try to clarify what is going on by looking at what we know and what we don’t know for sure. And I’ll start with what we don’t know.
Firstly we don’t know why some patients need more frequent replacement therapy injections than others. There are doctors who know that some of their patients need more frequent treatment than others because when their additional injections are sanctioned the patient ceases to make frequent return journeys to the doctors practice and go about their daily lives as best they can. Some doctors notice a marked improvement in their patient once treatment is prescribed according to the patient’s needs. However, and this is the tricky bit – the science behind all of this is simply not there. Nobody has fully investigated why some patients need more frequent injections than others. Instead doctors assume that because some patients manage perfectly well on an injection every three months (in the UK that is) then every patient should be able to benefit fully from an injection every twelve weeks and that this is perfectly adequate. Because the science to explain different patient needs is not there they look at the lowest denominator as being the norm rather than the other way around. Instead of taking the twelve weekly regimen as the norm they should, perhaps, think of a monthly injection as the norm and if patients can and do manage perfectly well on a three monthly treatment regime then all is well and good. The problem centres around the fact that there is simply no decent scientific data or evidence that will explain why some patients need more frequent injections than others. And here’s an interesting fact – it is often the case that it is not the patient who notices that he or she is experiencing the original symptoms of PA (irritability, mood swings, tiredness etc) but the family, friends and work colleagues of the patient who begin to notice changes in the behaviour of the patient. And this is especially true when it involves patients who are dependent on others for their care – children and those with special needs.
That isn’t to say that the whole of the medical profession is ignoring this issue. I know of several doctors who hold various hypotheses as to why different patients have different needs. Some believe it is due to molecular imperfections at cell level; or perhaps it is all due to faulty cell receptors; or maybe it’s to do with gut bacteria; or perhaps it’s to do with the way in which the patient turns the artificial B12 into the biologically active form. There are lots of theories, but sadly no hard and reliable research findings that would give a credible explanation of what is going on. And because there is this lack of scientific evidence doctors are left with only two options: either they can prescribe more frequent injections an in so doing fail to practice their art based on scientific knowledge or they make the only other option which is to assume, and it’s a big assume, that the patient is ‘imagining’ their need. I had this last week when a caller to the office told me that her doctor had told her that if he gave her more injections then she would soon return and ask for more; “the more I give you the more you will want them” the patient was told. I get this all the time.
So now let’s look at what we do know. Well, the first startling fact is that when the 1ml of 1mg/ml of Hydroxocobalamin was introduced in the UK as the B12 of choice in 1963 the British National Formulary (BNF which sets out the guidelines for treating all manner of diseases) stated that the injection was to be given every month. In 1974 that was changed to ever two months and, in Thatcher’s Britain, in 1984 it was changed to “every 12 weeks”. And I mention Margaret Thatcher for a very good reason. Every month she used to visit a doctor in Harley Street to receive a vitamin B12 injection – even though she didn’t have Pernicious Anaemia.
We also know that there is great dissatisfaction among patients with Pernicious Anaemia in the UK. Over 2/3 of respondents to the PA Society’s survey stated that they were ‘dissatisfied’ with their current treatment; and you have to remember that a great many of the 1/3 who were happy with their treatment were either being allowed more frequent injections by their doctor or were buying B12 from other sources and treating themselves with or without their doctors approval or knowledge. 10% of respondents to the survey were using Methylcobalamin as their choice of injection even though it isn’t licensed in the UK.
So what about these alternative sources of B12 Injections? Where are patients finding injectable B12 and perhaps more importantly why are they being forced into by-passing their doctors? The answer lies partly with what I have said above – that the science to explain why some patients need more frequent replacement therapy than others is not there and unfortunately the lowest treatment regimen is taken as the norm, and partly in the British Medicines Act of 1968 that states that any medical product that is delivered to the patient parenterally (via an injection) can only be obtained via a doctor;s prescription. That’s why you cannot walk into a pharmacy (or supermarket) in the UK and simply buy injectable B12.
So, patients who have Pernicious Anaemia who live in the UK and who cannot convince their doctor that they would benefit from more frequent replacement therapy injections of B12 either and experience the return of their symptoms before, sometimes long before their prescribed injection either suffer needlessly or obtain injectable B12 from other sources. And some of these sources are very dubious indeed.
I’ll start with the safest sources of injectable B12 – those prescribed by a doctor and dispensed by a pharmacist. And yes it does happen in the UK – there are GPs who are willing to depart from the guidelines for treating Pernicious Anaemia as set out in the BNF and will treat their patient according to his or her individual need. Unfortunately we in the Pernicious Anaemia Society don’t get to hear about these cases very often for a very good reason. Obviously, if a patient is receiving their replacement therapy B12 when they want it they are unlikely to seek help from a patient support group. This is the same reason why we have so few members who manage perfectly well on the three monthly regimen – they have no need for extra support and just go about their daily lives with their condition not affecting them in any way. However, we do get patients who are receiving their injections whenever they want them (usually every four or five weeks) but who contact the society because they are still experiencing their symptoms to some degree. Just why these patients should experience the symptoms of B12 deficiency when they are getting so many injections remains a mystery. I know of at least two doctors who inject themselves twice or three times a day – perhaps the patients on monthly injections need them even more frequently; what is certain is that the evidence to support this is solely anecdotal and lacks any scientific explanation. Prescribing injections to patients more frequently than the guidelines suggest does, unfortunately, have consequences for medical professionals who are investigated by the organisations responsible for overseeing quality and ‘good practice’. And this is why doctors are reluctant to prescribe more frequent injections than mentioned in the BNF.
The next safest option open to patients whose National Health Service doctors refuse to prescribe more frequent injections is to turn to the private sector. Here, the patient can pay for his or her extra B12 which is often offered in different forms, cyanocobalamin, hydroxocobalamin or the increasingly popular methylcobalamin. Some patients report responding better to one or the other various types of cobalamin though why this is so is again unexplained. Interestingly 10% of respondents to the survey used methylcobalamin which is not licensed for use in the UK. And it can be expensive – especially if the compounding pharmacy where it is made opens up its operation to third party quality assurance agencies.
The third option available to UK patients is to buy their injections from pharmacies in mainland Europe. This will usually be in the form of cyanocobalamin. The patient then injects him or herself or gets a family member or friend to inject them. In the best case scenario the person carrying out the injection will have received appropriate instruction, will use established hygiene practices and also use a lockable sharps bin. Unfortunately, best practice is not followed.
And now we get to the more worrying options of by-passing normal medical practice and sourcing B12 from what could be rather risky and potentially dangerous places.
Internet ‘Pharmacies’ have become an increasingly popular source for patients buying additional B12. The interesting point here is that individual suppliers are being championed and recommended by individuals and so in the process some are trusted more than others. The internet has shrunk the world and so it is not surprising that enterprising individuals are capitalising on the fact that many patients cannot get the treatment that they need. This sector continues to grow and now there are elements of price cutting and other promotions as the competition increases. These ‘pharmacies’ do not only supply injections of B12, they also offer various other forms of B12 including sub-lingual drops, lozenges and sprays (the B12 gets into the patient’s bloodstream via a membrane under the tongue), nasal drops, trans-dermal patches and even anal suppositories. The amazing thing about all of this is that nobody has evaluated the efficacy of these alternative treatments. The problem faced by anyone carrying out any evaluation will be how the products efficacy could be measured; they will all raise the patient’s serum B12, but will they make him or her feel better? I won’t go any further into this because it’s an enormous question that involves some highly complex biochemistry. One sub-lingual spray has been evaluated in a laboratory and shown to replenish B12 levels and is becoming increasingly popular as it’s available in high street health food stores.
Intravenous Drips of a ‘cocktail’ of vitamins including B12 are another option for patients who are not benefiting from the normal treatment regimen. This is the increasingly popular choice of ‘celebrities’ and there has been much press coverage of various people from the world of entertainment receiving these bagfuls of vitamins and minerals in various combinations. And I know that this is a popular treatment for more and more of the PA Society’s members. Alarmingly though, they are being offered by people, entrepreneurs, who are not medically qualified or trained. Even some hairdressers and beauty parlours are offering this procedure and these institutions are not subject to any regulations.
All of the above alternative sources of replacement B12 are readily available to anyone with a computer and internet connection and there is now a growing demand for their services. That demand is being enthusiastically met by health food shops and internet providers. It really is time for the whole issue of a ‘one size fits all’ treatment regimen to be thoroughly investigated. The way in which Pernicious Anaemia is currently treated is by far the single biggest cause of complaint by our members. It’s hard to get your head around the fact that in the UK patients with Pernicious Anaemia were better treated in the 1960s than they are now.