FAQs

You have a short window of opportunity, between diagnosing B12 deficiency, and the damage becoming permanent.

Once you have been diagnosed with B12 deficiency, there is no reason to hold off taking treatment. The only reason to hold off getting treatment is if you’re still waiting for a diagnosis. Once you begin to take additional B12, then it is difficult to do a blood test and get a confirmation of B12 deficiency. Of course, if your doctor has already taken a blood sample for the tests, then you can begin taking B12 straightaway.

B12 is a food substance, and there are no side effects from taking it. If it turns out that you are not B12 deficient, then your doctor will need to give your other treatment. But it won’t have done any harm if you have already started taking B12.

If you want to know about the medical literature that supports this, then please check out BMJ Best Practice. This is the section on the British Medical Journal web site where they summarise all of the research so that a busy doctor can take a subject in.  It’s a subscription only web site and restricted to medical professionals, but you could ask your GP to print off the relevant section to let you read it.

BMJ says

1. Diagnose on the basis of symptoms.  Blood serum level is not a reliable test so include it as one of the symptoms.
2. Start treatment if you have any suspicion of B12 deficiency.  It does no harm and doesn’t interfere with any medical treatment, whereas delaying could cause problems.  Vitamin B12 is likely to improve the patient’s mood so that will help with every dis-ease.
3. Tailor treatment to the needs of the patient.  If they need frequent (alternate days, daily) injections then give them these injections.  minimise symptoms.
4. Injections can be given by a nurse, HCA or by the patient at home, with a bit of training.  Review every 6 months.

Your B12 deficiency probably began sometime before you were diagnosed. The nervous symptoms occur when the myelin sheath has already broken down, whether they show as pains, numbness, memory loss, or depression. It is only a matter of time before the nerves themselves die, after which there isn’t much you can do to put it right.

Some of the other conditions that could be diagnosed, which might be B12 deficiency include (NOTE this web site is prepared by the B12deficiency Patient Support Group so the information may not be accurate, and certainly does not reflect current medical practice or there would be no need for the web site):

QUESTION: Horden in County Durham is a long way away – I’m thinking of starting my own event.

ANSWER: We’d be delighted to help you set up.  We haven’t produced lots of printed material yet, although we do have some – copies of the protocol, a booklet of case studies, we have pens and supermarket trolley coins, and of course teddy bears, to help you spread the word.

RELATED QUESTION: I’d like to start my own web site

ANSWER: This is where it gets more controversial.

There’s a lot of rubbish on the internet about Vitamin B12.  Do you need to take lots of folic acid? Which form of B12 is most effective?  Are lozenges or nasal sprays or skin patches as good as injections?

Dr Chandy has been studying the condition and the effects of different treatments since 1981.  As a GP, he’s followed the same patients throughout, with the original 1981 patient still under his care (34 years on, as at time of writing).  Everyone else working with B12 deficiency has seen patients pass through and not followed them through.  Dr Chandy knows a thing or two about B12 deficiency.

Therefore we’d much rather you didn’t start another B12 deficiency web site, and that you didn’t give medical answers on Facebook or anywhere else.  We believe it would be helpful for people if you provide support, but direct them to the definitive information about B12 deficiency and what to do about it.  

If you want to write about it, then submit your web page by email to notifications@b12d.org and our team of editors will review it for possible inclusion.  Please state the byline you’d like to see (ie how you want your name to show up, and whether you want to link it straight through to your email so people can email you)

QUESTION: I want to hold a fund-raising event or conference for B12 deficiency

We Love this.  We’d love for people to hold coffee mornings, events, and so on.

What we can’t do is jet off all over the country/ world giving talks at events that we haven’t been party to, and we generally don’t.  And similarly to the answer above, please don’t go telling people stuff about B12 that doesn’t have any information to back it up.

So you are worried about injections, or you’ve started them and wonder what’s happening?  Don’t expect miracles – things usually happen in a particular order.

About 1 in 10 people experience side-effects

The most common side effect is blotchiness of the skin or pimples.  We think this is caused by homocysteine – once there is enough B12 in the body to start to get rid of the homocysteine, the body gets rid of it as quickly as possible and some will come out in the skin.

Most people want to put a cream on like E45, however that just traps the homocysteine near the skin.  During this period (no more than 10 days) it’s probably better to wash it off with water, ie a shower or a flannel bath.

You may get palpitations, or phantom pains/ pins and needles, or other effects of the nerves starting to work again (the heart is a big bundle of a special sort of muscle which is also nerve, so when the other nerves start to work, so does the heart and this may cause palpitations).  Any of these effects should be gone within a couple of days so see your doctor if they last any longer.

If the B12 is working, then you should notice improvements in some areas even if you don’t notice the symptom that you most want to cure, improving.  B12 is natural to the human body, so its healing effect is going to be gentle; more like a good sleep (you often wake up tired) than a cup of coffee (artificial stimulant).

Get plenty of rest during the healing process.

When you stop eating B12 in your diet (for example by becoming a vegetarian), you may not notice if it on your B12 level for 10 years or more.

Conversely, when you develop a condition like pernicious anaemia, the effects can be devastating and very fast. We wondered why this was?

B12 stores in the body

The body stores 2-5mg Vitamin B12, of which around 80% is in the liver[1, 2]. B12 in the blood circulates either bound to Transcobalamin I or III, (the inactive forms), or transcobalamin II (active B12, or holotranscobalamin). Active B12 is 7%-20% of total blood B12, but this percentage varies [3-7].

Inactive B12 can’t be converted to active B12, either in the blood, or in the liver.
The Recommended Dietary Allowance/Recommended Dietary Intake (RDA/RDI) of vitamin B12 is around 2.4 µg per day[7], though it should be higher for people older than 51 years old.

Circulation via the liver, bile duct and small intestine

To get the active form, the body takes inactive forms from the liver (and the liver can take it from the blood), and pumps it out into the top of the small intestine through the bile duct

 B12 in the gut then combines with Intrinsic Factor from the stomach and can be absorbed by the villi of the small intestine to combine with TC-II and form holotranscobalamin.

This this enterohepatic circulation is also used for, for example: fatty acids and phospholipids [8-10], so it may be the most efficient way of converting stores for use in the body.

The Car Oil Sump analogy

The body doesn’t show signs of B12 deficiency until the level of active B12 drops below a certain level (probably around 50 pmol/L = 67ng/L). This means that the level of B12 in the blood can vary enormously, from over 2000µg/L down to the threshold (see discussions)

The level of B12 may be dropping, but the problem won’t be detected until it falls below a threshold causing symptoms.

This is exactly what happens in a motor car engine. Oil is pumped into the top of the engine and trickles down, lubricating all parts, until it gathers in the oil sump at the bottom of the engine. There is usually plenty of oil in the engine, and the oil pump will continue circulating oil even when the level drops a very long way below normal, as might occur perhaps with an oil leak (faulty seal, crack in the sump, etc). Checking the dip stick might reveal that levels are at the low end of normal, and need topping up, but we don’t check B12 levels in people (perhaps we should?).

Once the level of oil in the engine falls to the point where the oil pump can’t pump enough back up to the top to keep the engine lubricated, then you have a disaster on your hands – things will start to seize up; con rods will stick themselves to prop shafts, cam shafts will grind out of shape against tappets, the engine could become a wreck in a matter of minutes. Most engines have a warning light which informs us that the oil is running low, well before there is a problem. Sadly, humans don’t have this warning light for B12 shortage.

How long does it take to use up B12 stores?

So we know that the level of B12 in the body is usually large (Chanarin calculated, for example, that it should take 7 years to use up the body’s supply of B12 at 2µg/day (2 µg/5 mg = 2,500 days =approx. 6.8 ys) [11] – forgetting that B12 is water soluble and will therefore eliminate from the body via the urine if not kept topped up.

In our experience the circulation of B12 appears to be remarkably efficient; you can eliminate B12 from your diet by becoming a vegetarian and you may not suffer from B12 deficiency for up to 15 years (Hugo Minney – personal experience; Kevin Byrne – personal experience). On the other hand, if you have a problem with absorbing B12 from the gut, then not only do you have a problem absorbing B12 from your diet, but the entero-hepatic circulation system (“entero” – within or through; “hepatic” – the liver (dative form for to, within, through) ie circulation via the liver, bile duct and small intestine) also breaks down – B12 is secreted into the small intestine but then can’t be re-absorbed so the body’s levels of stored B12 will continue to drop dramatically

Once B12 runs out, the level of active or available B12 in the blood will fall suddenly and dramatically In Dr Chandy’s practice, we observe people with Serum B12 above the threshold (180µg/L at present) who exhibit signs and symptoms of deficiency (qv … ) but we are not allowed to commence treatment. We know from experience that once they exhibit signs and symptoms their serum B12 is already falling and it is no longer than 6 months and often considerably less before their serum B12 falls to a level where we can commence treatment.

It is absolutely vital at this stage to commence treatment as quickly as possible. Apart from the obvious discomfort to the patient caused by symptoms, we believe that there is a limited “window of opportunity” before the symptoms change from reversible to permanent[12].

What this means for treatment

Those at risk of B12 deficiency, ie vegetarians, the elderly, people taking PPIs (antacids for example), anyone who has had Gastro-intestinal surgery (eg gastric band, any ileal resections), and people with B12 absorption difficulties (eg presence of Intrinsic Factor antibodies) should consider taking oral B12 prophylactically (just in case)[7, 13]. Harrison’s ‘Principles of Internal Medicine’ 16th edition (2005) also indicates that people with diabetes and renal imbalance should also consider taking B12 prophylactically.

Those whose levels of serum B12 are falling should be monitored. We believe that the UK and USA should recognise both severe deficiency (200 µg/L), and preclinical, or interim deficiency (serum B12 less than 350 ng/L and raised MMA) [7, 14, 15]

At treatment initiation, patients need a ‘loading dose’ of very large quantities of B12 over an extended period to replenish the body’s stores – this is the recommendation of the British National Formulary but is often not adhered to[16, 17]. Once B12 treatment has commenced, we should assume that the B12 circulation “has a leak”, and that treatment should continue for life. We observe that some patients reverse all of their symptoms including problems absorbing B12, but this should be assumed to be the exception rather than the rule.

Documents referred to

1. Vegetarian Society. Information Sheet: Vitamin B12. 2009 [cited 2010 4 August 2010]; Available from: http://www.vegsoc.org/info/b12.html.

2. Chanarin, I., The megaloblastic anaemias. 1969, Oxford,: Blackwell Scientific. vii, 1000 p., 23 plates.

3. Nexo, E., et al., Quantification of holo-transcobalamin, a marker of vitamin B12 deficiency. Clin Chem, 2002. 48(3): p. 561-2.

4. Nexo, E., et al., Holo-transcobalamin is an early marker of changes in cobalamin homeostasis. A randomized placebo-controlled study. Clin Chem, 2002. 48(10): p. 1768-71.

5. Wickramasinghe, S.N., Diagnosis of Megaloblastic anaemias. Blood Reviews, 2006. 20(6): p. 299-318.

6. McCaddon, A., et al., Analogues, ageing and aberrant assimilation of vitamin B12 in Alzheimer’s disease. Dement Geriatr Cogn Disord, 2001. 12(2): p. 133-7.

7. Park, S. and M.A. Johnson, What is an Adequate Dose of Oral Vitamin B12 in Older People with Poor Vitamin B12 Status? Nutrition Reviews, 2006. 64(8): p. 373-378.

8. Vazquez, C.M., F.J. Muriana, and V. Ruiz-Gutierrez, Changes in fatty acid desaturation in hepatic and intestinal tissues induced by intestinal resection. Lipids, 1993. 28(5): p. 471-3.

9. Hendel, J. and H. Brodthagen, Entero-hepatic cycling of methotrexate estimated by use of the D-isomer as a reference marker. Eur J Clin Pharmacol, 1984. 26(1): p. 103-7.

10. Ejiri, K., [Studies on entero hepatic circulation of urea nitrogen in pregnant rat (author’s transl)]. Nippon Sanka Fujinka Gakkai Zasshi, 1980. 32(5): p. 601-10.

11. Chanarin, I., The Megaloblastic Anaemias. 3rd ed. 1986, Oxford: Blackwell Scientific Publications.

12. Chandy (Kayalackakom), J., A forgotten illness – Vitamin B12 Deficiency with Neuro Psychiatric signs and symptoms with or without Anaemia or Macrocytosis. 2006: Durham, UK. p. 26.

13. Baboir, B.M. and H.F. Bunn, Pernicious Anaemia, in Harrison’s Principles of Internal Medicine. 2005. p. 601-607.

14. McBride, J. B12 Deficiency May Be More Widespread Than Thought. Agricultural Research Service 2000 2 Aug [cited 2009 2 Oct]; Available from: http://www.ars.usda.gov/is/pr/2000/000802.htm.

15. Mitsuyama, Y. and H. Kogoh, Serum and cerebrospinal fluid vitamin B12 levels in demented patients with CH3-B12 treatment–preliminary study. Jpn J Psychiatry Neurol, 1988. 42(1): p. 65-71.

16. BNFC, British National Formulary for Children. 2008, Paediatric Formulary Committee, BMJ Publishing, RPS Publishing and RCPCH Publications.

17. BNF, British National Formulary. 2009, Joint Formulary Committee, British Medical Association & Royal Pharmaceutical Society of Great Britain, JFC.

Most of the questions coming in now are “where can I buy injectable methylcobalamin in the UK/ European Union” (other parts of the world – sorry, can’t help)?

The B12d charity can no longer supply B12 for injection.  We explain about the symptoms, and therefore we can’t get involved in supply.  However you can usually get hydroxocobalamin in glass ampoules from versandapo.de or mycare.de, and dry methylcobalamin (to be mixed with sterile saline before injecting) from Oxford BioSciences. This last one is the one I use – https://oxfordbiosciences.com/store/product/vitamin-b12-methylcobalamin-serv/ 

http://www.b12d.org/submit/document?id=44

http://www.b12d.org/submit/document?id=44

Download:

Instructions for using Methylcobalamin ampoules

Why does my bottle say it contains 160 times the total daily need (16,666%)?

The amount of B12 your body needs to consume from the diet is very individual, but the vitamin labelling rules don’t allow for this.

The entero-hepatic cycle is a special recycling process where B12 in the blood is collected by the liver, passes down the bile duct and into the intestine, and then gets reabsorbed into the blood.  We don’t know why, but it’s likely that the liver takes inactive B12 from the blood (in storage) and the intestine activates it when it’s reabsorbed.  ie to convert storage B12 into active B12.

How does this affect how much B12 we need?

In most people, this entero-hepatic cycle is very nearly 100% efficient.  Therefore most people only need a tiny amount of dietary B12, because they are reabsorbing so much from their entero-hepatic cyle – say 6mcg/day.

We estimate that there’s a total of about 30mcg in the body – around 91% in the cells, and only 9% (2.7mcg) in the blood.  However the entero-hepatic cycle is a busy one and churns the B12 perhaps 24x per day (average once per hour) – in other words, 65mcg of B12 goes through the cycle per day.  At 90% efficiency, we’d expect 6mcg loss in other words you need to make it up with 6mcg from the diet, fairly easy.

HOWEVER people with B12 deficiency are mostly far worse at absorbing B12.  At worst, with no active absorption, passive absorption is 1% – in other words a 99% loss.  That means that of the 65mcg circulating into the gut to be activated and reabsorbed, 64.4mcg is lost and needs to be made up from the diet. Let’s take an average value for a person with B12 deficiency, 5% efficiency (still 5 times the worst case). Every day, they lose 61mcg. But when they take 1000mcg in a tablet, they only absorb 5%, in other words tehy only absorb 50mcg – so they aren’t getting enough from the tablet to make up the amount lost.

How about “Daily Values”?

Daily Values are based on the assessed needs of a healthy person who doesn’t have absorption problems.  Because of this, the Daily Value for B12 is set at around 6mcg per day.  But 

1. If you have poor absorption, then you need much more in the tablet so that 6mcg goes into your bloodstream
2. if you have poor absorption, then the amount you need for daily activity goes up anyway.

What about injections?

Injections put the B12 directly into the blood so they aren’t affected by the absorption efficiency (well, they are to activate).  That’s why we say that you don’t need to inject very much, you just need to inject it more frequently.

You have around 10% of your body weight as blood, in other words if you weigh 80kg then you will have around 8lt of blood.  Therefore if the ideal blood serum B12 is 800ng/L (and blood cells have about the same concentration of B12 as the serum), then you will have 8lt * 800ng/L = 6,400ng = 6.4mcg of B12 floating around in your blood.  This means that if you inject 1000mcg (the usual amount), then you have temporarily increased the total B12 in the blood from 6.4mcg to 1000mcg.  Within seconds, a lot of this will be absorbed into cells to boost their B12 levels, but also a lot will go to waste out of the kidneys.

If you lose a lot through the kidneys, then there’s no point in putting more in with each injection because you’ll lose most of it.  It’s far more sense to give yourself another injection a few weeks later.  Personally I’ve tried with injections of 500mcg (0.1ml of 5mg/ml methylcobalamin) and 250mcg (half again) and settled on 500mcg per injection simply because it’s quite difficult to load the syringe with less and still manage to inject.  But I inject twice per week.