Vitamin B-12 deficiency
BMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c2305 (Published 01 June 2010) Cite this as: BMJ 2010;340:c2305
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I concede that oral treatment might be agood idea for several
reasons. But I wonder if anyone has noticed that in order to institute oral
replacement dose of 1 mg OD the patient will have to take 20 tablets of
cyanocobalamin 50 micrograms a day.
The only oral preparation I can find in the BNF in the UK for Vit B12 is
the cyanocobalamin 50 micrograms tablet.
Taking 20 tablets a day (if they are not taking that many already in other
medicines!) won't be welcomed by many patients I know. Would there be any
other alternatives?
Competing interests:
I get paid for Vitamin B12 injections
Competing interests: No competing interests
Dear Editor,
Dr. Hudson’s 10 Minute Consultation regarding vitamin B-12 deficiency
provided an excellent overview of the difficulties encountered with
patients. However, he did not address two clinical issues. One was the
duration of hydroxocobalamin treatment if the etiology of vitamin B-12
deficiency is treatable. If the etiology is only a dietary deficiency,
treatment could be terminated when the vitamin B-12 stores are replete and
the dietary choices corrected. If the etiology of the vitamin B-12
deficiency is not treatable (e.g. pernicious anemia) treatment must be
continued for the remainder of the patient’s life.
The second issue was the option of treating vitamin B-12 deficiency with
oral cyanocobolamin. Several randomized trials have established the
ability of daily oral therapy (1000 mcg and 2000 mcg) to be as effective
as injection therapy in achieving hematologic and neurologic responses,
due to the 1 – 2% passive absorption of vitamin B-12.1 Oral therapy may be
more cost-effective by saving nursing time, although long-term compliance
and efficacy have not been established.2, 3
Yours ever,
Herbert L. Muncie, Jr. M.D.
1. Vidal-Alaball J, Butler CC, Cannings-John R, et al. Oral vitamin
B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane
Database of Systematic Reviews. 2005:004655.
2. Dali-Youcef N, Andres E. An update on cobalamin deficiency in adults.
QJM. 2009;102:17-28.
3. Vidal-Alaball J, Butler CC, Potter CC. Comparing costs of intramuscular
and oral vitamin B12 administration in primary care: A cost-minimization
analysis. European Journal of General Practice. 2006;12:169-173.
Competing interests:
None declared
Competing interests: No competing interests
Dear editor,
I have read the article and
this international debate with great interest. At present I am conducting an observational
primary care study, with sixty-one patients followed-up for 6-12 months. I
could advance some provisional results: B12 deficiency is a common
condition with at least 3.8% prevalence (in attended population) with a
bimodal distribution and more frequent in females (2/3). Many patients
have been complaining of mild symptoms for years: fatigue or tiredness is
a cardinal feature alongside a miscellanea of other symptoms and signs,
where anaemia rarely is present.
A “gold standard test”(1) does not exist. Consequently diagnostic
essentially depends on clinical meticulous assessment(2)besides low values
of B12. I would dare to suggest the following indicative recommendation:
consider a B12 deficiency when levels are below 300 pmol/L, probable when
below 200 and quite certain if below 156, but always it should be based
on clinical response to a test treatment (3).
Most patients, roughly 3/4, have responded adequately to oral treatment
(improving symptoms and B12 level), and taking the vitamin with an empty
stomach should be emphasized to guarantee absorption, where only 1/4 will
need intramuscular injection. The dose and the frequency of the treatment
depend on individual needs and should be adjusted accordingly.
I do really think that B12 deficiency merits more attention among doctors
and needs much more research.
Dr Ferran Gali-Gorina.
Institut Català de la Salut, Spain
(1) Carmel R. How I treat cobolamin (vitamin B12 deficiency). Blood
2008;112:2214-2221
(2) Devalia V. Diagnosing vitamin B-12 deficiency on the basis of serum B-
12 assay. BMJ 2006; 333:385-386
(3) Glasziou P, Rose P, Balla J. Diagnosis using “testo f treatment”. BMJ;
2009; 338:b1312
Competing interests:
None declared
Competing interests: No competing interests
The excellent 10 minute consultation on B12 was extremely useful and
answered a longstanding question I never got round to finding an answer
for, 'why do people with active coeliac disease get B12 deficiency?'
I would ask any anyone interested their views on oral vs injectable B12. A
few years ago following a similar article we changed our pracice to using
oral B12 as our default option unless there were compelling reasons for
using injectable B12. i have not looked at the fugures recently (an audit
for the student I think) but most people were able to get back to normal
levels on one tablet daily
Competing interests:
None declared
Competing interests: No competing interests
Dear Editor,
This letter is in response to your article dated June 1st on the
“Assessment of Vit B 12 deficiency”. As a nursing lecturer teaching
General Nursing Science, I often encounter students who have great
difficulty integrating theory and practice. I applaud the author for the
simple yet excellent integration of physiology, nutrition and clinical
manifestations.
It is critical for educators of health related content to facilitate the
comprehension of physiology, pathophysiology and application to clinical
manifestation, as displayed in this article. This will make it easier for
students to understand how dysfunctional physiology translates to clinical
manifestation (signs and symptoms) of different medical conditions.
Competing interests:
None declared
Competing interests: No competing interests
Oral vitamin B12 is widely used in Sweden and Canada. In 2005
we conducted a systematic review for The Cochrane
Collaboration looking at oral vitamin B12 for the treatment of
vitamin B12 deficiency. With the evidence derived from the
limited studies we found comparing oral versus intramuscular
administration of vitamin B12 we concluded that 2000 mcg doses
of oral vitamin B12 daily and 1000 mcg doses initially daily
and thereafter weekly and then monthly may be as effective as
intramuscular administration in obtaining short term
haematological and neurological responses in vitamin B12
deficient patients.
(1) Vidal-Alaball J, Butler CC, Cannings-John R, Goringe A,
Hood K, McCaddon A, McDowell I, Papaioannou A. “Oral vitamin
B12 versus intramuscular vitamin B12 for vitamin B12
deficiency”. The Cochrane Database of Systematic Reviews 2005,
Issue 3. John Wiley & Sons, Ltd
Competing interests:
None declared
Competing interests: No competing interests
Herrmann and colleagues[1] found that the correlation between
methylmalonic acid (MMA) and serum B12 was -0.38 in sedentary subjects but
-0.01 in recreational athletes, suggesting that B12 metabolism in people
who exercise regularly differs from that in sedentary people. The same
group suggested that regular endurance training is associated with an
increase in B12 and folate requirements.[2] Herrmann and colleagues
suggest that people who exercise regularly can be functionally deficient
in B12 with normal or even high B12 levels.[1] In their study most of the
healthy recreational athletes they studied had elevated MMA levels,
suggesting critical intracellular B12 supply.[1] Possibly the best method
for detecting B12 deficiency is change in serum MMA after B12
supplementation.[3]
In the early stages of my small fibre sensory neuropathy in 2005 my
lower extremity parasthesia was apparent 24-48 hours after a high
intensity 2 hour bicycle ride, lasted less than 12 hours and recurred only
after the next bike ride. At that time my B12 and folate levels were 460
pmol/L and 1624 nmol/L respectively (Roche method). When my neuropathy
started I was 53 and had a four-year history of proton pump inhibitor and
ant-acid use, but the neurologists I consulted did not consider B12
supplementation and advised that B12 deficiency was very unlikely.
Gastroscopy revealed mild chronic gastritis and helicobacter pylori
infection. A test for intrinsic factor anti-bodies was normal but was
within 10% of the cut-off value. The temporal relationship between my
early neuropathy symptoms and exercise might have been explained by the
prolonged recovery of acute exercise-induced elevation of homocysteine
observed in some endurance athletes.[2] Plasma concentration of MMA is
also acutely increased by strenuous exercise.[1] Both homocysteine and
MMA are implicated in neuronal injury.[4]
After much reading prompted by an anaesthetist colleague who had seen
neuropathy develop in a patient exposed to nitrous oxide on multiple
occasions, I started oral B12 supplementation at 3 mg of
methylcobalamin/day. My neuropathy stopped progressing and partially
resolved over the following few years. It is important to start B12
supplements early because delay may contribute to residual neurological
damage,[5] and the consequences of prolonged B12 deficiency can be
devastating.[6] No toxic or adverse effects have been associated with
large intakes of B12, so the threshold for prescribing B12 supplements
should be very much lower than it appears to be at present. Further
research is needed in B12 metabolism and measurement, particularly in
older people who exercise regularly.
1. Herrmann M, Obeid R, Scharhag J, Kindermann W, Herrmann W. Altered
vitamin B12 status in recreational endurance athletes. Int J Sport Nutr
Exerc Metab. Aug 2005;15(4):433-441.
2. Herrmann M, Schorr H, Obeid R, Scharhag J, Urhausen A, Kindermann
W, et al. Homocysteine increases during endurance exercise. Clin Chem Lab
Med. Nov 2003;41(11):1518-1524.
3. Bolann BJ, Solli JD, Schneede J, Grottum KA, Loraas A, Stokkeland
M, et al. Evaluation of indicators of cobalamin deficiency defined as
cobalamin-induced reduction in increased serum methylmalonic acid. Clin
Chem. Nov 2000;46(11):1744-1750.
4. Dharmarajan TS, Adiga GU, Norkus EP. Vitamin B12 deficiency.
Recognizing subtle symptoms in older adults. Geriatrics. Mar 2003;58(3):30
-34, 37-38.
5. Larner AJ. Missed diagnosis of vitamin B12 deficiency presenting
with paraesthetic symptoms. Int J Clin Pract. Jun 2002;56(5):377-378.
6. Dharmarajan TS, Norkus EP. Approaches to vitamin B12 deficiency.
Early treatment may prevent devastating complications. Postgrad Med. Jul
2001;110(1):99-105;.
Competing interests:
None declared
Competing interests: No competing interests
In an 85-year old man with vitamin B12 deficiency, despite an
apparently good diet, one should suspect malabsorption due to
hypochlorhydria. Stomach acid levels diminish with age, and by 85, the
majority of people are likely to have hypochlorhydria.
Adequate stomach acid is also necessary for absorption of other
nutrients, including calcium. This patient should have bone density
testing, as he is at increased risk of osteoporosis.
Sublingual vitamin B12 tablets/drops/sprays are generally effective
and long-term intramuscular injections are rarely necessary.
Treatment of low stomach acid is with supplements of betaine
hydrochloride/pepsin, taken with meals; these are available from many
nutritional supplement manufacturers.
Competing interests:
None declared
Competing interests: No competing interests
I was interested and unsurprised to learn of this aspect of Clinical
Chemistry, whereby B12 transport systems may be so overwhelmed by IM B12
initiation regimes, that most is lost in the Urine. Parsimony may be
important, but my main concern is EASE ( Effectiveness, Acceptability,
Safety, Expense). How best to optimise the haematological/clinical
recovery ? And with a safety margin - for missed appointments, say. At
reasonable expense. So we plump straight for B12 replacement by
'overkill' injections, and refer to the practice Nurse, who hopefully
remembers to bill the NHS for reimbursements. Maybe that's why Oral B12
isn't too popular here, unlike Canada and Sweden ?
Current UK prices are:
Cyanocobalamin (Non-proprietary)
(1) Tablets , cyanocobalamin 50 micrograms. Net price 50-tab pack = £6.24
Brands include Cytacon®
Liquid , cyanocobalamin 35 micrograms/5 mL. Net price 200 mL = £2.77
Brands include Cytacon®
Injection , cyanocobalamin 1 mg/mL. Net price 1-mL amp = £1.67
Brands include Cytamen®
Injection , hydroxocobalamin 1 mg/mL. Net price 1-mL amp = 92p
Note The BP directs that when vitamin B12 injection is prescribed or
demanded hydroxocobalamin injection shall be dispensed or supplied
Could the discrepancies between blood B12 levels, transport
saturations, and B12 stores explain the common experience (eg. Phil Jones
and myself) of patients feeling that they need their B12 more often than
the schedule ?? It would be nice to have a non-psychological explanation.
Competing interests:
I get paid for B12 injections
Competing interests: No competing interests
Re: Vitamin B-12 deficiency
As a patient suffering from B12 deficiency I am shocked by some of the medical responses. Patients know their own bodies and know when they do not feel quite right. To say that a 3 monthly injection of B12 is satisfactory and any more than that creates a 'high' or is just a placebo effect shows how very little understanding the medical profession had in this area.
It is well known that, although from animal sources, B12 is a water soluble vitamin, which is unusual as most are fat soluble, therefore what is not needed within the body is urinated out. This happens within the first 24 hours. The body then uses the B12 to repair the body, anything from the nerve endings (neurological features of B12 deficiency, sometimes mistaken for MS etc) to mental issues (sometimes mistaken for depression etc) and many more in between. Back in the 1970s and 1980s B12 was given more frequently as routine. The injection hadn't changed but the recommendation has. B12 doesn't stay in the body any longer so patients become 'needy' sooner. What the medical profession lack is the knowledge that each patient is an individual and one size doesn't fit all. This leads to patients in serious pain and then having to self inject. Believe me when you've suffered from back ache, memory loss, the inability to remember day to day names of items etc this is not a high reaction or a placebo effect when, after the B12 injection, they stop hurting or get a little better!
B12 is so cheap under 70p per ampoule yet doctors would rather dish out pain relief and antidepressants like sweets which, of course, cost so much more. I wish that patients could mentally and physically pass on their pain to their GPs and others in the medical profession that write and say such twaddle as 'artificial high' 'placebo' etc then they would be able to more aptly treat B12 deficiency!
At this moment in time the B12 serum test is also flawed. B12 flows around your body with approximately 80% of it inactive and the remaining 20% being utilised by the body. If you look at the lower limit result say the range was from 200, this would mean the only 20% of this was actively used in the body. A patient could be told that they are not deficient, where in actual fact they would be and nerve damage would start!
Stop treating patients who ask for sooner B12 injections like drug addicts and start listening to them. Patients research themselves and are far more knowledgeable than GPs themselves. Doctors and specialist haematologists need to rethink their views in this subject and start reading and researching. In reading I do not mean flawed articals written by the medical profession to pat each other on their backs to why patients shouldn't have anything more than 3 monthly injections. I also mean thinking outside the ranges and focusing on the symptoms of their patients. I therefore ask you to think logically about ignoring B12 results once patients are on injections as the levels will be artificially high. Also remember that B12 isn't toxic, you can't overdose on it and it is very safe. I would very much like GPs and the whole of the medical profession to actually read the BNF guidelines regarding treatment of patients with B12 deficiency. You'll find what you are looking for in section 9.1.2!
Stop making patients feel like druggies (although I think they get treated better by doctors than B12 deficient patients do), give the injection more often or better still teach the patient to self inject (saving money by not using up practice nurses' time) so they do it safely.
Competing interests: No competing interests