Trip Answers

Question answered:10/03/08

The CKS guideline on macrocytic anaemia states:

 

“Autoantibody screen:
 -Intrinsic factor (IF) antibodies are virtually diagnostic of pernicious anaemia (PA). However, absence of IF antibodies does not exclude the diagnosis, as they are present in only 50% of people with PA (i.e. it has high specificity but low sensitivity).
 - Gastric parietal-cell antibodies are present in 85% of people with PA, but are also found in 3–10% of people who do not have PA (i.e. it has high sensitivity but low specificity).” [1]

 

An article published in the ‘American Family Physician’ on vitamin B12 deficiency adds:

 

“MALABSORPTION SYNDROMES
The classic disorder of malabsorption is pernicious anemia, an autoimmune disease that affects the gastric parietal cells. Destruction of these cells curtails the production of intrinsic factor and subsequently limits vitamin B12 absorption.

 

Laboratory evidence of parietal cell antibodies is approximately 85 to 90 percent sensitive for the diagnosis of pernicious anemia. However, the presence of parietal cell antibodies is nonspecific and occurs in other autoimmune states. Intrinsic factor antibody is only 50 percent sensitive, but it is far more specific for the diagnosis of pernicious anemia.” [2]

 

GPNotebook has an entry on treatment of vitamin B12 deficiency that reads:

 

“Treatment of vitamin B12 deficiency

 

…B12 deficiency is generally treated with vitamin B12 supplementation.

 

if B12 levels are particularly low then intramuscular B12 should be given and a haematology referral made
- treatment of pernicious anaemia and other macrocytic anaemias with neurological involvement - five to six loading doses of 1000 mcg over a period of one to two weeks followed by 1000 mcg every three months (see BNF for full details)
if B12 levels are borderline then response to oral B12 may be diagnostic and management should be discussed with the local haematology department
- treatment of vitamin B12 of dietary origin, cyanocobalamin 50-150 mcg daily in 1-3 divided doses (see BNF for full details).” [3]

 

Concerning the use of oral B12 at a daily dosage of 50-150mcg, the CKS guideline on macrocytic anaemia says poor diet is a very rare cause:

 

“ - Initial treatment: as above. ***
 - Maintenance treatment is not usually necessary if diet improved. Vegans should be advised to take oral vitamin B12 supplements following acute treatment, although a twice-yearly injection is an alternative.”

 

In the prescription section of the guideline, under maintenance treatment, CKS offers:

 

“Vegans/proven dietary deficiency only: cyanocobalamin (SLS)
Age from 16 years onwards
Cyanocobalamin 50mcg tablets. Take two tablets once a day, between meals. Supply 56 tablets.
NHS Cost £3.40
Licensed use: yes
Patient Information: It is important to make sure you get plenty of vitamin B12 from your diet. Vitamin B12 fortified foods (e.g. some soy products and some breakfast cereals) are good alternative sources of vitamin B12 to meat, eggs, and dairy products. If you are able to include more of these types of foods in your diet, you will no longer need to take these tablets.”

 

Later on, CKS adds:

 

“Oral vitamin B12 (cyanocobalamin) is included. It is suitable only for the very small minority of people with proven dietary deficiency of vitamin B12 (most vitamin B12 deficiency is due to malabsorption). It is available on an NHS prescription only for this indication, and the prescription must be endorsed 'SLS'.” [1]

 

We searched the TRIP and Medline databases for studies of low dose oral vitamin B12 and found just one  by Seal et al. The Medline abstract of this study reads:

 

“OBJECTIVES: To determine the effect of small doses of oral cyanocobalamin supplements in older patients with low or borderline serum vitamin B12 concentrations but no other evidence of pernicious anemia (PA). DESIGN: Randomized, double-blind, placebo-controlled study assessing the efficacy of oral cyanocobalamin 10 microg and 50 microg daily for 1 month. SETTING: Two geriatric hospitals in the North Western Health Care Network, Melbourne, Australia. PARTICIPANTS: Thirty-one inpatients with serum vitamin B12 levels between 100 and 150 pmol/L, without PA, other malabsorption disorders, or progressive neurological or terminal illness. The mean age was 81.4 years. INTERVENTION: After informed consent, a medical and drug history was taken and the Mini-Mental State Examination (MMSE) completed. A dietitian made assessment of oral cobalamin intake. Blood was taken for serum vitamin B12, serum and red cell folate assay, full blood examination, fasting serum gastrin, parietal and intrinsic factor antibodies, fasting serum homocysteine, and creatinine. Patients were then randomized to receive 10 microg oral cyanocobalamin, 50 microg oral cyanocobalamin, or placebo treatment for 1 month, after which the investigations and clinical examinations were repeated…

 
RESULTS: Mean serum vitamin B12 +/- standard deviation improved by 51.7 +/- 47.1% in the 50-microg group, 40.2 +/- 34.4% in the 10-microg group, and 11.7 +/- 24.5% in the placebo group. The change in the 50-microg cyanocobalamin group was significantly greater than that in the placebo group (P=.044). The change in the 10-microg cyanocobalamin group was not significantly different from that in the placebo group (P=.186). Eight of 10 subjects in each treatment group were classified as responders, compared with two of 11 in the placebo group (P=.004). Homocysteine levels fell in patients receiving cyanocobalamin, but this fall failed to reach statistical significance. There were no significant changes in the other parameters measured. CONCLUSION: Cyanocobalamin supplementation of 50 microg but not 10 microg daily produced a significant increase in serum vitamin B12. This result has implications for the management of patients with subnormal or borderline serum vitamin B12 concentrations and for food fortification with vitamin B12.” [4]

 

***”Initial treatment: if there has been no neurological involvement, hydroxocobalamin 1 mg intramuscularly every 2–4 days for six doses. If there has been neurological involvement, hydroxocobalamin intramuscularly 1 mg on alternate days until no further improvement.” [1]

 

References

1. CKS. Macrocytic anaemia. July 2005. (http://www.cks.library.nhs.uk/anaemia_macrocytic/)
2. Oh R and Brown DL. Vitamin B12 deficiency. Am Fam Physician. 2003 Mar 1;67(5):979-86. (http://www.hubmed.org/display.cgi?uids=12643357)
3. GPNotebook. Treatment of vitamin B12 deficiency. (http://www.gpnotebook.co.uk/simplepage.cfm?ID=1953169427&linkID=35565&cook=yes)
4. Seal EC, Metz J and Flicker L et al. A randomized, double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations. J Am Geriatr Soc. 2002 Jan;50(1):146-51. (http://www.hubmed.org/display.cgi?uids=12028259)
 

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