Oral Vitamin B12 for the treatment of Vitamin B12 deficiency:  A Systematic Review   Josep Vidal-Alaball 1 , Christopher C...
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Oral Vitamin B12 for the treatment of Vitamin B12 deficiency: A Systematic Review


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Oral Vitamin B12 for the treatment of Vitamin B12 deficiency: A Systematic Review

  1. 1. Oral Vitamin B12 for the treatment of Vitamin B12 deficiency: A Systematic Review Josep Vidal-Alaball 1 , Christopher C Butler 1 , Kerry Hood 1 , Rebecca Cannings 1 , Andrew McCaddon 1 , Alexandra Papaioannou 2 1 Department of General Practice, University of Wales College of Medicine 2 McMaster University, Canada Aims To assess the effectiveness of oral vitamin B12 versus parenteral vitamin B12 for vitamin B12 deficiency. <ul><li>Background </li></ul><ul><li>Vitamin B12 (cobalamin) deficiency is common, especially amongst the elderly where true prevalence ranges between 1.5 and 4.6 % 1 . </li></ul><ul><li>Vitamin B12 deficiency causes anaemia, chronic tiredness, loss of appetite and mood disturbance. If left untreated, serious neurological and neuropsychiatric complications occur. </li></ul><ul><li>Vitamin B12 was isolated in 1948 2 , and is now widely used for vitamin B12 deficiency. </li></ul><ul><li>The vitamin was initially administered intramuscularly although several studies have since demonstrated equal efficacy of the oral route 3 4 . </li></ul><ul><li>This is probably because: following its binding to intrinsic factor free Vitamin B12 can be absorbed passively in the terminal ileum as well as actively. </li></ul><ul><li>Passive diffusion accounts for 1.2% of total absorption unaffected by pernicious anaemia or gastro-duodenal surgical resection 5 6 . </li></ul><ul><li>High doses of Vitamin B12 (1,000 µcg) may be acceptable and safe alternative to parenteral route. </li></ul><ul><li>Despite the availability of oral therapy Vitamin B12 is rarely prescribed in this form, other than in Sweden where in 2000, 73% of the total Vitamin B12 prescribed was oral 7 . </li></ul><ul><li>Doctors may be unaware of the oral route or concerned about its unpredictable absorption 8 . </li></ul><ul><li>In the UK, oral Vitamin B12 is not currently available in high doses. </li></ul>Figure 1 . Patients on oral high-dose cyanocobalamin in Sweden 1990-2000 7 <ul><li>Criteria for considering studies for this review </li></ul><ul><li>Types of studies </li></ul><ul><li>Randomised Control Trials examining the use of oral versus parenteral vitamin B12 to treat vitamin B12 deficiency. </li></ul><ul><li>Types of participants </li></ul><ul><li>Individuals with demonstrated deficiency of serum vitamin B12 who met the criteria for vitamin B12 replacement therapy. </li></ul><ul><li>We took 100 p mol/L as threshold serum level for vitamin B12 deficiency. </li></ul><ul><li>Types of interventions </li></ul><ul><li>1. Oral vitamin B12 versus oral placebo or no treatment </li></ul><ul><li>2. Parenteral vitamin B12 versus parenteral placebo or no treatment </li></ul><ul><li>3. Oral versus parenteral vitamin B12 </li></ul><ul><li>Results </li></ul><ul><li>Studies identified </li></ul><ul><li>663 abstracts or titles </li></ul><ul><li>21 papers pre-selected and checked for inclusion and exclusion criteria. Disagreements resolved by consensus </li></ul><ul><li>3 papers selected </li></ul><ul><li>Included studies </li></ul><ul><li>Three randomised control trials fulfilled our original inclusion criteria: </li></ul><ul><li>1. Kuzminski 1998 (oral better than parenteral) </li></ul><ul><li>2. Kwok 1998 (parenteral better than placebo) </li></ul><ul><li>3. Seal 2002 (oral better than placebo) </li></ul><ul><li>Conclusions </li></ul><ul><li>The evidence collected with this systematic review shows that when treating Vitamin B12 deficiency, high doses (1000 µ cg) of daily oral Vitamin B12 are as, or more effective than the parenteral administration obtaining haematological and neurological responses 9 . </li></ul><ul><li>Lower doses of 50 µ cg daily also produce a haematological response when compared to placebo but seem not to produce a statistically significant neurological response. </li></ul><ul><li>Very low doses of Vitamin B12 (10 µ cg) orally do not produce a statistically significant haematological or neurological response when compared to placebo 10 . </li></ul>References 1. van Walraven C, Naylor C. Use of vitamin B12 injections among elderly patients by primary care practitioners in Ontario. Canadian Medical Association Journal 1999;161:146-9. 2. Rickes E, Brink N, Koniuszy F, Wood T, Folkers K. Crystalline vitamin B12. Science 1948;107:396. 3. Spies T, Stone R, Lopez G, Milanes F, Toca R, Aramburu T. Vitamin B12 by mouth in pernicious and nutritional macrocytic anaemia and sprue. Lancet 1949;2:454-6. 4. Ross G, Mollin D, Cox E, Ungley C. Hematologic responses and concentration of vitamin B12 in serum and urine following oral administration of vitamin B12 without intrinsic factor. Blood 1954;9:473-88. 5. Berlin H, Berlin R, Brante G. Oral treatment of pernicious anemia with high doses of vitamin B12 without intrinsic factor. Acta Medica Scandinavica 1968;184(4):247-58. 6. Berlin R, Berlin H, Brante G, Pilbrant A. Vitamin B12 body stores during oral and parenteral treatment of pernicious anaemia. Acta Medica Scandinavica 1978;204(1-2):81-4. 7. Norberg B. Oral high-dose cyanocobalamin - a contagious concept. Rondel , 2001. 8. Lederle FA. Oral cobalamin for pernicious anemia. Medicine's best kept secret? Journal of the American Medical Association 1991;265(1):94-95. 9. Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J. Effective treatment of cobalamin deficiency with oral cobalamin. Blood. 1998;92(4):1191-8. 10. Seal EC, Metz J, Flicker L, Melny J. A randomized, double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations. Journal of the American Geriatrics Society. 2002;50(1):146-51.