Serum B12

The serum B12 test is still widely used as thé test to confirm or rule out a vitamin B12 deficiency. However, a normal value cannot rule out a B12 deficiency as has often been shown in scientific medical literature.
Serum B12 can be false normal or even false high when a deficiency is present. And a (mildly) false low value does not automatically mean a B12 deficiency.
It is generally agreed that an obviously low value means a B12 deficiency; a serum-B12 below 150 pmol/L gives a specificity of >95%.
There is a large grey area however, in which a deficiency is possible, despite a normal serum B12 value. If 200 pmol/L is used as a cut-off point, the sensitivity of serum B12 is still 75% and the specificity 72%.
One to five per cent of people, with a value above 221 pmol/L, still have a deficiency.

Serum B12 can be false normal/high in:

  • Liver disease
  • Too much haptocorrin (TCI) as in kidney disease and myeloproliferative diseases
  • Lack of transcobalamin (TCII)
  • Inborn error in the B12 metabolism
  • Intestinal bacterial overgrowth
  • Hemolysis
  • Antibodies against TCI/TCII
  • Test failure

Serum-B12 can be false low in:

  • Folate deficiency
  • Low haptocorrinlevels (TCI)
  • Pregnancy (3rd trimester) and oral contraceptives (possibly)
  • Multiple myeloma and HIV

By using serum B12 alone, many patients are being missed. Because a B12 deficiency can lead to permanent neurological damage, one should never rely on serum B12 alone (unless obviously low) and always test MMA when a deficiency is suspected. This is even more essential when neurological and/or neuropsychiatric symptoms are present. Experts in the medical literature advise to combine serum B12 or Active B12 with MMA when a deficiency is suspected.



1. Diagnosis and treatment of vitamin B12 deficiency. An update. Anne-Mette Hvas, Ebba Nexo Haematologica 2006; 91:1506-1512
2. An IgG complexed form of vitamin B12 is a common cause of elevated serum concentrations. Jinny Jeffery, Helen Millar, Paul MacKenzie, Michael Fahie-Wilson, Malcolm Hamilton, Ruth M. Ayling Clinical Biochemistry 43 (2010) 82–88
3. Biomarkers of cobalamin (vitamin B-12) status in the epidemiologic setting: a critical overview of context, applications, and performance characteristics of cobalamin, methylmalonic acid, and holotranscobalamin. Ralph Carmel Am J Clin Nutr July 2011 vol. 94 no. 1 348S-358S
4. Laboratory diagnosis of vitamin B12 and folate deficiency. Christopher F. Snow Arch Intern Med Vol 159, jun 28 1999, 1289
5. Disorders of cobalamin (Vitamin B12) metabolism: Emerging concepts in pathophysiology, diagnosis and treatment. LR. Solomon, Blood Rev. 2007 May;21(3):113-30
6. Detection of vitamin B12 deficiency in older people by measuring vitamin B12 or the active fraction of vitamin B12, holotranscobalamin. Clarke R, Sherliker P, Hin H, Nexo E, Hvas AM, Schneede J, et al. Clin Chem. 2007; 53(5): 963-970.
7. Diagnosis of cobalamine deficiency: II. Relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations. Lindenbaum J, Savage DG, Stabler SP, Allen RH. Am J Hematol. 1990; 34(2): 99-107.
8. Performance of the serum cobalamin assay for diagnosis of cobalamin deficiency. Matchar DB, McCrory DC, Millington DS, Feussner JR. Am J Med Sci. 1994; 308(5): 276-283.
9. Biomarkers van cobalamine (vitamin B12) deficiency and its application. W. Chatthanawaree The Journal of Nutrition, Health & Aging© Volume 15, Number 3, 2011

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