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What is driving elevated levels of serum B12 when other markers indicate a B12 need or B12 deficiency?

Serum B12 reflects both free and bound B12 and do not assess intracellular B12.

Serum levels may be above normal even if insufficiency is present.

Increased levels could be due to excess supplementation, increased transport proteins, or a hematological or autoimmune process.

Chronic disorders such as renal failure, cancer, or hepatic disease may promote elevated serum B12.

B12 may also be sequestered by immune cells and be unavailable to cells.

B12 may be elevated in critical illness and when combined with an elevated CRP may be associated with poorer outcomes and mortality.

If other markers point to a B12 deficiency (e.g. increased MCV, homocysteine, and methylmalonic acid, or low holotranscobalamin) then a functional deficiency may be present and should be fully assessed.

A functional B12 deficiency reflects a decrease in cellular uptake, processing, transport, or utilization.

Oxidative stress can also cause a local functional B12 deficiency which can be seen in diabetes and Alzheimer’s. In such cases, glutathione or vitamin C may be of therapeutic value. 1

A significantly elevated B12 could be a sign of disease including leukemia, polycythemia vera, and hypereosinophilic syndrome. 2


  1. Vollbracht, Claudia et al. “Supraphysiological vitamin B12 serum concentrations without supplementation - the pitfalls of interpretation.” QJM : monthly journal of the Association of Physicians, hcz164. 28 Jun. 2019, doi:10.1093/qjmed/hcz164 [R]
  2. Ermens, A A M et al. “Significance of elevated cobalamin (vitamin B12) levels in blood.” Clinical biochemistry vol. 36,8 (2003): 585-90. doi:10.1016/j.clinbiochem.2003.08.004 https://pubmed.ncbi.nlm.nih.gov/14636871/