This document addresses the use of vitamin B12 blood test, methylmalonic acid blood test, and holotranscobalamin blood test for individuals with suspected or known vitamin B12 deficiency.

Clinical Indications

Medically Necessary:

Vitamin B12 blood testing is considered medically necessary for any of the following indications:

1. Alcohol dependence; or
2. Anemia; or
3. Autoimmune condition such as intrinsic factor deficiency, thyroid disease, or pernicious anemia; or
4. Blood dyscrasia (for example cytopenia, leukopenia, or thrombocytopenia); or
5. Diabetes mellitus with neurologic symptoms; or
6. Disorders of sulphur amino acid metabolism; or
7. Disruption of gastrointestinal anatomy or function (for example achlorhydria, gastrectomy, gastric bypass, gastric cancer, ileal resection, inflammatory bowel disease); or
8. Failure to thrive (pediatric); or
9. Glossitis; or
10. Homocystinuria; or
11. Inadequate dietary intake of vitamin B12 such as strict vegan diet without vitamin B12 supplementation; or
12. Infection known to be associated with vitamin B12 deficiency such as bacterial overgrowth syndrome, fish tapeworm infection, Helicobacter pylori infection, or human immunodeficiency virus (HIV); or
13. Malabsorption; or
14. Malignancy affecting absorption of nutrients or affecting blood or hematopoiesis; or
15. Malnutrition; or
16. Methylenetetrahydrofolate Reductase (MTHFR) deficiency; or
17. Neurologic or motor symptom abnormality; or
18. Pancreatic insufficiency; or
19. Unexplained mental status or cognitive changes; or
20. Chronic use of H₂ blocking agent and proton pump inhibitor (PPI) minimum of 1 year or metformin minimum of 4 months

Methylmalonic acid (MMA) testing is considered medically necessary for ANY of the following indications:

1. Vitamin B12 levels are low or borderline-low; or
2. Newborn screening; or
3. Use of metformin for Type 2 diabetes mellitus with neurologic symptoms.

Not Medically Necessary:

Vitamin B₁₂ and MMA testing is considered not medically necessary when the criteria above are not met and for all other indications.

Holotranscobalamin testing as a marker for vitamin B12 deficiency is considered not medically necessary for all indications.