Does vitamin B12 (B12) supplementation cause leukocytosis?

Does Vitamin B12 Supplementation Cause Leukocytosis?

Vitamin B12 supplementation does not cause leukocytosis; rather, treating B12 deficiency can unmask or reveal pre-existing leukocytosis that was suppressed by the deficiency itself.

Mechanism: B12 Deficiency Suppresses White Blood Cell Production

• Vitamin B12 deficiency causes ineffective hematopoiesis affecting all cell lines, including white blood cells, which can mask underlying conditions that would otherwise present with elevated white counts 1
• When B12 deficiency is corrected, normal or previously suppressed bone marrow function is restored, allowing any underlying myeloproliferative process to become clinically apparent 1
• In one documented case, a patient with chronic myelogenous leukemia (CML) presented with anemia and a normal white blood cell count of only 8.66×10⁹/L due to concurrent B12 deficiency; after B12 and folic acid administration, "marked leukocytosis became evident" as the underlying CML was unmasked 1

B12 Itself Does Not Cause Leukocytosis

• The FDA label for cyanocobalamin (vitamin B12) lists adverse reactions including anaphylactic shock, pulmonary edema, congestive heart failure, peripheral vascular thrombosis, polycythemia vera, mild diarrhea, and itching, but does not list leukocytosis as an adverse effect 2
• No guidelines or high-quality evidence suggest that B12 supplementation directly causes white blood cell elevation 3, 4, 5

Clinical Context: Elevated B12 Levels Associated with Leukemia

• Elevated serum vitamin B12 levels (not B12 supplementation) are characteristic of chronic myelogenous leukemia due to increased production of B12-binding proteins by leukemic granulocytes 1, 6, 7
• In CML, plasma levels of large molecular size B12-binding protein (LBP) can reach 8,009 pg/ml compared to 57 pg/ml in normal controls, reflecting the leukemic cell mass rather than B12 intake 6
• This represents endogenous B12-binding protein production by malignant cells, not an effect of B12 administration 6, 7

Important Distinction for Clinical Practice

• If leukocytosis develops after starting B12 treatment, investigate for underlying myeloproliferative disorders (CML, polycythemia vera, essential thrombocythemia) that were masked by the B12 deficiency 1, 8
• The leukocytosis represents restoration of normal hematopoiesis or unmasking of disease, not a drug effect 1
• B12 deficiency can impair neutrophil metabolic function (reducing hexose monophosphate shunt activation to 35-36% of normal), but this affects cell function rather than cell count 9

Key Pitfall to Avoid

• Do not attribute post-treatment leukocytosis to B12 supplementation itself; instead, perform appropriate workup including peripheral smear, cytogenetic studies, and BCR-ABL testing if clinical suspicion warrants, as the B12 treatment may have revealed an underlying hematologic malignancy 1, 8