What nutrient deficiencies can cause leukopenia (low white blood cell count)?

Nutrient Deficiencies Causing Leukopenia

The primary nutrient deficiencies that cause low white blood cell counts are vitamin B12, folate (vitamin B9), and copper, with vitamin B12 and folate being the most common and well-established causes. 1, 2, 3

Vitamin B12 Deficiency

Vitamin B12 deficiency is a well-documented cause of leukopenia and should be tested first when evaluating nutritional causes of low white blood cell counts. 1, 2

• Vitamin B12 deficiency causes megaloblastic changes affecting all blood cell lines, resulting in moderate leukopenia alongside anemia and thrombocytopenia 2, 3
• Beyond quantitative reduction, vitamin B12 deficiency impairs neutrophil function, specifically decreasing metabolic activation during phagocytosis to 35-36% of normal values and slightly reducing bacterial killing capacity 1
• These functional abnormalities reverse after specific vitamin B12 therapy, confirming the vitamin's essential role in normal leukocyte function 1
• Critical clinical pitfall: Always check and treat vitamin B12 deficiency BEFORE initiating folate treatment, as folate supplementation can mask B12 deficiency while allowing irreversible neurological damage to progress 4

Folate (Vitamin B9) Deficiency

Folate deficiency causes leukopenia through ineffective hematopoiesis but does not impair neutrophil function like B12 deficiency does. 1, 2, 3

• Folate deficiency produces megaloblastic anemia with moderate leukopenia and thrombocytopenia, morphologically identical to B12 deficiency 2, 3
• Unlike B12 deficiency, folate deficiency does not impair neutrophil metabolic activation or bacterial killing capacity 1
• The prevalence of folate deficiency has dramatically decreased in the United States since grain fortification began in 1998, with current rates less than 1% in the general population 4
• In cancer patients specifically, folate deficiency was found in 0% of 127 screened patients, making it a rare cause of leukopenia in modern practice 4

Copper Deficiency

Copper deficiency causes severe leukopenia and should be considered, particularly in patients with malabsorption or after bariatric surgery. 4

• Severe copper deficiency requires specialist referral for assessment and management 4
• When both zinc and copper are low, prescribe two Forceval capsules daily for 3 months and recheck levels 4
• Important interaction: High-dose zinc supplementation can precipitate copper deficiency, so maintain a ratio of 8-15 mg zinc to 1 mg copper when supplementing 4

Other Nutritional Considerations

Zinc, selenium, and protein deficiency may contribute to leukopenia but are less commonly the primary cause. 4

• For unexplained leukopenia with anemia or fatigue, investigate zinc, copper, selenium, and protein status 4
• Protein malnutrition should prompt investigation of underlying causes and referral to appropriate specialists 4

Diagnostic Approach

When evaluating leukopenia for nutritional causes, obtain a complete blood count with reticulocyte count, vitamin B12, folate, copper, and zinc levels simultaneously. 5, 2

• The reticulocyte count helps distinguish between decreased production (low/normal reticulocytes) versus increased destruction (elevated reticulocytes), with nutritional deficiencies typically showing low or inappropriately normal reticulocyte counts 5
• Blood and bone marrow morphology alone cannot differentiate between B12 and folate deficiency—serum levels are essential 2
• If serum vitamin levels are unavailable and severe leukopenia is present, initial treatment should include both vitamin B12 and folate until specific deficiency is identified 2
• The minimum workup should include CBC with reticulocyte count, serum ferritin, transferrin saturation, CRP, vitamin B12, and folate 5

Treatment Priorities

For vitamin B12 deficiency with leukopenia, administer hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks if no neurological involvement, or on alternate days until no further improvement if neurological symptoms are present. 4

• After initial treatment, provide maintenance therapy with 1 mg intramuscularly every 2-3 months lifelong 4
• For folate deficiency, prescribe folic acid 5 mg orally daily for a minimum of 4 months 4
• Never initiate folate therapy before excluding or treating B12 deficiency to prevent subacute combined degeneration of the spinal cord 4