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 deficiency, with vitamin B12 and folate causing megaloblastic changes affecting all blood cell lines including leukocytes, while copper deficiency specifically causes neutropenia and can mimic myelodysplastic syndrome. 1, 2, 3

Primary Deficiencies Affecting White Blood Cells

Vitamin B12 Deficiency

• Vitamin B12 deficiency causes pancytopenia (low counts of all blood cell types including white blood cells) due to impaired DNA synthesis affecting rapidly dividing cells in the bone marrow 1, 4, 5
• Morphological neutrophil abnormalities are common in vitamin B12 deficiency, including hypersegmented neutrophils and quantitative reductions in neutrophil counts 3
• Neutrophil function is specifically impaired in B12 deficiency, with metabolic activation decreased to 35-36% of normal values during phagocytosis, though this reverses after treatment 3
• Before treating suspected folate deficiency, always check and treat vitamin B12 deficiency first to avoid precipitating subacute combined degeneration of the spinal cord 1

Folate (Folic Acid) Deficiency

• Folate deficiency causes megaloblastic anemia with bone marrow megaloblastosis affecting white blood cell production, leading to leukopenia 1, 4, 5
• Severe megaloblastic anemia has been reported in adolescents and adults with inadequate folate consumption 1
• Treat confirmed folate deficiency with folic acid 5 mg orally daily for a minimum of 4 months, but only after excluding vitamin B12 deficiency 1

Copper Deficiency

• Copper deficiency causes neutropenia and can present with bicytopenia (anemia plus low white blood cells) with myelodysplastic features that mimic bone marrow disorders 2
• This deficiency is particularly seen after bariatric surgery or gastric reduction procedures 1, 2
• When both zinc and copper are low, prescribe two Forceval daily for 3 months and recheck levels; always check both zinc and copper levels together when considering replacement 1
• With severe copper deficiency, refer for specialist advice rather than attempting empiric treatment 1

Secondary Deficiencies

Zinc Deficiency

• Zinc deficiency has been reported in patients with various malabsorption conditions and can contribute to hematologic abnormalities 1
• When giving additional zinc and copper supplementation, maintain a ratio of 8-15 mg zinc to 1 mg copper with close monitoring 1

Protein Malnutrition

• Severe protein-energy malnutrition can cause pancytopenia including leukopenia due to inadequate substrate for protein synthesis in hematopoietic cells 1
• If protein malnutrition presents with edema, investigate potential causes and refer to appropriate specialist center 1

Selenium Deficiency

• Selenium deficiency has been reported in malabsorption conditions and should be investigated in unexplained cases of anemia or fatigue 1

Diagnostic Approach

Initial Laboratory Evaluation

• Obtain complete blood count with differential to characterize the leukopenia and identify associated cytopenias 4, 2
• Check serum vitamin B12, folate (red cell folate preferred), ferritin, and consider copper and zinc levels if malabsorption or bariatric surgery history exists 1, 4, 2
• Examine peripheral blood smear for hypersegmented neutrophils (suggesting B12/folate deficiency) or other morphological abnormalities 2, 5

When to Suspect Specific Deficiencies

• Vitamin B12 deficiency: Consider in vegetarians, elderly patients, those with pernicious anemia, gastric surgery, or malabsorption; may present with neurological symptoms even without anemia 1, 6, 5
• Folate deficiency: Consider in pregnancy, alcoholism, malabsorption disorders (celiac disease, inflammatory bowel disease), or inadequate dietary intake 1
• Copper deficiency: Strongly suspect in patients with prior bariatric surgery, gastric reduction, or excessive zinc supplementation 1, 2

Treatment Priorities

Vitamin B12 Deficiency Treatment

• For neurological involvement: Administer hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement, then 1 mg every 2 months 1
• Without neurological involvement: Hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks, then maintenance 1 mg every 2-3 months lifelong 1
• Seek urgent specialist advice from neurologist and hematologist if unexplained neurological symptoms exist 1

Folate Deficiency Treatment

• Critical: Check and treat vitamin B12 deficiency before initiating folic acid to avoid precipitating subacute combined degeneration of the spinal cord 1
• Treat with folic acid 5 mg orally daily for minimum 4 months 1
• Further investigation warranted if malabsorption suspected 1

Common Pitfalls to Avoid

• Never give folic acid first without excluding B12 deficiency, as this can mask B12 deficiency while allowing irreversible neurological damage to progress 1
• Do not assume normal B12/folate levels exclude deficiency if only checked once; coexisting iron deficiency can mask macrocytosis of B12/folate deficiency 6, 5
• Copper deficiency can mimic myelodysplastic syndrome; always consider nutritional causes before assuming primary bone marrow disorder in patients with malabsorption history 2
• Ethnicity and young age should not exclude consideration of pernicious anemia when clinical features suggest B12 deficiency 2
• When supplementing zinc, always monitor copper levels as excessive zinc can induce copper deficiency 1