Can low vitamin D (Vitamin D) levels cause elevated Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), and hyperferritinemia in an adult patient with normal Vitamin B12 and folate levels?

Can Low Vitamin D Cause Elevated MCV, MCH, and Ferritin?

No, low vitamin D does not directly cause elevated MCV, MCH, or ferritin—these findings suggest other underlying conditions that require specific investigation, particularly folate deficiency, medication effects, or chronic disease processes.

Understanding the Laboratory Pattern

Your combination of elevated MCV, elevated MCH, and elevated ferritin with normal B12 and folate creates a specific pattern that requires systematic evaluation:

Elevated MCV and MCH (Macrocytosis with Increased Hemoglobin Content)

• Folate deficiency remains a primary consideration even with "normal" serum levels, as tissue deficiency can exist despite normal serum measurements 1
• Elevated homocysteine and methylmalonic acid levels may reveal tissue deficiency of B12 or folate despite normal serum levels 1
• Medication-induced macrocytosis occurs commonly with thiopurines (azathioprine, 6-mercaptopurine), anticonvulsants, and methotrexate through myelosuppressive activity rather than vitamin deficiency 1, 2
• Chronic alcohol consumption causes macrocytosis independent of nutritional deficiencies 2
• Hypothyroidism can cause macrocytosis without anemia 2

Elevated Ferritin Pattern

• Ferritin is an acute phase protein that rises with inflammation, chronic disease, or infection—not from vitamin D deficiency 3
• A ferritin level of 195 μg/L (as suggested in your pattern) indicates adequate or elevated iron stores and suggests an inflammatory process rather than iron deficiency 2
• Ferritin above 150 μg/L is unlikely to occur with absolute iron deficiency, even in the presence of inflammation 3

Why Vitamin D Is Not the Cause

The evidence base provides no mechanistic link between vitamin D deficiency and these specific hematological parameters:

• Vitamin D deficiency does not cause macrocytosis or elevated MCH through any established pathway 3
• Vitamin D does not regulate ferritin production or iron metabolism in ways that would elevate ferritin 3
• Guidelines on macrocytosis evaluation do not include vitamin D assessment as part of the diagnostic algorithm 1, 2

Recommended Diagnostic Approach

First-Line Investigations

• Reticulocyte count is critical for distinguishing between ineffective erythropoiesis (low/normal) and increased red cell production from hemolysis or hemorrhage (elevated) 1
• Medication review for drugs known to cause macrocytosis, particularly thiopurines, anticonvulsants, methotrexate, and antiretrovirals 1, 2
• Thyroid function testing (TSH) to exclude hypothyroidism as a cause of macrocytosis 2
• Alcohol consumption history, as chronic use causes macrocytosis independent of nutritional deficiencies 2

Second-Line Investigations

• Homocysteine and methylmalonic acid levels to detect tissue deficiency of B12 or folate despite normal serum levels 1
• Liver function tests to evaluate for chronic liver disease, which can cause both macrocytosis and elevated ferritin 3
• Inflammatory markers (CRP, ESR) to assess for chronic inflammatory conditions that elevate ferritin 3
• Peripheral blood smear to evaluate red cell morphology and identify hemolysis or other abnormalities 1

Critical Clinical Pitfalls to Avoid

Mixed Deficiency States

• Concurrent iron deficiency can mask macrocytosis, resulting in a falsely normal MCV with elevated red cell distribution width (RDW) 1
• In your case with elevated ferritin, this is less likely, but MCH assessment remains valuable as reduced MCH despite macrocytosis suggests a mixed picture requiring iron studies 1
• More than 55% of vitamin B12 deficient patients show normal MCV, and 30% have no anemia or macrocytosis 4

Inflammatory Context

• In chronic inflammatory conditions, ferritin up to 100 μg/L may still represent iron deficiency due to its acute phase reactant properties 3, 1
• However, your elevated ferritin suggests inflammation or iron overload rather than deficiency 3
• A ferritin cut-off of 45 μg/L provides optimal sensitivity/specificity for iron deficiency in practice 3

Monitoring Requirements

• Regular CBC monitoring is necessary to track MCV stability, even if the cause remains unclear initially 1
• Reassess B12 and folate levels periodically, as deficiencies may develop over time despite initially normal levels 1
• Hematology consultation is recommended if the cause remains unclear after initial workup or if severe/progressive macrocytosis develops 1

Management Based on Findings

If medication-induced: Discuss risk/benefit with the prescribing physician, as macrocytosis from thiopurines may be acceptable if the medication is therapeutically necessary 1

If folate deficiency confirmed: Supplementation is indicated, with follow-up CBC to document response 2

If inflammatory condition identified: Address the underlying inflammatory process, as this explains the elevated ferritin 3

If unexplained: Consider bone marrow evaluation, particularly if other cytopenias develop, as this increases diagnostic yield for bone marrow disorders 1