Can a vitamin B12 deficiency cause iron deficiency in patients, particularly those with gastrointestinal disorders, older adults, or individuals on certain medications?

Does Low B12 Cause Low Iron?

Vitamin B12 deficiency does not directly cause iron deficiency, but both deficiencies frequently coexist due to shared underlying malabsorption conditions rather than one causing the other. 1

Understanding the Relationship

The connection between low B12 and low iron is primarily through common causative mechanisms, not a direct causal pathway:

Shared Malabsorption Conditions

• Autoimmune gastritis (pernicious anemia) causes parietal cell atrophy, reducing both intrinsic factor (needed for B12 absorption) and gastric acid (needed for iron absorption) 2
• Inflammatory bowel disease (particularly Crohn's disease with ileal involvement) impairs absorption of both nutrients, with one-third of active IBD patients having iron deficiency anemia 1
• Celiac disease damages the small intestinal mucosa, affecting absorption of both iron and B12 1, 3
• Post-bariatric surgery reduces gastric acid production and intrinsic factor availability, creating exceptionally high risk for both deficiencies 1, 4

Medication-Induced Dual Deficiency

• Proton pump inhibitors (PPIs) used for ≥2 years strongly associate with both iron deficiency (adjusted OR: 2.49 for high-dose use) and B12 deficiency (OR: 1.95 for high-dose use) by reducing gastric acid needed for both nutrients 1
• Metformin use >4 months increases B12 deficiency risk 1, 5
• H2 receptor antagonists similarly impair absorption of both nutrients through acid suppression 1, 3

Clinical Recognition Pattern

When evaluating patients with concurrent deficiencies, look for these specific features:

In Pernicious Anemia Patients

• 75% have concurrent iron deficiency at diagnosis or during follow-up 2
• Iron-deficient PA patients paradoxically have higher plasma B12 levels (p=0.04) and lower homocysteine levels (p=0.04) compared to iron-replete PA patients 2
• "APCA alone" immunological status (anti-parietal cell antibodies without anti-intrinsic factor antibodies) independently associates with iron deficiency (aOR 12.1, p=0.04) 2
• Higher APCA levels correlate with lower ferritin 2

In IBD Patients

• Consider folate deficiency, B12 deficiency, or bone marrow depression as other causes of anemia beyond iron deficiency 1
• Ferritin levels up to 100 µg/L in the presence of inflammation may still reflect iron deficiency; measure transferrin saturation (<20% supports deficiency) 1
• Systemic inflammation inhibits iron absorption, making oral iron ineffective in active disease 1

Diagnostic Algorithm

Step 1: Initial Testing

• Measure serum B12 (or active B12/holotranscobalamin) and complete iron panel (ferritin, transferrin saturation, TIBC) simultaneously 1, 3
• If B12 <180 pg/mL: confirmed deficiency 5
• If B12 180-350 pg/mL: measure methylmalonic acid (MMA); elevated MMA confirms functional deficiency 5
• If ferritin <30 µg/L without inflammation: confirmed iron deficiency 1, 3

Step 2: Identify Underlying Cause

• Test for H. pylori and autoimmune gastritis markers (anti-parietal cell antibodies, anti-intrinsic factor antibodies) 5
• Review medication history: PPIs, metformin, H2 blockers 1, 5
• Assess for malabsorption: celiac serology, IBD evaluation, history of GI surgery 1, 3

Step 3: Evaluate for GI Blood Loss

• Even without anemia, investigate sources of iron loss (most common cause in adults) 3
• Consider endoscopic evaluation if absolute iron deficiency present 1

Treatment Implications

For B12 Deficiency

• Oral B12 1,000-2,000 mcg daily is as effective as intramuscular administration for most patients 6, 5
• Use intramuscular B12 if severe neurologic manifestations, confirmed malabsorption, or oral therapy failure 5
• In pernicious anemia with ileal resection >20 cm: 1,000 mcg IM monthly for life 7, 3

For Iron Deficiency

• In pernicious anemia patients, intravenous iron is significantly more effective than oral supplementation (7/8 normalized iron status vs. 3/11 with oral iron at 3 months, p=0.02) 2
• In active IBD, use intravenous iron first-line for moderate-severe anemia (Hb <100 g/L) or oral iron intolerance; limit oral iron to ≤100 mg elemental iron daily in inactive disease 1
• In chronic heart failure with iron deficiency, use intravenous iron (prognostic benefit demonstrated); avoid oral iron due to poor absorption and side effects 1

Critical Pitfalls to Avoid

• Never supplement folate before treating B12 deficiency, as this may mask anemia while allowing irreversible neurological damage to progress 4
• Do not rely solely on serum B12 to rule out deficiency—up to 50% of patients with "normal" serum B12 have metabolic deficiency when measured by MMA 7, 4
• Do not assume elevated B12/folate levels exclude deficiency—recent supplementation may mask underlying absorption issues causing iron deficiency 3
• In elderly patients (>60 years), 18.1% have metabolic B12 deficiency despite normal serum levels; always consider functional markers 7
• Regular monitoring is essential: annual B12 and folate screening for patients with small bowel disease, ileal resection, or post-bariatric surgery 4