Can a Patient Have Concurrent Iron and Vitamin B12 Deficiency?
Yes, patients can absolutely have both iron and vitamin B12 deficiency simultaneously, and this combination is clinically common, particularly in conditions affecting gastrointestinal absorption. 1
Why These Deficiencies Coexist
The concurrent presentation of iron and B12 deficiency stems from shared underlying pathophysiology:
Malabsorption syndromes are the primary culprit, with conditions like celiac disease, inflammatory bowel disease, autoimmune gastritis, and post-bariatric surgery states impairing absorption of both nutrients simultaneously. 1
Autoimmune gastritis (leading to pernicious anemia) causes parietal cell atrophy and increased gastric pH, which impairs both intrinsic factor production (needed for B12 absorption) and iron absorption. 2
In pernicious anemia specifically, iron deficiency occurs in 75% of patients—either present at diagnosis or developing during follow-up—making combined deficiency the rule rather than the exception. 2
Clinical Presentation Patterns
When both deficiencies coexist, the anemia pattern can be confusing:
Iron deficiency may mask B12 deficiency initially, presenting as microcytic anemia. Once iron is repleted, the underlying macrocytic anemia from B12 deficiency becomes apparent. 3
Patients with combined deficiency may show mixed morphology or normocytic indices as the microcytic and macrocytic effects cancel each other out. 4
Iron deficient patients with pernicious anemia have higher plasma B12 levels and lower homocysteine compared to those without iron deficiency, suggesting iron deficiency may occur earlier in the disease course. 2
Critical Diagnostic Approach
Before treating either deficiency, obtain comprehensive baseline testing:
Check CBC, serum iron, ferritin, TSAT, vitamin B12, folate, and methylmalonic acid (MMA) before initiating any therapy. 1, 5
For iron deficiency: Ferritin <30 ng/mL or TSAT <20% confirms absolute iron deficiency in the absence of inflammation. 4, 1
For B12 deficiency: Serum B12 levels should be measured along with MMA and homocysteine for confirmation. 1
Macrocytic anemia (MCV >100 fL) suggests B12 or folate deficiency, but normal MCV does not exclude combined deficiency. 4
Treatment Sequence and Pitfalls
The most critical pitfall: Never give folate or folinic acid before ruling out B12 deficiency, as folate can mask B12 deficiency while allowing irreversible neurological damage to progress. 5
Treatment Protocol:
Correct B12 deficiency first or simultaneously with iron: Use cyanocobalamin 100 mcg IM daily for 6-7 days, then alternate days for seven doses, then every 3-4 days for 2-3 weeks, followed by 100 mcg monthly for life. 6
For iron deficiency in pernicious anemia patients, intravenous iron is significantly more effective than oral supplementation: 7/8 patients normalized iron status with IV iron versus only 3/11 with oral iron at 3 months. 2
Absolute iron deficiency (TSAT <20%, ferritin <30 ng/mL) should receive IV iron monotherapy preferentially. 4
Functional iron deficiency (TSAT 20-50%, ferritin 30-800 ng/mL) can be treated with IV iron alone or combined with erythropoiesis-stimulating agents if indicated. 4
Monitoring Response
Recheck folate and B12 levels at 3 months to confirm normalization. 4, 5
Monitor CBC to assess hematologic response and watch for unmasking of previously hidden deficiencies. 5
Iron studies should be rechecked if anemia persists despite vitamin supplementation. 5
In pernicious anemia patients, regular assessment of iron status is essential given the 75% prevalence of iron deficiency. 2
High-Risk Populations Requiring Vigilance
Post-bariatric surgery patients have impaired absorption of both nutrients and require lifelong monitoring. 1
Inflammatory bowel disease patients commonly develop both deficiencies due to chronic inflammation and malabsorption. 1
Autoimmune gastritis/pernicious anemia patients should be screened for iron deficiency at diagnosis and regularly thereafter. 2
Patients with chronic kidney disease may have altered metabolism of both nutrients requiring more frequent monitoring. 5