Does Iron Deficiency Cause Low B12 Levels?
No, iron deficiency does not directly cause vitamin B12 deficiency, but the two deficiencies frequently coexist because they share common underlying causes, particularly malabsorption conditions affecting the gastrointestinal tract. 1, 2
Why These Deficiencies Often Occur Together
The relationship between iron and B12 deficiency is primarily explained by shared underlying conditions rather than one causing the other:
Malabsorption syndromes are the most common link, including celiac disease, inflammatory bowel disease (Crohn's disease and ulcerative colitis), atrophic gastritis, and post-bariatric surgery states—all of which impair absorption of both nutrients simultaneously 1, 2
Autoimmune gastritis (pernicious anemia) causes both iron and B12 deficiency through parietal cell destruction, leading to reduced intrinsic factor (needed for B12 absorption) and increased gastric pH (impairing iron absorption) 3
H. pylori infection has been linked to both iron deficiency anemia and vitamin B12 deficiency through similar mechanisms of gastric dysfunction 1
Evidence on the Relationship
Iron deficiency is associated with lower B12 levels in clinical practice, but this represents concurrent deficiencies rather than causation:
In patients with iron deficiency anemia, low vitamin B12 levels (≤200 pmol/L) were found in 17.8% of cases 4
Among elderly patients with anemia, the most common causes are chronic disease and iron deficiency, with B12 deficiency representing a separate but frequently coexisting etiology 5
Importantly, treating iron deficiency can actually increase B12 levels: In young women with iron deficiency anemia treated with oral iron, serum B12 and folate levels increased significantly during treatment, even in those with baseline low B12 6
Clinical Implications for Diagnosis
When evaluating a patient with iron deficiency, you should actively screen for B12 deficiency, especially in high-risk populations:
Check B12 and folate levels at least annually in patients with inflammatory bowel disease, or if macrocytosis is present 1
In patients over 60 years with iron deficiency anemia, serum B12 should be routinely evaluated, as this age cutoff identifies 91% of patients with combined deficiency 4
For iron deficiency diagnosis: serum ferritin <30 μg/L indicates iron deficiency in the absence of inflammation; with inflammation present, ferritin up to 100 μg/L may still indicate iron deficiency 1
For B12 deficiency diagnosis: measure serum B12, and consider methylmalonic acid and homocysteine if B12 levels are equivocal 2
Key Diagnostic Pitfall to Avoid
Combined iron and B12 deficiency can mask the typical laboratory findings of each condition:
Iron deficiency causes microcytosis (low MCV), while B12 deficiency causes macrocytosis (high MCV)—when both are present, the MCV may appear falsely normal 1, 4
Do not rely on MCV alone to exclude either deficiency when both conditions may coexist 4
Macrocytosis, the hallmark of B12 deficiency, is frequently absent when iron deficiency is also present 4
Treatment Considerations
When both deficiencies are identified:
Treat both deficiencies simultaneously rather than sequentially 1
Iron supplementation: oral iron 100 mg/day for mild anemia (Hb >10 g/dL); intravenous iron is preferred for intolerance to oral iron, inadequate response, or moderate-to-severe anemia 1
B12 supplementation: hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks, then maintenance with 1 mg every 2-3 months for life in malabsorption conditions 2
Monitor response to treatment: failure of iron supplementation to correct anemia should prompt investigation for concurrent B12 or folate deficiency 1