Causes of Low Vitamin B12
Vitamin B12 deficiency results from three primary mechanisms: inadequate dietary intake, impaired gastrointestinal absorption, and medication-induced malabsorption. 1
Dietary Causes
- Vegan and vegetarian diets are the most common dietary cause, as B12 is found exclusively in animal-source foods including eggs, milk, red meat, poultry, fish, and shellfish 1, 2
- Food insecurity and malnutrition lead to deficiency in individuals who cannot afford or access B12-rich foods 1
- Restricted diets from eating disorders or food allergies (eggs, milk, fish) prevent adequate B12 intake 1
- Elderly patients with dementia or frailty who have difficulty buying or preparing food are at high risk 1
Gastrointestinal and Malabsorption Causes
Gastric Causes
- Atrophic gastritis affecting the gastric body impairs intrinsic factor production, which is essential for B12 absorption 1
- Pernicious anemia (autoimmune destruction of gastric parietal cells) is a classic malabsorption cause 3
Intestinal Causes
- Ileal resection >20 cm requires prophylactic monthly B12 injections for life, as the terminal ileum is the primary absorption site 3
- Crohn's disease with ileal involvement >30-60 cm causes deficiency even without surgical resection 3
- Bariatric surgery (especially Roux-en-Y gastric bypass and biliopancreatic diversion) permanently impairs B12 absorption 3
- Celiac disease and other malabsorption syndromes disrupt intestinal B12 uptake 1
Medication-Induced Causes
- Metformin is a well-documented cause requiring monitoring per MHRA safety advice 1
- Proton pump inhibitors (PPIs) and H2 receptor antagonists reduce gastric acid needed for B12 release from food 1, 2
- Colchicine interferes with B12 absorption 1
- Anticonvulsants (phenobarbital, primidone, pregabalin) deplete B12 stores 1
High-Risk Populations Requiring Screening
- Patients over 75 years have 18.1% prevalence of metabolic B12 deficiency 3
- Family history of B12 deficiency or autoimmune conditions (thyroid disease, Sjögren syndrome, type 1 diabetes) increases risk 1
- Chronic alcohol use disorder with or without liver involvement causes deficiency 2
- Pregnant and breastfeeding women have increased B12 requirements 1
Clinical Pitfall to Avoid
Never assume normal B12 levels exclude deficiency—if clinical suspicion is high based on symptoms (neurological findings, macrocytosis, cognitive impairment) or risk factors, measure methylmalonic acid (>271 nmol/L confirms functional deficiency) even when serum B12 is borderline (140-200 pmol/L). 1, 4 This is critical because irreversible neurological damage can occur before serum B12 drops to clearly deficient levels. 5