Signs of Vitamin B12 Deficiency
Vitamin B12 deficiency presents with a broad spectrum of neurological, hematological, psychiatric, and gastrointestinal manifestations that can occur independently or in combination—critically, neurological symptoms often appear before any blood abnormalities develop. 1
Neurological Manifestations (Most Important)
The neurological signs are the most concerning because they can become irreversible if treatment is delayed beyond 3 months, even when blood counts remain normal. 2
Sensory Symptoms (Typically Appear First)
- Paresthesias (pins and needles sensation) and numbness, particularly in the extremities and trunk, are the most common initial neurological complaints 1, 3
- Loss of proprioception and vibratory sensation in the lower extremities is the most common objective finding on examination 1, 4
- Impaired tactile and pain sensation can develop as deficiency progresses 1
Motor and Coordination Problems
- Gait ataxia and balance problems due to impaired proprioception represent early-stage deficiency 3
- Falls and difficulty walking without support may occur 1, 5
- Muscle weakness, abnormal reflexes, and spasticity develop as the condition progresses 1
- Subacute combined degeneration of the spinal cord with extensive demyelination represents severe, advanced deficiency 1, 3
Other Neurological Signs
- Blurred vision related to optic nerve dysfunction 1
- Cognitive difficulties, brain fog, concentration problems, and memory issues 3, 6
- Dementia, psychoses, and mood disturbances in severe cases 4
Hematological Manifestations
A critical pitfall: anemia is absent in one-third of cases, and normal blood counts do NOT exclude B12 deficiency. 3, 6
- Macrocytic anemia (enlarged red blood cells) when present 1, 3
- Hypersegmented neutrophils due to impaired DNA synthesis 3
- Anemia that doesn't respond to iron treatment, especially during pregnancy or breastfeeding 1
- In 27% of neurologically symptomatic patients, the hematocrit is normal, and in 23%, the mean corpuscular volume is normal 4
Other Physical Signs
- Glossitis (inflamed, smooth tongue) 1
- Severe fatigue and lethargy 7, 5
- Hypotonia (decreased muscle tone), particularly in infants and children 8, 5
Psychiatric and Cognitive Symptoms
- Depression and mood disturbances 7
- Disorientation and confusion 7
- Developmental arrest or regression in infants 8
Critical Diagnostic Pitfall
Up to 50% of patients with "normal" serum B12 levels (200-400 pg/mL) have functional metabolic deficiency when measured by methylmalonic acid (MMA). 1, 3 This means you cannot rely solely on serum B12 to rule out deficiency, especially in:
- Patients over 60 years old (18-25% have metabolic deficiency despite normal B12) 6
- Post-bariatric surgery patients 1
- Patients with autoimmune conditions (thyroid disease, type 1 diabetes) 1, 6
- Those on metformin, proton pump inhibitors, H2 blockers, or anticonvulsants for >4 months 1, 6
When to Suspect B12 Deficiency
Consider testing when patients present with:
- Any neurological symptoms listed above, even with normal blood counts 1, 3
- Unexplained fatigue with risk factors (vegetarian/vegan diet, age >60, autoimmune disease, gastric surgery, chronic medication use) 1, 9
- Anemia unresponsive to iron supplementation 1
- Cognitive decline or psychiatric symptoms in elderly patients 7
The key message: neurological damage can become permanent if deficiency progresses beyond 3 months untreated, so maintain high clinical suspicion and test liberally, especially when serum B12 is borderline (180-350 pg/mL) by adding MMA testing. 6, 2, 9