What are the early symptoms of vitamin B12 deficiency in an adult patient with a possible history of gastrointestinal issues or dietary restrictions?

Early Symptoms of Vitamin B12 Deficiency

The earliest symptoms of vitamin B12 deficiency are typically neurological—including pins and needles (paresthesia), numbness in the extremities, cognitive difficulties like brain fog and memory problems, and fatigue—often appearing before any blood count abnormalities develop. 1, 2

Neurological Symptoms (Often Appear First)

The neurological manifestations frequently mark the initial presentation and can occur even with normal hemoglobin levels:

• Peripheral neuropathy presenting as tingling, pins and needles, or numbness, typically starting in the hands and feet 1, 2
• Sensory disturbances affecting proprioception (position sense), vibratory sensation, and tactile sensation—proprioceptive and vibratory loss are particularly prominent 2
• Balance problems and gait ataxia due to impaired proprioception, leading to increased fall risk 1, 2
• Cognitive symptoms including difficulty concentrating, short-term memory loss, and "brain fog" 1, 2, 3
• Blurred vision related to optic nerve dysfunction 1, 2

Hematological Symptoms

Blood-related symptoms may develop later or concurrently:

• Anemia symptoms including fatigue, weakness, and pallor 1, 3
• Macrocytosis (enlarged red blood cells) on complete blood count, though this may be absent in one-third of cases 1

Other Early Manifestations

• Glossitis (tongue inflammation or soreness) 1, 2
• Fatigue and lethargy that doesn't respond to iron supplementation 1, 3, 4
• Depression and other psychiatric symptoms 3

Critical Clinical Pitfall

Up to 50% of patients with "normal" serum B12 levels (typically 180-350 pg/mL) actually have metabolic B12 deficiency when measured by methylmalonic acid (MMA). 1, 2 This means you cannot rely solely on serum B12 to rule out deficiency, especially in high-risk populations.

Neurological symptoms often present before hematological changes and can become irreversible if untreated, making early recognition crucial. 2, 5, 3 The most serious complication—subacute combined degeneration of the spinal cord with extensive demyelination—can develop even before anemia appears. 1, 2

High-Risk Populations to Screen

Consider testing for B12 deficiency in patients with these risk factors, even if asymptomatic:

• Age ≥75 years (18.1% have metabolic deficiency; 25% of those ≥85 years have low B12) 1, 6
• Vegan or strict vegetarian diet 1, 6, 3
• Metformin use >4 months 1, 6, 3
• Proton pump inhibitor or H2 blocker use >12 months 1, 6, 3
• Gastrointestinal conditions: atrophic gastritis, celiac disease, Crohn's disease, or history of gastric/intestinal resection 1, 6, 3
• Autoimmune conditions: thyroid disease, type 1 diabetes, Sjögren syndrome 1
• Pernicious anemia (baseline endoscopy should be considered in individuals aged ≥50 years with laboratory evidence of pernicious anemia) 7

Diagnostic Approach When Symptoms Present

When early symptoms are present:

1. Initial test: Serum total B12 (costs ~£2, rapid turnaround) 1, 3

   • <180 pg/mL = confirmed deficiency, treat immediately
   • 180-350 pg/mL = indeterminate, proceed to MMA testing

   • 350 pg/mL = deficiency unlikely, but consider MMA if high clinical suspicion

2. Confirmatory test for indeterminate results: Methylmalonic acid (MMA) 1, 6, 3

   • MMA >271 nmol/L confirms functional B12 deficiency with 98.4% sensitivity
   • MMA detects an additional 5-10% of patients with functional deficiency who have low-normal B12 levels 1

3. Complete blood count to assess for macrocytic anemia, though remember anemia may be absent in one-third of cases 1

The key is recognizing that neurological symptoms demand immediate attention and treatment, even before definitive laboratory confirmation, as delays can result in permanent neurological damage. 2, 5, 3