What are the symptoms of vitamin B12 deficiency?

Symptoms of Vitamin B12 Deficiency

Vitamin B12 deficiency presents with a broad spectrum of hematological, neurological, psychiatric, and gastrointestinal symptoms that can occur independently or in combination, with neurological manifestations often appearing before any blood abnormalities develop. 1

Neurological Symptoms (Often the First to Appear)

Sensory Manifestations

• Peripheral neuropathy with pins and needles, numbness, or tingling (paresthesia), particularly affecting the extremities and trunk, is one of the most common early symptoms 1, 2
• Sensory loss affecting proprioception (position sense), vibratory sensation, tactile sensation, and pain perception typically appears before motor dysfunction 1, 2
• Impaired balance and gait ataxia due to loss of proprioception can lead to falls and difficulty walking 1, 2

Motor and Coordination Problems

• Muscle weakness, abnormal reflexes, and spasticity occur as the deficiency progresses 1
• Inability to sit or walk without support may develop in severe cases 3
• Hand tremor can be present 3

Severe Neurological Complications

• Subacute combined degeneration of the spinal cord with extensive demyelination in the central nervous system represents a severe manifestation that can become irreversible if untreated 1, 2
• Axonal degeneration in distal afferent fibers of dorsal root ganglion neurons has been documented 1

Cognitive and Psychiatric Symptoms

• Brain fog, cognitive difficulties, and concentration problems are common complaints 2, 3
• Memory issues may be present 4
• Depressive symptoms can occur 5
• Mild disorientation may develop in some patients 5

Visual Symptoms

• Blurred vision related to optic nerve dysfunction can occur 1, 3

Hematological Symptoms

• Macrocytic anemia (enlarged red blood cells) is a classic finding, though it may be absent in one-third of cases 2, 4
• Anemia symptoms that don't respond to iron treatment, including fatigue and weakness 1, 6
• Hypersegmented neutrophils due to impaired DNA synthesis may be visible on blood smear 2

General Systemic Symptoms

• Severe fatigue is extremely common and may be the presenting complaint 6, 5, 3
• Glossitis (inflammation of the tongue) can be present 1, 4

Other Manifestations

• Syncope (fainting) has been reported, particularly in pediatric cases 3
• Dizziness can occur 3
• Convulsions have been documented in some cases 3

Critical Clinical Pitfalls

A major diagnostic pitfall is that normal serum B12 levels do not exclude functional B12 deficiency—up to 50% of patients with "normal" serum B12 have metabolic deficiency when measured by methylmalonic acid (MMA). 1, 2 This means patients can have all the symptoms listed above despite laboratory results showing B12 levels within the "normal" reference range.

Neurological damage from subacute combined degeneration can become permanent if treatment is delayed, making early recognition of symptoms critical even before hematological changes appear. 2 The neurological symptoms are often nonspecific and can be mistakenly attributed to other conditions, especially in elderly patients where they may be dismissed as normal aging. 5, 3

Symptoms can vary widely in severity and presentation, with some patients experiencing primarily neurological symptoms without any anemia, while others may have anemia without neurological manifestations. 3 The broad and nonspecific nature of these symptoms requires a high index of suspicion, particularly in high-risk populations including the elderly, vegetarians/vegans, patients on metformin or proton pump inhibitors, and those with gastrointestinal disorders. 1, 6