Can a vitamin B12 (cobalamin) deficiency cause leg weakness?

Vitamin B12 Deficiency Causes Leg Weakness

Yes, vitamin B12 deficiency definitively causes leg weakness through multiple mechanisms including spinal cord demyelination, peripheral nerve damage, and impaired proprioception, making it a critical diagnosis to identify and treat immediately. 1, 2, 3

Mechanisms of Leg Weakness in B12 Deficiency

Neurological Pathways

Vitamin B12 deficiency damages the nervous system through extensive demyelination in the spinal cord (subacute combined degeneration) and axonal degeneration in peripheral nerves, particularly affecting distal sensory fibers. 1, 2 This creates a dual assault:

• Spinal cord damage causes gait ataxia and balance problems due to impaired proprioception, leading to sensory ataxia and increased falls 2, 3
• Peripheral neuropathy manifests as muscle weakness affecting various muscle groups, with symptoms typically starting distally in the legs 2, 4
• Nerve conduction velocity becomes significantly impaired, directly affecting peripheral motor function 1

Clinical Progression Pattern

The weakness follows a characteristic pattern where sensory loss (proprioceptive, vibratory, tactile, and nociceptive) typically appears before motor dysfunction. 3 As deficiency progresses, you'll observe:

• Muscle weakness, abnormal reflexes (both diminished and hyperactive tendon jerks), and spasticity 1, 3
• Myelopathies and myelo-neuropathies in advanced cases 1, 2
• In severe cases, patients become unable to sit or walk without support 2

Critical Diagnostic Pitfalls

Up to 50% of patients with "normal" serum B12 levels have metabolic deficiency when measured by methylmalonic acid (MMA). 2, 3 This is the single most important pitfall to avoid.

When to Suspect B12 Deficiency

Test any patient with leg weakness who has at least one risk factor:

• Vegan/vegetarian diet, restricted diets, or limited fortified food consumption 3
• Medications: metformin, proton pump inhibitors, H2 blockers, colchicine, phenobarbital, pregabalin, primidone 3, 5
• Autoimmune conditions (thyroid disease, Sjögren syndrome, type 1 diabetes) 3
• Atrophic gastritis, celiac disease 3
• Post-bariatric surgery patients 3
• Age >60 years 5

Diagnostic Algorithm

1. Initial test: Serum B12 level 5

   • <180 pg/mL = diagnostic for deficiency
   • 180-350 pg/mL = borderline, proceed to step 2

   • 350 pg/mL but high clinical suspicion = still proceed to step 2

2. Confirmatory test: Methylmalonic acid (MMA) 5

   • Elevated MMA confirms metabolic B12 deficiency even with "normal" B12 levels

3. Additional workup: Check complete blood count (may show macrocytic anemia but neurological symptoms often appear before anemia develops) 2, 3

Treatment Urgency and Protocol

The FDA label explicitly warns that vitamin B12 deficiency allowed to progress for longer than 3 months may produce permanent degenerative lesions of the spinal cord. 6 Immediate treatment is mandatory.

Treatment Based on Neurological Involvement

With neurological symptoms (including leg weakness):

• Hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement 3
• Then maintenance: 1 mg intramuscularly every 2 months for life 3

Without neurological involvement:

• Hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks 3
• Then maintenance: 1 mg intramuscularly every 2-3 months for life 3

Critical Treatment Warnings

Never give folic acid before or without B12 supplementation. 3, 6 Folic acid can mask the anemia while allowing irreversible neurological damage to progress, precipitating subacute combined degeneration of the spinal cord. 3, 6

Recovery Timeline

Based on documented cases, recovery follows a predictable sequence:

• Proximal muscle power recovers first 4
• Hand function returns next 4
• Plantar flexion of feet improves (by 3.5 months) 4
• Dorsiflexion of feet recovers last (by 5.5 months) 4
• Sensory conduction may take 14+ months to show improvement 4

Motor nerve conduction studies show amplitude increases within 2.5 months of treatment initiation. 4

Long-Term Monitoring

Patients require lifelong monthly B12 injections. 6 Failure to maintain treatment will result in return of symptoms and development of incapacitating and irreversible spinal cord damage. 6