Objective:

To evaluate whether B12 insufficiency at fasting levels 400-600 pg/mL contributes to neuromuscular dysfunction, specifically weakness.

Background:

B12 deficiency is a recognized cause of neuropathy and CNS-related disorders at serum levels </= 200 pg/mL.  Current guidelines note abnormalities in 5-10% with levels up to 400 and < 1% above 400.  Weakness, however, has not been described as a primary manifestation at higher levels.

Design/Methods:

Between May 2022 and October 2025 patients found to have weakness underwent full neurological examination including multi-region strength testing (using MRC grading) as well as laboratory studies, EMG and MRI.  144 had fasting B12 < 600 and were supplemented with 1000 mcg sublingually daily.

Results:

Among patients 35% had B12 400-600 (10% > 500, 569 highest), 62% 200-400 and 3% < 200. Duration of symptoms ranged from 4-6 months to 10 years.  Most frequent complaints were sensory, gait impairment and pain, weakness less commonly reported. Weakness averaged MRC 4- to 4+ (in neck flexion, shoulder abduction/flexion/external rotation, elbow flexion/extention, hip flexion/abduction, knee flexion, and ankle dorsiflexion).  Tendon reflexes were variably reduced but occasionally brisk in association with weakness (likely related to upper motor neuron dysfunction).  Sensory loss (vibration and pinprick) was modest. Electrodiagnostic findings included sensory-motor mainly axon-loss polyneuropathy (<400 21%, 400-600 25%).  CBC, folate and MMA were normal.  Within 1 to 3 months, most patients improved to normal strength (MRC 5) along with improved balance and energy.  Sensory recovery usually lagged.  Some patients with longstanding weakness showed improvement in proximal muscles but weakness persisted mainly in ankle dorsiflexors and somewhat in hip flexors.

Conclusions:

B12 insufficiency, determined in the fasting state at 400-600 pg/mL, is an under recognized cause of weakness of both proximal and distal muscles of the upper and lower limbs and readily reversed by vitamin B12, taken sublingually.  Timely supplementation may prevent treatment-resistant weakness.