Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Aim: To investigate the effect of normalizing vitamin B12 (B12) levels with oral B12 (methylcobalamin) 1000 μg/day for one year in patients with diabetic neuropathy (DN). Patients and methods: In this prospective, double-blind, placebo-controlled trial, 90 patients with type 2 diabetes on metformin for at least four years and both peripheral and autonomic DN were randomized to an active treatment group (n = 44) receiving B12 and a control group (n = 46) receiving a placebo. All patients had B12 levels less than 400 pmol/L. Subjects underwent measurements of sural nerve conduction velocity (SNCV), sural nerve action potential (amplitude) (SNAP), and vibration perception threshold (VPT), and they performed cardiovascular autonomic reflex tests (CARTs: mean circular resultant (MCR), Valsalva test, postural index, and orthostatic hypotension). Sudomotor function was assessed with the SUDOSCAN that measures electrochemical skin conductance in hands and feet (ESCH and ESCF, respectively). We also used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE, respectively) and questionnaires to evaluate quality of life (QoL) and level of pain (pain score). Results: B12 levels increased from 232.0 ± 71.8 at baseline to 776.7 ± 242.3 pmol/L at follow-up, p < 0.0001, in the active group but not in the control group. VPT, MNSIQ, QoL, pain score, SNCV, SNAP, and ESCF significantly improved in the active group (p < 0.001, p = 0.002, p < 0.0001, p < 0.000, p < 0.0001, p < 0.0001, and p = 0.014, respectively), whereas CARTS and MNSIE improved but not significantly. MCR, MNSIQ, SNCV, SNAP, and pain score significantly deteriorated in the control group (p = 0.025, p = 0.017, p = 0.045, p < 0.0001, and p < 0.0001, respectively). Conclusions: The treatment of patients with DN with 1 mg of oral methylcobalamin for twelve months increased plasma B12 levels and improved all neurophysiological parameters, sudomotor function, pain score, and QoL, but it did not improve CARTS and MNSIE.

Long-term metformin therapy and vitamin B12 deficiency: an association to bear in mind

“…In a recent 12-mo, randomized, double-blind, placebo-controlled trial, 90 adults with T2D on metformin therapy for at least 4 years and with both diabetic peripheral and autonomic neuropathy were randomized to receive vitamin B12 (1 mg of oral methylcobalamin) or placebo on a daily basis[ 56 ]. All participants had baseline vitamin B12 levels of < 400 pmol/L.…”

“…All participants had baseline vitamin B12 levels of < 400 pmol/L. Compared with placebo, vitamin B12 supplementation led to a significant increase in vitamin B12 levels (from 232.0 ± 71.8 pmol/L at baseline to 776.7 ± 242.3 pmol/L at follow-up) that was accompanied by a significant improvement in Michigan Neuropathy Screening Instrument Questionnaire, quality of life and pain scores, vibration perception threshold, electrochemical skin conductance in the feet, and sural nerve conduction velocity and amplitude[ 56 ]. Overall, these findings highlight the importance of diagnosing and correcting vitamin B12 deficiency in metformin-treated patients with diabetes and neuropathy in order to prevent or halt the exacerbation and progression of nerve damage.…”

Screening, diagnosis and management of diabetic sensorimotor polyneuropathy in clinical practice: International expert consensus recommendations

“…In patients with deficient status, these vitamins should be supplemented. Vitamin B12 supplementation in deficient patients with DSPN has been shown to be effective in reducing neurophysiological parameters, pain intensity, and sudomotor function 131 . Excessive vitamin B6 ingestion may cause neurotoxicity [132][133][134][135] .…”

The role of vitamin B12 in viral infections: a comprehensive review of its relationship with the muscle–gut–brain axis and implications for SARS-CoV-2 infection

“… 22–25 Studies tested vitamin B 12 supplementation to alleviate some of the symptoms of various diseases that are also present in COVID-19 ( Table 2 ). 23 , 99–112 Two RCTs 99 , 110 and 5 meta-analyses 23 , 100–102 , 109 reported benefits of vitamin B 12 supplementation in methylcobalamin (0.5–1 mg orally or local injection for 2 weeks to 1 year) and cyanocobalamin (2000 mg orally or 1–1000 mg via intramuscular route for 90 days and 4 months) forms. The benefits were mainly in analgesic action and attenuation of neurologic symptoms.…”