What does the Research Show ?


In a review of seven randomized controlled trials that evaluate the efficacy of Vitamin B12 in the treatment of peripheral neuropathy, specifically diabetic neuropathy, Sun, Lai, and Lu showed that administration of Vitamin B12 improved symptomatic relief from neuropathy.

Studies that assessed any type of vitamin B12 therapy, including coenzyme forms of vitamin B12 (methylcobalamin, cyanocobalamin, hydroxycobalamin), in either oral or injection form were eligible for inclusion. The duration of treatment ranged from 4 to 16 weeks.

Pain or somatosensory symptoms (6 studies): all studies showed a statistically significant benefit compared with baseline or placebo.

Vibration perception threshold (4 studies): 3 studies showed a beneficial outcome with vitamin B12 compared with control or baseline, and one showed no improvement with methylcobalamin.

Autonomic symptoms (3 studies): all 3 studies found improvements with methylcobalamin.

Electophysiological measures (5 studies): in one trial that used a neuromotor assessment process to measure the current perception threshold, a beneficial treatment effect for vitamin B complex was observed. Of the 4 trials that included NCV testing, the only trial of vitamin B combination therapy and 2 of the 3 trials of methylcobalamin showed beneficial outcomes compared with placebo. The other study of methylcobalamin found no change.

Methylcobalamin versus conventional vitamin B12 (1 study): the study found that the outcomes were better with methylcobalamin than with conventional vitamin B12 in terms of autonomic symptoms, somatosensory symptoms and electrophysiological results.

Effectiveness of vitamin B12 on diabetic neuropathy: systematic review of clinical controlled trials

Sun Y, Lai M S, Lu C J. Effectiveness of vitamin B12 on diabetic neuropathy: systematic review of clinical controlled trials. Acta Neurologica Taiwanica 2005; 14(2): 48-54


Helps the body metabolize fats and proteins, and facilitates the conversion of carbohydrates into fuel (glucose), which is used to produce energy. Vitamin B6 is essential for proper nerve function. It is used by the body to make several neurotransmitters, chemicals that carry signals from one nerve cell to another.  In adults, neuropathy due to B6 deficiency starts with numbness, paresthesias, or burning pain in the feet which then ascends to affect the legs and eventually the hands. Vitamin B6 supplementation has been used to treat peripheral neuropathy and polyneuropathy due to Vitamin B6 deficiency


Methods: Pts starting treatment with a taxane were randomized to a 1/6 of 100% of the daily recommended dose of a multivitamin / day (placebo) versus the same multivitamin / day plus Vitamin B6, 50 mg three times a day, and Vitamin B12, 1 mg every 3-4 weeks. No other supplements were included. Formal neurologic examinations were performed prior to, and after 2 & 4 cycles of chemotherapy.

Results / Conclusion: 46 pts treated with taxanes were randomized; 22 to placebo (Daily Multi Vitamin) and 24 to Multivitamin+Vitamin B6 / B12. Based on neurologic examinations, the preliminary trends in this study suggested that vitamin supplementation with Vitamin B6 and B12 may reduce chemotherapy-induced neuropathy (CIN) during taxane-based chemotherapy.

Vitamins B6 and B12 supplementation to prevent chemotherapy-induced neuropathy (CiN): Interim analysis of the taxane cohort

C. F. Verschraegen, M. Royce, S. J. Lee, S. Movva, L. Susan, G. Michael; University of New Mexico, Albuquerque, NM. Vitamins B6 and B12 supplementation to prevent chemotherapy-induced neuropathy (CiN): Interim analysis of the taxane cohort. J Clin Oncol 27, 2009


Has been found to be a worthy adjuvant in the management of diabetic and peripheral neuropathy. Benfotiamine is a fat soluble analogue of Vitamin B1, also known as Thiamine. This compound has been found to help ameliorate pain from peripheral neuropathy, including neuropathy due to diabetes. Benfotiamine reduces the proliferation of metabolites that contribute to the damage of micro-vessels in the diabetic patient. The pathology of microvasculature damage is seen in diabetic retinopathy, nephropathy, and neuropathy.

MATERIALS AND METHODS: Forty inpatients (23 male, 18 female, age range 18 – 70 years) with a history of type 1 or 2 diabetes and polyneuropathy of not longer than two years, were included in the study. Twenty Patients received two 50 mg benfotiamine tablets four times daily and 20 patients received placebo over the three-week study period. Two clinical units were involved with 10 patients receiving placebo and 10 patients benfotiamine in each. The neuropathy score according to Katzenwadel et al. [1987] was used to evaluate symptoms of polyneuropathy, vibration perception threshold and both the physician’s and the patient’s own assessment were documented.

RESULTS: A statistically significant (p = 0.0287) improvement in the neuropathy score was observed in the group given active drug when compared to the placebo-treated controls. There was no statistically significant change observed in the tuning fork test. The most pronounced effect on complaints was a decrease in pain (p = 0.0414). More patients in the benfotiamine-treated group than in the placebo group considered their clinical condition to have improved (p = 0.052). No side effects attributable to benfotiamine were observed.

CONCLUSION: This pilot investigation (BEDIP Study) has confirmed the results of two earlier randomized controlled trials and has provided further evidence for the beneficial effects of benfotiamine in patients with diabetic neuropathy.

Benfotiamine in the treatment of diabetic polyneuropathy–a three-week randomized, controlled pilot study (BEDIP study).

Randomized controlled trial

Haupt E, et al. Int J Clin Pharmacol Ther. 2005.


In a randomized control trial, Ziegler D, et al sought to evaluate the effects of alpha-lipoic acid (ALA) on positive sensory symptoms and neuropathic deficits in diabetic patients with distal symmetric polyneuropathy (DSP).

RESEARCH DESIGN AND METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, 181 diabetic patients in Russia and Israel received once-daily oral doses of 600 mg (n = 45) (ALA600), 1,200 mg (n = 47) (ALA1200), and 1,800 mg (ALA1800) of ALA (n = 46) or placebo (n = 43) for 5 weeks after a 1-week placebo run-in period. The primary outcome measure was the change from baseline of the Total Symptom Score (TSS), including stabbing pain, burning pain, paresthesia, and asleep numbness of the feet. Secondary end points included individual symptoms of TSS, Neuropathy Symptoms and Change (NSC) score, Neuropathy Impairment Score (NIS), and patients’ global assessment of efficacy.

RESULTS: Mean TSS did not differ significantly at baseline among the treatment groups and on average decreased by 4.9 points (51%) in ALA600, 4.5 (48%) in ALA1200, and 4.7 (52%) in ALA1800 compared with 2.9 points (32%) in the placebo group (all P < 0.05 vs. placebo). The corresponding response rates (>/=50% reduction in TSS) were 62, 50, 56, and 26%, respectively. Significant improvements favoring all three ALA groups were also noted for stabbing and burning pain, the NSC score, and the patients’ global assessment of efficacy. The NIS was numerically reduced. Safety analysis showed a dose-dependent increase in nausea, vomiting, and vertigo.

CONCLUSIONS: Oral treatment with ALA for 5 weeks improved neuropathic symptoms and deficits in patients with DSP. An oral dose of 600 mg once daily appears to provide the optimum risk-to-benefit ratio.

Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial.

Randomized controlled trial

Ziegler D, et al. Diabetes Care. 2006.

QUATREFOLIC (Bioactive Folate)

Prescription medications and agents used to treat symptoms of diabetic peripheral neuropathy (DPN) are typically only palliative, not disease modifying. Thus, in this study, authors sought to assess the efficacy of oral administration of L-methylfolate (bioavailable folate), methylcobalamin, and pyridoxal 5’-phosphate for improving epidermal nerve fiber density (ENFD) in the lower extremities of patients with diabetic peripheral neuropathy.

Although studies of monotherapy with L-methylfolate, methylcobalamin, or pyridoxal 5′-phosphate suggest that each of these bioavailable B vitamins may reverse the pathophysiology and symptoms of DPN, data on the efficacy of this combination therapy were scarce.

METHODS: Eleven consecutive patients with type 2 diabetes with symptomatic DPN were assessed for ENFD at the calf by means of skin punch biopsy and then placed on twice daily oral-combination L-methylfolate, methylcobalamin, and pyridoxal 5′-phosphate.

RESULTS / CONCLUSIONS: After approximately 6 months of treatment, patients underwent follow-up biopsy. At the end of their treatment, 73% of patients showed an increase in calf ENFD, and 82% of patients experienced both reduced frequency and intensity of paresthesias and/or dysesthesias. This preliminary study suggests that combination L-methylfolate, methylcobalamin, and pyridoxal 5′-phosphate increases ENFD in patients with DPN.
Management of diabetic small-fiber neuropathy with combination L-methylfolate, methylcobalamin, and pyridoxal 5′-phosphate.

Jacobs AM1, Cheng D.

Reviews in Neurological Diseases. 2011;8 (1-2):39-47