Dr. Ron’s Research Review – October 15, 2014

© 2014

This week’s research review focuses on peripheral neuropathy and Alpha Lipoic Acid plus Methylcobalamin.

Methylcobalamin

High dose Methylcobalamin (25 mg/day x10 days, then 25 mg monthly for 5 months) was effective in 7 of 12 patients with peripheral neuropathy (Shibuya et al., 2014)

Alpha Lipoic Acid

A meta-analysis provided evidence that treatment with ALA (300-600 mg/day i.v. for 2-4 weeks) is safe and can significantly improve both nerve conduction velocity and positive neuropathic symptoms.  (Han et al., 2012)

LA-MC

A meta-analysis showed that daily lipoic acid (300-600 mg i.v.) plus methylcobalamin (500-1000 mg i.v. or im.) (LA-MC) for 2-4 weeks is associated with better outcomes in nerve conduction velocity. (Xu et al., 2013)

 

Dr. Ron


 

Articles

A systematic review and meta-analysis of alpha-lipoic acid in the treatment of diabetic peripheral neuropathy.
            (Han et al., 2012) Download
OBJECTIVE: To evaluate the effects and safety of 300-600 mg alpha-lipoic acid (ALA) given i.v. for diabetic peripheral neuropathy (DPN). METHODS: We searched the databases of Medline, Embase, and Cochrane central register of Controlled Trials and Chinese biological medicine for clinical trials of ALA in the treatment of DPN. Data were extracted to examine methodological quality and describe characteristics of studies. The primary outcomes were efficacy, median motor nerve conduction velocity (MNCV), median sensory nerve conduction velocity (SNCV), peroneal MNCV, and peroneal SNCV. Secondary outcomes were adverse events. RESULTS: Fifteen randomized controlled trials met the inclusion criteria. The treatment group involved the administration of ALA 300-600 mg i.v. per day. And the control group used the same interventions except for ALA. Compared with the control group, nerve conduction velocities increased significantly in the treatment group. The weighted mean differences in nerve conduction velocities were 4.63 (95% confidence interval 3.58-5.67) for median MNCV, 3.17 (1.75-4.59) for median SNCV, 4.25 (2.78-5.72) for peroneal MNCV, and 3.65 (1.50-5.80) for peroneal SNCV in favor of the treatment group. The odds ratio in terms of efficacy was 4.03 (2.73-5.94) for ALA. Furthermore, no serious adverse events were observed during the treatment period. CONCLUSIONS: The results of this meta-analysis provide evidence that treatment with ALA (300-600 mg/day i.v. for 2-4 weeks) is safe and that the treatment can significantly improve both nerve conduction velocity and positive neuropathic symptoms. However, the evidence may not be strong because most of the studies included in this meta-analysis have poor methodological quality.

Safety and Efficacy of Intravenous Ultra-high Dose Methylcobalamin Treatment for Peripheral Neuropathy: A Phase I/II Open Label Clinical Trial.
            (Shibuya et al., 2014) Download
Objective No clinically effective treatment for promoting peripheral axonal regeneration has yet been established. Several experimental studies in vitro and in vivo have shown that a high dose of methylcobalamin (MeCbl), an analogue of vitamin B12, promotes axonal growth in peripheral nerve injury. We herein assessed the safety and efficacy of an ultra-high dose MeCbl treatment for patients with peripheral neuropathy and chronic axonal degeneration. Methods Fourteen patients with immune-mediated or hereditary neuropathy in the chronic progressive or stable phase were enrolled. MeCbl, 25 mg/day for 10 days followed by monthly 25 mg for 5 months, was intravenously administered. The patients were evaluated before and 1 year following treatment. The primary endpoints were safety and improvement in the Medical Research Council (MRC) sum score in at least two muscles of the 20 muscles. This trial is registered with the University Hospital Medical Information Network (UMIN) Center in Japan under the ID: UMIN000009359. Results There were no adverse effects in twelve of the patients, whereas treatment was discontinued in two patients who had seborrheic dermatitis at 3 months and respiratory tract infection at 2 months, respectively. Therefore, twelve patients were evaluated for the primary outcomes; the MRC sum score was improved in seven of the patients and unchanged or worsened in the remaining five patients. Conclusion Intravenous ultra-high dose MeCbl treatment is a safe and potentially efficacious therapy for patients with peripheral neuropathy and chronic axonal degeneration.

Meta-analysis of methylcobalamin alone and in combination with lipoic acid in patients with diabetic peripheral neuropathy.
            (Xu et al., 2013) Download
AIMS: To compare the efficacy and safety of daily lipoic acid (300-600 mg i.v.) plus methylcobalamin (500-1000 mg i.v. or im.) (LA-MC) with that of methylcobalamin alone (MC) on diabetic peripheral neuropathy (DPN). METHODS: Electronic database were searched for studies published up to November 1, 2012 and study quality was assessed in duplicate. A random or a fixed effect model was used to analyse outcomes which were expressed as risk ratios (RRs) or mean difference (MD). I(2) statistic was used to assess heterogeneity. RESULTS: Seventeen studies were included. Combined data from all studies showed that the LA-MC combination therapy was significantly superior to MC monotherapy (RR=1.47; 95% CI: 1.37-1.58). Superiority of the LA-MC combination was shown in nerve conduction velocity (NCV) with WMDs of 6.89 (95% CI: 4.24-9.73) for median motor nerve conduction velocity (MNCV), 5.24 (4.14-6.34) for median sensory nerve conduction velocity (SNCV), 4.34 (3.03-5.64) for peroneal MNCV, and 4.53 (3.2-5.85) for peroneal SNCV. There were no serious adverse events associated with treatment. CONCLUSIONS: The results of the meta-analysis show that treatment with LA-MC for 2-4 weeks is associated with better outcomes in NCV and neuropathic symptoms relative to MC treatment. However larger well-designed studies are required to confirm this conclusion.


 

References

Han, T, et al. (2012), ‘A systematic review and meta-analysis of alpha-lipoic acid in the treatment of diabetic peripheral neuropathy.’, Eur J Endocrinol, 167 (4), 465-71. PubMedID: 22837391
Shibuya, K, et al. (2014), ‘Safety and Efficacy of Intravenous Ultra-high Dose Methylcobalamin Treatment for Peripheral Neuropathy: A Phase I/II Open Label Clinical Trial.’, Intern Med, 53 (17), 1927-31. PubMedID: 25175124
Xu, Q, et al. (2013), ‘Meta-analysis of methylcobalamin alone and in combination with lipoic acid in patients with diabetic peripheral neuropathy.’, Diabetes Res Clin Pract, 101 (2), 99-105. PubMedID: 23664235