JDM  Vol.4 No.2 , May 2014
Post-Marketing Surveillance of Fixed Dose Combination of Methylcobalamin, Alpha Lipoic Acid, Folic Acid, Biotin, Benfotiamine & Vitamin B6-Nutripathy for the Management of Peripheral Neuropathy
Abstract: Background: Peripheral neuropathy is a commonly encountered troublesome condition which is often disabling & worsens when left untreated. Traditional neuropathic pain medications primarily provide symptomatic relief; however, the pathogenesis of nerve damage remains unresolved. Extensive literature survey reveals that patients with peripheral neuropathy experience significant benefits with the use of B-vitamins like methylcobalamin (B12), folic acid (B9), biotin (B7), benfotiamine (B1) and pyridoxine (B6). The other well documented antineuropathic agents include alpha lipoic acid, glutathione, omega fatty acids, myoinositol, certain trace elements, etc. Materials and Methods: A multicentre, prospective, open-label, non-comparative clinical study was carried out in 497 patients with peripheral neuropathy. A fixed dose combination of methylcobalamin, alpha lipoic acid (ALA), folic acid, biotin, benfotiamine & vitamin B6 capsule was orally administered once daily for 12 weeks. Results: Treatment led to significant reduction from baseline score in various neuropathy symptoms from the 4th week itself. After 12 weeks of treatment, the mean pain score declined by 78.0%, numbness by 92.1% and muscle weakness by 96.9%. Also, there was 96.0% & 99.2% reduction in tingling & burning sensation respectively. No serious adverse events were reported.Conclusion: The current study confirms that fixed dose combination of methylcobalamin, ALA, folic acid, biotin, benfotiamine & vitamin B6 is effective & well tolerated in the management of peripheral neuropathy.
Cite this paper: Maladkar, M. , Tekchandani, C. and Dave, U. (2014) Post-Marketing Surveillance of Fixed Dose Combination of Methylcobalamin, Alpha Lipoic Acid, Folic Acid, Biotin, Benfotiamine & Vitamin B6-Nutripathy for the Management of Peripheral Neuropathy. Journal of Diabetes Mellitus, 4, 124-132. doi: 10.4236/jdm.2014.42019.

[1]   Bromberg, M.B. (2005) An Approach to the Evaluation of Peripheral Neuropathies. Seminars in Neurology, 25, 153-159.

[2]   John, C. P. and Gareth, W. (2003) Textbook of Diabetes 2. 3rd Edition, Blackwell Science Ltd., Oxford, 51.3.

[3]   Hammond, N., Wang, Y.X., Dimachkie, M.M and Barohn, R.J. (2013) Nutritional Neuropathies. Neurologic Clinics, 31, 477-489.

[4]   Food and Agriculture Organization of the United Nations (2012) The State of Food Insecurity in the World. Food and Agriculture Organization of the United Nations, Rome.

[5]   Fitzpatrick, T.B., Basset, G.J., Borel, P., Carrari, F., DellaPenna, D., Fraser P.D., et al. (2012) Vitamin Deficiencies in Humans: Can Plant Science Help. The Plant Cell, 24, 395-414.

[6]   Koike, H., Misu, K., Hattori, N., Ito, S., Ichimura, M., Ito, H., Hirayama, M., Nagamatsu, M., et al. (2001) Postgastrectomy Polyneuropathy with Thiamine Deficiency. Journal of Neurology, Neurosurgery & Psychiatry, 71, 357-362.

[7]   Rudnicki, S.A. (2010) Prevention and Treatment of Peripheral Neuropathy after Bariatric Surgery. Current Treatment Options in Neurology, 12, 29-36.

[8]   Alvarez, L. and Jacqueline, I. (2004) Nutrient Deficiencies Secondary to Bariatric Surgery. Current Opinion in Clinical Nutrition & Metabolic Care, 7, 569-575.

[9]   Healton, E.B., Savage, D.G., Brust, J.C., Garrett, T.J. and Lindenbaum, J. (1991) Neurologic Aspects of Cobalamin Deficiency. Medicine (Baltimore), 70, 229-245.

[10]   Tammy, J.L., Kirsten, V., Michael, T. and Christopher, M.H. (2012) Diabetic Neuropathic Pain: Real World Treatment Options. Clinical Medicine Insights: Therapeutics, 4, 169-183.

[11]   Lawrence, R.S. (2007) Disorders of Cobalamin (Vitamin B12) Metabolism: Emerging Concepts in Pathophysiology, Diagnosis and Treatment. Blood Reviews, 21, 113-130.

[12]   Reynolds, E. (2006) Vitamin B12, Folic Acid, and the Nervous System. The Lancet Neurology, 5, 949-960.

[13]   Beltramo, E., Berrone, E., Tarallo, S. and Porta, M. (2008) Effects of Thiamine and Benfotiamine on Intracellular Glucose Metabolism and Relevance in the Prevention of Diabetic Complications. Acta Diabetologica, 45, 131-141.

[14]   Stracke, H., Gaus, W., Achenbach, U., Federlin, K. and Bretzel, R. (2008) Benfotiamine in Diabetic Polyneuropathy (BENDIP): Results of a Randomised, Double Blind, Placebo-Controlled Clinical Study. Experimental and Clinical Endocrinology and Diabetes, 116, 600-605.

[15]   Maebashi, M., Makino, Y., Furukawa, Y., Kosaku, O., Kimura, S. and Sato, T. (1993) Therapeutic Evaluation of the Effect of Biotin on Hyperglycemia in Patients with Non-Insulin Dependent Diabetes Mellitus. Journal of Clinical Biochemistry and Nutrition, 14, 211-218.

[16]   Packer, L., Tritschler, H.J. and Wessel, K. (1997) Neuroprotection by the Metabolic Antioxidant α-Lipoic Acid. Free Radical Biology & Medicine, 22, 359-378.

[17]   Azhary, H., Farooq, M.U., Bhanushali, M., Majid, A. and Kassab, M.Y. (2010) Peripheral Neuropathy: Differential Diagnosis and Management. American Family Physician, 81, 887-892.

[18]   Kathleen, A. (2006) Peripheral Neuropathy: Pathogenic Mechanisms and Alternative Therapies. Alternative Medicine Review, 11, 294-329.

[19]   Maladkar, M., Saggu, N., Moralwar, P., Mhate, A.A., Zemse, D. and Bhoraskar, A. (2013) Evaluation of Efficacy and Safety of Epalrestat and Epalrestat in Combination with Methylcobalamin in Patients with Diabetic Neuropathy in a Randomized, Comparative Trial. Journal of Diabetes Mellitus, 3, 22-26.

[20]   Maladkar, M., Rajadhyaksha, G., Venkataswamy, N., Hariharan, R.S. and Lohati, S.R. (2009) Efficacy, Safety, and Tolerability of Epalrestat Compared to Methylcobalamine in Patients with Diabetic Neuropathy. International Journal of Diabetes in Developing Countries, 29, 28-34.

[21]   Manish, M., Srividya, S. and Parmi, P. (2013) Post-Marketing Surveillance of Epalrestat and Methylcobalamin—Game Changer in the Management of Diabetic Neuropathy: An Indian Perspective. The Indian Practitioner, 66, 683-688.

[22]   World Health Organization (2006) Neurological Disorders: Public Health Challenges. World Health Organization, 111-174.

[23]   Kumar, N. (2007) Nutritional Neuropathies. Neurologic Clinics, 25, 209-255.

[24]   Luo, J.J., Sivaraaman, K., Nouh, A. and Dun, N.J. (2014) Elevated Plasma Level of Homocysteine Is an Independent Risk Factor for Peripheral Neuropathy. British Journal of Medicine & Medical Research, 4, 161-169.

[25]   Areti, A., Yerra, V.G., Naidu, V.G.M. and Kumar, A. (2014) Oxidative Stress and Nerve Damage: Role in Chemotherapy Induced Peripheral Neuropathy. Redox Biology, 2, 289-295.

[26]   Bell, D.S. (2010) Metformin-Induced Vitamin B12 Deficiency Presenting as a Peripheral Neuropathy. Southern Medical Journal, 103, 265-267.

[27]   Steichen, O., Martinez-Almoyna, L. and De Broucker, T. (2006) Isoniazid Induced Neuropathy: Consider Prevention. Revue des Maladies Respiratoires, 23, 157-160.

[28]   Ito, T. and Jensen, R.T. (2010) Association of Long-Term Proton Pump Inhibitor Therapy with Bone Fractures and Effects on Absorption of Calcium, Vitamin B12, Iron, and Magnesium. Current Gastroenterology Reports, 12, 448-457.

[29]   Mintzer, S., Skidmore, C.T. and Sperling, M.R. (2012) B-Vitamin Deficiency in Patients Treated with Antiepileptic Drugs. Epilepsy & Behavior: E & B, 24, 341-344.

[30]   Zhang, M., Han, W.J., Hu, S.J. and Xu, H. (2013) Methylcobalamin: A Potential Vitamin of Pain Killer. Neural Plasticity, 2013, Article ID: 424651.

[31]   Sun, Y., Lai, M.S. and Lu, C.J. (2005) Effectiveness of Vitamin B12 on Diabetic Neuropathy: Systematic Review of Clinical Controlled Trials. Acta Neurologica Taiwanica, 14, 48-54.

[32]   Stracke, H., Lindemann, A. and Federlin, K. (1996) A Benfotiamine-Vitamin B Combination in Treatment of Diabetic Polyneuropathy. Experimental and Clinical Endocrinology & Diabetes, 104, 311-316.

[33]   Reljanovic, M., Reichel, G., Rett, K., Lobisch, M., Schuette, K., Moller, W., Tritschler, H.J. and Mehnert, H. (1999) Treatment of Diabetic Polyneuropathy with the Antioxidant Thioctic Acid (α-Lipoic Acid): A Two Year Multicenter Randomized Double-Blind Placebo-Controlled Trial (ALADIN II). Alpha Lipoic Acid in Diabetic Neuropathy. Free Radical Research, 31, 171-179.

[34]   Ziegler, D., Ametov, A., Barinov, A., Dyck, P.J., Gurieva, I., Low, P.A., Munzel, U., Yakhno, N., Raz, I., Novosadova, M., Maus, J. and Samigullin, R. (2006) Oral Treatment with α-Lipoic Acid Improves Symptomatic Diabetic Polyneuropathy: The SYDNEY 2 Trial. Diabetes Care, 29, 2365-2370.

[35]   Parry, T.E. (1994) Folate Responsive Neuropathy. Presse Médicale, 23, 131-137.

[36]   Yatzidis, H., Koutsicos, D., Agroyannis, B., Papastephanidis, C., Francos-Plemenos, M. and Delatola, Z. (1984) Biotin in the Management of Uremic Neurologic Disorders. Nephron, 36, 183-186.

[37]   Koutsikos, D., Agroyannis, B. and Tzanatos-Exarchou, H. (1990) Biotin for Diabetic Peripheral Neuropathy. Biomedicine & Pharmacotherapy, 44, 511-514. 90171-5