Objective: To study the effect of addition of Metanx on burning parasthesias in patients with symptomatic diabetic neuropathy who had obtained only partial symptom resolution with pregabalin. Research design and methods: This was an open-label pilot study. There were 16 patients (7 males, 9 females) in the study group and 8 patients (3 males, 5 females) in the control group. A patient numeric rating scale (0 - 10) of neuropathy associated pain was obtained at baseline and at 20 weeks. The control group con tinued on a fixed dosage of pregabalin (Lyrica ) without additional medication, while the study group was supplemented with Metanx (L-methylfolate, methylcobalamin, and pyridoxal 5- phosphate), in addition to being continued on a fixed dosage of pregabalin. Results: After 20 weeks, patients in the study group experienced greater pain relief compared to the control group, (87.5% vs. 25% respectively, p = 0.005). The average pain score reduction after 20 weeks in the study group was 3 compared to0.25 inthe control group (p < 0.001). Conclusion: Our study suggested that addition of Metanx may be used for the relief of pain in patients that have obtained only partial resolution of symptomatology from pregabalin.
Boulton, A.J., Vinik, A.I., Arezzo, J.C., et al. (2005) Diabetic neuropathies: A statement by the American Diabetes Association. Diabetes Care, 28, 956-962. doi:10.2337/diacare.28.4.956
Boulton, A.J., Vileikyte, L., Ragnarson-Tennvall, G. and Apelqvist, J. (2005) The global burden of diabetic foot disease. Lancet, 366, 1719-1724. doi:10.1016/S0140-6736(05)67698-2
Lesser, H., Sharma, U., LaMoreaux, L. and Poole, R.M. (2004) Pregabalin relieves symptoms of painful diabetic neuropathy: A randomized controlled trial. Neurology, 63, 2104-2110. doi:10.1212/01.WNL.0000145767.36287.A1
Argoff, C.E., Backonja, M.M., Belgrade, M.J., et al. (2006) Consensus guidelines: Treatment planning and options. Diabetic peripheral neuropathic pain. Mayo Clinic Proceedings, 81, S12-S25. doi:10.1016/S0025-6196(11)61474-2
Richter, R.W., Portenoy, R., Sharma, U., LaMoreaux, L., Bockbrader, H. and Knapp, L.E. (2005) Relief of painful diabetic peripheral neuropathy with pregabalin: A randomized, placebocontrolled trial. Journal of Pain, 6, 253-260. doi:10.1016/j.jpain.2004.12.007
Sadekov, R.A., Danilov, A.B. and Vein, A.M. (1999) Diabetic polyneuropathy treatment with Benfotimine. Arzneimittelforschung, 49, 220-224.
Yaqub, B.A., Siddique, A. and Sulimani, R. (1992) Effects of methylcobalamin on diabetic neuropathy. Clinical Neurology and Neurosurgery, 94, 105-111. doi:10.1016/0303-8467(92)90066-C
Walker, M. and Morris, L. (2007) Increased cutaneous sensibility in patients with diabetic neuropathy utilizing a pharmacological approach-clinical case evidence. Vascular Disease Management, 2, 1-8.
Walker Jr., M.J., Morris, L.M. and Cheng, D. (2010) Improvement of cutaneous sensitivity in diabetic peripheral neuropathy with combination L-methylfolate, methylcobalamin, and pyridoxal 5’-phosphate. Reviews in Neurological Diseases, 7, 132-139.
Head, K.A. (2006) Peripheral neuropathy: Pathogenic mechanisms and alternative therapies. Alternative Medicine Review, 11, 294-329.
Zhang, Y.F. and Ning, G. (2008) Mecobalamin. Expert Opinion on Investigational Drugs, 17, 953-964. doi:10.1517/13543784.17.6.953
American Diabetes Association (2008) Standards of medical care in diabetes—2008. Diabetes Care, 31, S12-S54. doi:10.2337/dc08-S012
Backonja, M., Beydoun, A., Edwards, K.R., et al. (1998) Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: A randomized controlled trial. Journal of the American Medical Association, 280, 1831-1836. doi:10.1001/jama.280.21.1831
Serpell, M.G. (2002) Gabapentin in neuropathic pain syndromes: A randomised, double-blind, placebo-controlled trial. Pain, 99, 557-566. doi:10.1016/S0304-3959(02)00255-5
Duby, J.J., Campbell, R.K., Setter, S.M., White, J.R. and Rasmussen, K.A. (2004) Diabetic neuropathy: An intensive review. American Journal of Health-System Pharmacy, 61, 160-173.
McQuay, H.J., Tramer, M., Nye, B.A., Carroll, D., Wiffen, P.J. and Moore, R.A. (1996) A systematic review of antidepressants in neuropathic pain. Pain, 68, 217-227. doi:10.1016/S0304-3959(96)03140-5
Goldstein, D.J., Lu, Y., Detke, M.J., Lee, T.C. and Iyengar, S. (2005) Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain, 116, 109-118. doi:10.1016/j.pain.2005.03.029
Sindrup, S.H., Bach, F.W., Madsen, C., Gram, L.F. and Jensen, T.S. (2003) Venlafaxine versus imipramine in painful polyneuropathy: A randomized, controlled trial. Neurology, 60, 1284-1289. doi:10.1212/01.WNL.0000058749.49264.BD
Gimbel, J.S., Richards, P. and Portenoy, R.K. (2003) Controlled-release oxycodone for pain in diabetic neuropathy: a randomized controlled trial. Neurology, 60, 927-934. doi:10.1212/01.WNL.000 0057720.36503.2C
Sindrup, S.H., Andersen, G., Madsen, C., Smith, T., Brosen, K. and Jensen, T.S. (1999) Tramadol relieves pain and allodynia in polyneuropathy: A randomised, double-blind, controlled trial. Pain, 83, 85-90. doi:10.1016/S0304-3959(99)00079-2
Ziegler, D., Ametov, A., Barinov, A., Dyck, P.J., Gurieva, I., Low, P.A., et al. (2006) Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: The Sydney 2 trial. Diabetes Care, 29, 2365-2370. doi:10.2337/dc06-1216
Bramswig, S. and Pietrzik, K. (2005) The relevance of selected vitamins (B-vitamins, vitamin C, vitamin E) in patients with type 2-diabetes. Aktuelle Ern?hrungsmedizin, 30, 311-322. doi:10.1055/s-2005-915301
Rosenstock, J., Tuchman, M., LaMoreaux, L. and Sharma, U. (2004) Pregabalin for the treatment of painful diabetic peripheral neuropathy: A double-blind, placebo-controlled trial. Pain, 110, 628-638. doi:10.1016/j.pain.2004.05.001
Ambrosch, A., Dierkes, J., Lobmann, R., Kuhne, W., Konig, W., Luley, C., et al. (2001) Relation between homocysteinaemia and diabetic neuropathy in patients with Type 2 diabetes mellitus. Diabetic Medicine, 18, 185-192. doi:10.1046/j.1464-5491.2001.00445.x
de Luis, D.A., Fernandez, N., Arranz, M.L., Aller, R., Izaola, O. and Romero, E. (2005) Total homocysteine levels relation with chronic complications of diabetes, body composition, and other cardiovascular risk factors in a population of patients with diabetes mellitus type 2. Journal of Diabetes and Its Complications, 19, 42-46. doi:10.1016/j.jdiacomp.2003.12.003
Guttormsen, A.B., Ueland, P.M., Svarstad, E. and Refsum, H. (1997) Kinetic basis of hyperhomocysteinemia in patients with chronic renal failure. Kidney International, 52, 495-502. doi:10.1038/ki.1997.359
Stabler, S.P., Estacio, R., Jeffers, B.W., Cohen, J.A., Allen, R.H. and Schrier, R.W. (1999) Total homocysteine is associated with nephropathy in non-insulin-dependent diabetes mellitus. Metabolism, 48, 1096-1101. doi:10.1016/S0026-0495(99)90121-X
Obeid, R., McCaddon, A. and Herrmann, W. (2007) The role of hyperhomocysteinemia and B vitamin deficiency in neurological and psychiatric diseases. Clinical Chemistry and Laboratory Medicine, 45, 1590-1606. doi:10.1515/CCLM.2007.356
Scalabrino, G., Buccellato, F.R., Veber, D. and Mutti, E. (2003) New basis of the neurotrophic action of vitamin B12. Clinical Chemistry and Laboratory Medicine, 41, 1435-1437. doi:10.1515/CCLM.2003.220
Wile, D.J. and Cory, T. (2010) Association of metformin, elevated homocysteine, and methylmalonic acid levels and clinically worsened diabetic peripheral neuropathy. Diabetes Care, 33, 156-161. doi:10.2337/dc09-0606
Kikuchi, M., Kashii, S., Honda, Y., Tamura, Y., Kaneda, K. and Akaike, A. (1997) Protective effects of methylcobalamin, a vitamin B12 analog, against glutamate-induced neurotoxicity in retinal cell culture. Investigative Ophthalmology & Visual Science, 38, 848-854.
Watanabe, T., Kaji, R., Oka, N., Bara, W. and Kimura, J. (1994) Ultra-high dose methylcobalamin promotes nerve regeneration in experimental acrylamide neuropathy. Journal of the Neurological Sciences, 122, 140-143. doi:10.1016/0022-510X(94)90290-9
Lonn, E., Yusuf, S., Arnold, M.J., Sheridan, P., Pogue, J., Micks, M., et al. (2006) Homocysteine lowering with folic acid and B vitamins in vascular disease. The New England Journal of Medicine, 354, 1567-1577. doi:10.1056/NEJMoa060900
Mangoni, A.A., Sherwood, R.A., Asonganyi, B., Swift, C.G., Thomas, S. and Jackson, S.H. (2005) Short term oral folic acid supplementation enhances endothelial function in patients with type 2 diabetes. American Journal of Hypertension, 18, 220-226. doi:10.1016/j.amjhyper.2004.08.036
Venn, B.J., Green, T.J., Moser, R. and Mann, J.I. (2003) Comparison of the effect of low-dose supplementation with L-5-methyltetrahydrofolate or folic acid on plasma homocysteine: A randomized placebo-controlled study. The American Journal of Clinical Nutrition, 77, 658-662.
Jones, C.L. and Gonzalez, V. (1978) Pyridoxine deficiency: A new factor in diabetic neuropathy. Journal of the American Podiatric Medical Association, 68, 646-653.