Neuropathy

Health Condition

Neuropathy

About This Condition

If you have type 1 or type 2 diabetes, you are at increased risk for developing nerve damage, or neuropathy. Some types of diabetic neuropathy can cause chronic pain and others can lead to foot ulcers that may ultimately require amputation. Managing your diabetes, especially if you have type 1 diabetes, can help to prevent neuropathy, and early diagnosis and intervention may slow its progression.1

Certain chemotherapy medications used to treat cancer commonly cause temporary or permanent neuropathy. You can work with your doctor to take steps to reduce the risk of developing chemotherapy-related neuropathy or to manage the condition if you already have it.2

The symptoms of neuropathy are varied and depend upon the nerves involved and the type of nerve damage. For most people with diabetes, neuropathy involves the peripheral nerves and causes symptoms such as tingling, pain, loss of sensations, or weakness in the feet, spreading to the legs and eventually the fingers and arms.1 Peripheral neuropathy is the most common type of chemotherapy-induced neuropathy, and often causes pain severe enough to limit cancer treatment.2 Because it is the most common form of neuropathy, this article addresses only peripheral neuropathy.

Symptoms

Neuropathy can have many symptoms. The symptoms experienced will depend upon which nerves are affected, or damaged. Symptoms may include tingling, pain, numbness, or weakness in the feet, legs, and hands; delayed stomach emptying (gastroparesis), diarrhea, or constipation; bladder paralysis and urine retention; erectile dysfunction in men and vaginal dryness or lack of arousal in women; fainting, dizziness, or rapid heart rate; blurry vision, or difficulty with vision, such as the eyes not adjusting well to changing light conditions. For people receiving chemotherapy medications, the most common neuropathy symptoms include tingling, pain, numbness, or weakness in the feet, legs, and hands.3,4

References

1. Yang H, Sloan G, Ye Y, et al. New Perspective in Diabetic Neuropathy: From the Periphery to the Brain, a Call for Early Detection, and Precision Medicine. Front Endocrinol (Lausanne) 2019;10:929.

2. Zajaczkowska R, Kocot-Kepska M, Leppert W, et al. Mechanisms of Chemotherapy-Induced Peripheral Neuropathy. Int J Mol Sci 2019;20.

3. Steps to Prevent or Delay Nerve Damage. American Diabetes Association [cited 2013 Nov 17]. Available from URL: www.diabetes.org/living-with-diabetes/complications/neuropathy/steps-to-prevent-or-delay.html.

4. Peripheral Neuropathy Fact Sheet. National Institute of Neurological Disorders and Stroke [cited 2013 Nov 17]. Available from URL: www.ninds.nih.gov/disorders/peripheralneuropathy/detail_peripheralneuropathy.htm.

5. Di Stefano G, Di Lionardo A, Galosi E, et al. Acetyl-L-carnitine in painful peripheral neuropathy: a systematic review. J Pain Res 2019;12:1341–51.

6. Dinicola S, Fuso A, Cucina A, et al. Natural products - alpha-lipoic acid and acetyl-L-carnitine - in the treatment of chemotherapy-induced peripheral neuropathy. Eur Rev Med Pharmacol Sci 2018;22:4739–54.

7. Sun Y, Shu Y, Liu B, et al. A prospective study to evaluate the efficacy and safety of oral acetyl-L-carnitine for the treatment of chemotherapy-induced peripheral neuropathy. Exp Ther Med 2016;12:4017–24.

8. Hershman D, Unger J, Crew K, et al. Two-Year Trends of Taxane-Induced Neuropathy in Women Enrolled in a Randomized Trial of Acetyl-L-Carnitine (SWOG S0715). J Natl Cancer Inst 2018;110:669–76.

9. Zhang Q, Ji L, Zheng H, et al. Low serum phosphate and magnesium levels are associated with peripheral neuropathy in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 2018;146:1–7.

10. Zhang Y, Li Q, Xin Y, et al. Association between serum magnesium and common complications of diabetes mellitus. Technol Health Care 2018;26:379–87.

11. Joy S, George T, Siddiqui K. Low magnesium level as an indicator of poor glycemic control in type 2 diabetic patients with complications. Diabetes Metab Syndr 2019;13:1303–7.

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13. Wesselink E, Winkels R, van Baar H, et al. Dietary Intake of Magnesium or Calcium and Chemotherapy-Induced Peripheral Neuropathy in Colorectal Cancer Patients. Nutrients 2018;10.

14. Jordan B, Jahn F, Beckmann J, et al. Calcium and Magnesium Infusions for the Prevention of Oxaliplatin-Induced Peripheral Neurotoxicity: A Systematic Review. Oncology 2016;90:299–306.

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16. Solomon L. Vitamin B12-responsive neuropathies: A case series. Nutr Neurosci 2016;19:162–8.

17. Shibuya K, Misawa S, Nasu S, et al. Safety and efficacy of intravenous ultra-high dose methylcobalamin treatment for peripheral neuropathy: a phase I/II open label clinical trial. Intern Med 2014;53:1927–31.

18. Franques J, Chiche L, De Paula A, et al. Characteristics of patients with vitamin B12-responsive neuropathy: a case series with systematic repeated electrophysiological assessment. Neurol Res 2019;41:569–76.

19. Tavares Bello C, Capitao R, Sequeira Duarte J, et al. Vitamin B12 Deficiency in Type 2 Diabetes Mellitus. Acta Med Port 2017;30:719–26.

20. Gupta K, Jain A, Rohatgi A. An observational study of vitamin b12 levels and peripheral neuropathy profile in patients of diabetes mellitus on metformin therapy. Diabetes Metab Syndr 2018;12:51–8.

21. Roy R, Ghosh K, Ghosh M, et al. Study of Vitamin B12 deficiency and peripheral neuropathy in metformin-treated early Type 2 diabetes mellitus. Indian J Endocrinol Metab 2016;20:631–7.

22. Biemans E, Hart H, Rutten G, et al. Cobalamin status and its relationship with depression, cognition and neuropathy in patients with type 2 diabetes mellitus using metformin. Acta Diabetol 2015;52:383–93.

23. Wang D, Zhai J, Liu D. Serum folate, vitamin B12 levels and diabetic peripheral neuropathy in type 2 diabetes: A meta-analysis. Mol Cell Endocrinol 2017;443:72–9.

24. Russo G, Giandalia A, Romeo E, et al. Diabetic neuropathy is not associated with homocysteine, folate, vitamin B12 levels, and MTHFR C677T mutation in type 2 diabetic outpatients taking metformin. J Endocrinol Invest 2016;39:305–14.

25. Trippe B, Barrentine L, Curole M, Tipa E. Nutritional management of patients with diabetic peripheral neuropathy with L-methylfolate-methylcobalamin-pyridoxal-5-phosphate: results of a real-world patient experience trial. Curr Med Res Opin 2016;32:219–27.

26. Jacobs A, Cheng D. Management of diabetic small-fiber neuropathy with combination L-methylfolate, methylcobalamin, and pyridoxal 5'-phosphate. Rev Neurol Dis 2011;8:39–47.

27. Walker M, Morris L, Cheng D. Improvement of cutaneous sensitivity in diabetic peripheral neuropathy with combination L-methylfolate, methylcobalamin, and pyridoxal 5'-phosphate. Rev Neurol Dis 2010;7:132–9.

28. Talaei A, Siavash M, Majidi H, Chehrei A. Vitamin B12 may be more effective than nortriptyline in improving painful diabetic neuropathy. Int J Food Sci Nutr 2009;60:71–6.

29. Xu Q, Pan J, Yu J, et al. Meta-analysis of methylcobalamin alone and in combination with lipoic acid in patients with diabetic peripheral neuropathy. Diabetes Res Clin Pract 2013;101:99–105.

30. Schloss J, Colosimo M. B Vitamin Complex and Chemotherapy-Induced Peripheral Neuropathy. Curr Oncol Rep 2017;19:76.

31. Schloss J, Colosimo M, Airey C, et al. A randomised, placebo-controlled trial assessing the efficacy of an oral B group vitamin in preventing the development of chemotherapy-induced peripheral neuropathy (CIPN). Support Care Cancer 2017;25:195–204.

32. Senyigit A. The association between 25-hydroxy vitamin D deficiency and diabetic complications in patients with type 2 diabetes mellitus. Diabetes Metab Syndr 2019;13:1381–6.

33. Zhang B, Zhao W, Tu J, et al. The relationship between serum 25-hydroxyvitamin D concentration and type 2 diabetic peripheral neuropathy: A systematic review and a meta-analysis. Medicine (Baltimore) 2019;98:e18118.

34. Yammine K, Hayek F, Assi C. Is there an association between vitamin D and diabetic foot disease? A meta-analysis. Wound Repair Regen 2020;28:90–6.

35. Shehab D, Al-Jarallah K, Abdella N, et al. Prospective evaluation of the effect of short-term oral vitamin d supplementation on peripheral neuropathy in type 2 diabetes mellitus. Med Princ Pract 2015;24:250–6.

36. Alam U, Fawwad A, Shaheen F, et al. Improvement in Neuropathy Specific Quality of Life in Patients with Diabetes after Vitamin D Supplementation. J Diabetes Res 2017;2017:7928083.

37. Yammine K, Wehbe R, Assi C. A systematic review on the efficacy of vitamin D supplementation on diabetic peripheral neuropathy. Clin Nutr 2020.

38. Grim J, Ticha A, Hyspler R, et al. Selected Risk Nutritional Factors for Chemotherapy-Induced Polyneuropathy. Nutrients 2017;9.

39. Wang J, Udd K, Vidisheva A, et al. Low serum vitamin D occurs commonly among multiple myeloma patients treated with bortezomib and/or thalidomide and is associated with severe neuropathy. Support Care Cancer 2016;24:3105–10.

40. Papazafeiropoulou A, Xourgia E, Papantoniou S, et al. Effect of 3-month alpha-lipoic acid treatment on sural nerve conduction velocity and amplitude in patients with diabetic neuropathy: a pilot study. Arch Med Sci Atheroscler Dis 2019;4:e141–3.

41. Agathos E, Tentolouris A, Eleftheriadou I, et al. Effect of alpha-lipoic acid on symptoms and quality of life in patients with painful diabetic neuropathy. J Int Med Res 2018;46:1779–90.

42. Zhao M, Chen J, Chu Y, et al. Efficacy of epalrestat plus alpha-lipoic acid combination therapy versus monotherapy in patients with diabetic peripheral neuropathy: a meta-analysis of 20 randomized controlled trials. Neural Regen Res 2018;13:1087–95.

43. Wang X, Lin H, Xu S, et al. Alpha lipoic acid combined with epalrestat: a therapeutic option for patients with diabetic peripheral neuropathy. Drug Des Devel Ther 2018;12:2827–40.

44. Wang X, Lin H, Xu S, Lu Y. Lipoic Acid Combined with Epalrestat versus Lipoic Acid in Treating Diabetic Peripheral Neuropathy:A Meta-analysis. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2017;39:656–64.

45. Guo Y, Jones D, Palmer J, et al. Oral alpha-lipoic acid to prevent chemotherapy-induced peripheral neuropathy: a randomized, double-blind, placebo-controlled trial. Support Care Cancer 2014;22:1223–31.

46. Maschio M, Zarabla A, Maialetti A, et al. The Effect of Docosahexaenoic Acid and alpha-Lipoic Acid as Prevention of Bortezomib-Related Neurotoxicity in Patients with Multiple Myeloma. Integr Cancer Ther 2019:1534735419888584.

47. Hernandez-Ojeda J, Cardona-Munoz E, Roman-Pintos L, et al. The effect of ubiquinone in diabetic polyneuropathy: a randomized double-blind placebo-controlled study. J Diabetes Complications 2012;26:352–8.

48. Akbari Fakhrabadi M, Zeinali Ghotrom A, Mozaffari-Khosravi H, et al. Effect of Coenzyme Q10 on Oxidative Stress, Glycemic Control and Inflammation in Diabetic Neuropathy: A Double Blind Randomized Clinical Trial. Int J Vitam Nutr Res 2014;84:252–60.

49. Ogbera A, Ezeobi E, Unachukwu C, Oshinaike O. Treatment of diabetes mellitus-associated neuropathy with vitamin E and Eve primrose. Indian J Endocrinol Metab 2014;18:846–9.

50. Hor C, Fung W, Ang H, et al. Efficacy of Oral Mixed Tocotrienols in Diabetic Peripheral Neuropathy: A Randomized Clinical Trial. JAMA Neurol 2018;75:444–52.

51. Anoushirvani A, Poorsaadat L, Aghabozorgi R, et al. Comparison of the Effects of Omega 3 and Vitamin E on Palcitaxel-Induced Peripheral Neuropathy. Open Access Maced J Med Sci 2018;6:1857–61.

52. Huang H, He M, Liu L, Huang L. Vitamin E does not decrease the incidence of chemotherapy-induced peripheral neuropathy: a meta-analysis. Contemp Oncol (Pozn) 2016;20:237–41.

53. Eum S, Choi H, Chang M, et al. Protective effects of vitamin E on chemotherapy-induced peripheral neuropathy: a meta-analysis of randomized controlled trials. Int J Vitam Nutr Res 2013;83:101–11.

54. Afonseca S, Cruz F, Cubero Dde I, et al. Vitamin E for prevention of oxaliplatin-induced peripheral neuropathy: a pilot randomized clinical trial. Sao Paulo Med J 2013;131:35–8.

55. Salehi Z, Roayaei M. Effect of Vitamin E on Oxaliplatin-induced Peripheral Neuropathy Prevention: A Randomized Controlled Trial. Int J Prev Med 2015;6:104.

56. Koutsikos D, Agroyannis B, Tzanatos-Exarchou H. Biotin for diabetic peripheral neuropathy. Biomed Pharmacother 1990;44:511–4.

57. Heidari N, Sajedi F, Mohammadi Y, et al. Ameliorative Effects Of N-Acetylcysteine As Adjunct Therapy On Symptoms Of Painful Diabetic Neuropathy. J Pain Res 2019;12:3147–59.

58. Lin P, Lee M, Wang W, et al. N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data. Support Care Cancer 2006;14:484–7.

59. Duran A, Salto L, Camara J, et al. Effects of omega-3 polyunsaturated fatty-acid supplementation on neuropathic pain symptoms and sphingosine levels in Mexican Americans with type 2 diabetes. Diabetes Metab Syndr Obes 2019;12:109–20.

60. Okuda Y, Mizutani M, Ogawa M, et al. Long-term effects of eicosapentaenoic acid on diabetic peripheral neuropathy and serum lipids in patients with type II diabetes mellitus. J Diabetes Complications 1996;10:280–7.

61. Ghoreishi Z, Esfahani A, Djazayeri A, et al. Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: a randomized double-blind placebo controlled trial. BMC Cancer 2012;12:355.

62. Hicks C, Selvin E. Epidemiology of Peripheral Neuropathy and Lower Extremity Disease in Diabetes. Curr Diab Rep 2019;19:86.

63. Iqbal Z, Azmi S, Yadav R, et al. Diabetic Peripheral Neuropathy: Epidemiology, Diagnosis, and Pharmacotherapy. Clin Ther 2018;40:828–49.

64. Parasoglou P, Rao S, Slade J. Declining Skeletal Muscle Function in Diabetic Peripheral Neuropathy. Clin Ther 2017;39:1085–103.

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66. Nomura T, Kawae T, Kataoka H, Ikeda Y. Aging, physical activity, and diabetic complications related to loss of muscle strength in patients with type 2 diabetes. Phys Ther Res 2018;21:33–8.

67. Ahmad Sharoni S, Minhat H, Mohd Zulkefli N, Baharom A. Health education programmes to improve foot self-care practices and foot problems among older people with diabetes: a systematic review. Int J Older People Nurs 2016;11:214–39.

68. Barshes N, Sigireddi M, Wrobel J, et al. The system of care for the diabetic foot: objectives, outcomes, and opportunities. Diabet Foot Ankle 2013;4.

69. Grisold A, Callaghan B, Feldman E. Mediators of diabetic neuropathy: is hyperglycemia the only culprit? Curr Opin Endocrinol Diabetes Obes 2017;24:103–11.

70. Xia N, Morteza A, Yang F, et al. Review of the role of cigarette smoking in diabetic foot. J Diabetes Investig 2019;10:202–15.

Copyright © 2024 TraceGains, Inc. All rights reserved.

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The information presented by TraceGains is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. Self-treatment is not recommended for life-threatening conditions that require medical treatment under a doctor's care. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires December 2024.

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