Diabetic Neuropathy

Article taken from pages 10-11 of the September/October Newsletter 2014

By Adriane Fugh-Berman and Charlea Massion

Diabetics often experience neuropathy (nerve pain or dysfunction); some people with diabetic neuropathy (DN) may be unaware of it because symptoms can be subtle. DN symptoms range from numbness or tingling to severe pain that interferes with daily activities and keeps people up at night. Numbness increases the risk of injury, especially to toes and feet. Combined with diabetics’ poor circulation and increased risk for infection, these injuries can lead to wounds that fail to heal, which can then require amputation of a diabetic’s toes, feet, and even legs!

Nerve pain is difficult to treat. Drugs for DN are often used in combination and include anti-seizure drugs (the effective ones are gabapentin and pregabalin),antidepressants (i.e., duloxetine, tricyclic antidepressants), tramadol and other opioids (i.e., hydrocodone and oxycodone). But, all have side effects; worse, none work very well.

Scientific evidence supports several alternative treatments for DN, which we describe below. None is a magic cure, but they are all safe and deserve a try. We’ve focused on alternative treatments supported by multiple, randomized controlled trials that have been analyzed through systematic reviews or meta-analyses, and the references include links to full text articles or abstracts. Don’t be surprised if your doctor doesn’t know about these options, however. If you or someone you know has DN, bring this article and references to your health care provider.

Exercise

Exercise helps prevent DN progression, and balance exercises (like yoga or Tai Chi) also helps manage DN symptoms.2 Small studies have shown benefit from the use of transcutaneous electrical neurostimulation (TENS) for DN,but not for the use of electromagnetic field therapy.4

Capsaicin

Capsaicin is what makes chili peppers hot; capsaicin in a cream or skin patch helps relieve nerve pain. A high-concentration (8%) prescription capsaicin treatment was found to be superior to placebo for chronic neuropathic pain.5 Lower-concentration over-the- counter creams (0.25 to 0.75% capsaicin) also help some people.6 Non-prescription creams should be applied several times daily. Wash your hands afterwards and avoid touching your eyes or other sensitive areas (yikes!). (This reminds us of a funny story about cooking with chili peppers…)

Dietary Supplements

Dietary supplements include herbs, vitamins and amino acids; these are not regulated in the same way drugs are, and are rarely approved by the Food and Drug Administration for treatment. Physicians and other health care providers are not educated about dietary supplements, so we’ve done some research for you and your doctor.

Alpha-lipoic acid

Alpha-lipoic acid (ALA) is an antioxidant that helps both the signs (i.e., things that can be measured) and symptoms (i.e., things that patients experience) of DN. A systematic review of 15 trials of 300 – 600 mg of ALA per day, taken intravenously, found it was better than placebo in improving nerve function and symptoms. An oral dose of 600 mg daily also appears to be effective; a study of 460 patients that lasted 4 years found the treatment provided some improvement and was tolerable.7,8 No serious adverse events were reported; a few people reported having upset stomachs.There is a concern that ALA might increase heart arrhythmias, however.

Vitamin B12

Several B vitamins, including vitamin B12 (cobalamin) and vitamin B6 (pyridoxine) are important for healthy nerves.  Many older people are deficient in vitamin B12, especially if they are taking medications to reduce stomach acidity. Most studies used intravenous treatments, but B12 absorption is also effective sublingually (taken under the tongue). A meta-analysis found that ALA and B12 were more effective when they are used together.10

Vitamin D

Vitamin D deficiency is widespread among diabetics, particularly among those with DN.11,12 There haven’t been large trials of vitamin D for DN, but it’s safe to take up to 1000 IUs a day, and worth a try. Vitamin D is fat-soluble (i.e., it is only absorbed when taken with fat or oil). Note, however, that we are not recommending taking it with a doughnut!

What We Recommend

Talk to your health care provider about trying one or a combination of alternative treatments. Here are doses we recommend; try each one — or a combination — for 4 to 6 weeks and see if it helps:

  • Alpha-lipoic acid: 300-600 mg/day
  • B-complex vitamin
  • Vitamin B12: 1000 mcg/day, sublingually
  • Vitamin D: 1000 IUs/day, taken with food
  • Capsaicin cream: 0.75% applied to painful areas 3 times a day.

How do the therapies we’ve discussed stack up against drugs? We couldn’t find comparative studies, and think this should be a priority. We urge the National Institutes of Health to fund research that compares these alternative treatments for DN to the use of drugs. In addition, educating physicians and patients about effective DN treatments can help people and probably lower treatment costs, too!

Charlea T. Massion, MD, is a NWHN Board member, family physician, hospitalist, and specialist in hospice and palliative care medicine. She is the Chief Medical Director of Hospice of Santa Cruz County and also teaches physicians about work-life balance and career development. Adriane Fugh-Berman, MD, is an associate professor in the Georgetown University Medical Center, a former chair of the NWHN, and director of PharmedOut, which educates prescribers about pharmaceutical marketing techniques.


References

1. Wiffen PJ, Derry S, Moore RA, et al, “Antiepileptic Drugs for Neuropathic Pain and Fibromyalgia — An Overview of Cochrane Reviews,” Cochrane Database Syst Rev. 2013; 11: CD010567. doi: 10.1002/14651858.CD010567.pub2. Available online: http://www.ncbi.nlm.nih.gov/pubmed/24217986.

2. Streckmann F, Zopf EM, Lehmann HC, et al., “Exercise Intervention Studies in Patients with Peripheral Neuropathy: A Systematic Review,” Sports Med. 2014; Jun 14. Available online: http://www.ncbi.nlm.nih.gov/pubmed/24927670.

3. Stein C, Eibel B, Sbruzzi G, et al., “Electrical Stimulation and Electromagnetic Field Use in Patients with Diabetic Neuropathy: Systematic Review and Neta-analysis,” Braz J Phys Ther. 2013;17(2): 93-104. doi: 10.1590/S1413-35552012005000083. Available online: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1413-35552013000200093&lng=en&nrm=iso&tlng=en.

4. Stein C, Eibel B, Sbruzzi G, et al., Electrical Stimulation and Electromagnetic Field Use in Patients with Diabetic Neuropathy: Systematic Review and Meta-analysis,” Braz J Phys Ther. 2013 Mar-Apr;17(2):93-104. doi: 10.1590/S1413-35552012005000083. Available online: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1413-35552013000200093&lng=en&nrm=iso&tlng=en.

5. Derry S, Sven-Rice A, Cole P, et al., “Topical Capsaicin (High Concentration) for Chronic Neuropathic Pain in Adults,” Cochrane Database Syst Review 2013 Feb 28; 2: CD007393. doi: 10.1002/14651858.CD007393.pub3. Available online: http://www.ncbi.nlm.nih.gov/pubmed/23450576.

6. Derry S1, Lloyd R, Moore RA, McQuay HJ. Topical capsaicin for chronic neuropathic pain in adults, [6]Cochrane Database Syst Rev. 2009 Oct 7;(4):CD007393. doi: 10.1002/14651858.CD007393.pub2. Available online: http://www.ncbi.nlm.nih.gov/pubmed/19821411.

7. McIlduff CE1, Rutkove SB, “Critical Appraisal of the Use of Alpha Lipoic Acid (Thioctic Acid) in the Treatment of Symptomatic Diabetic Polyneuropathy,” Ther Clin Risk Manag. 2011; 7: 377-85. doi: 10.2147/TCRM.S11325. Epub 2011 Sep 5. Available online: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3176171.

8. Ziegler D1, Low PA, Litchy WJ, et al., “Efficacy and Safety of Antioxidant Treatment with α-lipoic Acid over 4 Years in Diabetic Polyneuropathy: the NATHAN 1 Trial,” Diabetes Care 2011; 34(9): 2054-60. doi: 10.2337/dc11-0503. Epub 2011 Jul 20. Available online: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161301.

9. Han T, Bai J, Liu W, et al., “A Systematic Review and Meta-analysis of α-lipoic Acid in the Treatment of Diabetic Peripheral Neuropathy,” Eur J Endocrinol. 2012; 167(4): 465-71. doi: 10.1530/EJE-12-0555. Epub 2012 Jul 2. Available online: http://eje-online.org/content/167/4/465.long.

10. Xu Q1, 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(2):99-105. doi: 10.1016/j.diabres.2013.03.033. Epub 2013 May 9. Available online: http://www.ncbi.nlm.nih.gov/pubmed/23664235.

11. Skalli S, Muller M, Pradines S, et al., “Vitamin D Deficiency and Peripheral Diabetic Neuropathy,” Eur J Intern Med. 2012; 23(2):e67-8. doi: 10.1016/j.ejim.2011.11.008. Epub 2011 Dec 10. Available online: http://www.ejinme.com/article/S0953-6205%2811%2900272-X/abstract.

12. Soderstrom LH, Johnson SP, Diaz VA, et al., “Association Between Vitamin D and Diabetic Neuropathy in a Nationally Representative Sample: Results from 2001-2004 NHANES. Diabet Med. 2012; 29(1):50-5. doi: 10.1111/j.1464-5491.2011.03379.x. Available online: http://www-ncbi-nlm-nih-gov.proxy.library.georgetown.edu/pmc/articles/PMC3461835.