What Is Peripheral Neuropathy?

by Jill Northrup, ND

Peripheral neuropathy (PN) is one of the most commonly encountered neurological concerns in primary-care settings1. Characterized by its anatomic distribution in a “stocking and glove” pattern affecting the extremities, PN presents as loss of sensation, pins and needles, numbness, tingling, and sometimes burning pain2. Underlying causes include diabetes, nerve compression, nutritional deficiencies, and genetic diseases, to name a few. Peripheral neuropathy can often become progressive, leading to muscle weakness or atrophy 3.

Prevention and Restoration 

Lifestyle factors can reduce the risk of developing PN by addressing some of the conditions that may cause it. These include avoiding alcohol, limiting exposure to toxins, maintaining a healthy weight, and ensuring sufficient nutrients are consumed every day4.

Various nutraceuticals can also be used to relieve symptoms associated with peripheral neuropathy.

Acetyl-L-carnitine

Diabetes mellitus is one of the main causes of PN5 and PN is one of the most common systemic complications related to diabetes6. Acetyl‑ʟ‑carnitine is a dietary supplement used as an adjunctive support for diabetics, due to its glucose-metabolism modulating and insulin-sensitizing effects7. A review that examined the treatment of diabetic PN with acetyl‑ʟ‑carnitine found significant reductions in pain8. Participants rated pain associated with diabetic neuropathy using a 100‑point visual analogue scale, with higher scores indicating more pain. Overall, doses of acetyl‑ʟ‑carnitine ranging from 1,500 to 3,000 mg/d for 6–12 months contributed to a 15‑point pain reduction score. Lower doses, less than 1,500 mg/d, did not contribute to significant improvements9.

Two studies included in this review also found that, with acetyl‑ʟ‑carnitine supplementation (compared to placebo), there were small increases in nerve conduction velocity (NCV), an objective measure of how quickly electrical signals move through our nerves. Abnormal results can confirm the diagnosis of PN10. The clinical significance, however, is uncertain11.

B-Vitamins

Symptoms of deficiencies of vitamins B₁, B₆, and B₁₂ are often found in those with PN11,12. Deficiencies can result from inadequate dietary intake. Malabsorption symptoms include various gastrointestinal diseases such as Crohn’s disease and autoimmune conditions like pernicious anaemia, which can be the case for vitamin B₁₂ deficiency14. Additionally, alcoholism is a common cause of vitamin B₁ deficiency15. Vitamin B₁₂ deficiency is also associated with elevated methylmalonic acid (MMA) and homocysteine levels16, which are toxic and contribute to nerve damage17. Correcting vitamin levels is an important component of treatment for those with PN caused by nutrient deficiency18,19. Among those with diabetic PN and alcohol-related neuropathy, vitamin B₁ supplementation has shown significant improvement in symptoms20.

alpha-Lipoic Acid

alpha‑Lipoic acid (ALA) has antioxidant activity on its own and increases that of the body’s primary antioxidant, glutathione21. Treatment with ALA, both orally and intravenously, can reduce pain and numbness associated with diabetic PN22. Oral supplementation of 600 mg of ALA taken daily for 5 weeks significantly reduced subjective total symptom scores—which assess the presence, severity, and duration of stabbing pain, burning pain, paresthesia, and numbness—compared to placebo23.Higher doses were not seen to be more effective than 600 mg/d of ALA. After 5 weeks, 62% achieved a greater-than-50% reduction in total symptom scores with 600 mg/d ALA, compared to 26% with placebo24. A meta-analysis examining intravenous ALA at the same dosage (600 mg/d) found significant improvements in total symptom scores after 3 weeks in comparison to placebo25.

Curcumin

Curcumin, derived from turmeric, has anti-inflammatory, antioxidant, and blood-sugar– and lipid-modulating effects26. Clinical research supporting the use of curcumin as a therapeutic for PN is lacking. However, preclinical data suggests that curcumin may be a promising therapeutic option for managing components of neuropathies in various populations27.Current evidence suggests that curcumin may have a useful role in alleviating chronic neuropathic pain due to carpal tunnel, disc herniation, or lumbar canal stenosis in humans, alongside pharmaceuticals28, and was shown to help with peripheral nerve regeneration in an animal model29. Further research is required to elucidate the effects and use of curcumin for peripheral neuropathy.

Fish oils

Omega‑3 fatty acids are a key component of cellular membranes and help modulate inflammation30. Various case studies have shown omega‑3 supplementation as a potential therapeutic option for various types of neuropathic pain, including cervical radiculopathy and neuropathic leg pain31. A meta-analysis and systematic review concluded (with low certainty) that omega‑3 supplementation reduces sensory loss and neuropathy incidence due to chemotherapeutics in comparison to placebo32. Among diabetics, following one year of omega‑3 supplementation, corneal nerve–fibre lengths were found to have increased33. Corneal-nerve abnormalities, including reduced length, is a finding among diabetic patients34.

NAC

N‑Acetylcysteine (NAC) is a potent antioxidant, an anti-inflammatory, and a glutathione precursor35. Among patients with painful diabetic PN, treatment with adjunctive NAC (600 mg twice daily) alongside pregabalin, a standard pharmaceutical for neuropathic pain relief, experienced significant pain reductions compared to pregabalin and placebo36. NAC also has potential therapeutic value for chemotherapy-induced peripheral neuropathy, with 1,200 mg/d NAC significantly lowering the severity of neuropathic symptoms37.

Conclusion

Peripheral neuropathy can significantly affect daily life, but a combination of lifestyle modifications, nutritional support, and evidence-based supplements offers a holistic approach to managing symptoms. By addressing underlying causes and promoting nerve health, these naturopathic interventions can help improve both comfort and quality of life.

References

1. Doughty, C.T., and R. Seyedsadjadi. “Approach to peripheral neuropathy for the primary care clinician.” The American Journal of Medicine, Vol. 131, No. 9 (2018): 1010–1016.
2. Castelli, G., K.M. Desai, and R.E. Cantone. “Peripheral neuropathy: Evaluation and differential diagnosis.” American Family Physician, Vol. 102, No. 12 (2020): 732–739.3. ibid.
4. [No author listed.] “Peripheral neuropathy.” Johns Hopkins Medicine, [no date listed], https://www.hopkinsmedicine.org/health/conditions-and-diseases/peripheral-neuropathy.5. Castelli, Desai, and Cantone, op. cit.6. Doughty and Seyedsadjadi, op. cit.
7. Ko, J., E.Y. Wong, H.N. Tran, R.J.C. Tran, and D.X. Cao. “The glycemic, cholesterol, and weight effects of ʟ‑carnitine in diabetes: A systematic review and meta-analysis of randomized controlled trials.” Diabetes Epidemiology and Management, Vol. 10 (2023): 100122.
8. Rolim, L.C., E.M. da Silva, R.L. Flumignan, M.M. Abreu, and S.A. Dib. “Acetyl‑ʟ‑carnitine for the treatment of diabetic peripheral neuropathy.” The Cochrane Database of Systematic Reviews, Vol. 6, No. 6 (2019): CD011265.
9. Rolim et al, op. cit.
10. Azhary, H., M.U. Farooq, M. Bhanushali, A. Majid, and M.Y. Kassab. “Peripheral neuropathy: Differential diagnosis and management.” American Family Physician, Vol. 81, No. 7 (2010): 887–892.
11. Rolim et al, op. cit.
12. Staff, N.P., and A.J. Windebank. “Peripheral neuropathy due to vitamin deficiency, toxins, and medications.” Continuum, Vol. 20, No. 5 (2014): 1293–1306.
13. Hammond, N., Y. Wang, M.M. Dimachkie, and R.J. Barohn. “Nutritional neuropathies.” Neurologic Clinics, Vol. 31, No. 2 (2013): 477–489.
14. Ankar, A., and A. Kumar. “Vitamin B12 deficiency.” In StatPearls [Internet]. StatPearls Publishing.
15. Staff and Windebank, op. cit.
16. Stein, J., J. Geisel, and R. Obeid. “Association between neuropathy and B‑vitamins: A systematic review and meta‐analysis.” European Journal of Neurology, Vol.28, No.6 (2021): 2054–2064.
17. Ankar and Kumar, op. cit.
18. Hammond et al, op. cit.
19. Langan, R.C., and A.J. Goodbred. “Vitamin B12 deficiency: Recognition and management.” American Family Physician, Vol. 96, No. 6 (2017): 384–389.20. Stein, Geisel, and Obeid, op. cit.21. Vallianou, N., A. Evangelopoulos, and P. Koutalas. “Alpha-lipoic acid and diabetic neuropathy.” The Review of Diabetic Studies: RDS, Vol. 6, No. 4 (2009): 230–236.
22. ibid.
23. Ziegler, D., A. Ametov, A. Barinov, P.J. Dyck, I. Gurieva, P.A. Low, U. Munzel, et al. “Oral treatment with α‑lipoic acid improves symptomatic diabetic polyneuropathy: The SYDNEY 2 trial.” Diabetes Care, Vol. 29, No. 11 (2006): 2365–2370.
24. ibid.
25. Ziegler, D., H. Nowak, P.  Kempler, P. Vargha, and P.A. Low. “Treatment of symptomatic diabetic polyneuropathy with the antioxidant α‑lipoic acid: A meta‐analysis.” Diabetic Medicine, Vol. 21, No. 2 (2004): 114–121.
26. Zhang, D.W., M. Fu, S.H. Gao, and J.L. Liu. “Curcumin and diabetes: A systematic review.” Evidence-Based Complementary and Alternative Medicine, Vol. 2013 (2013): 636053.
27. Caillaud, M., Y.P. Aung Myo, B.D. McKiver, U. Osinska Warncke, D. Thompson, J. Mann, E. Del Fabbro, A. Desmoulière, F. Billet, and M.I. Damaj. “Key developments in the potential of curcumin for the treatment of peripheral neuropathies.” Antioxidants, Vol. 9, No. 10 (2020): 950.
28. Di Pierro, F., and R. Settembre. “Safety and efficacy of an add-on therapy with curcumin phytosome and piperine and/or lipoic acid in subjects with a diagnosis of peripheral neuropathy treated with dexibuprofen.” Journal of Pain Research, Vol. 6 (2013): 497–503. Erratum in: Journal of Pain Research, Vol. 6 (2013): 641.
29. Ma, J., J. Liu, H. Yu, Q. Wang, Y. Chen, and L. Xiang. “Curcumin promotes nerve regeneration and functional recovery in rat model of nerve crush injury.” Neuroscience Letters, Vol. 547 (2013): 26–31.
30. Ko, G., L. Arseneau, N. Nowacki, and S. Mrkoboda. “Omega‑3 fatty acids and neuropathic pain.” Practical Pain Management, Vol. 8, No. 7 (2008).
31. ibid.
32. Zhang, A.C., M.E.H. De Silva, R.J. MacIsaac, L. Roberts, J. Kamel, J.P. Craig, L. Busija, and L.E. Downie. “Omega‑3 polyunsaturated fatty acid oral supplements for improving peripheral nerve health: A systematic review and meta-analysis.” Nutrition Reviews, Vol. 78, No. 4 (2020): 323–341.
33. Lewis, E.J.H., B.A. Perkins, L.E. Lovblom, R.P. Bazinet, T.M.S. Wolever, and V. Bril. “Effect of omega‑3 supplementation on neuropathy in type 1 diabetes: A 12‑month pilot trial.” Neurology, Vol. 88, No. 24 (2017): 2294–2301.
34. Malik, R.A., P. Kallinikos, C.A. Abbott, C.H.M. van Schie, P. Morgan, N. Efron, and A.J.M. Boulton. “Corneal confocal microscopy: A non‑invasive surrogate of nerve fibre damage and repair in diabetic patients.” Diabetologia, Vol. 46, No. 5 (2003): 683–688.
35. Heidari, N., F. Sajedi, Y. Mohammadi, M. Mirjalili, and M. Mehrpooya. “Ameliorative effects of N‑acetylcysteine as adjunct therapy on symptoms of painful diabetic neuropathy.” Journal of Pain Research, Vol. 12 (2019): 3147–3159.
36. ibid.
37. Khalefa, H.G., M.A. Shawki, R. Aboelhassan, and L.M. El Wakeel. “Evaluation of the effect of N‑acetylcysteine on the prevention and amelioration of paclitaxel-induced peripheral neuropathy in breast cancer patients: A randomized controlled study.” Breast Cancer Research and Treatment, Vol. 183, No. 1 (2020): 117–125.