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As a rapidly growing pandemic, Type-2 Diabetes (T2D) represents one of the most pressing health challenges afflicting the human population, global economy, and healthcare systems worldwide.1 Unlike Type-1 Diabetes, which develops from autoimmune pathology, T2D is attributed primary to environmental influences consisting largely of dietary factors. 1
Modifiable Risk Factors
Several modifiable risk factors have been implicated in the initiation and progression of T2D1, including:
- high BMI
- excessive sugar intake
- excessive red meat intake
- sedentary behaviors
- poor antioxidant status
However, disease management remains a focus in western medicine considering the multitude of complications that can result from uncontrolled blood glucose levels. Atherosclerosis, hypertension, and renal disease are among the most concerning comorbidities associated with T2D, yet diabetic peripheral neuropathy (DPN) represents a significant complication affecting roughly half of all diabetic patients.11.12
Clinical Symptoms of DPN
The clinical symptoms of DPN include pain, numbness, tingling, cramps, and intense heat in the feet and/or hands, though perhaps more concerning is the influence of DPN on quality of life and disability.7.11.12 Specifically, resultant pain and numbness in the feet can limit mobility and exercise capacity, thus perpetuating sedentary behaviors that further promote disease progression, with potential detriment to mental and emotional health as well. Additionally, skin ulceration, severe infection, and gangrene in the feet can lead to amputation and life threating complications.8.12 Interventions directed at improving DPN are likely to produce an impact beyond the reduction of clinical symptoms alone, especially when considering the influences of disability and mood on treatment outcomes.
Oxidative stress is believed to play a focal role in the manifestation of DPN, yet the pathogenesis is complex and remains unclear.7.11.12 Alpha lipoic acid (ALA), a potent antioxidant having both hydrophilic and hydrophobic properties and serving as a cofactor for several mitochondrial enzymes, represents one potential intervention for improving DPN.18.104.22.168.11.12 Though many potential mechanisms have been proposed by which ALA may improve DPN symptoms, most experimental evidence suggests improvements as a result of reduced oxidative stress, improved nerve blood flow, increased nerve Na+/K+ ATPase activity, and elevated nerve conduction velocity (NVC), which is further supported by a series of human studies and meta-analyses.22.214.171.124 However, it’s essential to recognize that stronger evidence supporting the efficacy of ALA is limited to studies in which ALA is provided at clinical doses (e.g. 600 mg/d), and in combination with pharmaceutical agents targeting pathways identified in DPN pathology.126.96.36.199
Evidence for Efficacy
All studies included in this review found the use of ALA to be safe and well-tolerated.188.8.131.52.12 As to whether ALA may serve to prevent DPN in patients with T2D remains to be studied. However, considering the role of oxidative stress in DPN pathology, as well as identified mechanisms by which ALA may alleviate DPN symptoms, it would seem reasonable to assume that regular intake of ALA (e.g., 300 – 600 mg/d) may offer some protection against developing DPN symptoms, even when used as a monotherapy.
In addition to ALA, several other nutrients are supported for their effect on DPN symptoms. In human clinical trials, specific combinations of B vitamins, including B6, B12, and folate, were found to significantly improve nerve conduction velocity and Neuropathy Total Symptom Score compared to placebo.3.10 Acetyl-L-Carnitine (ALC) is supported by double-blind trials for its effect on relieving pain, improving objective neurological signs and neurophysiological parameters, and enhanced nerve fiber regeneration in patients with diabetic neuropathy.2.9
Lastly, a double-blind trial that included 49 type-2 diabetes patients with polyneuropathy found a 60% improvement in severity of diabetic symptoms following 12 weeks of Co-Q-10 supplementation (400 mg/day), with no improvements among those given placebo.6 Co-Q-10 was also shown to significantly improve mean neuropathy impairment score and nerve conduction parameters.6 Like ALA, Co-Q-10 is thought to improve neuropathy symptoms in part through its effect on oxidative stress.
While the nutrients included in this review are by no means a comprehensive list of therapeutics for neuropathy symptom relief, available evidence from human trials is sufficient to support clinical recommendations, especially when considering their excellent safety profile when used correctly. As always, any nutraceutical intervention should first be discussed with a licensed healthcare practitioner. In closing, it is worth mentioning that most of the nutrients discussed are likely to confer greater benefits when combined with conventional medical interventions and specific lifestyle approaches including diet and exercise.
- Bellou, V., Belbasis, L., Tzoulaki, I., & Evangelou, E. (2018). Risk factors for type 2 diabetes mellitus: An exposure-wide umbrella review of meta-analyses. PloS one, 13(3), e0194127.
- De Grandis D, Minardi C. (2002). Acetyl-L-carnitine (levacecarnine) in the treatment of diabetic neuropathy. A long-term, randomised, double-blind, placebo-controlled study. Drugs R D., 3(4):223‐231. doi:10.2165/00126839-200203040-00001
- Fonseca VA, Lavery LA, Thethi TK, et al. (2013). Metanx in type 2 diabetes with peripheral neuropathy: a randomized trial. Am J Med, 126(2):141‐149. doi:10.1016/j.amjmed.2012.06.022
- Galeshkalami, N. S., Abdollahi, M., Najafi, R., Jamshidzade, A., Falak, R., Gholami, M. D., Hassanzadeh, G., Mokhtari, T., Hassani, S., Rahimifard, M., & Hosseini, A. (2019). Alpha-lipoic acid and coenzyme Q10 combination ameliorates experimental diabetic neuropathy by modulating oxidative stress and apoptosis. Life Sciences, 216(1), 101-110.
- Han, T., Bai, J., Liu, W., & Hu, Y. (2012). THERAPY OF ENDOCRINE DISEASE: A systematic review and meta-analysis of α-lipoic acid in the treatment of diabetic peripheral neuropathy. European Journal of Endocrinology, 167(4), 465-471.
- Hernández-Ojeda J, Cardona-Muñoz EG, Román-Pintos LM, et al. (2012). The effect of ubiquinone in diabetic polyneuropathy: a randomized double-blind placebo-controlled study. J Diabetes Complications., 26(4):352‐358. doi:10.1016/j.jdiacomp.2012.04.004
- Jiang, D-Q., Li, M-X., Ma, Y-J., Wang, Y., & Wang, Y. (2016). Efficacy and safety of prostaglandin E1 plus lipoic acid combination therapy versus monotherapy for patients with diabetic peripheral neuropathy. Journal of Clinical Neuroscience, 27, 8-16.
- Jiang, D-Q., Xu, L-C., Jiang, L-L., Li, M-X., & Wang, Y. (2018). Fasudil combined with methylcobalamin or lipoic acid can improve the nerve conduction velocity in patients with diabetic peripheral neuropathy. Medicine (Baltimore), 97(27): e11390.
- Sima AA, Calvani M, Mehra M, Amato A; Acetyl-L-Carnitine Study Group. (2005). Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials. Diabetes Care., 28(1):89‐94. doi:10.2337/diacare.28.1.89
- Stracke H, Lindemann A, Federlin K. (1996). A benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy. Exp Clin Endocrinol Diabetes, 104(4):311‐316. doi:10.1055/s-0029-1211460
- Wang, X., Lin, H., Xu, S., Jin, Y., & Zhang, R. (2018). Alpha lipoic acid combined with epalrestat: a therapeutic option for patients with diabetic peripheral neuropathy. Drug design, development and therapy, 12, 2827–2840.
- Zhao, M., Chen, J. Y., Chu, Y. D., Zhu, Y. B., Luo, L., & Bu, S. Z. (2018). Efficacy of epalrestat plus α-lipoic acid combination therapy versusmonotherapy in patients with diabetic peripheral neuropathy: a meta-analysis of 20 randomized controlled trials. Neural regeneration research, 13(6), 1087–1095. doi:10.4103/1673-5374.233453.
Related Resources & Links
BioSpec Nutritionals is not affiliated or endorsed by any of the organizations related to off-site links shared in this newsletter
• Oxidative Stress – VIDEO by Dr. Eric Berg DC
• Enhance Mitochondrial Function – VIDEO by Dr. Rudy Mueller
• Peripheral Neuropathy Exercises – PDF from OSU.edu
• DPN Pathophysiology & Therapeutic Approaches – BLOG by Dr. Melissa Mitchell
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