Global Advanced Research Journal of Medicine and Medical Sciences (GARJMMS) ISSN: 2315-5159
December 2018 Special Issue, Vol. 7(10), pp. 214-220
Copyright © 2018 Global Advanced Research Journals


Full Length Research Article

Efficacy of α-lipoic acid in the treatment of diabetic polyneuropathy. A Randomized, Double–Blind Study

Millán-Guerrero RO MD. DSc1*, García-Ramírez AL MD2, Trujillo-Hernández B MD. DSc1, Caballero-Hoyos R DSc1, González–Pérez O MD.DSC3, Isais-Millán S MD1 and Trujillo-Magallón Erick MD1

1Unidad de Investigación en Epidemiología Clínica, Instituto Mexicano del Seguro Social, Colima, Col.
2Medicina Física y de Rehabilitación, HGZ No.1 Instituto Mexicano del Seguro Social, Colima.
3Facultad de Psicología, Universidad de Colima, Colima, México.

Registration number: 2009-601-13

*Corresponding Author E-mail:; Phone: 01312-31-4-17-57; Fax: 01312-31-4-17-57

Accepted 19 June, 2018


To evaluate the efficacy of α-lipoic acid in the treatment of diabetic polyneuropathy focusing on sensory symptoms, nerve conduction velocity and H reflex in type 2 diabetes mellitus. 100 diabetic patients presenting with symptomatic polyneuropathy were enrolled in a randomized, double-blind, placebo-controlled study. They received a daily dosage of 1200mg of α-lipoic acid (n = 50) or placebo (n = 50) for 4 weeks. Main results were evaluated with the Total Symptom Score (TSS). Secondary results included nerve conduction velocity, individual symptom score, and H-reflex. Mean age was 50.9±8.0 years, mean disease duration was 10±6.3 years and mean fasting glucose was 169±110 mg/mL. The statistical analysis of data collected showed no significant differences between the baseline values obtained for the alpha lipoic acid and the placebo groups (p>0.05). Analysis showed that by the end of the 4th week, there was not a significant difference between both groups in the Michigan variable, Motor Nerve Conduction Velocity and H-reflex variable. In our study after 4 weeks of treatment, the effects of α-lipoic acid oral not shown significant clinical improvement; results from both the α-lipoic acid group and the placebo group. 

Keywords: Diabetic neuropathy, type 2 diabetes mellitus, α-lipoic acid, double–Blind Study



Al-Geffari M (2012). Comparison of different screening tests for diagnosis of diabetic peripheral neuropathy in primary health care setting. Int. J. Health Sci. (Qassim). 6:127-134.

American Diabetes Association (2011). Standards of medical care in diabetes--2011. Diabetes Care. 34(Suppl 1):S11-S61.

American Diabetes Association (2013). Standards of medical care in diabetes--2013. Diabetes Care. 36(Suppl 1):S11-S66.

American Diabetes Association, American Academy of Neurology (1988). Report and recommendations of the San Antonio Conference on Diabetic Neuropathy. Diabetes Care. 11:592–597.

Ametov AS, Barinov A, Dyck PJ, Hermann R, Kozlova N, Litchy WJ, et al (2003). The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Diabetes Care. 26:770–776

Bax G, Fagherazzi C, Piarulli F, Nicolucci A, Fedele D (1996). Reproducibility of Michigan Neuropathy Screening Instrument (MNSI). A comparison with tests using the vibratory and thermal perception thresholds. Diabetes Care. 19:904-905.

Boulton AJ, Vinik AI, Arezzo JC,Bril V, Feldman EL, Freeman R, et al (2005). Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care. 28:956-962.

Burns TM, Mauermann ML (2011). The Evaluation of Polyneuropathies. Neurol. 76 (Suppl 2):S6–S13

Busui RP, Sima A, Stevens M (2006). Diabetic neuropathy and oxidative stress. Diabet. Metab. Res. Rev. 22:257–273.

Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL (2012). Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol. 11:521–534.

Callaghan BC, Feldman E, Liu J, Kerber K, Pop-Busui R, Moffet H,et al (2011). Triglycerides and amputation risk in patients with diabetes: ten-year follow-up in the DISTANCE study. Diabetes Care. 34:635-640.

Callaghan BC, Hur J, Feldman EL (2012). Diabetic neuropathy: one disease or two? Curr. Opin. Neurol. 25:536–541.

Callaghan BC, Kerber K, Smith AL, Fendrick AM, Feldman EL (2012). The Evaluation of Distal Symmetric Polyneuropathy A Physician Survey of Clinical Practice. Arch. Neurol. 69:339-345.

Dyck PJ (1988). Detection, characterization, and staging of polyneuropathy: assessed in diabetics. Muscle Nerve. 11:21–32.

Dyck PJ, Albers JW, Andersen H, Arezzo JC, Biessels GJ, Bril V, et al (2011). Diabetic polyneuropathies: update on research definition, diagnostic criteria and estimation of severity. Diabetes Metab. Res. Rev. 27:620–628

 Freund FG, Martin WE, Hornbein TF (1969). The H-reflex as a measure of anesthetic potency in man. Anesthesiol. 30:642–647.

Gonçalves NP, Vægter CB, Andersen H, Østergaard L, Calcutt NA, Jensen TS (2017). Schwann cell interactions with axons and microvessels in diabetic neuropathy. Nat. Rev. Neurol. 13:135-147.

Gu XM, Zhang SS, Wu JC, Tang ZY, Lu ZQ,Li H, et al (2010). Efficacy and safety of high-dose α-lipoic acid in the treatment of diabetic polyneuropathy. Zhonghua Yi XueZaZhi. 90:2473-2476.

Hulley SB, Gove S, Cummings SR (1997). Elección de los individuos que participarán en el estudio: especificación y muestreo. En: Hulley SB, Cummings SR.eds. Diseño de la Investigación Clínica. España: Harcourt Brace; pp. 21-55.

Izenberg A, Perkins BA, Bril V (2015). Diabetic Neuropathies. Semin. Neurol. 35:424-430.

Jensen TS, Baron R (2003). Translation of symptoms and signs into mechanisms in neuropathic pain. Pain. 102:1–8.

 Jensen TS, Finnerup NB (2014). Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. Lancet Neurol. 13:924–935.

Kamei N, Yamane K, Nakanishi S, Yamashita Y, Tamura T, Ohshita K, et al (2005). Effectiveness of Semmes-Weinstein monofilament examination for diabetic peripheral neuropathy screening. J. Diabetes Complications. 19:47-53.

Lachman T, Shahani BT, Young RR (1980). Late responses as aides to diagnosis of peripheral neuropathies. J. Neurol. Neurosurg. Psychiatry. 43:156-162.

Martin CL, Albers JW, Pop-Busui R, DCCT/EDIC Research Group (2014). Neuropathy and related findings in the diabetes control and complications trial/Epidemiology of diabetes interventions and complications study. Diabetes Care. 37:31-38.

Mijnhout GS,Boudewijn J,  Kollen BJ, Alkhalaf A, Kleefstra N, Bilo HJ (2012). Alpha lipoic Acid for symptomatic peripheral neuropathy in patients with diabetes: a meta-analysis of randomized controlled trials. IntJEndocrinol. 2012:456279.

Mizisin AP (2014). Mechanisms of diabetic neurophaty: Schwann cells. Handb Clin. Neurol. 126:401–428.

Peltier A, Goutman SA, Callaghan BC (2014). Painful diabetic neuropathy. BMJ. 348:g1799.

Russell JW, Zilliox LA (2014). Diabetic Neuropathies. Continuum (MinneapMinn). 20:1226–1240.

Singh U, Jialal I (2008). Alpha-lipoic acid supplementation and diabetes.Nutr Rev. 66: 646–657.

Singleton JR, Smith AG (2012). The Diabetic Neuropathies: Practical and Rational Therapy. Semin. Neurol. 32:196–203.

 Smith AG, Singleton JR (2012). Diabetic Neuropathy. Continuum (MinneapMinn). 18:60–84.

Strakowski JA, Redd DD, Johnson EW, Pease WS (2001). H reflex and F wave latencies to soleus normal values and side-to-side differences. Am. J. Phys. Med. Rehabil. 80:491–493.

Strakowski JA, Redd DD, Johnson EW, Pease WS (2001). H reflex and F wave latencies to soleus normal values and side-to-side differences. Am. J. Phys. Med. Rehabil. 80:491-493.

Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, et al (2010). Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 33:2285-2293.

Truini A (2013). Peripheral nociceptor sensitization mediates allodynia in patients with distal symmetric polyneuropathy. J. Neurol. 260:761–766.

Vincent AM, Hayes JM, McLean LL, Vivekanandan-Giri A, Pennathur S, Feldman EL (2009). Dyslipidemia-induced neuropathy in mice: the role of oxLDL/LOX-1. Diabetes. 58:2376–2385.

Vinik AI, NevoretM, CaselliniC, Parson H (2013). Neurovascular function and sudorimetry in health and disease. Curr. Diab. Rep. 13:517–532.

Watson JC, Dyck PJB (2015). Peripheral Neuropathy: A Practical Approach to Diagnosis and Symptom Management. Mayo Clin. Proc. 90:940-951.

Ydens E, Lornet G, Smits V, Goethals S, Timmerman V, Janssens S (2013). The neuroinflammatory role of Schwann cells in disease. Neurobiol. Dis. 55:95–103

Zhou HH, Jin TT, Qin B, Turndorf H (1998). Suppression of spinal cord motoneuron excitability correlates with surgical immobility during isoflurane anesthesia. Anesthesiol. 88:955–961.

 Ziegler D (2004). Thioctic acid for patients with symptomatic diabetic polyneuropathy: a critical review. Treat Endocrinol. 3:173-189.

Ziegler D, Ametov A, Barinov A, Dyck PJ, Gurieva I, Low PA, et al (2006). Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care. 29:2365-2370.

Ziegler D, Low PA, Litchy WJ, Boulton AJ, Vinik AI, Freeman R, et al (2011). Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care. 34:2054-2060.

Ziegler D, Nowak H, Kempler P, Vargha P, Low PA (2004). Treatment of symptomatic diabetic polyneuropathy with the antioxidant alphalipoic acid: a meta-analysis. Diabet. Med. 21:114–121.

 ZieglerD, ReljanovicM, Mehnert H, Gries FA (1999). Alpha-lipoic acid in the treatment of diabetic polyneuropathy in Germany: current evidence from clinical trials. Exp. Clin. Endocrinol. Diabetes. 107:421–430.

Zilliox L, Russell JW (2011). Treatment of diabetic sensory polyneuropathy. Curr. Treat. Options Neurol. 13:143-159.

Related Articles

Original Research Article
Gede Wira Mahadita, Made Jawi and Ketut Suastika
Purple sweet potato tuber extract lowers mallondialdehyde and improves glycemic control in subjects with type 2 diabetes mellitus
Glo. Adv. Res. J. Med. Med. Sci. July 2016 Vol: 5(7): - [Abstract] [Full Text - PDF] (224 KB)
Mostafa Q Alshamiri
Diabetic Cardiomyopathy Pathophysiology and Update on Treatment
Glo. Adv. Res. J. Med. Med. Sci. November 2019 Vol: 8(4): - [Abstract] [Full Text - PDF] (185 KB)
Case Report
Lopez Goerne T, Arevalo A, Ramirez P and Larraza P
Copper nanoparticles as treatment of diabetic foot ulcers: A case report
Glo. Adv. Res. J. Med. Med. Sci. October 2017 Vol: 6(10): - [Abstract] [Full Text - PDF] (960 KB)
Original Research Articles
Ayşegül Mavi Yıldız, Dilek Güven, Ali Atakhan Yıldız, Selam Yekta Şendül, Saniye Üke Uzun and Rumeysa Selvinaz Erol
Does Vitamin D Level Effect the Response to Intravitreal Ranibizumab Therapy for Diabetic Macular Edema ?
Glo. Adv. Res. J. Med. Med. Sci. March 2015 Vol: 4(3): - [Abstract] [Full Text - PDF] (341 KB)
Rajech Sharkia, Muhammad Mahajnah, Ahmad Sheikh-Muhammad, Mohammad Khatib and Abdelnaser Zalan
Trends in the prevalence of type 2 diabetes mellitus among Arabs in Israel: A community health survey
Glo. Adv. Res. J. Med. Med. Sci. April 2018 Vol: 7(4): - [Abstract] [Full Text - PDF] (139 KB)

Current Issue

Viewing Options

View Full Article - PDF
Download Full Article - PDF

Search for Articles

Millán-Guerrero RO on Google Scholar
Millán-Guerrero RO on Pubmed
García-Ramírez AL on Google Scholar
García-Ramírez AL on Pubmed
Trujillo-Hernández B on Google Scholar
Trujillo-Hernández B on Pubmed
Caballero-Hoyos R on Google Scholar
Caballero-Hoyos R on Pubmed
González–Pérez O on Google Scholar
González–Pérez O on Pubmed
Isais-Millan S on Google Scholar
Isais-Millan S on Pubmed
Trujillo-Magallon Erick on Google Scholar
Trujillo-Magallon Erick on Pubmed


Viewed 1613
Printed 550
Downloaded 763
Powered By iPortal Works