Diabetes is characterized by chronic hyperglycemia that produces dysregulation of insulin secretion, insulin action, or both.1 It is a major public health problem affecting 9% of adults worldwide. One out of eleven adults worldwide now have type 2 diabetes mellitus.2 Despite efforts to increase awareness of the disease and its risk factors, many remain undiagnosed.3 Peripheral neuropathy is a common complication in patients with diabetes.
Diabetic neuropathy (DPN) is the most common neuropathy in industrialized countries and it is associated with a wide range of clinical manifestations.4 It is also associated with older age, long duration of diabetes mellitus, poor glycemic control, increased lipid levels, and high blood pressure. Despite its prevalence, there is neither good prevention nor treatment for DPN.5
Alpha lipoic acid (ALA) is an essential co-enzyme for energy production in mitochondria and has an effect on whole-body physiology. It can be found in very low quantities in almost all foods and is used as a dietary supplement and a pharmaceutical agent. ALA has been used as a dietary supplement at different doses in patients with diabetes mellitus type 2 due to its antioxidant, anti-inflammatory, and hypoglycemic effects. 6
Clinical studies investigating the effect of ALA on diabetic neuropathy have revealed promising results in terms of neuropathic symptoms. This technical article reviews such effects.
DPN is linked with morbidity, increased mortality, and impaired quality of life compared with patients who have diabetes but no neuropathy. Oxidative stress poses a significant role in the pathogenesis of DPN. ALA is a very potent oxidative agent and it has been shown to improve nerve blood flow, reduce oxidative stress, and improve distal nerve conduction in a rat model of diabetic neuropathy agent.
The 2018 study by Agathos, E. et al aims to investigate the effect of orally administered 600mg/day ALA on symptoms, laboratory parameters, quality of life, and overall health status of patients with painful diabetic neuropathy over 40 days.
Statistically significant reductions in neuropathic symptoms were noted by patients following the 40-day administration of a-lipoic acid, indicated by changes in questionnaires used such as Neuropathy Symptoms Score (NSS), Subjective Peripheral Neuropathy Screen (SPNSQ) and Douleur Neuropathique (DN4) scores.
Administration of 600 mg ALA over 40 days has been found to have a clinically significant and prompt reduction in neuropathy symptoms and an overall improvement in patients’ quality of life (QOL). The improvement in QOL was reflected by the reduction in pain severity and pain interference in terms of Brief Pain Inventory (BPI) scores.
Included in the BPI are the improvement in total score, burning spontaneous pain, pressing spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia in Neuropathic Pain Symptom Inventory (NPSI) scores; and work disability score, social life disability score, and family life disability score in the Sheehan Disability Scale (SDS). Reported adverse reactions were mild which range from nausea and vomiting to mild skin reactions.
In terms of laboratory parameters, fasting triglyceride levels were significantly reduced with ALA administration during the 40-day period. No statistically significant difference was found in terms of fasting glucose, total cholesterol, LDL-C, high-density lipoprotein cholesterol, HbA1c, BMI, arterial blood pressure or heart rate between the baseline and day 40 visit.
Administration of 600 mg/day ALA for 40 days to patients with painful diabetic neuropathy has a clinically significant impact on controlling neuropathy symptoms, fasting triglycerides, and quality of life. Furthermore, half of the treated patients rated their health status as ‘much better’ or ‘very much better’ following 40 days of treatment.
Overall, it has yet to be determined if the improvement of neuropathy symptoms could be further enhanced if prolonged beyond 40 days and more importantly if this will have an impact on the long-term course of diabetic neuropathy.
- Diagnosis and Classification of Diabetes Mellitus. American Diabetes Association. 2013.
- Zheng, Y., et al. Global Aetiology And Epidemiology of Type 2 Diabetes Mellitus and Its Complications. Nature Reviews Epidemiology. 2018.
- Improving Outcomes in Patients with Diabetes Melllitus. Journal American Heart Association. 2019.
- Said, G. Diabetic Neuropathy- A Review. Nature Clinical Practice Neurology. 2007.
- Frank, T., et al. Structure-Function Relationships in Peripheral Nerve Contributions to Diabetic Neuropathy. PAIN. May 2019.
- Nunez, V., Et Al. The Effect Of 600mg Alpha Lipoic Acid Supplementation on Oxidative Stress, Inflammation, And RAGE in Older Adults with Type 2 Diabetes Mellitus. Hindawi. 2019.