Acetyl-L-Carnitine Improves Symptoms of Diabetic Neuropathy

by | Apr 23, 2018 | 2016, Carnitine, Diabetes

Written by Angeline A. De Leon, Staff Writer. This study of 232 Chinese diabetic patients demonstrates that acetyl-L-carnitine was as effective as methylcobalamin (a current treatment choice in China) in reducing neuropathic pain.

diabetesFor individuals with diabetes mellitus, one of the most common chronic conditions involves diabetic peripheral neuropathy (DPN), a type of nerve damage that causes pain, numbness, and sensory or motor dysfunction in almost 50% of all patients 1. Symptoms can include sharp pain, tingling, burning sensation, or simply exaggerated sensitivity to touch. Although the majority of current treatments for DPN are unable to achieve complete neuropathic pain reduction, clinical studies support acetyl-L-carnitine (ALC) as a promising therapeutic agent for DPN. Meta-analyses report a pattern of ALC deficiency in DPN patients 2 and a growing number of randomized controlled trials on ALC suggests that ALC is not only safe and effective, but also outperforms placebo in reducing diabetes-related neuropathic pain 3,4. Supplementation with ALC has been shown to correct conditions associated with DPN, including abnormal energy production in nerves and disordered fatty acid oxidation 5,6. As a cofactor facilitating the metabolism of fatty acids in the mitochondria, ALC is helpful in reducing insulin resistance and has also been found to improve chemotherapy-induced and HIV-associated neuropathy 7,8. Current treatment guidelines support the use of methylcobalamin (MC), a methylated derivative of vitamin B12 which also demonstrates efficacy in improving nerve conduction and reducing neuropathic pain 9, but thus far, the clinical value of MC has not been studied in comparison to ALC. In 2016, researchers in China conducted a comparative study 10 evaluating the efficacy and safety of ALC vs. MC in the treatment of DPN.

The multi-center, randomized, double-blind, placebo-controlled trial involved a total of 232 diabetic patients (aged 18-70 years) diagnosed with DPN and presenting with abnormal nerve conduction velocity (NCV) in at least one nerve of the extremities. Patients were randomized in a 1:1 ratio to receive ALC (500 mg) or MC (0.5 mg) three times daily for 24 weeks. The neuropathy symptoms score and neuropathy disability score were administered to evaluate changes in neuropathy from baseline to Week 24. Changes in NCV and amplitude were also assessed at baseline and follow-up as a neurophysiological measure of DPN.

Results indicated that at Week 24, both ALC and MC groups experienced significant reduction in both neuropathy symptoms score (ALC vs. MC: 2.35 +/- 2.23, p < 0.0001 vs. 2.11 +/- 2.48, p < 0.0001; intergroup p = 0.38) and neuropathy disability score (ALC vs. MC: 1.66 +/- 1.90, p < 0.0001 vs. 1.35 +/- 1.65, p < 0.0001; intergroup p = 0.23), with no significant difference found between the two groups. In the ALC group, NCV and amplitude of all investigated motor and sensory nerves were shown to improve from baseline to follow-up (including NCV in the median sensory nerve and response amplitude in the ulnar motor nerve, p < 0.0001 for both) while in the MC group, NCV and amplitude were seen to improve in the majority of nerves tested (including NCV in the peroneal motor nerve, p = 0.0006, and response amplitude in the tibial motor nerve, p = 0.0009).

Overall, findings demonstrate that ALC is comparable to MC, the current medication recommended by Chinese guidelines for the treatment of diabetes, in improving DPN symptoms. As the first active-controlled randomized trial of ALC on DPN, evidence suggests that ALC and MC are similar in their capacity to ameliorate neuropathic symptoms as well as improve electrophysiological parameters in diabetic patients. While further clinical trials with long-term follow-up periods are still required, ALC appears to be a safe, well-tolerated, and effective potential treatment option for DPN.

Source: Li S, Chen X, Li Q, et al. Effects of acetyl-L-carnitine and methylcobalamin for diabetic peripheral neuropathy: a multicenter, randomized, double-blind, controlled trial. Journal of Diabetes Investigation. 2016; 7: 777-785. DOI: 10.1111/jdi.12493.

© 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd J Diabetes Investig Vol. 7 No. 5 September 2016 777. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Click here to read the full text study.

Posted April 23, 2018.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

References:

  1. Sugimoto K, Murakawa Y, Sima A. Diabetic neuropathy–a continuing enigma. Diabetes/metabolism research and reviews. 2000;16(6):408-433.
  2. Scarpini E, Doneda P, Pizzul S, et al. L-carnitine and acetyl-L-carnitine in human nerves from normal and diabetic subjects. Journal of the peripheral nervous system: JPNS. 1996;1(2):157-163.
  3. Li S, Li Q, Li Y, Li L, Tian H, Sun X. Acetyl-L-carnitine in the treatment of peripheral neuropathic pain: a systematic review and meta-analysis of randomized controlled trials. PloS one. 2015;10(3):e0119479.
  4. Uzun N, Sarikaya S, Uluduz D, Aydin A. Peripheric and automatic neuropathy in children with type 1 diabetes mellitus: the effect of L-carnitine treatment on the peripheral and autonomic nervous system. Electromyography and clinical neurophysiology. 2005;45(6):343-351.
  5. Greene DA, Winegrad AI. In vitro studies of the substrates for energy production and the effects of insulin on glucose utilization in the neural components of peripheral nerve. Diabetes. 1979;28(10):878-887.
  6. Sass RL, Werness P. Acetylcarnitine: on the relationship between structure and function. Biochemical and biophysical research communications. 1973;55(3):736-742.
  7. Mondal S, Choudhury KB, Sharma S, Gupta A, Dutta S. Comparative study among glutamine, acetyl-L-carnitine, vitamin-E and methylcobalamine for treatment of paclitaxel-induced peripheral neuropathy. Clinical Cancer Investigation Journal. 2014;3(3):213.
  8. Youle M, Osio M, Group AS. A double‐blind, parallel‐group, placebo‐controlled, multicentre study of acetyl L‐carnitine in the symptomatic treatment of antiretroviral toxic neuropathy in patients with HIV‐1 infection. HIV medicine. 2007;8(4):241-250.
  9. Zhang M, Han W, Hu S, Xu H. Methylcobalamin: a potential vitamin of pain killer. Neural plasticity. 2013;2013.
  10. Li S, Chen X, Li Q, et al. Effects of acetyl‐L‐carnitine and methylcobalamin for diabetic peripheral neuropathy: A multicenter, randomized, double‐blind, controlled trial. Journal of diabetes investigation. 2016;7(5):777-785.