Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea

Abstract

BackgroundDiabetic cardiac autonomic neuropathy (CAN) is one of the important complications of diabetes. It is characterized by reduced heart rate variability (HRV).MethodsIn this randomized, double-blind, placebo-controlled, multicenter trial, 75 patients were randomly assigned to one of two groups. One group (n=41) received α-lipoic acid (ALA) at an oral dose of 600 mg/day for the first 12 weeks and then 1,200 mg/day for the next 12 weeks. The other group (n=34) received placebo treatment for 24 weeks. CAN was assessed by measuring HRVs in people with diabetes.ResultsMost of the baseline measures for HRVs were similar between the ALA and placebo groups. Although there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial, we found a positive tendency in some of the HRV parameters of the ALA group. The standard deviations of normal-to-normal RR intervals in the standing position increased by 1.87 ms in the ALA group but decreased by −3.97 ms in the placebo group (P=0.06). The power spectrum of the low frequency (LF) band in the standing position increased by 15.77 ms2 in the ALA group, whereas it declined by −15.04 ms2 in the placebo group (P=0.08). The high frequency/LF ratio in the upright position increased by 0.35 in the ALA group, whereas it declined by −0.42 in the placebo group (P=0.06). There were no differences between the two groups regarding rates of adverse events.ConclusionAlthough a slight improvement tendency was seen in HRV in the ALA group, there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial. However, the high oral dose of ALA was well-tolerated.

Update on the Impact, Diagnosis and Management of Cardiovascular Autonomic Neuropathy in Diabetes: What Is Defined, What Is New, and What Is Unmet

“…Most of these pathways are involved in diabetic neuropathy pathogenesis. Pharmacological interventions with α-lipoic acid achieved some limited effect in the Deutsche Kardiale Autonome Neuropathie (DEKAN) Study of 73 patients with T2DM through the oral administration of 800 mg for 4 months [149], a significant improvement in CARTs in an uncontrolled study of 49 participants with T1DM through 600 mg intravenous for 10 days followed by 600 mg oral for 50 days [150], and borderline efficacy in another study of 75 patients with T2DM on a HRV measure (i.e., SDNN) with an oral administration of 600 and 1,200 mg for 12 weeks each [151]. Moreover, the combination of α-lipoic acid 1,200 mg oral with nicotinamide 1,500 mg and allopurinol 300 mg failed to influence CAN measures in 31 patients with T1DM [152], pointing to possible negative metabolic interactions between the three antioxidants.…”

Safety Evaluation of α-Lipoic Acid Supplementation: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Clinical Studies

“…Additional 139 papers were excluded due to being pre-print papers ( n = 2), study protocols ( n = 6), reporting data from studies lacking of an appropriate placebo-controlled design for the supplementation ( n = 64), lacking of randomisation ( n = 5), testing the acute effect of ALA supplementation ( n = 7), testing ALA supplementation combined in nutraceutical compounds ( n = 27), testing intravenous treatment with ALA ( n = 11), testing topical treatment with ALA ( n = 4), lacking sufficient information about the nature of the adverse events ( n = 9), or reporting data overlapped with other publications ( n = 4) ( Supplementary file B ). Finally, 71 studies were eligible and included in the systematic review [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ,…”

Response: Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea (Diabetes Metab J 2017;41:275-83)

“…We appreciate Professor Lee's interest and agree with the comments on our article entitled “Effects of high-dose α-lipoic acid on heart rate variability of type 2 diabetes mellitus patients with cardiac autonomic neuropathy in Korea” which was published in Diabetes and Metabolism Journal [ 1 ].…”