Effects of Treatment With the Antioxidant α-Lipoic Acid on Cardiac Autonomic Neuropathy in NIDDM Patients: A 4-month randomized controlled multicenter trial (DEKAN Study)

Ziegler, Dan; Schatz, H; Conrad, Frank; Gries, F. A.; Ulrich, H; Reichel, G

doi:10.2337/diacare.20.3.369

Cited by 270 publications

(154 citation statements)

References 16 publications

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“…Alpha-lipoic acid, the most powerful pathogenetic therapeutic option of diabetic peripheral neuropathy [40][41][42] is also considered as the best choice for the treatment of CAN [43]. Alpha-lipoic acid enhances endoneurial blood flow by preventing the inhibition of nitric oxide synthetase and this way precludes ischaemic damage to nerve tissues [41].…”

Section: Discussionmentioning

confidence: 99%

Why Not to Use the Handgrip Test in the Assessment of Cardiovascular Autonomic Neuropathy Among Patients with Diabetes Mellitus?

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et al. 2016

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Section: Discussionmentioning

confidence: 99%

Why Not to Use the Handgrip Test in the Assessment of Cardiovascular Autonomic Neuropathy Among Patients with Diabetes Mellitus?

Körei

Kempler

Istenes

et al. 2016

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“…[9][10][11][12] In many studies, ALA treatment has been shown to improve diabetic-induced endothelial dysfunction, probably due to the antioxidant effect of ALA. 13) 14) However, the effect of ALA treatment in patients with hypertension associated endothelial dysfunction is unknown.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Alpha Lipoic Acid(Thioctacid HR®) on Endothelial Function in Diabetic and Hypertensive Patients

et al. 2006

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Background and Objectives：α-Lipoic acid (ALA) is known to improve endothelial function in patients with diabetes. However, the effect of ALA on endothelial function in hypertensive patients is unknown. The aim of this study was to investigate whether ALA improves endothelial function in diabetic and hypertensive patients. Subjects and Methods：This study included 40 patients who were treated with ALA (Group I: 20 diabetic patients, 54.9±10.2 years, Group II: 20 hypertensive patients, 56.5±9.0 years). ALA was administered in 600 mg/day doses during the first four weeks, and 1,200 mg/day doses during the second four weeks. Clinical characteristics and endothelial function were assessed at baseline, 4 weeks and 8 weeks after ALA administration. Evaluation of patients included: assessment of the brachial artery for flow mediated vasodilation (FMD) and the inflammatory marker (high sensitive CRP: hsCRP). Results：Clinical characteristics (body mass index, total cholesterol/HDL-cholesterol and hsCRP) were unchanged in each group. However, FMD was significantly improved at 8 weeks after ALA therapy in both groups. Group I-baseline：4 weeks：8 weeks=4.1±3.3：6.5±2.2：8.0± 2.7, Group II-baseline：4 weeks：8 weeks=5.5±3.7：7.4±3.3：9.3±2.7, p<0.05. The level of fibrinogen was observed to have an inverse correlation with FMD at 8 weeks after ALA therapy in Group I (p<0.05). Conclusion： ALA improves endothelial function in both diabetic and hypertensive patients.

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“…term clinical trials of symptomatic and cardiac autonomic neuropathy showed some beneficial effects of racLPA treatment [13,14]. R-LPA may be more effective than the S enantiomer in increasing tissue glucose uptake and metabolism and also as an antioxidant [15,16], although the latter has been disputed for nervous tissue in vitro [17].…”

Section: ±1mentioning

confidence: 99%

Effects of α-lipoic acid on neurovascular function in diabetic rats: interaction with essential fatty acids

et al. 1998

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Oxidative stress contributes to the vascular and neuropathic complications of experimental diabetes mellitus. This is evidenced by measures of tissue oxidant damage such as nerve lipid peroxidation and changes in antioxidant protection systems, for example decreased nerve reduced glutathione (GSH) and superoxide dismutase content [1,2]. Functional effects of antioxidant treatment include protection of vascular endothelium function [3±5], and improved nerve blood flow, conduction velocity (NCV) and regenerative capacity [2, 6±10]. a-Lipoic acid (LPA) is a naturally occurring free radical scavenger and transition metal chelator. LPA is also a cofactor for mitochondrial pyruvate dehydrogenase and has been termed a ªmetabolic antioxidantº [11]. Recent studies from Low's group [2,12] showed that treatment with LPA racemate (racLPA) prevented the development of digital sensory NCV deficits, impaired sciatic nerve blood flow, diminished nerve GSH, and deficient glucose uptake by neural tissues in diabetic rats. Short- Diabetologia (1998) Summary Elevated oxidative stress and impaired n-6 essential fatty acid metabolism contribute to defective nerve conduction velocity (NCV) and perfusion in diabetic rats, which may be corrected by free radical scavenger and g-linolenic acid (GLA) treatments. a-Lipoic acid (LPA) has antioxidant actions and both LPA racemate (racLPA) and GLA treatments produced benefits in clinical neuropathy trials. The aims were to study LPA action on neurovascular function in diabetic rats and to investigate potential interactions for co-treatment with GLA and other essential fatty acids. After 6 weeks of diabetes, 2 weeks of racLPA treatment corrected 20 % sciatic motor and 14 % saphenous sensory NCV deficits. The ED 50 for motor NCV restoration was approximately 38 mg kg ±1 day ±1. racLPA also corrected a 49 % diabetic deficit in sciatic endoneurial blood flow. R and S-LPA enantiomers were equipotent in correcting NCV and blood flow deficits. Treatment of diabetic rats with low doses (20 mg kg ±1 day ±1 ) of racLPA and GLA, while having modest effects on their own, showed evidence of marked synergistic action in joint treatment, completely correcting motor NCV and blood flow deficits. This was also noted for the novel compound, SOC0150, which contains equimolar proportions of LPA and GLA (ED 50 9.3 mg kg ±1 day ±1 , containing 3.5 mg LPA). NCV effects also showed marked synergism when racLPA:GLA ratios were varied over a 1:3±3:1 range. In contrast, a compound containing LPA and the n-3 component, docosahexaenoic acid, showed similar activity to LPA alone. Thus, LPA-GLA interactions yield drug combinations and compounds with an order of magnitude increase in efficacy against experimental diabetic neuropathy and are worthy of consideration for clinical trials. [Diabetologia (1998) 41: 390±399]

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Effects of Treatment With the Antioxidant α-Lipoic Acid on Cardiac Autonomic Neuropathy in NIDDM Patients: A 4-month randomized controlled multicenter trial (DEKAN Study)

Abstract: These findings suggest that treatment with ALA using a well-tolerated oral dose of 800 mg/day for 4 months may slightly improve CAN in NIDDM patients.

Cited by 270 publications

References 16 publications

Why Not to Use the Handgrip Test in the Assessment of Cardiovascular Autonomic Neuropathy Among Patients with Diabetes Mellitus?

Why Not to Use the Handgrip Test in the Assessment of Cardiovascular Autonomic Neuropathy Among Patients with Diabetes Mellitus?

The Effect of Alpha Lipoic Acid(Thioctacid HR®) on Endothelial Function in Diabetic and Hypertensive Patients

Effects of α-lipoic acid on neurovascular function in diabetic rats: interaction with essential fatty acids

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