Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial (DEKAN Study). Deutsche Kardiale Autonome Neuropathie.
OBJECTIVE
To evaluate the efficacy and safety of oral treatment with the antioxidant alpha-lipoic acid (ALA) in NIDDM patients with cardiac autonomic neuropathy (CAN), assessed by heart rate variability (HRV).


METHODS
In a randomized, double-blind placebo-controlled multicenter trial (Deutsche Kardiale Autonome Neuropathie [DEKAN] Study), NIDDM patients with reduced HRV were randomly assigned to treatment with daily oral dose of 800 mg ALA (n = 39) or placebo (n = 34) for 4 months. Parameters of HRV at rest included the coefficient of variation (CV), root mean square successive difference (RMSSD), and spectral power in the low-frequency (LF; 0.05-0.15 Hz) and high-frequency (HF; 0.15-0.5 Hz) bands. In addition, cardiovascular autonomic symptoms were assessed.


RESULTS
Seventeen patients dropped out of the study (ALA n = 10; placebo n = 7). Mean blood pressure and HbA1 levels did not differ between the groups at baseline and during the study, but heart rate at baseline was higher in the group treated with ALA (P < 0.05). RMSSD increased from baseline to 4 months by 1.5 ms (-37.6 to 77.1) [median (minimum-maximum)] in the group given ALA and decreased by -0.1 ms (-19.2 to 32.8) in the placebo group (P < 0.05 for ALA vs. placebo). Power spectrum in the LF band increased by 0.06 bpm2 (-0. 09 to 0.62) in ALA, whereas it declined by -0.01 bpm2 (-0.48 to 1.86) in placebo (P < 0.05 for ALA vs. placebo). Furthermore, there was a trend toward a favorable effect of ALA versus placebo for the CV and HF band power spectrum (P = 0.097 and P = 0.094 for ALA vs. placebo). The changes in cardiovascular autonomic symptoms did not differ significantly between the groups during the period studied. No differences between the groups were noted regarding the rates of adverse events.


CONCLUSIONS
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.
Ziegler
D
D
Diabetes-Forschungsinstitut an der Heinrich-Heine-Universität, Düsseldorf, Germany.
Schatz
H
H
Conrad
F
F
Gries
F A
FA
Ulrich
H
H
Reichel
G
G
D001342:Autonomic Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D015986:Confounding Factors, Epidemiologic; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008063:Thioctic Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D006442:Glycated Hemoglobin; D008063:Thioctic Acid