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)

OBJECTIVE - To evaluate the efficacy and safety of oral treatment with the antioxidant alpha-lipoic acid (ALA) in NIDDM patients with cardia c autonomic neuropathy (CAN), assessed by heart rate variability (HRV) . RESEARCH DESIGN AND 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 a daily oral dose of 800 mg ALA (n = 39) or placebo (n = 34) for 4 months. Parameters of HRV at rest included the coeffici ent of Variation (CV), root mean square successive difference (RMSSD), and spectral power in the low-frequency (LF; 0.05-0.15 Hz) and high-f requency (HF; 0.15-0.5 Hz) bands. In addition, cardiovascular autonomi c symptoms were assessed. RESULTS - Seventeen patients dropped out of the study (ALA n = 10; placebo n = 7). Mean blood pressure and HbA(1) levels did not differ between the groups at baseline and during the st udy, but heart rate at baseline was higher in the group treated with A LA (P < 0.05). RMSSD increased from baseline to 4 months by 1.5 ms (-3 7.6 to 77.1) [median (minimum-maximum)] in the group given ALA and dec reased by -0.1 ms (-19.2 to 32.8) in the placebo group (P < 0.05 for A LA vs. placebo). Power spectrum in the LF band increased by 0.06 bpm(2 ) (-0.09 to 0.62) in ALA, whereas it declined by -0.01 bpm(2) (-0.48 t o 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. place bo). The changes in cardiovascular autonomic symptoms did not differ s ignificantly between the groups during the period studied. No differen ces between the groups were noted regarding the rates of adverse event s. CONCLUSIONS - These findings suggest that treatment with ALA using a well-tolerated oral dose of 800 mg/day for 4 months may slightly imp rove CAN in NIDDM patients.