Table 2 Clinical studies with ALA in patients with diabetes
Author | Study type | ALA/other drugs | Analyzed parameters | Total participants | Duration of DM (years) | Follow up (weeks/ years) | Results |
|---|---|---|---|---|---|---|---|
Type 2 diabetes treatment | |||||||
Udupa, AS [134] | Randomized, double- blind placebo-controlled | Vitamin E, omega 3 fatty acids ALA 300 mg All of them daily/orally | Weight, waist glucose | 104 with IR | 5-10 y | 12 w | < HbA1c, weight, waist Better results with omega-3 followed by vitamin E and ALA |
Porasuphatana S [135] | Randomized, placebo- controlled | ALA 300 mg -1200 mg/d | HbA1c, FBG | 38 | 2.07 ± 0.26 | 24 w | <HbA1c, FBG |
De Oliveira AM [136] | Randomized, double- blind placebo-controlled | ALA 600 mg or Vitamin E 800 mg or ALA 600 mg plus Vitamin E 800 mgr | HOMA index, glucose, lipid profile insulin | 102 | 16 w | ||
Diabetic retinopathy | |||||||
Haritoglou C [139] | Randomized ,double-blind placebo-controlled | ALA 600 mg/daily | Development of macular edema | 232 patients with type 2 and 170 with T1D | 86 w | no effect | |
Nebioso M [140] | Randomized not placebo-controlled | ALA 400 mg daily plus vitamins and genistein | ERG | 32 | NA | 4 w | Improvement in ERG |
Diabetic nephropathy | |||||||
Borcea V [143] | Cross-sectional not placebo-controlled | ALA 600 mg/daily/orally | Lipid ROOH, HbA1c, urine albumin, α tocopherol | 107 patients [45 with T1D and 29 with T2D] | 21.7 ± 11.1 (with ALA); 15.3 ± 10.4 (without ALA) | >12 w | < ROOH < ROOH/(,α tocopherol/cholesterol The decrease was independent of HbA1c and urine albumin level |
Cicek M [144] | Randomized not placebo-controlled | ALA 600 mg/ /orally | CIN Plasma creatinine, Cystation C | 79 | NA | Prior coronary angiography | No effect in the incidence of CIN, creatinine, Cystatin C pré /pos exam |
Chang JW [145] | Randomized placebo-controlled | ALA 600 mg/orally | Cholesterol, HbA1c C-reactive protein, oxidizedLDL- ADMA | 50 patients on hemodyalisis treatment | NA | 12 w | Decrease the level of ADMA |
Diabetes endothelial dysfunction | |||||||
Heinisch BB [147] | Randomized, Controlled,double- blind placebo parallel | Daily 600 mg of ALA IV | Endothelial function endothelium dependent and independent HbA1c, lipid profile | 30 patients with TD2 | 7 ± 6 | 3 w | Improvement in endothelium dependent function |
Diabetic cardiovascular autonomic neuropathy | |||||||
Pop-Busui R [150] | Prospective, randomized, double- blind, placebo- controlled | ALA 600 mg/twice daily Nicotinamide 750 mg/twice daily Allupurinol 300 mg/daily All of them orally | Autonomic tests PET F2 urinary isoprostane HbA1c | 44 patients with T1D with mild/moderate cardiovascular autonomic neuropathy and retinopathy or microalbuminuria | 27 ± 12 | 2 y | No improvement in any analyzed parameter |
Ziegler D [151] | Randomized, double- blind, placebo- controlled | ALA 800 mg/daily (orally) | Heart rate variability HbA1c Autonomic symptoms | 73 patients with T2D | 15.3 ± 8.3 | 16 w | Improvement on root mean square successive difference and power spectrum in low frequency band No difference in the prevalence of symptoms |
Diabetic polyneuropathy | |||||||
ZiegleR D [153] ALADIN I | Randomized,double- blind controlled parallel | ALA:1200 or 600 or 100 mg/daily (orally) | TSS HbA1c | 328 patients with T2D with symptomatic peripheral neuropathy | 10.4/12.3 | 3 w | Improvement in TSS HbA1c: no difference |
Reljanovic M [154] ALADIN II | Prospective randomized,double- blind controlled | ALA 1200 mg or 600 mg orally | Sensory and motor nerve function | 299 patients (T1D and T2D) with symptomatic polyneuropathy | NA | 2 y | Improvement in electrophysiological tests HbA1c: no difference |
Ziegler D.[155] ALADIN III | Prospective randomized, double- blind controlled | ALA 600 mg/ IV followed by 1800 mg of ALA or placebo orally | TSS NIS | 516 patients with T2D with symptomatic polyneuropathy | 11 | 3 w (IV) 24 w (orally) | No effect HbA1c:no difference |
Ametov As [157] Sidney I | Randomized, double- blind ,parallel controlled, mono-center | ALA 600 mg IV | TSS | 120 (T1D and T2D) with DSPN | 15.1 ± 8.8 | 3 | Improvement |
Ziegler D [158] Sidney II | Randomized, double- blind, parallel controlled, multicenter | ALA 600 to 1800 mg/orally | TSS | 181 (T1D and T2D) with DSPN | 14 | 5 | Improvement |
Ziegler D [159] Nathan I | Randomized, double- blind, parallel controlled, multicenter | ALA 600 mg/orally | TSS Composite score( NIS–lower limbs plus 7 neurophisiologic tests (NIS-LL+7) | 460 (T1D and T2D) with DSPN | 13.3 | 4 years | TSS: no improvement NSI-LL+7:improvement |
Ziegler D [160] | Meta-analysis | ALA 600mg IV | TSS, NIS-LL | 1258 | 132 months | 3 w | Improvement in TSS (papin-prick,touch-pressure), burning,numbness) Improvement in NIS-LL |
Mijnhout GS [161] | Meta-analysis | ALA orally ( 600 to 1800 mg daily) ALA IV (100 to 1200 mg/daily) | TSS | 653 | NA | 3 to 5 w | Improvement in TSS but greater than 30% only in intravenously treated patients |