Introduction
Synthesis, biochemical properties, absorption and bioavailability
Antioxidant properties
Reactive oxygen species | ALA | DHLA |
---|---|---|
Hydrogen peroxide | Yes (12) | Yes (12) |
(H2O2) | No (23) | No (23) |
Superoxide | ||
(O2-) | No (23) | Yes (12, 27,28) |
No (23) | ||
Hydroxyl radical | ||
(HO-) | Yes | Yes |
(23,24,27) | (27) | |
SInglet oxygen | Yes (12,29) | Yes (29) |
(O2 *) | No (24) | |
Peroxynitrite | Yes (12,25) | Yes 12,(25) |
(ONOO-) | ||
Nitric oxide radical | Yes | Yes (12) |
(NO) | (12, 26) | No (26) |
Hypochlous acid | Yes (23, 24, 31) | Yes (31) |
(HOCL) | ||
Peroxyl radical | Yes (23) | Yes (23, 30) |
(HO2..) | No (30) |
Metal chelator properties
Action upon transduction signaling systems
Insulin pathway
Nuclear factor kappa B
Adenosine monophosfatase protein kinase
Relationship between the dose of ALA and its effects in experimental studies
Clinical use of ALA in conditions other than diabetes
Brain diseases and cognitive dysfunction
Obesity
Nonalcoholic fatty liver disease
Burning mouth syndrome
Cardiovascular disease and endothelial function
Cancer
Miscelaneous disorders
Clinical use of ALA in diabetes
Use of ALA in diabetes treatment
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 |