Combination Of Alpha-lipoic Acid Research Articles

Ameliorative effect of Metformin / alpha-lipoic acid combination on diabetic nephropathy via modulation of YAP/ miR-29a/PTEN/p-AKT axis

Diabetic nephropathy (DN) is the most frequent and serious complication of type 2 diabetes (T2DM). Lack of a precise remedy and socio-economic burden of DN patients implements searching about alternative therapies. This study aims to evaluate the possible beneficial effect of alpha-lipoic acid (α-LA) alone or in combination with metformin (Met) in ameliorating STZ/High fat diet (HFD)-induced DN. T2DM was induced via HFD administration for 15 weeks and single ip injection of STZ (35 mg/kg) at week 7. Male Sprague–Dawley rats were randomly grouped as follows: control group, STZ/HFD-induced DN, Met/T; daily treated with 150 mg/kg Met, α-LA/T group; daily treated with 100 mg/kg α-LA, and Met/T + α-LA/T group; daily treated with Met and α-LA at same doses. Administration of Met and α-LA succeeded in attenuating STZ/HFD-induced DN as manifested by significant decrease in kidney weight as well as renal and cardiac hypertrophy index. Moreover, Met and α-LA improved glycemic control, kidney functions and lipid profile as well as restored redox balance. Additionally, Met and α-LA administration significantly upregulated PTEN level accompanied by significant downregulation in renal p-AKT and miR-29a levels. Histopathologically, Met and α-LA administration mitigated STZ/HFD-induced histopathological alterations in kidney and heart. Moreover, immunohistochemical examination revealed a significant decrease in renal YAP, collagen I and Ki-67. Taken together, these observations revealed that Met and α-LA administration could protect against STZ/HFD-induced DN.

Anti-cancer effects of alpha lipoic acid, cisplatin and paclitaxel combination in the OVCAR-3 ovarian adenocarcinoma cell line.

Ovarian cancer is the leading cause of gynecological cancer deaths. One of the major challenges in treating ovarian cancer with chemotherapy is managing the resistance developed by cancer cells to drugs, while also minimizing the side effects caused by these agents In the present study, we aimed to examine the effects of a combination of alpha lipoic acid (ALA), with cisplatin and paclitaxel in ovarian cancer(OVCAR-3). The cytotoxic effects of ALA, cisplatin and paclitaxel on OVCAR-3 cells were determined. Four groups were formed: Control, ALA, Cisplatin + Paclitaxel, ALA + Cisplatin + Paclitaxel. The effects of single and combined therapy on cell migration, invasion and colony formation were analyzed. Changes in the expression of genes related to apoptosis, cell adhesion and cell cycle were analyzed with Real-time polymerase chain reaction(RT-PCR). The oxidative stress index and The Annexin V test were performed. The reduction in rapamycin-insensitive companion of mTOR(RICTOR) expression in the ALA + Cisplatin + Paclitaxel group was found statistically significant(p < 0.05). The decrease in MMP-9 and - 11 expressions the ALA + Cisplatin + Paclitaxel group was statistically significant(p < 0.05). The lowest values for mitogen-activated protein kinase(MAPK) proteins were found in the ALA + Cisplatin + Paclitaxel group. No colony formation was observed in the Cisplatin + Paclitaxel and ALA + Cisplatin + Paclitaxel groups. The lowest wound healing at 24h was seen in the ALA + Cisplatin + Paclitaxel group. This study is the first one to investigate the combined treatment of ALA, Cisplatin, Paclitaxel on OVCAR-3. While ALA alone was not effective, combined therapy with ALA, has been found to reduce cell invasion, especially wound healing in the first 24h, along with tumor cell adhesion.

Combination of High-Dose Parenteral Ascorbate (Vitamin C) and Alpha-Lipoic Acid Failed to Enhance Tumor-Inhibitory Effect But Increased Toxicity in Preclinical Cancer Models.

Intravenous vitamin C (IVC, ascorbate [Asc]) and alpha-lipoic acid (ALA) are frequently coadministered in integrative oncology clinics, with limited understanding of combination effects or drug-drug interactions. As high-dose IVC has anticancer activity through peroxide (H2O2), it is hypothesized that IV ALA, a thiol antioxidant, might have untoward effects when combined with IVC. In vitro combination index (CI) was investigated in 6 types of human cancer cells, using clinically relevant concentrations of Asc (0.625-20 mM) and ALA (0.25, 0.5, and 1 mM) evaluated by nonconstant ratio metrics. Cellular H2O2 was measured using HeLa cells expressing a fluorescent probe HyPer. Mouse xenografts of the metastatic breast cancer MDA-MB-231 were treated with intraperitoneal injections of ALA (10, 20, and 50 mg/kg) and Asc (0.2, 0.5, and 4 g/kg) at various dose levels. Cancer cell lines were sensitive to Asc treatment but not to ALA. There is no evidence ALA becomes a prooxidant at higher doses. The CIs showed a mixture of synergistic and antagonistic effects with different ALA and Asc combination ratios, with a "U" shape response to Asc concentrations. The ALA concentrations did not influence the CIs or cellular H2O2 formation. Adding ALA to Asc dampened the increase of H2O2. Toxicity was observed in mice receiving prolonged treatment of ALA at all doses. The Asc at all doses was nontoxic. The combination of ALA and Asc increased toxicity. The ALA at all doses did not inhibit tumor growth. The Asc at 4 g/kg inhibited tumor growth. Adding ALA 50 mg/kg to Asc 4 g/kg did not enhance the effect, but lower doses of ALA (10 or 20 mg/kg) dampened the inhibitory effect of Asc. These data do not support the concurrent or relative concurrent use of high-dose intravenous ALA with prooxidative high-dose IVC in clinical oncology care with potentially increased toxicity.

Combination of Alpha-Lipoic Acid and Auraptene Induces Apoptosis and Prevents Proliferation of the Human U-87 Glioblastoma Cells

Combination of Alpha-Lipoic Acid and Auraptene Induces Apoptosis and Prevents Proliferation of the Human U-87 Glioblastoma Cells

Synergistic antihyperglycemic effect of alpha lipoic acid with antidiabetic agents in the normoglycemic and streptozotocin-induced type 2 diabetic rats

The current study's main goal was to assess the supplementation effect of alpha lipoic acid with antidiabetic medications (metformin and sitagliptin) on normal and streptozotocin-induced blood glucose levels in normal and streptozotocin-induced diabetic rats. For this purpose, forty-two rats were randomly divided into two groups: normal control (n = 6) and diabetic (n = 36) groups, which were submitted to the following treatments: A: normal rats; B: diabetic rats; C: diabetic rats with sitagliptin (1 mg/kg); D: diabetic rats with metformin (10 mg/kg); E: diabetic rats with alpha lipoic acid (10 mg/kg); F: diabetic rats with a combination of alpha lipoic acid and sitagliptin; G: diabetic rats with a combination of alpha lipoic acid and metformin. The glycemia of these animals was monitored weekly; the use of alpha lipoic acid resulted in a significant decrease in glycemic levels. Combining alpha lipoic acid with either metformin or sitagliptin is most effective for reducing blood glucose levels in animals with acute and chronic hyperglycemia, even at different treatment times. Thus, associated with either metformin or sitagliptin, alpha lipoic acid improved their anti-diabetic effects.

Alpha-Lipoic Acid, Auraptene, and Particularly Their Combination Prevent the Metastasis of U87 Human Glioblastoma Cells.

The primary malignant brain tumor glioblastoma multiforme (GBM) is most commonly detected in individuals over 60 years old. The standard therapeutic approach for GBM is radiotherapy combined with temozolomide. Recently, herbal products, such as alpha-lipoic acid (ALA) and auraptene (AUR), have shown promising anticancer effects on various cancer cells and animal models. However, it is not well understood how ALA, AUR, and their combination in GBM work to combat cancer. Thus, the purpose of this study was to investigate the antimetastatic effects of the ALA-AUR combination on U87 human glioblastoma cells. The inhibitory effects of ALA, AUR, and the ALA/AUR combination on the migration and metastasis of U87 cells were evaluated using a wound healing test and gelatin zymography. The expression levels of matrix metalloproteinase MMP-2 and MMP-9 were assessed at the transcriptional and translational levels using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. Our findings revealed that combination therapy reduced cell migration and metastasis, which was indicated by the reduction in MMP-2/-9 expression both at mRNA and protein levels, as well as their enzymatic activity in U87 cells. This study demonstrated that the combination of ALA and AUR effectively inhibited the migration and metastasis of U87 cells. Thus, given their safety and favorable specifications, the combination of these drugs can be a promising candidate for GBM treatment as primary or adjuvant therapy.

Combination of alpha lipoic acid and metformin supplement improve assisted reproductive technologies outcomes in polycystic ovary syndrome patients.

We aimed to investigating the effects of metformin (MET) in combination with alpha lipoic acid (ALA) on hormonal and biochemical parameters, in polycystic ovary syndrome (PCOS) women undergoing intracytoplasmic sperm injection (ICSI). This experimental pilot study with a randomized design was carried out on 40 PCOS women in two groups: (1) MET group, administered 1,500 mg/day MET, and (2) MET (1,500 mg/day)+ALA (1,800 mg/day) group. Drugs were administered from the third day of the previous cycle until the day of oocyte aspiration (six weeks of treatment in total). MET+ALA significantly increased the number of maturated oocytes and the rate of fertilization when compared to the MET group. Combination MET+ALA could increase significantly the number of oocytes retrieval and the number of good-quality embryos. Also, the malondialdehyde (MDA) level decreased significantly in the MET+ALA group and the total antioxidant capacity (TAC) level increased significantly in the MET+ALA group compared to the MET group. Also, fasting blood sugar (FBS), insulin, luteinizing hormone (LH), and LH/follicle stimulating hormone (FSH) levels were significantly lower in the MET+ALA group. The pregnancy outcomes showed no significant difference in the rates of biochemical pregnancy, clinical pregnancy, miscarriage, and live births between the control and study groups. The combination of MET+ALA treatment could moderate the complications of PCOS and subsequently improve oocyte and embryo quality.

Post Marketing Surveillance Study to evaluate the Efficacy and Safety for the Combination of Alpha Lipoic Acid, Gingko Biloba, Vitamin C, Zinc, Magnesium, Vitamin B6, Methylcobalamin, Vitamin E and Chromium Picolinate in the Patients of Tinnitus

Introduction: Tinnitus is the false perception of sound. Normally it is considered to be developed due to oxidative stress to the inner ear. This study was conducted to test the efficacy and safety for the combination of Alpha lipoic acid, Gingko biloba, Vitamin C, Zinc, Magnesium, Vitamin B6, Methylcobalamin, Vitamin E and Chromium Picolinate in the patients of tinnitus. Method: The study was conducted on 165 patients out of which 142 completed the study. Efficacy was evaluated by tinnitus symptom score (TSS). Patients were asked to rate the TSS ranging from 0 to 10 where 0 means no symptom and 10 means maximum tolerable symptoms. Safety assessment was made by analysing the adverse events reported by the patient. Efficacy and safety evaluation was done on day 0, 10 and 22. Results: Patients had TSS 6.26 on baseline visit which was reduced to 4.50 at day 10 and was further reduced to 2.47 at day 22. Also, in the clinical trial duration of 22 days, only 5 episodes of the adverse drug reactions were reported by the patient and all of them were of non-serious in nature and mild in intensity. Conclusion: The fixed dose combination of Alpha lipoic acid 200 mg, Gingko biloba 120 mg, Vitamin C 30 mg, Zinc 12 mg, Magnesium 10 mg, Vitamin B6 3 mg, Methylcobalamin 1500 mcg, Vitamin E 10 IU and Chromium Picolinate 1.66 mg equivalent to elemental chromium 200 mcg was found to be efficacious and safe for the treatment of Tinnitus.

Safety and Efficacy for the Combination of Alpha Lipoic Acid, Gingko Biloba, Vitamin C, Zinc, Magnesium, Vitamin B6, Methylcobalamin, Vitamin E and Chromium Picolinate for the Medical Management of Age Related Hearing Loss: Post Marketing Surveillance Study

Introduction: Age related hearing loss is defined as a bilateral, progressive, symmetrical age-related sensorineural hearing loss, which is most pronounced at the higher frequencies. It is considered that oxidative stress has a central role in the pathology of age-related hearing loss so, this study was conducted to test the efficacy and safety for the combination of antioxidants for the treatment of age-related hearing loss. Methodology: This was a multi-centric study conducted at 11 clinical trial sites. Out of total 176 enrolled, 160 trial subjects completed the study. For efficacy assessment, 2 parameters were used including hearing related quality of life score and score obtained from hearing impairment questionnaire on day 0 (visit 1), 45 (visit 2) and 90 (visit 3). Results: At visit 1, the mean hearing related quality of life score was 4.437 increased to 5.725 at visit 2 and further increased to 6.906 at visit 3. At visit 2 and 3, the increase in hearing related quality of life score was 29.028% and 55.645% respectively as compared to baseline. The score obtained from hearing impairment questionnaire was 25.581 at visit 1 reduced to 16.200 and further reduced to 9.943 at visit 3. Conclusion: The combination of Alpha lipoic acid, Gingko biloba, Vitamin C, Zinc, Magnesium, Vitamin B6, Methyl cobalamin, Vitamin E and Chromium Picolinate can be used for the medical management of age related hearing loss.

Effect of vitamin E and alpha lipoic acid on intestinal development associated with wooden breast myopathy in broilers

Intestinal development is closely associated with inflammatory wooden breast (WB) myopathy. Vitamin E (VE) and alpha lipoic acid (ALA) with antioxidant and anti-inflammatory effects were used independently and in combination to evaluate their effects on intestinal developmental changes in ileal morphology and expression of genes related with gut nutrient transport, structure, and inflammation in broilers during the first 3 wk posthatch. A total of 160 newly hatched Ross 708 broiler chicks were randomly assigned into a control and 3 dietary treatments with 10 replicates of 4 birds each. Supplementation of VE (160 mg/kg) and ALA (500 mg/kg) independently and in combination were fed during the first 3 wk. At 1, 2, and 3 wk of age, one chick from each pen was harvested. Plasma VE concentration and ileal morphology were determined. Gene expression was measured by real-time quantitative PCR. Broilers in VE and combination of ALA and VE group had higher plasma VE concentration than the control and ALA group at 1, 2, and 3 wk of age (P < 0.01). All dietary treatments increased ileal villus height at 1 wk of age (P < 0.01) and decreased intraepithelial lymphocytes at 3 wk of age compared to the control (P ≤ 0.05). Combination of VE and ALA increased collagen type IV alpha 1 chain expression (P ≤ 0.05) and improved basement membrane structure indicating increased gut basement membrane integrity at 2 and 3 wk of age compared to the control. Expression of lipopolysaccharide-induced tumor necrosis factor-alpha factor associated with inflammation was decreased in all dietary treatments at 3 wk of age compared to the control (P < 0.01). Ileal morphology and gene expression were closely correlated with breast muscle morphology and gene expression. These results suggest that VE and ALA especially when they were combined in the diet had positive effects on mitigating intestinal inflammation and improving nutrient transport beginning at 1 wk of age, which is likely critical in reducing the severity of WB.

1680-P: A Novel Immunomodulatory Combination That Decreases Adipose Tissue and Systemic Inflammation and Improves Metabolism in Dio Mice

β3-adrenoceptors (B3AR) are major activators of lipolysis and thermogenesis in adipose tissue (AT). Obesity increases oxidative stress and AT inflammation leading to the attenuation of β3AR signaling. Alpha-lipoic acid (ALA) is a potent antioxidant. We hypothesized that the combination of ALA with CL316,243 (CL) -a selective B3AR agonist- restores the immune balance in diet-induced obesity (DIO) leading to increased B3AR function. We separated 40 DIO C57BL/6 male mice into 4 groups (n=10; individually caged) and treated them for five weeks with 1. vehicle control [IP (saline) + PO (drinking water)] 2. CL alone (0.01 mg/kg IP daily) 3. ALA alone (250 mg/kg orally in drinking water) 4. ALA+CL combination. All mice received ad-lib HFD (60% kcal fat). Systemic and epididymal white AT (epi-WAT) inflammation was decreased in ALA+CL compared to other groups, with lower serum IL-6 and IL-17 and lesser crown-like structures (CLS) on IHC for F4/80 and CD11c (M1-MΦ). Both IHC staining and mRNA expression of CD206 (M2-MΦ marker) confirm increased M2 MΦ’s in ALA+CL compared to other groups. Food intake was similar in all groups, yet mice receiving ALA+CL had a better metabolic profile: Lower body weight [+1.7 vs. -2.5g (-7%); p&amp;lt;0.01] and % body fat (+1.0 vs. -2.8g; (-9%), p&amp;lt;0.001) compared to controls preserved lean mass. Moreover, ALA+CL showed improved glucose tolerance compared to controls (intraperitoneal glucose tolerance test; AUC glycemia 31,033 ± 950 vs. 25,919 ± 620 min*ml/dl; p&amp;lt;0.01; AUC insulinemia 441.2 ± 55.7 vs. 279.3 ± 42.2 min*ng/ml; P&amp;lt;0.001). The downstream function of B3AR(lipolysis and thermogenesis) in WAT was improved in the combination group compared to all groups evidenced by markedly higher activated lipases and UCP-1 on Western blots (WB), and ucp-1 expression on mRNA analysis. Our study suggests that ALA, in combination with CL, modulates the immune response to obesity and augment catecholamine effect on lipolysis and thermogenesis in WAT. Disclosure Z.A. Sater: None. C. Cero: None. H.J. Lea: None. K.Y. Zhu: None. O. Gavrilova: None. A.M. Cypess: None.

Effect of d-chiro-inositol and alpha-lipoic acid combination on COH outcomes in overweight/obese PCOS women

Insulin resistance (IR) plays a central role in the onset of polycystic ovary syndrome (PCOS). Insulin so insulin-sensitizing like inositols have been proposed as first line therapy. Among them d-chiro-inositol (DCI) seems to improve glucose metabolism and to increase ovulation frequency. Other studies have demonstrated that alpha-lipoic acid (ALA), with its antioxidant role, can also improve endocrine and metabolic profile of PCOS patients especially with familial diabetes. This a retrospective observational study with the aim to evaluate possible advantages of an integrative preparation combining DCI 500 mg and ALA 300 mg in overweight/obese PCOS patients with or without diabetic relatives who underwent IVF. Twenty PCOS patients who were taking the integrative preparation underwent controlled ovarian hyperstimulation in our center. The group with diabetic relatives tended to have a lower dose of gonadotropin, shorter stimulation days, higher number of MII oocytes, and higher number of fertilized oocytes. A combined regimen of DCI and ALA could be an interesting strategy in overweight PCOS patients with familial diabetes underwent ART.

Alpha lipoic acid and vitamin E improve atorvastatin-induced mitochondrial dysfunctions in rats

To determine the effects of alpha lipoic acid (ALA) and vitamin E (Vit E) on mitochondrial dysfunction caused by statins. A total of 38 Wistar Albino rats were used in this study. The control group received dimethyl sulfoxide. The atorvastatin (A) group received atorvastatin (10 mg/kg). The A + ALA group received atorvastatin (10 mg/kg) and ALA (100 mg/kg). The A + Vit E group was administered atorvastatin (10 mg/kg) and Vit E (100 mg/kg). The A + ALA + Vit E group was administered atorvastatin (10 mg/kg), ALA (100 mg/kg) and Vit E (100 mg/kg). All applications were administered simultaneously by gavage for 20 days. ATP level and complex I activity were measured from liver, muscle, heart, kidney and brain. Atorvastatin significantly decreased the ATP levels in heart and kidney, while a slight decrease was seen in liver, muscle and brain. Atorvastatin caused an insignificant decrease in the complex I activity in all tissues examined. ALA administration significantly improved the ATP levels in the liver, heart and kidney, while Vit E improved the ATP levels in all tissues except the muscle compared to Atorvastatin group. Single administration of both ALA and vit E ameliorated complex I activity in the muscle, heart, kidney and brain. The combination of ALA and Vit E significantly improved the ATP levels in the liver, heart, kidney and brain and also provided significant improvements the complex I activity in all tissues. The undesirable effects of Atorvastatin on mitochondrial functions in this study ameliorated by using ALA and/or Vit E alone and in combination.

Effect of alpha-lipoic acid at the combination with mefenamic acid in girls with primary dysmenorrhea: randomized, double-blind, placebo-controlled clinical trial

Primary dysmenorrhea is a common gynecologic disorder and is one of the main causes for referral to the gynecology clinic. This study aimed to determine the effects of alpha-lipoic acid (ALA) and mefenamic acid and a combination compared with placebo on the girls with primary dysmenorrhea. This double-blind, placebo-controlled clinical trial done on population consisted of female students living in dormitories of Qazvin University of Medical Sciences who had moderate to severe dysmenorrhea using the Visual Analog Scale (VAS) questionnaire. Participants were randomly divided into four groups (n = 100): ALA, mefenamic acid, ALA + mefenamic acid and placebo groups. ALA and mefenamic acid were administrated in 600 mg and 250 mg, respectively. The severity of the pain was measured in the beginning and the end of the study. Statistical analysis was performed using SPSS software (SPSS Inc., Chicago, IL). Our final results suggested that, although mefenamic acid significantly decreased the menstrual pain, ALA supplementation, 600 mg, would be more efficient than mefenamic acid in 250 mg. Also, the combination of ALA and mefenamic acid significantly has been far. Considering the ALA supplementation effect on pain relief in patients with primary dysmenorrhea, this antioxidant can be recommended for the healing of symptoms of these patients.Trial registration: Iranian Registry of Clinical Trials identifier: IRCT20141025019669N8.

Antileukemic effects of piperlongumine and alpha lipoic acid combination on Jurkat, MEC1 and NB4 cells in vitro.

This research indicated to evaluate the effects of piperlongumine (PL), a biologically active alkaloid, and alpha lipoic acid (ALA), a naturally occurring cofactor existed in multienzyme complexes regulating metabolism on leukemia cells. Excessive production of reactive oxygen species (ROS) can lead to oxidative stress, a state that has been observed in several hematopoietic malignancies, including acute and chronic myeloid leukemias. The importance of the association between oxidative stress and malignancy is not currently clear; however, there is evidence that tumor.derived ROS may promote cell survival, migration and metastasis, proliferation and even drug.resistance depending on the origin of the cancer. Increased oxidative stress in leukemic cells may represent a potential therapeutic target, although there are differing opinions on whether therapeutic strategies should aim to antagonize or further promote oxidative stress in leukemic cells. The effects of PL alone (5, 15, 30 μM) and in combination (30 μ M) with ALA (200 μ M) on Jurkat, NB4 and MEC1 leukemia cell lines were investigated through MTT, caspase-3 and cyclooxygenase-2 (COX-2) activities. Inhibition of COX-2 and the induction of caspase.3 cleavage in Nb4 (acute promyelocytic leukemia) cells were found to be significant following PL application and synergistic effects with combination of ALA (inhibition of COX-2 as 23.74% and 3.55-fold increase of caspase-3). PL and ALA may have a potential value as a therapeutic agent for patients with acute promyelocytic leukemia.

The Protective Effects of Alpha-Lipoic Acid and Coenzyme Q10 Combination on Ovarian Ischemia-Reperfusion Injury: An Experimental Study.

Objective. This study aims to evaluate whether alpha-lipoic acid and/or coenzyme Q10 can protect the prepubertal ovarian tissue from ischemia-reperfusion injury in an experimental rat model of ovarian torsion. Materials and Methods. Forty-two female preadolescent Wistar-Albino rats were divided into 6 equal groups randomly. The sham group had laparotomy without torsion; the other groups had torsion/detorsion procedure. After undergoing torsion, group 2 received saline, group 3 received olive oil, group 4 received alpha-lipoic acid, group 5 received coenzyme Q10, and group 6 received both alpha-lipoic acid and coenzyme Q10 orally. The oxidant-antioxidant statuses of these groups were compared using biochemical measurement of oxidized/reduced glutathione, glutathione peroxidase and malondialdehyde, pathological evaluation of damage and apoptosis within the ovarian tissue, and immunohistochemical assessment of nitric oxide synthase. Results. The left ovaries of the alpha-lipoic acid + coenzyme Q10 group had significantly lower apoptosis scores and significantly higher nitric oxide synthase content than the left ovaries of the control groups. The alpha-lipoic acid + coenzyme Q10 group had significantly higher glutathione peroxidase levels and serum malondialdehyde concentrations than the sham group. Conclusions. The combination of alpha-lipoic acid and coenzyme Q10 has beneficial effects on oxidative stress induced by ischemia-reperfusion injury related to ovarian torsion.

Effects of a Combination of Alpha Lipoic Acid and Myo-Inositol on Insulin Dynamics in Overweight/Obese Patients with PCOS

Myo-inositol increases insulin sensitivity in insulin resistant patients with PCOS since it improves the insulin postreceptor pathways. Since previous reports suggested that also alpha lipoic acid has specific positive effects on glucose control, we aimed to evaluate the specific effects of a combination of alpha lipoic acid and myo-inositol on insulin resistance in obese patients with PCOS. We studied a group of obese PCOS patients (n=34, BMI= 30.1 ± 0.9) according to the revised 2003 Rotterdam consensus diagnostic criteria. Among the PCOS patients, 16 out of 34 had diabetic type II relatives (parents and/or grandparents). Patients were administered a combination of alpha lipoic acid (400 mg) and myo-inositol (1 gr.) (Sinopol, Laborest, Italy) every day for at least 12 weeks. Patients underwent to baseline hormone determination and to an oral glucose tolerance test (OGTT) before and at the 12th week of treatment. After the treatment interval, HOMA index decreased significantly as well as the glucose-induced insulin response with no changes of BMI. Interestingly the treatment did not change insulin dynamics in normo-insulinemic PCOS while significant insulin decrease was observed in hyperinsulinemic PCOS patients. 87.5% (14 out of 16) of the PCOS patients with diabetic relatives resulted to be among the hyperinsulinemic patients. Hyperinsulinemic PCOS patients showed the significant decrease of the insulin plasma levels (from 14 ± 2.1 to 9.5 ± 0.8 μU/ml, p<0.05), of HOMA index (from 3.3 ± 0.4 to 2.1 ± 0.1, p<0.05) and showed the significant decrease of insulin response to glucose load. In conclusion, the combination of alpha lipoic acid plus MYO was effective in improving insulin sensitivity in obese PCOS patients that resulted to be hyperinsulinemic under OGTT. Moreover the more peculiar and relevant positive changes were observed in obese PCOS with diabetic first grade relatives.

Experimental Study of the Neuroprotective Properties of Alpha-Lipoic Acid and Superoxide Dismutase in Cerebral Ischemia in Rats

The aim of the present work was to study the neuroprotective roles of alpha-lipoic acid and superoxide dismutase in focal and total cerebral ischemia in rats. Experiments were performed on Wistar rats (n = 125): 1) to assess neuroprotective effects in conditions of permanent occlusion of the left middle cerebral and left common carotid arteries (n = 26); 2) to study the effects of these agents and their combination on survival in conditions of occlusion of both carotid arteries (n = 81). An infarct-limiting effect was seen in the group in which alpha-lipoic acid was given 30 min before ischemia (p = 0.00004). Administration of superoxide dismutase 30 min before ischemia or alpha-lipoic acid immediately before ischemia did not decrease the size of the necrotic area. Administration of alpha-lipoic acid or the combination of alphalipoic acid and superoxide dismutase led to an increase in the animals’ survival time (p = 0.003, p = 0.013), while use of superoxide dismutase alone produced no increase (p = 0.127). Alpha-lipoic acid induced a neuroprotective effect in focal and total cerebral ischemia. Superoxide dismutase did not have a protective effect in ischemia.

Combination of Alpha Lipoic Acid and Superoxide Dismutase Leads to Physiological and Symptomatic Improvements in Diabetic Neuropathy

Background and Objective: The management of diabetic neuropathy is still a challenge for physicians. The aim of this study was to assess the efficacy of a new combination of alpha lipoic acid and superoxide dismutase for the treatment of diabetic neuropathy. p] Methods: The setting of this study was ambulatory (outpatient) care. A prospective, non-randomized, open-label study was conducted in 50 patients with diabetes mellitus and with a deficit in both motor and sensory nerve conduction. Treatment was with a new combination of alpha lipoic acid and superoxide dismutase (ALA600SOD®) for 4 months. Electroneurographic parameters and perceived pain were assessed at baseline and after treatment.Results: After 4 months of treatment, patients significantly (p < 0.001) improved their electroneurographic parameters and their perception of pain. Best improvements were observed in sensory nerve conduction.Conclusion: The combination of two powerful antioxidant agents leads to improvement in both subjective and objective parameters in patients with diabetic neuropathy. New profitable directions for investigations are opened for a non-invasive treatment of diabetic neuropathy in the future.

Combination of Alpha Lipoic Acid and Superoxide Dismutase Leads to Physiological and Symptomatic Improvements in Diabetic Neuropathy

Combination of Alpha Lipoic Acid and Superoxide Dismutase Leads to Physiological and Symptomatic Improvements in Diabetic Neuropathy