Alpha-Lipoic Acid (ALA)

INTRODUCTION: In this article, we perform a systematic review and meta-analysis evaluating the effects of alpha-lipoic acid (ALA) supplementation on biochemical, clinical, inflammatory, and functional parameters in patients with diabetic polyneuropathy or diabetic peripheral neuropathy (DPN). A total of 15 articles were included, of which 12 were analyzed for outcomes. DPN is a chronic complication of Diabetes Mellitus (DM) characterized by symptoms, such as pain, sensory disturbances, and reduced quality of life. Currently, there is no definitive cure. Management focuses on controlling blood glucose and alleviating symptoms through pharmacological and non-pharmacological therapies. The aim of this study is to analyze the evidence regarding the efficacy of alpha-lipoic acid (ALA) supplementation in the management of DPN. RESULTS: A systematic search across multiple databases was conducted using keywords, such as "diabetes mellitus," "diabetes mellitus type I," "diabetes mellitus type II," "alpha-lipoic acid," and "ALA supplementation." A total of 15 studies met the inclusion criteria. Of the 23 outcomes analyzed, 19 showed significant differences in favor of alpha-lipoic acid (ALA) supplementation at different doses versus a placebo or other treatments. Notable improvements were observed in Total Symptom Score (TSS) paresthesia (SMD = -1.04; 95 % CI = -1.24 to -0.84; p < 0.00001), TSS numbness (SMD = -0.23; 95 % CI = -0.44 to -0.01; p = 0.04), and the Hamburg Pain Adjective List (HPAL) (SMD = -1.00; 95 % CI = -1.15 to -0.85; p < 0.00001), among others. These improvements were particularly evident for symptoms, such as paresthesia, numbness, and burning sensations, especially at a dose of 600 mg/day. In contrast, four of the outcomes HbA1c, nitric oxide levels, sural sensory nerve action potential, and peroneal motor nerve conduction velocity showed no significant changes. CONCLUSION: The evidence suggests that ALA, especially at 600 mg/day, is a safe and potentially effective adjunct therapy for symptom management in DPN, although its impact on nerve conduction and long-term glycemic control remains inconclusive.

AIMS: There is no definitive consensus regarding the impacts of alpha-lipoic acid (ALA) supplementation on the risk factors of cardiometabolic syndrome (CMS). This systematic review and meta-analysis evaluated the effects of ALA supplementation on CMS risk factors. DATA SYNTHESIS: A comprehensive search of several databases identified 63 eligible randomized controlled trials (RCTs) published until May 2025. The meta-analysis revealed that supplementation with ALA substantially decreased homeostatic model assessment for insulin resistance (weighted mean difference (WMD): -0.74, 95 % confidence interval (CI): -1.17, -0.31; P = 0.001), waist circumference (WMD: -1.10 cm, 95 % CI: -1.66, -0.54; P < 0.001), body mass index (WMD: -0.27 kg/m2, 95 % CI: -0.44, -0.10; P = 0.002), fat mass (WMD: -1.42 kg, 95 % CI: -2.53, -0.31; P = 0.012), body weight (WMD: -0.64 kg, 95 % CI: -1.04, -0.24; P = 0.002), serum levels of fasting blood glucose (WMD: -5.28 mg/dL, 95 % CI: -7.21, -3.35; P < 0.001), total cholesterol (WMD: -3.91 mg/dL, 95 % CI: -7.35, -0.46; P = 0.026), hemoglobin A1C (WMD: -0.40 %, 95 % CI: -0.66, -0.14; P = 0.003), triglycerides (WMD: -2.90 mg/dL, 95 % CI: -5.21, -0.59; P = 0.014), and fasting insulin (WMD: -1.70 mU/mL, 95 % CI: -2.88, -0.53; P = 0.004) in the ALA group compared with the control group. However, no substantial effect of ALA was identified on low-density lipoprotein cholesterol, blood pressure, and high-density lipoprotein cholesterol. CONCLUSIONS: ALA supplementation may improve certain cardiometabolic risk factors by ameliorating anthropometric and glycemic parameters, as well as through its potential lipid-lowering effects. PROSPERO REGISTRATION: CRD420251038360.

INTRODUCTION: Male factors contribute to 30 to 50% of infertility in couples. Treatment options for male infertility are limited, so antioxidant supplementation for idiopathic male infertility is currently being studied. Alpha lipoic acid (ALA) has a high antioxidant capacity and the potential to penetrate tissues, cells, and organelles, including mitochondria, due to its water and lipid solubility properties. The recent inclusion of randomized trials in the literature has required a new systematic review and meta-analysis to evaluate the efficacy of alpha lipoic acid in sperm parameter changes. PURPOSE: We aimed to perform a systematic review and meta-analysis of the currently available randomized trials comparing the effects of ALA supplementation versus placebo on sperm function in infertile male patients. MATERIAL AND METHODS: Pubmed, Embase, Cochrane Library, and Scopus databases were searched from inception to June 2024. A random-effects model was employed to compute mean differences and risk ratios for continuous and binary endpoints. Heterogeneity was evaluated through the prediction interval. A sensitivity analysis was conducted by systematically excluding one study at a time and recalculating the pooled effect. All statistical analysis was conducted using R software 4.4.1. The certainty of evidence was evaluated with the GRADE approach. Results were reported following the PRISMA statement guidelines. This study was registered in PROSPERO. RESULTS: Five randomized trials comprising 250 patients with a mean age of 28 to 40 years were included in this analysis. Over a mean follow-up time of 3 months, ALA was associated with a reduced proportion of abnormal sperm morphology (MD -0.89; 95% CI -1.48 to -0.29; p=0.003), increased total motility (MD 13.49; 95% CI 3.52 to 23.46; p=0.008), and increased sperm progressive motility (MD 12.43; 95% CI 2.89 to 21.97; p=0.01). Additionally, ALA was associated with a higher pregnancy rate in two individual studies reporting the outcome, however, no significance was found in our pooled analysis (RR 2.28; 95% CI 0.66 to 7.85; p=0.1). Finally, ALA did not change ejaculation volume (MD 0.14; 95% CI -0.54 to 0.83; p=0.6), s

OBJECTIVES: To evaluate the associations between alpha-lipoic acid (ALA) intake and intermediate disease markers in overweight or obese adults. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, EMBASE, Medline, APA PsycINFO, SocINDEX, CINAHL, SSRN, SocArXiv, PsyArXiv, medRxiv, and Google Scholar (from inception to October 2024). ELIGIBILITY CRITERIA: This study included English-language randomised controlled trials (RCTs) on adults (body mass index ≥25 kg/m²) to assess the impact of ALA on intermediate disease markers. Studies lacking outcome data, duplicates or inaccessible full texts were excluded. DATA EXTRACTION AND SYNTHESIS: Paired reviewers independently extracted the data. We used frequentist meta-analysis to summarise the evidence, employing the DerSimonian and Laird estimator to account for heterogeneity across study designs, settings and measurement methods. Heterogeneity was assessed via the I² statistic with CIs and τ² values. The risk of bias was independently assessed by two reviewers according to the Cochrane Handbook, covering domains such as randomisation, blinding and data completeness. Publication bias was assessed using Begg's test, while funnel plots and Egger's test were applied to outcomes with 10 or more studies. RESULTS: This meta-analysis included 11 RCTs from an initial screening of 431 studies, encompassing a total of 704 adults. The meta-analysis results revealed no significant associations were detected between ALA supplementation and changes in intermediate disease markers, including triglyceride (TG) (standardised mean difference (SMD): -0.08, 95% CI: -0.24 to 0.09, p=0.36, I²=0.00%, τ²=0.00), total cholesterol (TC) (SMD: 0.08, 95% CI: -0.55 to 0.71, p=0.80, I²=87.50%, τ²=0.52), high-density lipoprotein cholesterol (HDL-C) (SMD: -0.05, 95% CI: -0.22 to 0.11, p=0.52, I²=0.00%, τ²=0.00), low-density lipoprotein cholesterol (LDL-C) (SMD: -0.13, 95% CI: -0.40 to 0.15, p=0.37, I²=0.00%, τ²=0.00), homeostasis model assessment of insulin resistance (HOMA-IR) (SMD: -0.23, 95% CI: -0.60 to 0.15, p=0.23, I²=26.20%, τ²=0.05) and fasting blood glucose (FBS) (SMD: 0.13, 95% CI: -0.16 to 0.41, p=0.39, I²=29.40%, τ²=0.04). Acco

BACKGROUND: A growing body of evidence indicates the regulating effects of alpha-lipoic acid on iron metabolism. However, findings from clinical trials are equivocal. This systematic review and meta-analysis aimed to evaluate the quantitative effect of alpha lipoic acid (ALA) supplementation on iron metabolism parameters including serum iron, total iron binding capacity, hemoglobin, and ferritin. METHODOLOGY: Online databases, including PubMed, Scopus, and Web of Science were searched, up to 29 May 2022, to obtain all relevant studies. RESULTS: A total of 1901 publications were identified in the systematic search; of which, 10 studies with a total of 529 participants were included in this meta-analysis. Pooled analysis of the studies showed no statistically significant effects of ALA on ferritin (weighted mean difference (WMD) = -11.01 ng/mL; 95% CI: -40.07, 18.05 ng/mL; I2 = 0.0%, p = 0.670), serum iron (WMD = -0.47 μ/dL; 95% CI: -24.48, 23.54 μ/dL; I2 = 94.7%, p < 0.001), hemoglobin (WMD = 0.49 g/dL; 95% CI: -0.54, 1.52 g/dL; I2 = 95.7%, p < 0.001), and total iron binding capacity (TIBC) (WMD = 3.95 μ/dL; 95% CI: -21.3, 29.2 μ/dL; I2 = 53.1%, p = 0.094). In subgroup analysis, ALA significantly increased hemoglobin in patients with hematological disorders (WMD = 1.23 g/dL; 95% CI: 1.00, 1.45 g/dL; I2 = 96.6%, p < 0.001) and in studies with durations longer than 8 weeks (WMD = 1.03 g/dL; 95% CI: 0.82, 1.25 g/dL; I2 = 96.5%, p = 0.02). CONCLUSION: ALA supplementation had no statistically significant effect on iron-related parameters. Subgroup analysis revealed a significant increasing effect of ALA on hemoglobin in patients with hematological disorders and in studies with durations >8 weeks. © 2024 The Author(s). Published by IMR Press.

OBJECTIVES: The effects of alpha-lipoic acid (ALA) supplementation on cardiovascular-related factors have been evaluated in a number of randomized clinical trials, with different results. Thus, in this meta-analysis, the effects of ALA on blood levels of inflammatory, lipid, and hematological markers as well as anthropometric indices in patients with chronic kidney disease (CKD) were evaluated. METHODS: Five electronic databases were used to conduct a comprehensive search through October 2023. Risk of bias assessment and data extraction were carried out separately by 2 reviewers on the included papers. The data were analyzed using the random-effects model in meta-analyses. The data were analyzed using the random-effects model in meta-analyses. We assessed inter-study heterogeneity with I2 and Cochran's Q test. RESULTS: Nine of the 421 potential reports were included. Using random-effects models, no significant changes were observed in weight loss, body mass index, hemoglobin, and iron following ALA supplementation (600 mg/day). Results exhibited that ALA significantly reduced high-sensitivity C-reactive protein levels in individuals with CKD (weighted mean difference (WMD) = -2.91 mg/L, 95% CI: -4.65, -1.17, I2 = 50.5%, P = .09); however, there were no significant variations in levels of interleukin-6 (IL-6) or malondialdehyde. Regarding lipid profiles, findings revealed that ALA administration had no significant impact on high-density lipoprotein cholesterol and triglycerides levels among patients with CKD. However, compared to the control group, total cholestrol levels were considerably lower in CKD patients (WMD = -5.48 mg/dL, 95% CI: -10.55, -0.41, I2 = 0.0%, P = .50). Moreover, the sensitivity analyses showed that pooled WMDs for low-density lipoprotein cholesterol levels were significantly changed (-6.88 mg/dL, 95% CI, -12.78, -0.98). CONCLUSIONS: These findings revealed that ALA supplementation slightly but significantly reduced blood levels of high-sensitivity C-reactive protein, total cholestrol, and low-density lipoprotein cholesterol, but did not affect IL-6, malondialdehyde, high-density lipoprotein cholesterol, weight, body mass index, iron, and hem

Background: Many studies have investigated the effect of alpha-lipoic acid (ALA) supplementation on lipid profile, and different results have been obtained from these studies. The current systematic review and dose-response meta-analysis was conducted to achive a strong conclusion about the effect of ALA supplementation on lipid profile including total cholesterol (TC), low- and high-density lipoprotein cholesterol (LDL, HDL) and triglycerides (TG). Methods: A systematic search was performed in PubMed, SCOPUS, ProQuest and Embase for randomized placebo-controlled human trials that examined the effect of ALA supplementation on lipid profile up to November 2020. The dose and duration of ALA supplementation for included studies were ranged between 300-1200 mg/d and 2-16 weeks respectively. Weighted mean differences (WMD) and 95% confidence intervals (CIs) were used to evaluate the effect size. Cochran's Q and I2 tests were also used to assess between-study's heterogeneity. In addition, subgroup analysis was performed to investigate potential sources of heterogeneity. Dose-response relationship was done using fractional polynomial modeling. Results: Among all eligible studies, 12 studies with a total number of 548 participants were selected. ALA caused a significant reduction on TC (WMD): -10.78 mg/dl, 95% CI: -20.81, -0.74, P=0.002), LDL (WMD: -10.88 mg/dl, 95% CI: -19.52, -2.24, P=0.014) and TG (WMD: -31.02 mg/dl, 95% CI: -49.63, -12.42, P<0.001). There was also a non-significant increaes in HDL concentrations. In addition, dose-response analysis showed a positive association between LDL (Pnon-linearity=0.026), TG (Pnon-linearity<0.001) and duration of intervention in a non-linear model. Conclusion: The present meta-analysis revealed the beneficial effects of ALA supplementation on TC, LDL and TG levels. Moreover, the beneficial effects of ALA supplementation on LDL and TG levels was duration-dependent.

Data about the effects of alpha-lipoic acid (ALA) supplementation on inflammatory markers are inconsistent. This systematic review and dose-response meta-analysis of randomized controlled trials was performed to summarize the effects of ALA supplementation on inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in adults. A comprehensive literature search was conducted in the electronic databases of PubMed, Web of Science, ProQuest, Embase, and SCOPUS from inception to February 2020. Among all of the eligible studies, 20 articles were selected. The weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated to evaluate the pooled effect size. Between-study heterogeneity was evaluated using Cochran's Q test and I2. Subgroup analysis was done to evaluate the potential sources of heterogeneity. The dose-response relationship was evaluated using fractional polynomial modeling. Twenty eligible studies with a total sample size of 947 participants were included in the current meta-analysis. The findings of the meta-analysis showed that ALA supplementation significantly reduced CRP (WMD: -0.69 mg/L, 95% CI: -1.13, -0.26, P=0.002), IL-6 (WMD: -1.83 pg/ml, 95% CI: -2.90, -0.76, P=0.001), and TNF-α concentrations (WMD: -0.45 pg/ml, 95% CI: -0.85, -0.04, P=0.032). No evidence of departure from linearity was observed between dose and duration of the ALA supplementation on serum CRP, IL-6 and TNF-α concentration. In subgroup analysis, ALA dosage, baseline concentrations of the parameter, sample size, and gender were considered as possible sources of heterogeneity. In summary, ALA supplementation improves inflammatory markers without any evidence of non-linear association to dose or duration of the trial.

This systematic review and dose-response meta-analysis was conducted to summarize data from available clinical trials on the effects of α-lipoic acid (ALA) supplementation on glycemic markers including glucose, hemoglobin A1c (HbA1c), insulin, homeostatic model assessment of insulin resistance (HOMA-IR), HOMA-β, and quantitative insulin check index in adults. A comprehensive literature search was conducted in the electronic databases of PubMed, Web of Science, ProQuest, Embase and SCOPUS from inception to February 2020. Among all of the eligible studies, 28 articles were selected. The weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated to evaluate the pooled effect size. Between-study heterogeneity was evaluated using Cochran's Q test and I2. Subgroup analysis was done to evaluate the potential sources of heterogeneity. The dose-response relationship was evaluated using fractional polynomial modeling. Twenty eight eligible studies with a total sample size of 1,016 participants were included in the current meta-analysis. The findings of the meta-analysis showed that ALA supplementation significantly reduced insulin (WMD: -0.64; CI: -1.287 to 0.004, P = .04), HOMA-IR (WMD: -0.48; 95% CI: -0.79 to -0.16; P = .002). No change in glucose or HbA1C was reported. Moreover, the effect of ALA on insulin was duration-dependent (Pnon-linearity = 0.04). No evidence of departure from linearity was observed between dose and duration of the ALA supplementation on other markers. The subgrouping revealed that ALA dosage and duration of ALA supplementation, health status of participants, geographic locations and the studies' quality are possible sources of heterogeneity. In summary, ALA supplementation improves serum insulin and insulin resistance in a two-class and duration dependent non-linear analysis.

BACKGROUND: There are numerous trials reported the effect of alpha-lipoic acid (ALA) on obesity measurements; while no summarised dose-response meta-analysis is available to address the effects of dose and duration of ALA supplementation on obesity measurements. We aimed to summarise the results of studies evaluating the effects of ALA supplementation on obesity measurements in a systematic review and dose-response meta-analysis. METHODS AND MATERIALS: In a systematic search from Scopus, PubMed, Embase, Proquest electronic databases up to January 2020 relevant studies were retrieved. Randomised, placebo-controlled trials investigating the effect of ALA supplementation on obesity measurements including weight, body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) and fat mass (FM) were included. Two class and dose-response meta-analysis were performed to data analysis. RESULTS: Totally, 18, 21 and 8 studies were included for the meta-analysis of ALA-weight, ALA-BMI, ALA-WC, respectively. In the two-class meta-analysis, ALA treatment significantly reduced weight (WMD: -2.29 kg, 95% CI: -2.98, 1.60, P < .01) and BMI (WMD: -0.49 kg/m2 , 95% CI:-0.83,-0.15, P = .005) but no effect on WC (WMD: -2.57 cm, 95% CI: -8.91, 3.76; P = .426). While the dose-response meta-analysis revealed that the duration of ALA treatment is a significant factor affecting WC reduction (Pnon-linearity = .047). While no evidence of departure from linearity was observed for other variables; moreover, subgrouping also revealed that gender could be an important factor affecting the ALA impact on WC which was significant among women (WMD: -4.099; CI: -7.837, -0.361; P = .032). CONCLUSION: According to our finding, ALA treatment significantly reduced BMI, weight in a two-class meta-analysis without evidence of departure from linearity in terms of dose or duration. While the association of ALA treatment on WC is dependent to the duration of the study. Although further trials evaluating the other obesity measurements specially central obesity will be helpful to infer a more reliable result. © 2020 John Wiley & Sons Ltd.

BACKGROUND: Ischemic cardiomyopathy (ICM) is caused by oxidative stress, inflammation, and apoptosis. Alpha-lipoic acid (ALA) has antioxidant and anti-inflammatory effects. However, its effects on left ventricular dysfunction and myocardial fibrosis remain unclear. OBJECTIVE: This study aims to investigate the effects of ALA on cardiac inflammation, fibrosis, and myocardial function as an adjuvant therapy for ICM. METHODS: This double-blind, randomized, placebo-controlled, single-center trial enrolled 67 diabetic patients with ICM, who were randomized to receive either ALA 600 mg once daily or placebo for three months, in addition to ICM medications. Both groups were evaluated for tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), tissue growth factor-β1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and some echocardiographic indices before and after treatment. RESULTS: Sixty patients (aged 45-75 years; 70% males) completed the study (ALA group n = 30; placebo group n = 30). After three months, the ALA group exhibited significantly lower levels of TNF-α [443 (326/515) vs. 499 (448/657) pg/ml], CRP [4.5 (4.2/6.1) vs. 11 (6.3/12.1) mg/l], TGF-β1 [161 (104/189) vs. 206 (158/248) pg/ml], and MMP-2 [1450 (1164/1894) vs. 1815 (1339/2133) pg/ml] (p < 0.05) compared to the placebo group. Furthermore, in the ALA group, there was a significant increase in LVEF [36% (34/40) vs. 28% (25/31.8)], whereas LVESD, LVEDD, and LAD were significantly decreased compared to the placebo group [4.7 (3.9/5.8) vs. 5.6 (5.1/5.6) cm; 6.1 ± 0.7 vs. 6.5 ± 0.5 cm; 4.2 (3.9/4.7) vs. 4.8 (4.4/5.1) cm] (p < 0.05), respectively. CONCLUSION: Adjunctive ALA therapy considerably reduced inflammation and improved cardiac function in patients with ICM. Additionally, our findings suggest that ALA may influence profibrotic signaling.

AIM: Evaluate the oxidant-antioxidant balance and the efficacy of Alpha-lipoic acid (ALA) as an adjuvant therapy for diabetic nephropathy (DN) among individuals with type 1 diabetes (T1D). MATERIALS AND METHODS: A 3 months prospective randomized controlled trial including 50 participants with DN randomly allocated (1:1) to one of two arms; an interventional arm receiving 300 mg/day of ALA (n = 25) and a non-interventional arm (n = 25). Initial assessments included HbA1c, urinary albumin excretion rate (UAER), malondialdehyde (MDA), and total antioxidant capacity (TAC). Baseline data was compared with 50 participants with T1D without DN and 50 healthy controls. RESULTS: T1D participants had significantly higher MDA and lower TAC levels compared to controls (P < 0.01). Within the T1D cohort, participants with DN showed significantly higher MDA and lower TAC levels (P < 0.01). MDA positively correlated with triglycerides (r = 0.53), UAER (r = 0.70), and HbA1c (r = 0.5) (p < 0.01), while TAC negatively correlated triglycerides (r = -0.41), UAER (r = -0.88), and HbA1c (r = -0.64) (p < 0.01). After 3 months of ALA supplementation, significant reductions in HbA1c, UAER, and MDA were observed, along with an increase in TAC (P < 0.01). CONCLUSION: The study demonstrates that 3 months of ALA supplementation effectively reduced oxidative stress and UAER, demonstrating a potential role in protecting renal tissue from diabetes-induced oxidative damage.

AIM: To investigate neurofunctional parameters of motor nerves in breast cancer (BCa) patients with paclitaxelinduced peripheral neuropathy (PIPN) and to determine the feasibility of using alpha-lipoic acid (ALA) in combination with ipidacrine hydrochloride (IPD) for PIPN prevention. MATERIALS AND METHODS: The study included 100 patients with BCa stages II-IV, who were treated with polychemotherapy (PCT) according to the AT (paclitaxel, doxorubicin) or ET (paclitaxel, epirubicin) scheme in the neoadjuvant, adjuvant, or palliative regimens. Patients were randomized into two groups (n = 50 in each): group I received PCT only; group II - PCT in combination with ALA + IPD. Electroneuromyographic (ENMG) studies of the motor fibular and tibial nerves were performed before the start of chemotherapy and after the 3rd and 6th cycles of PCT. RESULTS: Comparison of ENMG parameters of the motor nerves of the lower extremities of BCa patients before the start of PCT with these parameters after 3 and 6 PCT cycles indicated a slightly pronounced but significant decrease in the M-response and partly the nerve conduction velocity, which progressed with an increase in the cumulative dose of paclitaxel. Despite this, the average values of ENMG parameters remained within normal limits even after 6 cycles of PCT. The detected changes indicated a tendency toward axonal damage and mild myelinopathy. Significantly higher M-response rates of motor nerves were found in patients of group II compared to group I only after 6 cycles of PCT with paclitaxel. CONCLUSION: The use of ALA and IPD improves the functional state of the axons in patients with BCa treated with paclitaxel.

Background/Objectives: This study aimed to evaluate the effects of four weeks of combined Acetyl-l-Carnitine and alpha-lipoic acid (ALA) supplementation on anaerobic and aerobic performance and fatigue resistance in trained cyclists, hypothesizing improvements in maximal aerobic power (MAP), Wingate test performance, and reduced lactate accumulation. Methods: In a double-blind, randomized trial, 41 male trained cyclists (age: 36 ± 12 years; MAP: 4.35 ± 0.60 W·kg-1) were assigned to a supplement group (SUP, n = 19; 1200 mg/day Acetyl-l-Carnitine, 300 mg/day ALA, 1.1 mg Vitamin B1, 2.5 µg Vitamin B12) or placebo group (PLA, n = 22) for four weeks. Performance was assessed pre- and post-intervention via counter-movement jumps (CMJs), Wingate tests (WG1, WG2), and a graded exercise test (GXT). Blood lactate ([La-]) was measured post-Wingate. A three-way mixed ANOVA analyzed Wingate performance (session, order, and group), and a two-way ANOVA assessed MAP and fatigue effects. Results: MAP increased by 3.4% (314 ± 32 W to 324 ± 37 W; p = 0.005) with no group interaction (p = 0.457). Wingate peak power showed main effects for order (p < 0.001) and session (p = 0.011) but no group interaction (p = 0.676). SUP reduced [La-] by 1.5 mmol·L-1 post-WG2 in POST (p = 0.049). No significant group differences were found for CMJ or fatigue metrics. Conclusions: Four weeks of Acetyl-l-Carnitine and ALA supplementation did not enhance aerobic or anaerobic performance in trained cyclists, despite reducing blood lactate after high-intensity exercise, suggesting no ergogenic benefits.

OBJECTIVE: This study investigates whether daily supplementation of 120-150 mg of caffeine can relieve symptoms of Burning Mouth Syndrome (BMS) compared to alpha-lipoic acid (ALA) and a control group. METHODS: In this randomised controlled trial, 118 BMS patients were divided into three groups: caffeine, ALA, and control. The caffeine group received 120-150 mg of caffeine daily, the ALA group received 200 mg of ALA three times daily, and the control group received no interventions. Symptom relief was assessed over 2 weeks using the Visual Analog Scale (VAS), with subgroup analyses based on symptom subtypes, disease duration, symptom sites, and characteristics. RESULTS: The VAS of BMS patients in the caffeine and ALA groups exhibited significant reductions (p < 0.0005). The caffeine group exhibited a 65.1% symptom relief rate compared to 46.5% in the ALA group and 12.5% in the control group. Significant differences in symptom relief were noted between the caffeine and control groups (p < 0.0005) and between the ALA and control groups (p = 0.0032). No significant difference was observed between the caffeine and ALA groups (p = 0.084). Type I BMS patients in the caffeine group showed greater symptom relief than those in the ALA group (p = 0.026). CONCLUSIONS: Both caffeine and ALA effectively treated BMS, with caffeine showing higher efficacy in Type I patients. Treatments were well-tolerated with minimal adverse effects, suggesting caffeine and ALA as promising treatments for BMS, warranting further research on their long-term effects and mechanisms of action. [The study was registered on ClinicalTrials.gov (Identification No. NCT06195137).]. © 2025 John Wiley & Sons Ltd.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a chronic microvascular complication in diabetic mellitus patients due to chronic hyperglycemia, resulting in platelet hyperactivity and dyslipidemia. Alpha-lipoic acid (ALA) is a potent antioxidant which has antiplatelet activity and lipid-modulating characteristics and plays a major role in the prevention of disease progression. AIM: To evaluate the effect of ALA on inhibition of platelet aggregation and lipid profile. SETTINGS AND DESIGN: This was a prospective, randomized, double-blind, placebo-controlled study conducted at the Department of Clinical Pharmacology and Therapeutics at a tertiary care hospital. MATERIALS AND METHODS: We recorded efficacy parameters including changes in inhibition of platelet aggregation, lipid profile, blood sugars, and glycated hemoglobin over 12 weeks of ALA (600 mg once daily orally) supplementation in DPN patients on gabapentin (300 mg twice daily [BD]) or pregabalin (75 mg BD) compared to placebo. We used Student's t-test paired and unpaired for within-group and between-group comparisons, respectively. RESULTS: A total of 52 study participants (males = 22, females = 30) with a mean age 55.63 ± 7.5 years were randomized to receive either ALA or placebo. Between-group analysis at 12 weeks showed that ALA significantly inhibited both collagen-induced platelet aggregation (from 32.61 ± 8.00 to 24.88 ± 5.30; P < 0.001) and adenosine diphosphate-induced platelet aggregation (from 34.00 ± 6.97 to 25.96 ± 6.45; P < 0.001) compared to placebo. Significant reduction in total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and triglycerides was found in the ALA group at 12 weeks compared to baseline. No serious adverse events were reported. CONCLUSION: ALA, an antioxidant, demonstrated a protective effect against DPN by the virtue of its inhibitory effect on platelet aggregation and lipid-modulating effects and was found to have good safety.

AIM: To investigate the efficacy of Palmitoylethanolamide (PEA, 300 mg), Superoxide Dismutase (SOD, 70 UI), Alpha Lipoic Acid (ALA, 300 mg), vitamins B6 (1.5 mg), B1 (1.1 mg), B12 (2.5 mcg), E (7.5 mg), nicotinamide (9 mg), and minerals (Mg 30 mg, Zn 2.5 mg) in one tablet in people with Diabetic Neuropathy (DN). PATIENTS-METHODS: In the present pilot study, 73 people (age 63.0 ± 9.9 years, 37 women) with type 2 Diabetes Mellitus (DMT2) (duration 17.5 ± 7.3 years) and DN were randomly assigned to receive either the combination of ten elements (2 tablets/24 h) in the active group (n = 36) or the placebo (n = 37) for 6 months. We used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE), measured vibration perception threshold (VPT) with biothesiometer, and Cardiovascular Autonomic Reflex Tests (CARTs). Nerve function was assessed by DPN Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. Sudomotor function was assessed with SUDOSCAN, which measures electrochemical skin conductance in hands and feet (ESCH and ESCF). Pain score (PS) was assessed with Pain DETECT questionnaire. Quality of life was assessed by questionnaire. RESULTS: In the active group, there was a large improvement of pain (PS from 20.9 to 13.9, p < 0.001). There was also a significant improvement of vitamin B12 (B12) levels, MNSIQ, SNCV, VPT, and ESCF (222.1 vs. 576.3 pg/ mL, p < 0.001; 6.1 vs. 5.9, p = 0.017; 28.8 vs. 30.4, p = 0.001; 32.1 vs. 26.7, p = 0.001; and 72.2 vs. 74.8, p < 0.001 respectively). In the placebo group, neither pain (21.6 vs. 21.7, p = 0.870) or any other aforementioned parameters changed significantly, and MNSIE worsened (2.9 vs. 3.4, p < 0.001). As a result, changes from baseline to follow-up in pain, B12 levels, VPT, and MNSIQ differed significantly between the two groups (p < 0.001, 0.025, 0.009, and <0.001, respectively). CARTs, SNAP, ESCH did not significantly change in either of the two groups. CONCLUSIONS: The combination of the ten elements in one tablet for 6 months at a daily dose of two tablets in people with DN significantly improves pain, vibration perception threshold, and B12 levels.

We compared a combination of the nonsedating antioxidant, alpha-lipoic acid (ALA), with the sedating anticonvulsant, pregabalin, vs each monotherapy to treat neuropathic pain due to peripheral neuropathies. In this randomized, double-blind, 3-period crossover trial, participants received oral ALA, pregabalin, and their combination-each for 6 weeks. The primary outcome was mean daily pain intensity at maximal tolerated doses (MTD); secondary outcomes included quality of life (SF-36), sleep (Medical Outcomes Study-Sleep Scale), adverse effects, drug doses, and other measures. Of 55 participants randomized (20-diabetic neuropathy, 19-small fiber neuropathy, and 16-other neuropathies), 46 completed 2 periods, and 44 completed 3. At MTD, the primary outcome of mean pain intensity (0-10) was 5.32 (standard error, SE = 0.18), 3.96 (0.25), 3.25 (0.25), and 3.16 (0.25) at baseline, ALA, pregabalin, and combination, respectively ( P < 0.01 for ALA vs combination and pregabalin). Treatment differences were similar in subgroups with diabetic neuropathy and with other neuropathies. SF-36 total scores (higher number indicates better quality of life) were 66.6 (1.88), 70.1 (1.88), and 69.4 (1.87) with ALA, pregabalin, and combination ( P < 0.05 for ALA vs combination and pregabalin). At MTD, there were no statistically significant treatment differences in adverse effects or drug doses. This trial demonstrates superiority of pregabalin vs ALA but provides no evidence to suggest added benefit of combining ALA with pregabalin to treat neuropathic pain.

Nutraceuticals like alpha-lipoic acid (ALA) may have potential benefits as prophylactic agents for adolescent migraine, with fewer adverse events than existing medications. The present study was conducted to evaluate the safety and efficacy of add-on ALA for prophylaxis in adolescent migraine. A randomized, open-label, add-on clinical trial was conducted with 60 adolescent migraineurs, who were randomized to receive flunarizine or flunarizine with an add-on ALA. A clinical evaluation of the frequency and severity of migraine, responder rate, Pediatric Migraine Disability Assessment (PedMIDAS) scoring, serum thiol, and serum calcitonin gene-related peptide (CGRP) was performed both at baseline and following 12 weeks of treatment. The frequency of acute attacks of migraine decreased significantly (P = .001) in the test group compared with the control group. The responder rate was found to be significantly higher (80%) in the test group than in the control group (33.3%) (P = .001). The mean monthly migraine headache days in the test group showed a significant reduction (-7.7 days, 95%CI -9.1 to -6.3 days; P = .010). The severity of acute migraine attacks (mild, moderate, severe) also showed a significant reduction in the test group (P = .001). PedMIDAS scores showed significant improvement in the test group (P = .021), in comparison with the control group. Serum thiol levels were significantly increased in the test group (18 mmol/L, 95%CI 13.5 to 36.1 mmol/L; P = .001). Serum CGRP levels showed a significant reduction with adjunctive ALA therapy (-122.4 pg/mL, 95%CI -142.3 to -89.0 pg/mL; P = .006). Add-on ALA with flunarizine as a prophylactic agent for migraine in adolescents can improve clinical outcomes by improving clinical and biochemical parameters. © 2023, The American College of Clinical Pharmacology.

BACKGROUND: To compare the effects of α-lipoic acid (ALA), myo-inositol (MI) and propolis supplementation on metabolic parameters and liver function in obese patients with non-alcoholic fatty liver disease (NAFLD) METHODS: Ninety-two obese patients with NAFLD were randomly allocated into one of the four groups (ALA, MI, propolis, and control groups) for 8 weeks. At pre-and post-intervention, anthropometric measures, metabolic parameters and liver function were assessed. Clinical effectiveness was assessed using Absolute Risk Reduction (ARR) and Number Needed to Treat (NNT). RESULTS: After 8 weeks, apart from waist-to-hip ratio, all studied anthropometric measures decreased significantly in each of the groups over the trial. Although the greatest improvements in glycemic indices were observed in MI group (p < 0.05), the differences among the groups were not significant. Control group showed the greatest reduction in serum triglyceride level (p = 0.026) while the greatest improvements in serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were observed in MI group (p = 0.043, p = 0.019 and p = 0.041, respectively). Alanine aminotransferase (ALT) levels reduced significantly in all groups, particularly in propolis group (p = 0.012). The greatest reduction in serum aspartate transaminase (AST) level was observed in control group (p < 0.001), however, the difference among the groups was statistically marginal (p = 0.058). The estimated NNTs for one grade reduction in liver steatosis for MI, ALA and propolis supplementation compared with control group were 1.5, 2.2 and 3, respectively. CONCLUSION: Dietary recommendation for weight loss accompanied by MI and then ALA supplementation improved metabolic parameters and liver steatosis. "Registered under ClinicalTrials.gov Identifier no: IRCT20100209003320N22".

Cognitive impairment is present in patients with depression. We hypothesized that alpha-lipoic acid (ALA) can reduce cognitive impairment, especially when combined to antidepressants. Female mice received vehicle or corticosterone (CORT) 20 mg/kg, s.c. for 14 days. From the 15th to 21st day, the animals were divided in groups: vehicle, CORT, CORT+desvenlafaxine (DVS) 10 or 20 mg/kg, ALA 100 or 200 mg/kg, DVS10+ALA100, DVS20+ALA100, DVS10+ALA200, or DVS20+ALA200. Tail suspension (TST), social interaction (SIT), novel object recognition (NOR), and Y-maze tests were conducted. Acetylcholinesterase activity (AChE) was measured in the prefrontal cortex (PFC), hippocampus (HC), and striatum (ST). CORT caused depressive-like behavior, impairment in SIT, and cognitive deficits. Alpha-lipoic acid and DVS, alone or combined, reversed CORT effect on TST. In the NOR, ALA200 alone, DVS10+ALA100, or DVS10+ALA200 reversed the deficits in short-term memory, while DVS20 alone or DVS20+ALA200 reversed the deficits in long-term memory. In the Y-maze test, ALA200 alone, DVS20+ALA100, or DVS20+ALA200 reversed the deficits caused by CORT in the working memory. CORT increased AChE in the PFC, HC, and ST. ALA200 alone or DVS20+ALA200 reversed this effect in the PFC, while DVS20 or DVS20+ALA100 reversed this effect in the HC. In the ST, DVS10 or 20, alone or combined, and ALA100 reversed the effects of CORT. These results suggest that DVS+ALA, by reversing CORT-induced memory and social deficits, seems to be a promising therapy for the treatment of depression and reversal of cognitive impairment observed in this disorder.

The study was aimed at evaluating the protective role of α-lipoic acid (ALA) on long-term exposure of rats to the combination of chlorpyrifos (CPF) and deltamethrin (DLT). Forty-two (42) male Wistar rats were divided into 6 exposure groups with 7 animals in each group: (I) soya oil (2 ml kg-1), (II) ALA (60 mg kg-1), (III) DLT (6.25 mg kg-1), (IV) CPF (4.75 mg kg-1), (V) (CPF + DLT) DLT (6.25 mg kg-1) and CPF (4.75 mg kg-1; 1/20th of the previously determined median lethal dose) and (VI) (ALA + CPF + DLT) pretreated with ALA (60 mg kg-1) and then co-exposed to CPF and DLT, 45 min later. The regimens were administered by gavage once daily for a period of 16 weeks. Sera obtained from blood collected at the end of the experimental period were used for the evaluation of serum glucose, total protein, albumin, urea, creatinine and the activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase and acetylcholinesterase. The liver homogenate was used to assay for the activities of superoxide dismutase and glutathione peroxidase and the concentrations of malondialdehyde, cytokine and tumour necrotic factor α. The result showed that the combination of CPF and DLT resulted in marked alterations of these biochemical parameters in most cases compared to either of the pesticides singly, supplementation with ALA ameliorated these alterations.

Diazinon (DZN) is a common organophosphorus insecticide extensively used for agriculture and veterinary purposes. DZN toxicity is not limited to insects; it also induces harmful effects in mammals and birds. Our experiment evaluated the protective and antioxidant potential of sesame oil (SO) and (or) alpha-lipoic acid (ALA) against DZN toxicity in male Wistar albino rats. DZN-treated animals exhibited macrocytic hypochromic anemia and significant increases in serum biochemical parameters related to liver injury, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (γGT), cholesterol, and triglycerides. They also had elevated levels of markers related to cardiac injury, such as lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), and increased biomarkers of renal injury, urea and creatinine. DZN also increased hepatic, renal, and cardiac lipid peroxidation and decreased antioxidant biomarker levels. SO and (or) ALA supplementation ameliorated the deleterious effects of DZN intoxication. Treatment improved hematology and serum parameters, enhanced endogenous antioxidant status, and reduced lipid peroxidation. Importantly, they exerted synergistic hepatoprotective, nephroprotective, and cardioprotective effects. Our findings demonstrate that SO and (or) ALA supplementation can alleviate the toxic effects of DZN via their potent antioxidant and free radical-scavenging activities.

156. Lipids Health Dis. 2013 Apr 23;12:52. doi: 10.1186/1476-511X-12-52. Selective deposition of dietary α-lipoic acid in mitochondrial fraction and its synergistic effect with α-tocoperhol acetate on broiler meat oxidative stability. Parveen R, Asghar A, Anjum FM, Khan MI, Arshad MS, Yasmeen A. The use of bioactive antioxidants in feed of broiler to mitigate reactive oxygen species (ROS) in biological systems is one of promising nutritional strategies. The aim of present study was to alleviate ROS production in mitochondrial fraction (MF) of meat by supplemented dietary antioxidant in feed of broiler. For this purpose, mitochondria specific antioxidant: α-lipoic acid (25 mg, 75 mg and 150 mg) with or without combination of α-tocopherol acetate (200 mg) used in normal and palm olein oxidized oil (4%) supplemented feed. One hundred and eighty one day old broiler birds were randomly divided into six treatments and provided the mentioned feed from third week. Feed intake, feed conversion ratio (FCR) remained statistically same in all groups while body weight decreased in supplemented groups accordingly at the end of study. The broiler meat MF antioxidant potential was significantly improved by feeding supplemented feed estimated as 1,1-di phenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, 2,2-azinobis-(3- ethylbenzothiazoline-6-sulphonic acid) (ABTS+) and thiobarbituric acid reactive substances (TBARS). The maximum antioxidant activity was depicted in group fed on 150 mg/kg α-lipoic acid (ALA) and 200 mg/kg α-tocopherol acetate (ATA) (T4) in both breast and leg MF. Moreover, TBARS were higher in leg as compared to breast MF. Although, oxidized oil containing feed reduced the growth, lipid stability and antioxidant potential of MF whilst these traits were improved by receiving feed containing ALA and ATA. ALA and ATA showed higher deposition in T4 group while least in group received oxidized oil containing feed (T5). Positive correlation exists between DPPH free radical scavenging activity and the ABTS + reducing activity. In conclusion, ALA and ATA supplementation in feed had positive effect on antioxidant status of MF that consequently diminished

INTRODUCTION: Patients with metastatic thyroid cancers that do not uptake iodine need effective therapeutic option. Differentiation-inducing agents have been tried to restore functional expression of sodium iodide symporter (NIS) without success. Our objective was to assess the effect of alpha-lipoic acid (ALA), known as potential antioxidant, on expression of sodium iodide symporter in thyroid cancer cells. METHODS: Human thyroid cancer-derived cell lines, TPC-1, were treated with ALA, and changes in NIS mRNA and protein expression were measured. ALA's effect on NIS gene promoter was evaluated, and functional NIS expression was assessed by iodide uptake assay. RESULTS: Treatment with ALA increased NIS mRNA expression up to ten folds of control dose-dependently after 24 h of exposure. ALA increased NIS promoter activity, and increased iodide uptake by 1.6 fold. ALA induced expression of NIS protein, but had no significant effect on the plasma membrane trafficking. ALA increased phosphorylation of CREB and nuclear translocation of pCREB, and co-treatment of ALA and trichostatin A increased iodide uptake by three folds in TPC-1 cells. CONCLUSIONS: ALA is a potential agent to increase NIS transcription in TPC-1. It could be used as an adjunctive agent to increase efficacy of radioiodine therapy if combined with a strategy to increase NIS protein trafficking to cell membrane.

Erratum in Cardiovasc Toxicol. 2011 Mar;11(1):89-90. Present study evaluates cardioprotective role of melatonin (Mel), alpha lipoic acid (ALA), a combination of melatonin and alpha lipoic acid (Mel + ALA) against cadmium (Cd)-induced oxidative damage. Female albino rats were subjected to 15-day exposure to Cd (5.12 mg/kg bw) alone or treated with ML (10 mg/kg bw) + ALA (25 mg/kg bw) simultaneously. Plasma markers of cardiac damage, cardiac free radical generation, lipid peroxidation, endogenous antioxidant status, cadmium load, metallothionein induction, and histopathology were evaluated in various experimental groups. Combination of Mel + ALA significantly prevented leakage of marker enzymes of cardiac damage, changes in cardiac free radical generation, endogenous antioxidants, antioxidant status, structural alterations and augmented the degree of metallothionein (MT) induction. The results demonstrate that ML + ALA co-administration effectively protected against Cd-induced cardiac oxidative damage.

Oxidative stress and protein glycation can contribute to the development of insulin resistance and complications associated with type 2 diabetes mellitus. The antioxidant alpha-lipoic acid (ALA) reduces oxidative stress and the formation of advanced glycation end products (AGEs) and improves insulin sensitivity in skeletal muscle and liver. The AGE inhibitor pyridoxamine (PM) prevents irreversible protein glycation, thereby reducing various diabetic complications. The potential interactive effects of ALA and PM in the treatment of whole-body and skeletal muscle insulin resistance have not been investigated. Therefore, this study was designed to determine the effects of combined ALA and PM treatments on reducing muscle oxidative stress and ameliorating insulin resistance in prediabetic obese Zucker rats. Obese Zucker rats were assigned to either a control group or to a treatment group receiving daily injections of the R-(+)-enantiomer of ALA (R-ALA, 92 mg/kg) or PM (60 mg/kg), individually or in combination, for 6 weeks. The individual and combined treatments with R-ALA and PM were effective in significantly (P < .05) reducing plantaris muscle protein carbonyls (33%-40%) and urine-conjugated dienes (22%-38%), markers of oxidative stress. The R-ALA and PM in combination resulted in the largest reductions of fasting plasma glucose (23%), insulin (16%), and free fatty acids (24%) and of muscle triglycerides (45%) compared with alterations elicited by individual treatment with R-ALA or PM. Moreover, the combination of R-ALA and PM elicited the greatest enhancement of whole-body insulin sensitivity both in the fasted state and during an oral glucose tolerance test. Finally, combined R-ALA/PM treatments maintained the 44% enhancement of in vitro insulin-mediated glucose transport activity in soleus muscle of obese Zucker rats treated with R-ALA alone. Collectively, these results document a beneficial interaction of the antioxidant R-ALA and the AGE inhibitor PM in the treatment of whole-body and skeletal muscle insulin resistance in obese Zucker rats.

PURPOSE: The purpose of this article is to review current evidence available for alpha-lipoic acid (ALA) and its ability to improve symptoms of peripheral diabetic neuropathy (PDN). METHODS: This article searched MEDLINE from 1966 to November 2005 to identify clinical trials that supplemented ALA to individuals with type 1 or type 2 diabetes and positive sensory symptoms of PDN. Clinical trials to be included in this review met specific criteria of randomization, double masking, and placebo-controlled design. RESULTS: The search results produced 5 clinical trials that met the prerequisites for this review. ALA appears to improve neuropathic symptoms and deficits when administered via parenteral supplementation over a 3-week period. Oral treatment with ALA appears to have more conflicting data whether it improves sensory symptoms or just neuropathic deficits alone. An oral regimen of ALA and optimal length of treatment remains unclear. Both parenteral and up to a 2-year time period of oral supplementation of ALA appears to be safe without affecting glycemic control. CONCLUSIONS: Based on these results, ALA should be considered as a treatment option for patients with PDN. When discussing supplementation with patients, it is important to discuss potential side effects; vitamin, mineral, and drug interactions; and current evidence available regarding efficacy.

We have demonstrated previously the ability of the antioxidant alpha lipoic acid (ALA) to suppress and treat a model of multiple sclerosis (MS), relapsing experimental autoimmune encephalomyelitis (EAE). We describe the effects of ALA and its reduced form, dihydrolipoic acid (DHLA), on the transmigration of human Jurkat T cells across a fibronectin barrier in a transwell system. ALA and DHLA inhibited migration of Jurkat cells in a dose-dependent fashion by 16-75%. ALA and DHLA reduced matrix metalloproteinase-9 (MMP-9) activity by 18-90% in Jurkat cell supernatants. GM6001, a synthetic inhibitor of MMP, reduced Jurkat cell migration, but not as effectively as ALA and DHLA did. Both ALA and DHLA downmodulated the surface expression of the alpha4beta1 integrin (very late activation-4 antigen; VLA-4), which binds fibronectin and its endothelial cell ligand vascular cell adhesion molecule-1 (VCAM-1). Moreover, ALA, but not DHLA, reduced MMP-9-specific mRNA and extracellular MMP-9 from Jurkat cells and their culture supernatants as detected by relative reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. ALA and DHLA inhibited Jurkat cell migration and have different mechanisms for inhibiting MMP-9 activity. These data, coupled with its ability to treat relapsing EAE, suggest that ALA warrants investigation as a therapy for MS. Copyright 2004 Wiley-Liss, Inc.

One consequence of trauma to the CNS is the production and liberation, from damaged tissue, of large amounts of oxygen-centered free radicals or reactive oxygen species (ROS). An excessive production of ROS can overwhelm the endogenous antioxidant defense system resulting in lipid peroxidation, DNA strand breaks, protein denaturation and cross-linking. The brain is particularly vulnerable to oxidative injury, because it contains high concentrations of readily oxidizable poly-unsaturated fatty acids, has a high rate of oxygen consumption per unit mass, and has only a relatively modest antioxidant defense system. We have conducted studies in vitro to determine the feasibility of reducing ROS-mediated damage in neurons by bolstering endogenous neuronal antioxidant defenses. Primary cultures of neurons derived from embryonic rat forebrain were pre-treated with the free radical scavenger dihydrolipoic acid (DHLA), the reduced form of Alpha-lipoic acid (ALA), and then subjected to H(2)O(2)-mediated oxidative stress. Neuroprotection was determined using the colorimetric MTT reduction assay. As has been reported by others, pre-treatment of neurons with DHLA (4 h) provided dose-dependent neuroprotection against a subsequent exposure to H(2)O(2). The addition of spin trapping nitrones N-tert-butyl-Alpha-phenyl-nitrone (PBN) or its sulfonated analog N-tert-butyl-Alpha(2-sulfophenyl)-nitrone (SPBN) to the pre-treatment cocktail enhanced neuroprotection at every dihydrolipoate concentration. Greater therapeutic efficacy in antioxidant treatment might be realized by employing combinations of complementary antioxidants.