title: Evaluation of laser therapy and alpha-lipoic acid for the treatment of burning mouth syndrome: a randomized clinical trial Does Lipoic Acid Consumption Affect the Cytokine Profile in Multiple Sclerosis Patients: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial Effects of alpha-lipoic acid supplementation in peripheral arterial disease: a pilot study. α-lipoic acid can improve endothelial dysfunction in subjects with impaired fasting glucose. Effects of α-lipoic acid therapy on sympathetic heart innervation in patients with previous experience of transient takotsubo cardiomyopathy. Lipoic Acid Attenuates Inflammation via cAMP and Protein Kinase A Signaling Effect of α-Lipoic Acid on Platelet Reactivity in Type 1 Diabetic Patients Role of alpha-lipoic acid in the management of anemia in patients with chronic renal failure undergoing hemodialysis The Delphi list: a criteria list for quality assessment of randomized clinical trials for conducting systematic reviews developed by Delphi consensus. Effects of alpha lipoic acid supplementation on serum levels of IL-8 and TNF-α in patient with ESRD undergoing hemodialysis Effects of alpha-lipoic acid supplementation on inflammation, oxidative stress, and serum lipid profile levels in patients with end-stage renal disease on hemodialysis. The effect of alpha-lipoic acid (ALA) supplementation on cardiovascular risk factors in men with chronic spinal cord injury: a clinical trial Effect of alpha-lipoic acid and vitamin E supplementation on oxidative stress, inflammation, and malnutrition in hemodialysis patients. Clinical Efficacy of Alprostadil Combined with α-lipoic Acid in the Treatment of Elderly Patients with Diabetic Nephropathy Effect of Probiotic Soy Milk on Serum Levels of Adiponectin, Inflammatory Mediators, Lipid Profile, and Fasting Blood Glucose Among Patients with Type II Diabetes Mellitus Investigations on the pharmacokinetics of alpha-lipoic acid in healthy volunteers. Effect of alpha-lipoic acid on blood glucose, insulin resistance and glutathione peroxidase of type 2 diabetic patients. Impact of therapy with alpha-lipoic acid (ALA) on the oxidative stress in the controlled NIDDM: a possible preventive way against the organ dysfunction? Alpha-lipoic acid improves subclinical left ventricular dysfunction in asymptomatic patients with type 1 diabetes. Lipoic Acid Prevents High-Fat Diet-Induced Hepatic Steatosis in Goto Kakizaki Rats by Reducing Oxidative Stress Through Nrf2 Activation Effects of Alpha Lipoic Acid on Multiple Cytokines and Biomarkers and Recurrence of Atrial Fibrillation Within 1 Year of Catheter Ablation.
abstract: The aim of this study was to evaluate the efficacy of low-level laser therapy ( LLLT ) and alpha-lipoic acid ( ALA ) in the treatment of  burning mouth syndrome ( BMS ) and secondary oral burning ( SOB ) by unstimulated sialometry , symptom assessment , and measurement of salivary TNF-α levels . Forty-four patients were r and omized into four treatment groups : BMS/laser ( n = 10 ) , BMS/ALA ( n = 5 ) , SOB/laser ( n = 15 ) , and SOB/ALA ( n = 14 ) . The control group consisted of eight healthy female subjects . Unstimulated salivary flow was measured before and after treatment , and the collected saliva was stored at − 20 ° C for the analysis of TNF-α . Symptoms were evaluated before and after treatment using a pain visual analog scale . Most patients were women ( 81.8 % ) during menopause ( 72.2 % ) . LLLT and ALA were efficient in increasing salivary flow only in BMS but provided symptom relief in both conditions . TNF-α levels did not differ between patients with BMS and SOB or between those patients and the control group . No differences were observed in posttreatment TNF-α levels in either condition . The results of this study suggest that LLLT and ALA are efficient therapies in reducing burning mouth symptoms , with LLLT being more efficient than ALA Background : A limited amount of data exists regarding the effect of lipoic acid ( LA ) , an oral antioxidant supplement , on cytokine profiles among multiple sclerosis ( MS ) patients . Objective : We aim ed to assess the effect of daily consumption of LA on the cytokine profiles in MS patients . Methods : In this double-blind , placebo-controlled , r and omized clinical trial , 52 relapsing-remitting MS patients with an age range of 18 - 50 years were recruited into 2 groups : LA consumption ( 1,200 mg/day ) or placebo . Patients followed their prescribed supplements for 12 weeks  . Fasting blood sample s for cytokine profile measurement were collected at baseline and after the intervention . Anthropometric parameters were measured based on the st and ard guidelines . Results : INF-γ , ICAM-1 , TGF-β and IL-4 were significantly reduced in the LA group compared to the placebo group [ ( INF-γ : 0.82 ± 0.2 vs. 0.2 ± 0.2 pg/ml , p < 0.0001 ) , ( ICAM-1 : 20.2 ± 9.4 vs. 8 ± 10 ng/ml , p = 0.0001 ) , ( TGF-β : 103.1 ± 20.2 vs. 54.9 ± 26 ng/ml , p < 0.0001 ) and ( IL-4 : 0.1 ± 0.1 vs. 1.02 ± 1.7 ng/ml , p = 0.0112 ) ] . No significant changes in TNF-α , IL-6 , EDSS and MMP-9 were found between the LA and placebo groups ( p = 0.6 , p = 0.8 , p = 0.09 and p = 0.8 , respectively ) . Conclusion : The results suggested that consumption of 1,200 mg LA per day beneficially affects several inflammatory cytokines including INF-γ , ICAM-1 TGF-β and IL-4 . Further investigations are needed to verify the beneficial role of LA on other cytokine profiles among MS patients OBJECTIVE To examine whether 3 months of lipoic acid ( LA ) supplementation improved walking tolerance and delayed claudication pain onset in peripheral arterial disease ( PAD ) . DESIGN R and omized , double-blind , controlled study . SETTING General Clinical Research Center . SUBJECTS Twenty-eight ( 28 ) participants ( 15 men , 13 women ) with PAD ( ankle brachial index range 0.9 - 0.4 , mean age 73.2 + /- 1.6 years ) . INTERVENTION LA ( 600 mg/day ) or placebo for 3 months . OUTCOME MEASURES Walking tolerance was assessed by 6-minute walk test distance , 4-meter walk time , initial claudication pain time ( ICT ) and distance ( ICD ) , and peak claudication pain . Serum was assessed for inflammation ( C-reactive protein [ CRP ] ) and oxidative stress ( lipid hydroperoxides ) as potential mechanisms for changes in walking tolerance . RESULTS ICT increased 34.4 % and 15 % , ICD was reduced by 40.5 % and 18 % , and peak claudication pain ratings were reduced by 93 % and 7 % in LA and placebo groups , respectively . Although the improvements in peak pain and ICT achieved significance within the LA group ( both p<0.05 ) , the interactions of group by time were not found to be significant ( p>0.05 ) . Oxidative stress and CRP measures were not different between groups by month 3 ( p>0.05 ) . There were no serious side-effects associated with the LA . CONCLUSIONS LA may confer pain relief during exercise . However , longer and larger trials are warranted to determine long-term effects of LA alone or combined with other interventions on PAD symptoms Several studies showed that impairment of endothelium-dependent arterial dilation ( EDAD ) exists in subjects with impaired fasting glucose ( IFG ) . The crucial mechanism of this endothelial dysfunction remains unclear . We hypothesized that oxidative stress may be partially responsible for the impairment in EDAD in subjects with IFG . Thus , the present study was design ed to assess whether the antioxidant α-lipoic acid can improve endothelial dysfunction in subjects with IFG . Sixty subjects with newly diagnosed IFG and 32 healthy individuals with normal glucose tolerance were enrolled . Subjects were r and omized into 2 groups : untreated experimental group ( n = 30 ) and α-lipoic acid treatment group ( n = 30 , α-lipoic acid 600 mg via intravenous infusion once a day for 3 weeks ) . We measured EDAD at baseline and after 3 weeks of intervention . At baseline , EDADs in α-lipoic acid and untreated experimental groups were 4.03 % and 4.14 % , respectively , which were significantly lower than that in controls ( 5.72 % ) ( P < .001 ) . After 3 weeks of intervention , there was a remarkable increase in EDAD ( reaching 5.10 % ; ΔEDAD , 26.5 % ) ( P < .01 ) and a significant decrease in plasma thiobarbituric acid reactive substances ( TBARS ) ( 29.1 % ) ( P < .05 ) in IFG subjects treated with α-lipoic acid . Endothelium-dependent arterial dilation and TBARS remained unchanged before and after intervention in the untreated experimental group . The absolute changes in EDAD showed a significant negative correlation with the changes in TBARS ( r = -0.444 , P = .014 ) . Our data showed that IFG subjects have impaired endothelial function  and that antioxidant α-lipoic acid can improve endothelial function through a decrease of oxygen-derived free radicals BACKGROUND Takotsubo syndrome is a stress cardiomyopathy , characterized by reversible left ventricle ( LV ) apical ballooning in the absence of significant angiographic coronary artery stenosis . The frequent association with emotional stress suggests in this disease an autonomic nervous system involvement . We could think that a therapeutic treatment targeting heart sympathetic dysfunction could be of crucial importance . METHODS From January 2010 to June 2012 , 886 patients were consecutively evaluated at Cardarelli Hospital , Naples , Italy . Among these , 48 patients met takotsubo cardiomyopathy ( TCM ) criteria . Each patient was assessed with history and physical examination , 12-lead electrocardiogram , serum troponin , coronary arteriography , and left ventricular angiogram , perfusion myocardial scintigraphy with technetium 99 m , with echocardiography and 123I-metaiodobenzylguanidine ( MIBG ) myocardial scintigraphy . At discharge , the surviving patients were r and omly assigned to α-lipoic acid ( ALA ) treatment ( 600 mg once daily ) or placebo . Following discharge , after the initial TCM event , patients returned to our outpatient clinic at Internal Medicine of the Second University Naples for the follow-up evaluation quarterly until 12 months . Routine analysis , myocardial damage serum markers , oxidative stress serum markers , pro-inflammatory cytokines , and sympathetic tone activity were evaluated in all patients . RESULTS ALA administration improved MIBG defect size at 12 months compared to placebo . CONCLUSIONS Adrenergic cardiac innervation dysfunction in TCM patients persists after previous experience of transient stress-induced cardiac dysfunction . ALA treatment improves the adrenergic cardiac innervation . This study evaluates whether sympatho-vagal alterations are TCM event-related Background Abnormal regulation of the inflammatory response is an important component of diseases such as diabetes , Alzheimer 's disease and multiple sclerosis ( MS ) . Lipoic acid ( LA ) has been shown to have antioxidant and anti-inflammatory properties and is being pursued as a therapy for these diseases . We first reported that LA stimulates cAMP production via activation of G-protein coupled receptors and adenylyl cyclases . LA also suppressed NK cell activation and cytotoxicity . In this study we present evidence supporting the hypothesis that the anti-inflammatory properties of LA are mediated by the cAMP/PKA signaling cascade . Additionally , we show that LA oral administration elevates cAMP levels in MS subjects . Methodology /Principal Findings We determined the effects of LA on IL-6 , IL-17 and IL-10 secretion using ELISAs . Treatment with 50 µg/ml and 100 µg/ml LA significantly reduced IL-6 levels by 19 and 34 % , respectively , in T cell enriched P BMC s. IL-17 levels were also reduced by 35 and 50 % , respectively . Though not significant , LA appeared to have a biphasic effect on IL-10 production . Thymidine incorporation studies showed LA inhibited T cell proliferation by 90 % . T-cell activation was reduced by 50 % as measured by IL-2 secretion . Western blot analysis showed that LA treatment increased phosphorylation of Lck , a downstream effector of protein kinase A. Pretreatment with a peptide inhibitor of PKA , PKI , blocked LA inhibition of IL-2 and IFN gamma production , indicating that PKA mediates these responses . Oral administration of 1200 mg LA to MS subjects result ed in increased cAMP levels in P BMC s four hours after ingestion . Average cAMP levels in 20 subjects were 43 % higher than baseline . Conclusions / Significance Oral administration of LA in vivo result ed in significant increases in cAMP concentration . The anti-inflammatory effects of LA are mediated in part by the cAMP/PKA signaling cascade . These novel findings enhance our underst and ing of the mechanisms of action of LA OBJECTIVE Type 1 diabetes is associated with increased platelet reactivity . We investigated whether α-lipoic acid ( ALA ) has any effect on platelet reactivity in these patients . RESEARCH DESIGN AND METHODS We r and omly assigned 51 type 1 diabetic patients to ALA  ( 600 mg once daily ) or placebo for 5 weeks . Platelet reactivity was evaluated by the PFA-100 method and by measuring CD41 and CD62 platelet expression . C-reactive protein ( CRP ) and 8-iso-prostagl and in F2α serum levels also were measured . RESULTS Baseline variables were similar in the two groups . After treatment , closure time was longer ( P = 0.006 ) and CD62P platelet expression was lower , both before ( P = 0.002 ) and after ( P = 0.009 ) ADP stimulation in the ALA group compared with the placebo group . CRP and 8-iso-prostagl and in F2α levels showed no differences between the two groups . CONCLUSIONS Our data show that ALA reduces measures of platelet reactivity ex vivo in type 1 diabetic patients , independently of antioxidant or anti-inflammatory effects Introduction Anemia associated with chronic kidney disease is a serious complication necessitating expenditure of huge medical efforts and re sources . This study investigates the role of alpha-lipoic acid ( ALA ) in end stage renal disease patients undergoing hemodialysis . By the virtue of its antioxidative effects , ALA is expected to act as an erythropoietin ( EPO ) adjuvant , and also has extended beneficial effects on endothelial dysfunction . Methods Forty-four patients undergoing hemodialysis and receiving EPO  were r and omized into two groups : the first group received ALA 600 mg once daily for 3 months ; while the other group represented the control group . Parameters measured at baseline and at end of study were hemoglobin , EPO doses , EPO resistance index ( ERI ) , iron store indices , malondialdehyde , oxidized low-density lipoprotein ( ox-LDL ) , interleukin-6 ( IL-6 ) , tumor necrosis factor-α ( TNF-α ) , and asymmetric dimethylarginine ( ADMA ) , as well as routine laboratory follow-up . Results EPO doses and ERI were significantly decreased in the treatment group , while they did not change in the control group . Hemoglobin , iron store indices , malondialdehyde , oxidized ox-LDL , IL-6 , TNF-α , and ADMA were similar in both treatment and control groups at baseline , and did not change by the end of study period . Likewise , routine laboratory measures were not affected by the treatment . Conclusion ALA could be used in hemodialysis patients to reduce requirements for EPO . However , larger and longer term studies are required to clarify the exact role of ALA in hemodialysis as well as in pre-hemodialysis patients Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists Background Chronic renal failure is a progressive and irreversible loss of kidney function , and the hemodialysis ( HD ) is one of the most common modalities in this regard . Oxidative stresses [ like interleukin-8 ( IL-8 ) and tumor necrosis factor-alpha ( TNF-α ) ] and inflammation are the main risk factors associated with cardiovascular diseases and other complications in many organs in hemodialysis patients ; meanwhile , antioxidants like alpha lipoic acid ( ALA ) may reduce the oxidative stress markers and the levels of inflammatory cytokines , so can improve of the patient ’s quality of life . Methods In this r and omized clinical trial study , 60 HD patients were r and omly categorized in two case and control groups . Case group received a daily capsule of 600 mg of ALA supplementation for 8 weeks , and the control group received placebo capsules daily . The serum level of IL-8 and TNF-α was measured in both groups before and after the intervention . Results There were no significant differences in age , gender , duration of dialysis , and causative factor for dialysis between both groups ( P > 0.05 ) . The mean of IL-8 and TNF-α after the intervention in case group was 26.20 ± 15.34 and 21.25 ± 9.61 , respectively ; the difference between both groups was not statistically significant ( P > 0.05 ) . Conclusion Based on the better feeling and other beneficial effects of ALA were found in our study ; we can conclude that it is a beneficial and recommended supplement , especially , for diabetic and dialysis patients OBJECTIVE We examined the effects of alpha-lipoic acid ( ALA ) supplementation on inflammation , oxidative stress , and serum lipid profile levels in hemodialysis ( HD ) patients . DESIGN This was a double-blinded , r and omized , placebo-controlled clinical trial . SETTING The present study involved HD centers in Tabriz , Iran . PATIENTS Participants included 63 patients with end-stage renal disease ( 43 men and 20 women ; age range : 22 - 79 years ) undergoing maintenance HD . INTERVENTION HD patients were r and omly assigned into the supplemented group ( n = 31 ) , receiving a daily dose of ALA ( 600 mg ) , or a control group ( n = 32 ) , receiving placebo for 8 weeks . MAIN OUTCOME MEASURES High sensitivity C-reactive protein ( hsCRP ) , malondialdehyde , total antioxidant status , total cholesterol , triglyceride , high-density lipoprotein cholesterol ( HDL-C ) , and low-density lipoprotein cholesterol ( LDL-C ) were measured at baseline and after 8 weeks of supplementation . RESULTS At the end of intervention , 11 patients were excluded from the study .  HsCRP levels decreased by 18.7 % in the supplemented group after 8 weeks of supplementation , and the reduction was significant in comparison with the placebo group ( P < .05 ) ; this finding was also significant after adjusting for baseline values of hsCRP . The mean malondialdehyde and total antioxidant status levels did not change significantly in the 2 groups during the study . The mean high-density lipoprotein cholesterol concentrations increased significantly in the supplemented group at the end of the study ( P < .05 ) ; however , this improvement was not statistically significant as compared with the placebo group . No significant alterations were observed in the other lipid profile parameters within each group during the study . CONCLUSION ALA supplementation significantly reduced hsCRP levels , which is a risk factor for cardiovascular disease in HD patients Study design : A r and omized , double-blind , placebo-controlled clinical trial . Objective : To assess the effect of alpha-lipoic acid ( ALA ) supplementation on IL-6 , hs-CRP , FBS , anthropometric indices , food intake and blood pressure in male patients with chronic spinal cord injury ( SCI ) . Setting : Imam Khomeini Hospital , Tehran University of Medical Sciences , Tehran , Iran . Methods : Fifty-eight men with chronic SCI participated in the study . Participants were divided in two groups : one group received 600 mg of supplemental ALA ( n=28 ) and the other group received placebo ( n=30 ) for 12 weeks . At the beginning and end of the study , biochemical parameters , anthropometric indices , blood pressure and dietary intakes were measured . Dietary intake was measured using N4 software , and statistical analyses were carried out using SPSS16 . Results : No significant reduction was found in IL-6 ( P=0.97 ) and hs-CRP levels ( P=0.23 ) . There was significant reduction in fasting blood sugar ( P=0.001 ) , body weight ( P=0.001 ) , BMI ( P=0.001 ) , waist circumference ( P=0.001 ) and blood pressure ( P=0.001 ) . Dietary intake was significantly reduced , including fat ( P=0.001 ) , carbohydrate ( P=0.001 ) , protein ( P=0.002 ) and energy intakes ( P=0.001 ) . Conclusion : Lipoic acid supplementation had no significant effect on the measured inflammatory markers but it reduces fasting blood sugar , anthropometric parameters , food intake and blood pressure in men with chronic SCI INTRODUCTION Increased oxidative stress , inflammation , and malnutrition are present in hemodialysis patients and these factors exacerbate cardiovascular comorbidities . Vitamin E and alpha-lipoic acid ( ALA ) may have a protective role against cardiovascular disease risk factors via anti-oxidative and anti-inflammatory properties . The aim of this study was to evaluate the effect of ALA and vitamin E administration ( alone or combined ) on hemodialysis-induced stress oxidation , inflammation , and malnutrition . MATERIAL S AND METHODS In a r and omized placebo-controlled trial , we examined the effects of 2-month supplementation by vitamin E and ALA ( alone or combined ) on biomarkers of lipid peroxidation ( malondialdehyde ) , inflammation ( high-sensitivity C-Reactive protein and interleukin-6 ) , and malnutrition ( Subjective Global Assessment and body mass index ) in 85 hemodialysis patients receiving ALA ( 600 mg ) , vitamin E ( 400 IU ) , ALA and vitamin E , and placebo .  RESULTS After supplementation , no significant changes were observed in malondialdehyde level ; however , there was a decrease in the ALA and vitamin E group during the period of the study . Also , a nonsignificant decrease was seen in the high-sensitivity C-Reactive protein concentration of the interventional groups . Supplementation of vitamin E with and without ALA significantly reduced interleukin-6 concentration . A significant improvement was observed in malnutrition status of all groups . CONCLUSIONS Vitamin E and ALA supplementation , especially their combination , might improve inflammation and malnutrition status , which suggest it as a potential preventive strategy against CVD among end-stage renal disease patients Abstract Objective To evaluate the effect and toxicity of alprostadil combined with thioctic acid injection in the treatment of patients with diabetic nephropathy ( DN ) . Methods Sixty two patients with DN were included in this study and r and omly divided into control group ( n=32 ) and experiment group ( n=30 ) . Patients in the control group were given alprostadil 20ug+NS 100ml ivgtt , qd and patients in the experiment group were given alprostadil 20ug+NS 100ml ivgtt combined with thioctic acid injection of 0.45g+100ml ivgtt , qd for 14 days . After treatment , the renal function and serum level of CRP , IL-6 and TNF-α were compared between the two groups . Results After two weeks of treatment , the serum level of CysC and UAER significant decreased for both control and experiment group with statistical difference of p<0.05 . After treatment , the serum level of CysC were 1.40 ±0.46 mg/L and 1.02±0.33 for control and experiment group respectively ( p<0.05 ) . The post-treatment UAER in experiment group was significantly lower than those of control group with statistical difference ( 81.02±0.33 vs112.45±20.32 , p<0.05 ) ug/min . The serum level of CRP , IL-6 and TNF-α were significantly decreased after treatment for both control and experiment group ( p<0.05 ) . And the post-treatment serum CRP , IL-6 and TNF-α in experiment group were significantly lower than those of control group with statistical difference ( p<0.05 ) . No significant side effects were found for the two groupsin the course of treatment . Conclusion Alprostadil combined with α-lipoic acid may improve  renal function in patients with diabetic nephropathy by decreasing the levels of serum inflammatory factors Probiotic therapies are going to be an effective alternative therapeutic strategy in the treatment and management of diabetes . The mechanism behind the essential effects of probiotic therapies in diabetic patients was not fully understood . The objective of this study was to evaluate the effects of probiotic soy milk containing Lactobacillus planetarum A7 on inflammation , lipid profile , fasting blood glucose , and serum adiponectin among patients with type 2 diabetes mellitus . Forty patients with type 2 diabetes , at the age of 35–68 years old , were assigned to two groups in this r and omized , double-blind , controlled clinical trial . The patients in the intervention group consumed 200 ml/day of probiotic soy milk containing L. planetarum A7 and those in control group consumed 200 ml/day of pure soy milk for 8 weeks  . Serum TNF-α , C reactive protein , adiponectin , lipid profile , and fasting blood glucose were determined before and after intervention . In intervention group , serum adiponectin in pre- and post-treatment did not show any significant changes ( 2.52 ± 0.74 vs 2.84 ± 0.61 , P = 0.658 ) , as well as changes in serum TNF-α and C reactive protein ( 172.44 ± 5.7 vs 172.83 ± 7.6 , P = 0.278 , 4.2 ± 1.4 vs 4.5 ± 1.9 , P = 0.765 , respectively ) . Low-density cholesterol and high-density cholesterol changed significantly ( P = 0.023 , P = 0.017 , respectively ) , but fasting blood glucose did not show any significant changes . The results of this study showed that consumption of probiotic soy milk and soy milk has no effect on serum adiponectin and inflammation , but it can change lipid profile among type 2 diabetic patients AIM The aim of the present study was to examine the pharmacokinetics of racemic alpha-lipoic acid in twelve healthy volunteers following single oral administration of 200 and 600 mg ( Thioctacid 200 film tablets )  . SUBJECTS , MATERIAL AND METHODS Each film tablet contained 200 mg of alpha-lipoic acid . In addition , an injection solution containing 200 mg of alpha-lipoic acid was administered . Plasma concentrations of alpha-lipoic acid were determined using a vali date d reversed-phase HPLC method with electrochemical detection having a lower limit of quantitation of 1 ng/ml . The areas under curve ( AUC ) were 46.82 + /- 21.46 and 157.97 + /- 35.05 microg x min/ml for the oral and intravenous administration of 200 mg , respectively . RESULTS The AUC following oral administration of 600 mg was 157.83 + /- 35.82 microg x min/ml . The difference in mean t(1/2 ) for the two oral doses and the i.v . dose ( in the range of 25.3 - 32.7 min ) was not statistically significant . CONCLUSION The lack of a significant difference between values for apparent total plasma clearance for the 200 and 600 mg doses indicates non-saturable kinetics of alpha-lipoic acid in healthy volunteers in this dose range . The absolute bioavailability after the 200 mg dose was 29.1 + /- 10.3 % OBJECTIVE To examine the effects of alpha-lipoic acid ( ALA ) treatment over a period of 2 months on fasting blood glucose ( FBG ) , insulin resistance ( IR ) , and glutathione peroxidase ( GH-Px ) activity in type 2 diabetes ( T2DM ) patients . METHODS This study took place in Motahari Clinic , Shiraz , Iran , which is affiliated to Shiraz University of Medical Sciences from May to October 2006 . Type 2 DM patients ( n=57 ) were divided into 2 groups to receive either ALA ( 300 mg daily ) or placebo by systematic r and omization , and were followed-up for 8 weeks . After an overnight fasting and 2 hours after breakfast , patients ' blood sample s were drawn and tested for FBG , 2 hours  PPG , serum insulin level , and GH-Px activity .  RESULTS The result of the study showed a significant decrease in FBG and PPG levels , IR-Homeostasis Model Assessment ( IR-HOMA index ) and GH-Px level in the ALA group . The comparison of differences between FBG and IR at the beginning and at the end of study in the ALA treated group and the placebo group were also significant . CONCLUSION This study supports the use of ALA as an antioxidant in the care of diabetic patients There is a growing evidence that excess generation of highly reactive free radicals , largely due to hyperglycemia , causes oxidative stress , which further exacerbates the development and progression of diabetes and its complications . The purpose of this study was to evaluate the impact of ALA on lipid profile , oxidative pattern and inflammation in patients with controlled non-insulin dependent diabetes mellitus ( NIDDM ) .  ALA , 400mg/day was investigated in NIDDM patients over a period of 4 weeks using a r and omized , placebo-(PLA)-controlled study with two parallel groups . The marker of oxidative stress was the concentration of reactive oxygen metabolites , evaluated using a commercially available test , called d-ROMs  test  , and the  biological antioxidant potential ( BAP ) ; besides , the lipid profile ( total cholesterol = TC , high-density lipoprotein-cholesterol = HDL-C ; low-density lipoprotein-cholesterol = LDL-C , and triglycerides = TG ) and the C-reactive protein ( CRP ) , marker of inflammation were measured at the beginning and at the end of the treatment . A total of 14 patients were r and omly assigned to the two groups . ALA was safe and well tolerated in the only oral daily administration . The d-ROMs test ( p=0.03 ) and HDL-C ( p=0.04 ) showed a significant difference between the two groups . BAP ( p=0.06 ) tended to be higher in the treated patients , while LDL-C ( p=0.07 ) presented a moderate decline . There were no significant differences in TC ( p=0.65 ) , TG ( p=0.78 ) and CRP ( p=0.96 ) between the ALA and PLA groups . ALA therapy appears to reduce significantly d-ROMs and to improve HDL-C value , especially in men with metabolic syndrome treated with oral hypoglycemic drugs . These findings will be useful in patient selection in future clinical trials with ALA in long term studies BACKGROUND Oxidative stress plays an important role in the development of diabetic cardiomyopathy . Alpha-lipoic acid ( ALA ) is a powerful antioxidant that may have a protective role in diabetic cardiac dysfunction . AIM We investigated the possible beneficial effect of alpha-lipoic acid on diabetic left ventricular ( LV ) dysfunction in children and adolescents with asymptomatic type 1 diabetes ( T1D ) . SUBJECTS AND METHODS Thirty T1D patients ( aged 10 - 14 ) were r and omized to receive insulin treatment ( n = 15 ) or insulin plus alpha-lipoic acid 300 mg twice daily ( n = 15 ) for four months . Age and sex matched healthy controls ( n = 15 ) were also included . Patients were evaluated with conventional 2-dimensional echocardiographic examination ( 2D ) , pulsed tissue Doppler ( PTD ) , and 2-dimensional longitudinal strain echocardiography ( 2DS ) before and after therapy .  Glutathione , malondialdhyde ( MDA ) , nitric oxide ( NO ) , tumor necrosis factor-alpha ( TNF-alpha ) , Fas lig and ( Fas-L ) , matrix metalloproteinase 2 ( MMP-2 ) , and troponin-I were determined and correlated to echocardiographic parameters . RESULTS Diabetic patients had significantly lower levels of glutathione and significantly higher MDA , NO , TNF-alpha , Fas-L , MMP-2 , and troponin-I levels than control subjects . The expression of transforming growth factor beta ( TGF-beta ) mRNA in peripheral blood mononuclear cells was also increased in diabetic patients . Significant correlations of mitral e'/a ' ratio and left ventricular global peak systolic strain with glutathione , MDA , NO , TNF-alpha , and Fas-L were observed in diabetic patients . Alpha-lipoic acid significantly increased glutathione level and significantly decreased MDA , NO , TNF-alpha , Fas-L , MMP-2 , troponin-I levels , and TGF-beta gene expression . Moreover , alpha-lipoic acid significantly increased mitral e'/a ' ratio and left ventricular global peak systolic strain in diabetic patients . CONCLUSION These findings suggest that alpha-lipoic acid may have a role in preventing the development of diabetic cardiomyopathy in type 1 diabetes Prevention of hepatic fat accumulation may be an important approach for liver diseases due to the increased relevance of hepatic steatosis in this field . This study was conducted to investigate the effects of the antioxidant α-lipoic acid ( α-LA ) on hepatic steatosis , hepatocellular function , and oxidative stress in a model of type 2 diabetes fed with a high fat diet ( HFD ) . Goto-Kakizaki rats were r and omly divided into four groups . The first group received only a st and ard rat diet ( control GK )  including groups 2 ( HFD ) , 3 ( vehicle group ) , and 4 ( α-LA group ) , which were given HFD , ad libitum during three months . Wistar rats are the non-diabetic control group . Carbohydrate and lipid metabolism , liver function , plasma and liver tissue malondialdehyde ( MDA ) , liver GSH , tumor necrosis factor-α ( TNF-α ) and nuclear factor E2 ( erythroid-derived 2)-related factor-2 ( Nrf2 ) levels were assessed in the different groups . Liver function was assessed using quantitative hepatobiliary scintigraphy , serum aspartate , and alanine aminotransferases ( AST , ALT ) , alkaline phosphatase , gamma-glutamyltranspeptidase , and bilirubin levels . Histopathologically steatosis and fibrosis were evaluated . Type 2 diabetic animals fed with HFD showed a marked hepatic steatosis and a diminished hepatic extraction fraction and both were fully prevented with α-LA  . Plasma and liver tissue MDA and hepatic TNF-α levels were significantly higher in the HFD group when compared with the control group and significantly lower in the α-LA  group . Systemic and hepatic cholesterol , triglycerides , and serum uric acid levels were higher in hyperlipidemic GK rats and fully prevented with α-LA . In addition , nuclear Nrf2 activity was significantly diminished in GK rats and significantly augmented after α-LA treatment . In conclusion , α-LA strikingly ameliorates steatosis in this animal model of diabetes fed with HFD by decrementing the inflammatory marker TNF-α and reducing oxidative stress . α-LA might be considered a useful therapeutic tool to prevent hepatic steatosis by incrementing antioxidant defense systems through Nrf2 and consequently decreasing oxidative stress and inflammation in type 2 diabetes Catheter ablation ( CA ) is a procedure commonly used to restore sinus rhythm in patients with atrial fibrillation ( AF ) . However , AF recurrence after CA remains a relevant clinical issue . We tested the effects of an oral antioxidant treatment ( alpha lipoic acid [ ALA ] ) on AF recurrence post-CA . Patients with paroxysmal AF have been enrolled in a r and omized , prospect i ve , double-blind , controlled placebo trial . After CA , patients have been r and omly assigned to receive ALA oral supplementation ( ALA group ) or placebo ( control group ) and evaluated at baseline and after a 12-month follow-up : 73 patients completed the 12-month follow-up  ( ALA : 33 and control : 40 ) . No significant difference has been detected between the 2 groups at baseline . Strikingly , 1 year after CA , ALA therapy significantly reduced serum markers of inflammation . However , there was no significant difference in AF recurrence events at follow-up comparing ALA with placebo group . Multivariate analysis revealed that the only independent prognostic risk factor for AF recurrence after CA is age . In conclusion , ALA therapy reduces serum levels of common markers of inflammation in ablated patients . Nevertheless , ALA does not prevent AF recurrence after an ablative treatment
target: Our results indicated possible decreasing effect of ALA on inflammatory mediators especially in high dose .
background: & NA ; Alpha‐Lipoic Acid ( ALA ) is a natural antioxidant compound which is naturally found in plant sources .
  New evidence revealed that ALA can reduce inflammation .
  Our objective in this meta‐ analysis was to conduct a systematic review and meta‐ analysis on r and omized controlled trials to indicate ALA effects on serum inflammatory mediators concentration such as tumor necrosis factor‐alpha ( TNF‐&agr ; ) , c‐reactive protein ( CRP ) , and interleukin‐6 ( IL‐6 ) .