title: Effects of α-lipoic acid therapy on sympathetic heart innervation in patients with previous experience of transient takotsubo cardiomyopathy. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. Role of alpha-lipoic acid in the management of anemia in patients with chronic renal failure undergoing hemodialysis Effects of alpha lipoic acid supplementation on serum levels of IL-8 and TNF-α in patient with ESRD undergoing hemodialysis Effects of α-Lipoic Acid on the Plasma Levels of Asymmetric Dimethylarginine in Diabetic End-Stage Renal Disease Patients on Hemodialysis: A Pilot Study Effects of alpha-lipoic acid supplementation on inflammation, oxidative stress, and serum lipid profile levels in patients with end-stage renal disease on hemodialysis. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. 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 Effects of combination tocopherols and alpha lipoic acid therapy on oxidative stress and inflammatory biomarkers in chronic kidney disease. 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. Effects of Alpha Lipoic Acid on Multiple Cytokines and Biomarkers and Recurrence of Atrial Fibrillation Within 1 Year of Catheter Ablation.
abstract: 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 CONTEXT Inflammation is hypothesized to play a role in development of type 2 diabetes mellitus ( DM ) ; however , clinical data addressing this issue are limited . OBJECTIVE To determine whether elevated levels of the inflammatory markers interleukin 6 ( IL-6 ) and  C-reactive protein ( CRP ) are associated with development of  type 2 DM in healthy middle-aged women . DESIGN Prospect i ve , nested case-control study . SETTING The Women 's Health Study , an ongoing US primary prevention , r and omized clinical trial initiated in 1992 . PARTICIPANTS From a nationwide cohort of 27 628 women free of diagnosed DM , cardiovascular disease , and cancer at baseline , 188 women who developed diagnosed DM over a 4-year follow-up period were defined as cases and matched by age and fasting status with 362 disease-free controls . MAIN OUTCOME MEASURES Incidence of confirmed clinical ly diagnosed type 2 DM by baseline levels of IL-6 and CRP . RESULTS Baseline levels of IL-6 ( P<.001 ) and CRP ( P<.001 ) were significantly higher among cases than among controls . The relative risks of future DM for women in the highest vs lowest quartile of these inflammatory markers were 7.5 for IL-6 ( 95 % confidence interval [ CI ] , 3.7 - 15.4 ) and 15.7 for CRP ( 95 % CI , 6.5 - 37.9 ) . Positive associations persisted after adjustment for body mass index , family history of diabetes , smoking , exercise , use of alcohol , and hormone replacement therapy ; multivariate relative risks for the highest vs lowest quartiles were 2.3 for IL-6 ( 95 % CI , 0.9 - 5.6 ; P for trend = .07 ) and 4.2 for CRP ( 95 % CI , 1.5 - 12.0 ; P for trend = .001 ) . Similar results were observed in analyses limited to women with a baseline hemoglobin A(1c ) of 6.0 % or less and after adjustment for fasting insulin level . CONCLUSIONS Elevated levels of CRP and IL-6 predict the development of type 2 DM . These data support a possible role for inflammation in diabetogenesis 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 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 Background / Aim : Endothelial dysfunction due to reduced nitric oxide ( NO ) availability precedes the development of atherosclerosis . Asymmetric dimethylarginine ( ADMA ) , an endogenous inhibitor of NO synthase , is not only a cause of endothelial dysfunction , but also a predictor of the cardiovascular outcome in end-stage renal disease ( ESRD ) patients on hemodialysis ( HD ) .  α-Lipoic acid ( ALA ) , a strong antioxidant , increases NO-mediated vasodilation in diabetic patients . We investigated whether ALA could decrease the plasma level of ADMA in diabetic ESRD patients on HD . Methods : Fifty patients undergoing HD three times per week were r and omized to a treatment group receiving ALA 600 mg/day for 12 weeks or a control group . We measured the plasma levels of cholesterol , albumin , high-sensitivity C-reactive protein , oxidized low-density lipoprotein , hemoglobin A1c , and ADMA in both groups at baseline and at 12 weeks . Results : In the control group , the levels of total cholesterol , serum albumin , high-sensitivity C-reactive protein , oxidized low-density lipoprotein , hemoglobin A1c , and ADMA did not change . In the treatment group , the plasma levels of ADMA decreased significantly from a median of 1.68 ( range 0.45–3.78 ) µM to a median of 1.31 ( range 0.25–3.19 ) µM ( p = 0.001 ) . Conclusion : Considering that ADMA is an independent risk factor for cardiovascular outcome in ESRD patients  , ALA may have the potential of a beneficial effect in them , in part by decreasing the plasma level of ADMA 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 BACKGROUND C-reactive protein is an inflammatory marker believed to be of value in the prediction of coronary events . We report data from a large study of C-reactive protein and other circulating inflammatory markers , as well as up date d meta-analyses , to evaluate their relevance to the prediction of coronary heart disease . METHODS Measurements were made in sample s obtained at base line from up to 2459 patients who had a nonfatal myocardial infa rct ion or died of coronary heart disease during the study and from up to 3969 controls without a coronary heart disease event in the Reykjavik prospect i ve study of 18,569 participants .  Measurements were made in paired sample s obtained an average of 12 years apart from 379 of these participants in order to quantify within-person fluctuations in inflammatory marker levels . RESULTS The long-term stability of C-reactive protein values ( within-person correlation coefficient , 0.59 ; 95 percent confidence interval , 0.52 to 0.66 ) was similar to that of both blood pressure and total serum cholesterol . After adjustment for base-line values for established risk factors , the odds ratio for coronary heart disease was 1.45 ( 95 percent confidence interval , 1.25 to 1.68 ) in a comparison of participants in the top third of the group with respect to base-line C-reactive protein values with those in the bottom third , and similar overall findings were observed in an up date d meta- analysis involving a total of 7068 patients with coronary heart disease . By comparison , the odds ratios in the Reykjavik Study for coronary heart disease were somewhat weaker for the erythrocyte sedimentation rate ( 1.30 ; 95 percent confidence interval , 1.13 to 1.51 ) and the von Willebr and factor concentration ( 1.11 ; 95 percent confidence interval , 0.97 to 1.27 ) but generally stronger for established risk factors , such as an increased total cholesterol concentration ( 2.35 ; 95 percent confidence interval , 2.03 to 2.74 ) and cigarette smoking ( 1.87 ; 95 percent confidence interval , 1.62 to 2.16 ) . CONCLUSIONS C-reactive protein is a relatively moderate predictor of coronary heart disease . Recommendations regarding its use in predicting the likelihood of coronary heart disease may need to be review ed 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 OBJECTIVE Although increased oxidative stress and inflammation are highly prevalent in chronic kidney disease ( CKD ) , few studies have investigated whether oral antioxidant therapy can alter markers of inflammation or oxidative stress in patients with CKD . The purpose of this study was to investigate whether a combination of mixed tocopherols and alpha lipoic acid ( ALA ) would alter biomarkers of oxidative stress and inflammation in subjects with stage 3 to 4 CKD . METHODS This was a prospect i ve , r and omized , double-blind , placebo-controlled pilot trial . In all , 62 subjects were enrolled and were r and omly assigned to receive a combination of mixed tocopherols 666 IU/day , in addition to ALA 600 mg/day , or their matching placebos for a total of 8 weeks . Plasma F(2)-isoprostane and protein thiol concentration were measured as biomarkers of oxidative stress , and C-reactive protein and interleukin-6 concentration as biomarkers of systemic inflammation . RESULTS There were no significant differences in demographics , diabetic status , or estimated glomerular filtration rate between study treatment and placebo groups at baseline . Of the 62 r and omized subjects , 58 ( 93 % ) completed the study protocol . After 2 months of treatment , there were no significant changes in the concentrations of F(2)-isoprostanes , protein thiols , C-reactive protein , and interleukin-6 with respect to treatment with mixed tocopherols and ALA as compared with matching placebos , whether analyzed as intention to treat or as treated . Diabetic status and baseline body mass index did not influence the results . CONCLUSIONS Combination of oral mixed tocopherols and ALA treatment for 2 months does not influence biomarkers of oxidative stress and inflammation in patients with stage 3 to 4 CKD 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 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: Conclusion In summary , the current meta- analysis demonstrated the promising impact of ALA administration on decreasing inflammatory markers such as CRP , IL-6 and TNF-α among patients with MetS and related disorders
background: Objective This systematic review and meta- analysis of r and omized controlled trials ( RCTs ) was conducted to determine the effect of alpha-lipoic acid ( ALA ) supplementation on the inflammatory markers among patients with metabolic syndrome ( MetS ) and related disorders .