***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE To evaluate the efficacy and safety of alpha-lipoic acid given intravenously , followed by oral treatment in type 2 diabetic patients with symptomatic polyneuropathy . RESEARCH DESIGN AND METHODS In a multicenter r and omized double-blind placebo-controlled trial ( Alpha-Lipoic Acid in Diabetic Neuropathy [ ALADIN ] III Study ) , 509 out patients were r and omly assigned to sequential treatment with 600 mg alpha-lipoic acid once daily intravenously for 3 weeks , followed by 600 mg alpha-lipoic acid three times a day orally for 6 months ( A-A ; n = 167 ) ; 600 mg alpha-lipoic acid once daily intravenously for 3 weeks , followed by placebo three times a day orally for 6 months ( A-P ; n = 174 ) ; and placebo once daily intravenously for 3 weeks , followed by placebo three times a day orally for 6 months ( P-P ; n = 168 ) . Outcome measures included the Total Symptom Score ( TSS ) for neuropathic symptoms ( pain , burning , paresthesias , and numbness ) in the feet , and the Neuropathy Impairment Score ( NIS ) . Data analysis was based on the intention to treat . RESULTS No significant differences between the groups were noted for the demographic variables and the nerve function parameters at baseline . The TSS in the feet decreased from baseline to day 19 ( median [ range ] ) by -3.7 ( -12.6 to 5.0 ) points in the group given alpha-lipoic acid intravenously and by -3.0 ( -12.3 to 8.0 ) points in the placebo group ( P = 0.447 ) , but the area under curve on a daily basis was significantly smaller in the active as compared with the placebo group ( 85.6 [ 0 - 219 ] vs. 95.9 [ 5.5 - 220 ] ) ; P = 0.033 ) . After 7 months , the changes in the TSS from baseline were not significantly different between the three groups studied , which could be due to increasing intercenter variability in the TSS during the trial . The NIS decreased after 19 days by -4.34+/-0.35 points ( mean + /- SEM ) in A-A and A-P and -3.49+/-0.58 points in P-P ( P = 0.02 for alpha-lipoic acid versus placebo ) and after 7 months by -5.82+/-0.73 points in A-A , -5.76+/-0.69 points in A-P , and -4.37+/-0.83 points in P-P ( P = 0.09 for A-A vs. P-P ) . The rates of adverse events were not different between the groups throughout the study . CONCLUSIONS These findings indicate that a 3-week intravenous treatment with alpha-lipoic acid , followed by a 6-month oral treatment , had no effect on neuropathic symptoms distinguishable from placebo to a clinical ly meaningful degree , possibly due to increasing intercenter variability in symptom scoring during the study . However , this treatment was associated with a favorable effect on neuropathic deficits without causing significant adverse reactions . Long-term trials that focus on neuropathic deficits rather than symptoms as the primary criterion of efficacy are needed to see whether oral treatment with alpha-lipoic acid over several years may slow or reverse the progression of diabetic neuropathy BACKGROUND Amelioration of insulin resistance could improve both glycaemic control and cardiovascular risk factors in patients with type 2 diabetes mellitus .  Alpha-lipoic acid has been shown to improve insulin action after parenteral administration . OBJECTIVE the aim of the study was to assess the effect of oral administration of alpha-lipoic acid on insulin sensitivity in patients with type 2 diabetes . DESIGN twelve patients ( mean+/-sD ; age 52.9+/-9.9 yrs ; body mass index 33.9+/-7.4 kg/m(2 ) ) were treated with oral alpha-lipoic acid , 600 mg twice daily over a period of 4 weeks . twelve subjects with normal glucose tolerance served as a control group in terms of insulin sensitivity ( Is ) . Is was measured by a 2h manual hyperinsulinaemic ( insulin infusion rate-40 mU/m(2 ) body surface area/min ) euglycaemic ( blood glucose kept at 5 mmol/l ) clamp technique and expressed as a glucose disposal rate ( M ) and insulin sensitivity index ( IsI ) . RESULTS At the end of the treatment period , Is of diabetic patients was significantly increased : M from 3.202+/-1.898 to 5.951+/-2.705 mg/kg/min ( mean+/-sD ) , p<0.01 ; and IsI from 4.706+/-2.666 to 7.673+/-3.559 mg/kg/min per mIU/l x 100 ( mean+/-sD ) , p<0.05 . the difference was not statistically significant between the Is of diabetic patients after alpha-lipoic acid therapy and control subjects . CONCLUSION short-term oral alpha-lipoic acid treatment increases peripheral insulin sensitivity in patients with type 2 diabetes mellitus BACKGROUND The diabetic state , in both humans and experimental animals , is associated with oxidative stress . Lipid peroxidation of nerve membranes has been suggested as a mechanism by which peripheral nerve ischemia and hypoxia could cause neuropathy . Lipoic acid ( LA ) is a powerful inhibitor of iron-dependent lipid peroxidation and reactive oxygen species . The treatment of diabetic peripheral and cardiac autonomic neuropathy with LA is based on good clinical and experimental evidence . MATERIAL S AND METHODS To investigate the magnitude of the oxidative stress , serum ceruloplasmin ( Cp ) and lipid peroxide ( Lp ) levels were measured in 10 patients with diabetic neuropathy , before and 70 days after treatment with single dose of 600 mg LA/day  . For other 12 healthy age- and sex-matched control subjects the serum Cp and Lp levels were evaluated . RESULTS Our results show that hyperglycemia is a factor for an increase in serum ceruloplasmin in patients with diabetic neuropathy compared to healthy subjects ( p < 0.0001 ) . High serum ceruloplasmin ( Cp ) level in patients with diabetes may be related to antioxidant defense . The treatment of diabetic neuropathy with LA does not affect significantly the serum Cp activity . The serum Lp levels after LA administration were significantly lower ( p < 0.005 ) than those before treatment . CONCLUSIONS The antioxidant therapy with LA improves and may prevent diabetic neuropathy . This improvement is associated with a reduction in the indexes of lipid peroxidation . Oxidative stress appears to be primarily due to the processes of nerve ischemia and hyperglycemia autooxidation Diabetic polyneuropathy is a serious complication in patients with diabetes mellitus . In addition to the maintenance of a sufficient metabolic control , alpha-lipoic acid ( ALA ) ( Thioctacid , Asta Medica ) is known to have beneficial effects on diabetic polyneuropathy although the exact mechanism by which ALA exerts its effect is unknown . In order to study the effect of ALA on microcirculation in patients with diabetes mellitus and peripheral neuropathy one group of patients ( 4 female , 4 male , age 60+/-3 years , diabetes duration 19+/-4 years , BMI 24.8+/-1.3 kg/m2 ) received 1200 mg ALA orally per day over 6 weeks ( trial 1 ) . A second group of patients ( 5 female , 4 male , age 65+/-3 years , diabetes duration 14+/-4 years , BMI 23.6+/-0.7 kg/m2 ) was studied before and after they had received 600 mg ALA or placebo intravenously over 15 minutes in order to investigate whether ALA has an acute effect on microcirculation ( trial 2 ) . Patients were investigated by nailfold video-capillaroscopy  . Capillary blood cell velocity was examined at rest and during postreactive hyperemia ( occlusion of the wrist for 2 minutes , 200 mmHg ) which is a parameter of the perfusion reserve on dem and . The oral therapy with ALA result ed in a significant decrease in the time to peak capillary blood cell velocity ( tpCBV ) during postocclusive hyperemia ( trial 1 : 12.6+/-3.1 vs 35.4+/-10.9 s , p<0.05 ) . The infusion of ALA also decreased the tpCBV in patients with diabetic neuropathy ( trial 2 : before : 20.8+/-4,5 , ALA : 11.74+/-4.4 , placebo : 21.9 - 5.0 s , p<0.05 ALA vs both placebo and before infusions ) indicating that ALA has an acute effect on microcirculation . Capillary blood cell velocity at rest ( rCBV ) , hemodynamic parameters , hemoglobinA1c and local skin temperature remained unchanged in both studies . These results demonstrate that in patients with diabetic polyneuropathy  ALA improves microcirculation as indicated by an increased perfusion reserve on dem and . The observed effects are apparently acute effects . With the restriction of the pilot character of this investigation the findings support the assumption that ALA might exert its beneficial effects at least partially by improving microcirculation which is likely to occur also at the level of the vasa nervorum OBJECTIVE —The aim of this trial was to evaluate the effects of α-lipoic acid ( ALA ) on positive sensory symptoms and neuropathic deficits in diabetic patients with distal symmetric polyneuropathy ( DSP ) . RESEARCH DESIGN AND METHODS —In this multicenter , r and omized , double-blind , placebo-controlled trial , 181 diabetic patients in Russia and Israel received once-daily oral doses of 600 mg ( n = 45 ) ( ALA600 ) , 1,200 mg ( n = 47 ) ( ALA1200 ) , and 1,800 mg ( ALA1800 ) of ALA ( n = 46 ) or placebo ( n = 43 ) for 5 weeks after a 1-week placebo run-in period . The primary outcome measure was the change from baseline of the Total Symptom Score ( TSS ) , including stabbing pain , burning pain , paresthesia , and asleep numbness of the feet . Secondary end points included individual symptoms of TSS , Neuropathy Symptoms and Change ( NSC ) score , Neuropathy Impairment Score ( NIS ) , and patients ’ global assessment of efficacy . RESULTS —Mean TSS did not differ significantly at baseline among the treatment groups and on average decreased by 4.9 points ( 51 % ) in ALA600 , 4.5 ( 48 % ) in ALA1200 , and 4.7 ( 52 % ) in ALA1800 compared with 2.9 points ( 32 % ) in the placebo group ( all P < 0.05 vs. placebo ) . The corresponding response rates ( ≥50 % reduction in TSS ) were 62 , 50 , 56 , and 26 % , respectively . Significant improvements favoring all three ALA groups were also noted for stabbing and burning pain , the NSC score , and the patients ’ global assessment of efficacy . The NIS was numerically reduced . Safety analysis showed a dose-dependent increase in nausea , vomiting , and vertigo . CONCLUSIONS —Oral treatment with ALA for 5 weeks improved neuropathic symptoms and deficits in patients with DSP . An oral dose of 600 mg once daily appears to provide the optimum risk-to-benefit ratio Aims To evaluate the efficacy and safety of short‐term oral treatment with the antioxidant thioctic acid ( TA ) on neuropathic symptoms and deficits in patients with Type 2 diabetes mellitus with symptomatic polyneuropathy Anti-oxidant treatment has been shown to prevent nerve dysfunction in experimental diabetes mellitus , thus providing a rationale of potential therapeutic value for diabetic patients . The effects of the anti-oxidant alpha-lipoic acid ( thioctic acid ) were studied in a 3-week multicentre , r and omized , double-blind placebo-controlled trial ( Alpha-Lipoic Acid in Diabetic Neuropathy ; ALADIN ) in 328 non-insulin-dependent diabetic patients with symptomatic peripheral neuropathy who were r and omly assigned to treatment with intravenous infusion of alpha-lipoic acid using three doses ( 1200 , 600 , or 100 mg ALA ) or placebo ( PLAC ) . Neuropathic symptoms ( pain , burning , paraesthesiae , and numbness ) were scored at baseline and at each visit ( days 2 - 5 , 8 - 12 , and 15 - 19 ) prior to infusion . In addition , the Hamburg Pain Adjective List , a multidimensional specific pain question naire , and the Neuropathy Symptom and Disability Scores were assessed at baseline and day 19 . According to the protocol 260 ( 65/63/66/66 ) patients 
    Output:
    
The results of this meta- analysis provide evidence that treatment with ALA ( 300 - 600 mg/day i.v .
for 2 - 4 weeks ) is safe and that the treatment can significantly improve both nerve conduction velocity and positive neuropathic symptoms .