***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: IMPORTANCE Although vitamin E and memantine have been shown to have beneficial effects in moderately severe Alzheimer disease ( AD ) , evidence is limited in mild to moderate AD . OBJECTIVE To determine if vitamin E ( alpha tocopherol ) , memantine , or both slow progression of mild to moderate AD in patients taking an acetylcholinesterase inhibitor . DESIGN , SETTING , AND PARTICIPANTS Double-blind , placebo-controlled , parallel-group , r and omized clinical trial involving 613 patients with mild to moderate AD initiated in August 2007 and concluded in September 2012 at 14 Veterans Affairs medical centers . INTERVENTIONS Participants received either 2000 IU/d of alpha tocopherol ( n = 152 ) , 20 mg/d of memantine ( n = 155 ) , the combination ( n = 154 ) , or placebo ( n = 152 ) . MAIN OUTCOMES AND MEASURES Alzheimer 's Disease Cooperative Study /Activities of Daily Living ( ADCS-ADL ) Inventory score ( range , 0 - 78 ) . Secondary outcomes included cognitive , neuropsychiatric , functional , and caregiver measures .  RESULTS Data from 561 participants were analyzed ( alpha tocopherol = 140 , memantine = 142 , combination = 139 , placebo = 140 ) , with 52 excluded because of a lack of any follow-up data . Over the mean ( SD ) follow-up of 2.27 ( 1.22 ) years , ADCS-ADL Inventory scores declined by 3.15 units ( 95 % CI , 0.92 to 5.39 ; adjusted P = .03 ) less in the alpha tocopherol group compared with the placebo group . In the memantine group , these scores declined 1.98 units less ( 95 % CI , -0.24 to 4.20 ; adjusted P = .40 ) than the placebo group 's decline . This change in the alpha tocopherol group translates into a delay in clinical progression of 19 % per year compared with placebo or a delay of approximately 6.2 months over the follow-up period . Caregiver time increased least in the alpha tocopherol group . All-cause mortality and safety analyses showed a difference only on the serious adverse event of " infections or infestations , " with greater frequencies in the memantine ( 31 events in 23 participants ) and combination groups ( 44 events in 31 participants ) compared with placebo ( 13 events in 11 participants ) . CONCLUSIONS AND RELEVANCE Among patients with mild to moderate AD , 2000 IU/d of alpha tocopherol compared with placebo result ed in slower functional decline . There were no significant differences in the groups receiving memantine alone or memantine plus alpha tocopherol . These findings suggest benefit of alpha tocopherol in mild to moderate AD by slowing functional decline and decreasing caregiver burden . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00235716 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 Background : Antioxidant nutrients may reduce the risk of MS . In a recent case-control study , vitamin C intake was significantly inversely associated with  MS risk among women . However , no prospect i ve data are available . Objective : To examine prospect ively the associations of intakes of carotenoids , vitamin C , and vitamin E with the  risk of MS among women . Methods : The authors documented the occurrence of definite and probable MS within two large cohorts of women who completed detailed and vali date d semiquantitative food frequency question naires . One cohort ( Nurses ’ Health Study ) comprised 81,683 women aged 38 to 63 years in 1984 , who were followed for 12 years ; the other ( Nurses ’ Health Study II ) comprised 95,056 women aged 27 to 44 years in 1991 , who were followed for 6 years . Results : The authors documented a total of 214 cases of MS . After adjustments for age , latitude of birthplace , pack-years of smoking , and total energy intake , the pooled multivariate relative risks ( 95 % CIs ) comparing women in the highest quintile with those in the lowest quintile were 1.1 ( 0.7 to 1.7 ) for α-carotene , 1.1 ( 0.7 to 1.6 ) for β-carotene , 1.4 ( 0.8 to 2.2 ) for β-cryptoxanthin , 1.0 ( 0.6 to 1.5 ) for lycopene , 1.0 ( 0.7 to 1.6 ) for lutein/zeaxanthin , 1.4 ( 0.9 to 2.1 ) for total vitamin C , 1.3 ( 0.9 to 2.0 ) for dietary vitamin C , 0.8 ( 0.6 to 1.3 ) for total vitamin E , and 0.9 ( 0.6 to 1.4 ) for dietary vitamin E. The authors found no associations between intakes of fruits and vegetables and risk of MS . Use of vitamin C , vitamin E , and multivitamin supplements was also unrelated to risk of MS . Conclusions : These findings do not support hypotheses relating higher intakes of dietary carotenoids , vitamin C , and vitamin E to reduced risk of MS in women 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 Background Vitamin A has different functions in the body and after being converted to acid form ; it can play many roles in immune system regulation . Therefore , this vitamin can be used as a supplement in the treatment of diseases , such as cancer and autoimmune diseases . Vitamin A is a fat-soluble compound and its long-term consumption in high doses can have some adverse effects . Objective The current study aim ed to investigate the possible complications and find solutions to minimize the adverse effects . Patients and Methods This study was a double blind r and omized clinical trial . In the main study , vitamin A ( as retinyl palmitate ) was given to 35 multiple sclerosis ( MS ) patients in order to regulate their immune system with a dose of 25000 IU/day for a period of six months . To investigate the possible biochemical complications , lipid profiles , fasting blood sugar ( FBS ) , liver enzymes , and C-reactive protein ( CRP ) were tested . Results Vitamin A did not have a significant difference in lipid profiles , FBS and liver enzymes between the two groups receiving vitamin A and the placebo , but CRP increased in patients who were taking vitamin A , 1.65±0.43 ( mg/L ) and 2.88±0.67 , ( Mean±SEM ) , before and after the intervention respectively ( P=0.029 ) , and statistical analysis showed significant differences with the group receiving placebo ( P=0.011 ) and CRP level  in vitamin A group was 1.3 mg/L more than those of the placebo group after intervention ( P=0.011 ) . Conclusions Considering that no significant difference was found in the proven vitamin A side effects , due to the increase in CRP , frequent clinical and biochemical controls are required along with vitamin A supplementation Objective To assess whether three novel interventions , formulated based on a systems medicine therapeutic concept , reduced disease activity in patients with relapsing – remitting multiple sclerosis ( MS ) who were either treated or not with disease-modifying treatment . Design A 30-month r and omised , double-blind , placebo-controlled , parallel design , phase II proof-of-concept clinical study . Setting s Cyprus Institute of Neurology and Genetics . Participants 80 participants were r and omised into four groups of 20 each . A total of 41 ( 51 % ) patients completed the 30-month trial . The eligibility criteria were an age of 18–65 ; a diagnosis of relapsing – remitting MS according to the McDonald criteria ; a score of 0.0–5.5 on the Exp and ed Disability Status Scale ( EDSS ) ; MRI showing lesions consistent with MS ; at least one documented clinical relapse and either receiving or not a disease-modifying treatment within the 24-month period before enrolment in the study . Patients were excluded because of a recent ( < 30 days ) relapse , prior immunosuppressant or monoclonal antibody therapy , pregnancy or nursing , other severe disease compromising organ function , progressive MS , history of recent drug or alcohol abuse , use of any additional food supplements , vitamins or any form of polyunsaturated fatty acids , and a history of severe allergic or anaphylactic reactions or known specific nutritional hypersensitivity . Interventions The first intervention ( A ) was composed of Ω-3 and Ω-6 polyunsaturated fatty acids at 1:1 wt/wt . Specifically , the Ω-3 fatty acids were docosahexaenoic acid and eicosapentaenoic acid at 3:1 wt/wt , and the Ω-6 fatty acids were linoleic acid and γ-linolenic acid at 2:1 wt/wt . This intervention also included minor quantities of other specific polyunsaturated , monounsaturated and saturated fatty acids as well as vitamin A and vitamin E ( α-tocopherol ) . The second intervention ( B , PLP10 ) was a combination of A and γ-tocopherol . The third intervention ( C ) was γ-tocopherol alone . The fourth group of 20 
    Output:
    
The strongest evidence to support  OTC anti-oxidants  was for compounds EGCG and ALA in animal models ; both consistently showed anti-inflammatory/anti-oxidant effects and reduced neurological impairment .
Only vitamin E , Ginkgo biloba and ALA were examined for efficacy in pilot clinical trials with either conflicting evidence or evidence of no benefit .
Conclusion : OTC anti-oxidants EGCG and ALA show the most consistent benefit , however only in pre clinical studies .
There is no evidence that they alter MS relapses or progression .