***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: Decreasing the population and activation of inflammatory T helper cells in multiple sclerosis ( MS ) patients using vitamin A derivatives ( retinoic acids ) has been well documented . The present study determined the effect of vitamin A supplementation on psychiatric signs in MS patients . The subjects were 101 relapsing-remitting MS patients enrolled in a placebo-controlled r and omized clinical trial . The treatment group was administered 25000 IU/d retinyl palmitate ( RP ) for 6 months followed by 10000 IU/d RP for another 6 months . The results for baseline characteristics , modified fatigue impact scale and Beck Depression Inventory-II were recorded at the beginning and end of the one-year study . The non-normal distribution data was compared between groups using a nonparametric test and normal distribution data was analyzed using a parametric test . ( Clinical Trials.gov Identifiers : NCT01417273 ) . The results showed significant improvement in the treatment group for fatigue ( p=0.004 ) and depression ( p=0.01 ) . Vitamin A supplementation helped during interferon therapy in the treatment process and improved psychiatric outcomes for anti-inflammatory mechanisms There has been interest in the use of exogenous creatine ( Cr ) as an adjunct treatment for neurological disorders .  Creatine enhances bouts of activity through augmenting phosphocreatine for increased synthesis of ATP ; however , multiple sclerosis ( MS ) individuals suffering from muscle weakness have not been shown to improve muscle work after 5 days of Cr supplementation . This study 's purpose was to determine whether the extended duration would increase muscle capacity . In a double-blind , crossover trial , with a 3-week washout period , eleven MS subjects were r and omly assigned to either Cr ( 5 g 4/day , day 1–7 : 2.5 g 2/day , day 8–14 ) or placebo groups for two 14-day periods . Biodex Dynamometer recorded total work and power over three bouts of 30 maximal knee extensions and flexions . Total work was nonsignificant with Cr for knee extension ( pretest 1277.7 ± 214.9 J vs. posttest = 1313.14 ± 200.5 J ; p = 0.81 ) and flexion ( pretest = 1220.7 ± 200.5 J vs. posttest = 1302.10 J ± 189.64 J ; p = 0.93 ) . Creatine did not enhance muscle power in knee extension ( p = 0.31 ; pretest = 82.1 ± 12.7 W vs. posttest = 87.7 ± 12.6 W ) or flexion ( p = 0.29 ; pretest = 75.3 ± 12.1 W vs. posttest = 81.2 ± 11.1 W ) . Therefore , 14 days of Cr supplementation did not improve muscle capacity or habitual fatigue in MS individuals Background : In the 2-year CLARITY study , cladribine tablets significantly improved clinical and magnetic resonance imaging ( MRI ) outcomes ( vs placebo ) in patients with relapsing – remitting multiple sclerosis ( MS ) . Objective : To assess the safety and efficacy of cladribine treatment in a 2-year Extension study . Methods : In this 2-year Extension study , placebo recipients from CLARITY received cladribine 3.5 mg/kg ; cladribine recipients were re-r and omized 2:1 to cladribine 3.5 mg/kg or placebo , with blind maintained . Results : A total of 806 patients were assigned to treatment . Adverse event rates were generally similar between groups , but lymphopenia Grade ⩾ 3 rates were higher with cladribine than placebo ( Grade 4 lymphopenia occurred infrequently ) . In patients receiving cladribine 3.5 mg/kg in CLARITY and experiencing lymphopenia Grade ⩾ 3 in the Extension , > 90 % of those treated with cladribine 3.5 mg/kg and all treated with placebo in the Extension , recovered to Grade 0–1 by study end . Cladribine treatment in CLARITY produced efficacy improvements that were maintained in patients treated with placebo in the Extension ; in patients treated with cladribine 3.5 mg/kg in CLARITY , approximately 75 % remained relapse-free when given placebo during the Extension . Conclusion : Cladribine tablets treatment for 2 years followed by 2 years ’ placebo treatment produced durable clinical benefits similar to 4 years of cladribine treatment with a low risk of severe lymphopenia or clinical worsening . No clinical improvement in efficacy was apparent following further treatment with cladribine tablets after the initial 2-year treatment period in this trial setting Objective : Our aim was to assess the usefulness of cranberry extract in multiple sclerosis ( MS ) patients suffering from urinary disorders . Methods : In total , 171 adult MS out patients with urinary disorders presenting at eight centers were r and omized ( stratification according to center and use of clean intermittent self-catheterization ) to cranberry versus placebo in a 1-year , prospect i ve , double-blind study that was analyzed using a sequential method on an intent-to-treat basis . An independent monitoring board analyzed the results of the analyses each time 40 patients were assessed on the main endpoint . Cranberry extract ( 36 mg proanthocyanidins per day ) or a matching placebo was taken by participants twice daily for 1 year . The primary endpoint was the time to first symptomatic urinary tract infection ( UTI ) , subject to validation by a validation committee . Results : The second sequential analyses allowed us to accept the null hypothesis ( no difference between cranberry and placebo ) . There was no difference in time to first symptomatic UTI distribution across 1 year , with an estimated hazard ratio of 0.99 , 95 % CI [ 0.61 , 1.60 ] ( p = 0.97 ) . Secondary endpoints and tolerance did not differ between groups . Conclusion : Taking cranberry extract versus placebo twice a day did not prevent UTI occurrence in MS patients with urinary disorders . Trial Registration NCT00280592 Background / objective A Paleolithic diet may improve fatigue and quality of life in progressive multiple sclerosis ( MS ) patients , but past research has evaluated the effects of this dietary intervention in combination with other treatments such as exercise . Thus , the purpose of this pilot study was to evaluate a modified Paleolithic dietary intervention ( MPDI ) in the treatment of fatigue and other symptoms in relapsing-remitting MS ( RRMS ) . Methods We measured the effects of a MPDI in 17 individuals with RRMS . Of 34 subjects r and omly assigned to control ( maintain usual diet ) and intervention ( MPDI ) groups , nine subjects ( one man ) completed the control group and eight subjects ( one man ) completed the MPDI .  Results Significant improvements were seen in Fatigue Severity Scale score and also in Multiple Sclerosis Quality of Life-54 and time to complete ( dominant h and ) 9-Hole Peg Test from baseline in MPDI subjects compared to controls . Increased vitamin K serum levels were also observed in MPDI subjects post protocol compared to controls . Conclusion A Paleolithic diet may be useful in the treatment and management of MS , by reducing perceived fatigue , increasing mental and physical quality of life , increasing exercise capacity , and improving h and and leg function . By increasing vitamin K serum levels , the MPDI may also reduce inflammation Vitamin A derivatives such as retinoic acid may improve the impaired balance of CD4 + T cells in autoimmune and inflammatory diseases . This study is a double-blind r and omized trial to evaluate the effect of vitamin A ( as form of retinyl palmitate ) supplementation on multiple sclerosis ( MS ) patients . Thirty-nine patients were enrolled and r and omly assigned to two groups . Both groups were followed for 6 months . The experimental group received 25,000 IU of retinyl palmitate daily , while the control group received a placebo . Before and after the study , the expression of interferon gamma ( IFN-γ ) and T-bet genes was evaluated in peripheral blood mononuclear cells of patients by RT-PCR . The results showed that after 6 months of supplementation , expression of IFN-γ and T-bet was significantly decreased . These data suggest that retinyl palmitate supplementation can modulate the impaired balance of Th1 and Th2 cells and vitamin A products that may be involved in the therapeutic mechanism of vitamin A in MS patients . This study provides information regarding the decreased gene expression of IFN-γ and T-bet in MS by retinyl palmitate supplementation Treatment with acetyl L-carnitine ( ALCAR ) has been shown to improve fatigue in patients with chronic fatigue syndrome , but there have been no trials on the effect of ALCAR for treating fatigue in multiple sclerosis ( MS ) . To compare the efficacy of ALCAR with that of amantadine , one of the drugs most widely used to treat MS-related fatigue , 36 MS patients presenting fatigue were enrolled in a r and omised , double-blind , crossover study . Patients were treated for 3 months with either amantadine ( 100 mg twice daily ) or ALCAR ( 1 g twice daily ) . After a 3-month washout period , they crossed over to the alternative treatment for 3 months . Patients were rated at baseline and every 3 months according to the Fatigue Severity Scale ( FSS ) , the primary endpoint of the study . Secondary outcome variables were : Fatigue Impact Scale ( FIS ) , Beck Depression Inventory ( BDI ) and Social Experience Checklist ( SEC ) .  Six patients withdrew from the study because of adverse reactions ( five on amantadine and one on ALCAR )  . Statistical analysis showed significant effects of ALCAR compared with amantadine for the Fatigue Severity Scale ( p = 0.039 ) . There were no significant effects for any of the secondary outcome variables . The results of this study show that ALCAR is better tolerated and more effective than amantadine for the treatment of MS-related fatigue 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 determine whether combination therapy with lofepramine , L-phenylalanine , and intramuscular vitamin B-12 ( the “ Cari Loder regime ” ) reduces disability in patients with multiple sclerosis . Methods : A placebo controlled , double blind , r and omised study carried out in five United Kingdom centres on out patients with clinical ly definite multiple sclerosis , measurable disability on Guy 's neurological disability scale ( GNDS ) , no relapse in the preceding six months , and not on antidepressant drugs . Over 24 weeks all patients received vitamin B-12 , 1 mg intramuscularly weekly , and either lofepramine 70 mg and L-phenylalanine 500 mg twice daily , or matching placebo tablets . Outcome was assessed using the GNDS , the Kurtzke exp and ed disability status scale ; the Beck depression inventory , the Chalder fatigue scale , and the Gulick MS specific symptom scale . Results : 138 patients were entered , and two were lost from each group . There was no statistically significant difference between the groups at entry or at follow up . Analysis of covariance suggested that treated patients had better outcomes on four of the five scales used . Both groups showed a reduction of 2 GNDS points within the first two weeks , and when data from all time points were considered , the treated group had a significant improvement of 0.6 GNDS points from two weeks onwards . Conclusions : Patients with multiple sclerosis improved by 2 GNDS points 
    Output:
    
PUFA administration may not differ when compared to alternatives with regards to relapse rate , disability worsening , or overall clinical status in people with MS , but evidence is uncertain .
Similarly , at present , there is insufficient evidence to determine whether supplementation with antioxidants or other dietary interventions have any impact on MS-related outcomes