***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: Multiple sclerosis ( MS ) presents with optic neuritis ( ON ) in 20 % of cases and 50 % of ON patients develop MS within 15 years . In this study , we evaluated the preventive effects of vitamin D3 administration on the conversion of ON to MS ( primary outcome ) and on the MRI lesions ( secondary outcome ) of ON patients with low serum 25 ( OH ) D levels . Thirty ON patients ( 15 in each of 2 groups , aged 20–40 years ) with serum 25 ( OH ) D levels of less than 30 ng/ml were enrolled in a double blind , r and omized , parallel-group trial . The treatment group ( cases ) received 50,000 IU of vitamin D3 weekly for 12 months and the control group ( controls ) received a placebo weekly for 12 months . Finally , the subsequent relapse rate and changes in MRI plaques were compared between the two groups . Risk reduction was 68.4 % for the primary outcome in the treatment group ( relative risk = 0.316 , p = 0.007 ) . After 12 months , patients in the treatment group had a significantly lower incidence rate of cortical , juxtacortical , corpus callosal , new T2 , new gadolinium-enhancing lesions and black holes . The mean number of total plaques showed a marginally significant decrease in the group receiving vitamin D3 supplementation as compared with the placebo group ( p = 0.092 ) . Administration of vitamin D3 supplements to ON patients with low serum vitamin 25 ( OH ) D levels may delay the onset of a second clinical attack and the subsequent conversion to MS Background Flu-like symptoms ( FLS ) are common side effects of interferon beta ( IFN-β ) treatment in patients with Multiple Sclerosis ( PwMS ) and are associated with post-injection cytokine surge . We hypothesized that vitamin D3 supplementation would ameliorate FLS by decreasing related serum cytokines ’ levels . Methods In a r and omized , double blind study of 45 IFNβ-treated PwMS , 21 patients were assigned to  800 IU of vitamin D3 per day ( low dose ) , while 24 patients received 4,370 IU per day ( high dose ) for one year . FLS were assessed monthly by telephonic interviews . Serum levels of 25-hydroxy-D ( 25-OH-D ) , calcium , PTH , IL-17 , IL-10 and IFN-γ were measured periodically . EDSS , relapses , adverse events and quality of life ( QoL ) were documented . Results 25-OH-D levels increased to a significantly higher levels and PTH levels decreased in the high dose group . There was no significant change in FLS . IL-17 levels were significantly increased in the low dose group , while patients receiving high dose vitamin D had a heterogeneous IL-17 response . No significant differences in relapse rate , EDSS , QoL , serum IL-10 and IFNγ were found . Hypercalcemia or other potential major adverse events were not observed . Conclusion Vitamin D supplementation to IFN−β treated PwMS , at the doses used , seems safe and associated with dose-dependent changes in IL-17 serum levels , while not affecting IFN−β related FLS.Trial registration Clinical Trials.gov ID : Context : Fatigue is one of the most common and disabling symptoms of multiple sclerosis ( MS ) ; however , there is no medication that has been approved specifically to treat MS-related fatigue . Objective : We aim ed to evaluate the effect of vitamin D analogue , Alfacalcidol , on MS-related fatigue . Design , setting s , participants : This was a r and omized , double-blind , parallel group , placebo-controlled trial in patients with clinical ly definite MS by McDonald criteria conducted in a single university-affiliated medical center in Israel . R and omly selected patients from the Sheba MS Registry computerized data base ( N=600 ) were assessed using the self-report Fatigue Severity Scale ( FSS ) . Patients with clinical ly meaningful fatigue ( N=259 ) were further assessed for trial eligibility , and MS patients with significant fatigue ( N=158 ; 61 % , 118 females , mean age 41.1 ± 9.2 years and mean disease duration of 6.2 ± 5.5 years ) were included in the study and r and omized to receive treatment or placebo . Intervention : Alfacalcidol ( 1 mcg/d , N=80 ) or placebo ( N=78 ) was administered for six consecutive months . Main outcome measure : The primary endpoint of the study was the change between Alfacalcidol and placebo-treated patients in the Fatigue Impact Scale ( FIS ) score ; the cut-off point for improvement was defined as 30 % decrease . All analyses followed the intention-to-treat principle and were performed for all participants based on the group they were r and omly allocated regardless of whether or not they dropped out . Results : Alfacalcidol decreased the mean relative FIS score as compared with placebo ( –41.6 % vs. –27.4 % , p=0.007 , respectively ) . This advantage was further emphasized when the modified FIS ( MFIS ) relative change was calculated . Quality of Life ( QoL ) improved in Alfacalcidol-treated patients as compared with placebo in the RAYS psychological ( p=0.033 ) and social ( p=0.043 ) sub-scales . The Alfacalcidol-treated group had reduced number of relapses ( p=0.006 ) and higher proportion of relapse-free patients ( p=0.007 ) . Reduction of relapses  by Alfacalcidol became significant at 4 months of treatment , was sustained at 6 months and decayed 2 months after drug discontinuation . Alfacalcidol treatment was safe and no serious adverse events were recorded . Conclusion : Alfacalcidol is a safe and effective treatment strategy to decrease fatigue and improve QoL in patients with MS In all species tested , except humans , biological differences between vitamins D2 and D3 are accepted as fact . To test the presumption of equivalence in humans , we compared the ability of equal molar quantities of vitamin D2 or D3 to increase serum 25-hydroxyvitamin D [ 25(OH)D ] , the measure of vitamin D nutrition .  Subjects took 260 nmol ( approximately 4000 IU ) vitamin D2  ( n=17 ) or vitamin D3  ( n=55 ) daily for 14 d. 25(OH)D was assayed with a method that detects both the vitamin D2 and D3 forms . With vitamin D3 , mean ( + /-SD ) serum 25(OH)D increased from 41.3+/-17.7 nmol/L before to 64.6+/-17.2 nmol/L after treatment . With vitamin D2 , the 25(OH)D concentration went from 43.7+/-17.7 nmol/L before to 57.4+/-13.0 nmol/L after . The increase in 25(OH)D with vitamin D3  was 23.3+/-15.7 nmol/L , or 1.7 times the increase obtained with vitamin D2 ( 13.7+/-11.4 nmol/L ; P=0.03 ) . There was an inverse relation between the increase in 25(OH)D and the initial 25(OH)D concentration . The lowest 2 tertiles for basal 25(OH)D showed larger increases in 25(OH)D : 30.6 and 25.5 nmol/L , respectively , for the first and second tertiles . In the highest tertile [ 25(OH)D > 49 nmol/L ] the mean increase in 25(OH)D was 13.3 nmol/L ( P < 0.03 for comparison with each lower tertile ) . Although the 1.7-times greater efficacy for vitamin D3 shown here may seem small , it is more than what others have shown for 25(OH)D increases when comparing 2-fold differences in vitamin D3 dose . The assumption that vitamins D2 and D3 have equal nutritional value is probably wrong and should be reconsidered CONTEXT Epidemiological and experimental evidence suggests that high levels of vitamin D , a potent immunomodulator , may decrease the risk of  multiple sclerosis .  There are no prospect i ve studies addressing this hypothesis . OBJECTIVE To examine whether levels of 25-hydroxyvitamin D  are associated with risk of multiple sclerosis . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve , nested case-control study among more than 7 million US military personnel who have serum sample s stored in the Department of Defense Serum Repository . Multiple sclerosis cases were identified through Army and Navy physical disability data bases for 1992 through 2004 , and diagnoses were confirmed by medical record review . Each case ( n = 257 ) was matched to 2 controls by age , sex , race/ethnicity , and date s of blood collection . Vitamin D status was estimated by averaging 25-hydroxyvitamin D levels of 2 or more serum sample s collected before the date of initial multiple sclerosis symptoms . MAIN OUTCOME MEASURES Odds ratios of multiple sclerosis associated with continuous or categorical levels ( quantiles or a priori-defined categories ) of serum 25-hydroxyvitamin D within each racial/ethnic group . RESULTS Among whites ( 148 cases , 296 controls ) , the risk of multiple sclerosis significantly decreased with increasing levels of 25-hydroxyvitamin D ( odds ratio [ OR ] for a 50-nmol/L increase in 25-hydroxyvitamin D , 0.59 ; 95 % confidence interval , 0.36 - 0.97 ) . In categorical analyses using the lowest quintile ( < 63.3 nmol/L ) as the reference , the ORs for each subsequent quintile were 0.57 , 0.57 , 0.74 , and 0.38 ( P = .02 for trend across quintiles ) . Only the OR for the highest quintile , corresponding to 25-hydroxyvitamin D levels higher than 99.1 nmol/L , was significantly different from 1.00 ( OR , 0.38 ; 95 % confidence interval , 0.19 - 0.75 ; P = .006 ) . The inverse relation with multiple sclerosis risk was particularly strong for 25-hydroxyvitamin D levels measured before age 20 years . Among blacks and Hispanics ( 109 cases , 218 controls ) , who had lower 25-hydroxyvitamin D levels than whites , no significant associations between vitamin D and multiple sclerosis risk were found . CONCLUSION The results of our study suggest that high circulating levels of vitamin D are associated with a lower risk of multiple sclerosis OBJECTIVE Vegetarians and vegans exclude certain food sources of vitamin D from their diet , but it is not clear to what extent this affects plasma concentrations of 25-hydroxyvitamin D ( 25(OH)D ) . The objective was to investigate differences in vitamin D intake and plasma concentrations of 25(OH)D among meat eaters , fish eaters , vegetarians and vegans . DESIGN A cross-sectional analysis . SETTING United Kingdom . SUBJECTS Plasma 25(OH)D concentrations were measured in 2107 white men and women ( 1388 meat eaters , 210 fish eaters , 420 vegetarians and eighty-nine vegans ) aged 20 - 76 years from the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-Oxford cohort . RESULTS Plasma 25(OH)D concentrations reflected the degree of animal product exclusion and , hence , dietary intake of vitamin D ; meat eaters had the highest mean intake of vitamin D ( 3·1 ( 95 % CI 3·0 , 3·2 ) μg/d ) and mean plasma 25(OH)D concentrations ( 77·0 ( 95 % CI 75·4 , 78·8 ) nmol/l ) and vegans the lowest ( 0·7 ( 95 % CI 0·6 , 0·8 ) μg/d and 55·8 ( 95 % CI 51·0 , 61·0 ) nmol/l , respectively ) . The magnitude of difference in 25(OH)D concentrations between meat eaters and vegans was smaller ( 20 % ) among those participants who had a blood sample collected during the summer months ( July-September ) compared with the winter months ( 38 % ; January-March ) . The prevalence of low plasma concentrations of 25(OH)D ( < 25 nmol/l ) during the winter and spring ranged from < 1 % to 8 % across the diet groups . CONCLUSIONS Plasma 25(OH)D concentrations were lower in vegetarians and vegans than in meat and fish eaters ; diet is an important determinant of plasma 25(OH)D in this British population Early studies had suggested that vitamin D intake was inversely associated with neurodegenerative diseases , such as Alzheimer ’s disease and multiple sclerosis . However , the associations of vitamin D intake and outdoor activities with Parkinson ’s disease ( PD ) are still unclear , so this study is to evaluate these relationships from a case-control study in elderly Chinese . The study population involved 209 cases with new onsets of PD and 210 controls without neurodegenerative diseases . The data on  dietary vitamin D and outdoor activities  were collected using a food-frequency question naire and self-report question naire . Multivariable 
    Output:
    
Results indicate there is insufficient evidence to comprehensively reflect on a potential neuroprotective role for vitamin D and if this was dependent on route of administration .
Solid evidence is lacking to support the current hypothesis that the beneficial effect of UV exposure results from the synthesis of vitamin D. Sun exposure , independent of vitamin D production , may be protective against multiple Sclerosis , Parkinson 's disease and Alzheimer 's disease .
It is unclear if vitamin D mediates a protective benefit in neurodegenerative disease or whether it is an associative marker of UV exposure , which may contribute to as of yet unidentified neuroprotective factors