human
***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: Background : Moderate vitamin B-12 deficiency is relatively common in older people . However , there is little robust evidence on the effect of vitamin B-12 supplementation on neurologic and cognitive outcomes in later life . Objective : We investigated whether vitamin B-12 supplementation benefits neurologic and cognitive function in moderately vitamin B-12–deficient older people . Design : We conducted a double-blind , r and omized , placebo-controlled trial in 7 general practice s in South East Engl and , United Kingdom . Study participants were aged ≥75 y and had moderate vitamin B-12 deficiency ( serum vitamin B-12 concentrations : 107–210 pmol/L ) in the absence of anemia and received 1 mg crystalline vitamin B-12 or a matching placebo as a daily oral tablet for 12 mo . Peripheral motor and sensory nerve conduction , central motor conduction , a clinical neurologic examination , and cognitive function were assessed before and after treatment . Results : A total of 201 participants were enrolled in the trial , and 191 subjects provided outcome data . Compared with baseline , allocation to vitamin B-12 was associated with a 177 % increase in serum concentration of vitamin B-12 ( 641 compared with 231 pmol/L ) , a 331 % increase in serum holotranscobalamin ( 240 compared with 56 pmol/L ) , and 17 % lower serum homocysteine ( 14.2 compared with 17.1 μmol/L ) . In intention-to-treat analysis of covariance models , with adjustment for baseline neurologic function , there was no evidence of an effect of supplementation on the primary outcome of the posterior tibial compound muscle action potential amplitude at 12 mo ( mean difference : −0.2 mV ; 95 % CI : –0.8 , 0.3 mV ) . There was also no evidence of an effect on any secondary peripheral nerve or central motor function outcome , or on cognitive function or clinical examination . Conclusion : Results of the trial do not support the hypothesis that the correction of moderate vitamin B-12 deficiency , in the absence of anemia and of neurologic and cognitive signs or symptoms , has beneficial effects on neurologic or cognitive function in later life . This trial was registered at www.is rct n.com as IS RCT N54195799 BACKGROUND Methylation of genomic DNA is dependent on an adequate supply of folate coenzymes . Previous data support the hypothesis that abnormal DNA methylation plays an integral role in carcinogenesis . To date , no studies assessing the effect of inadequate folate status on DNA methylation in older women ( aged > 63 y ) have been reported . OBJECTIVE The effect of moderate folate depletion followed by folate repletion on leukocyte genomic DNA methylation was investigated in elderly women ( aged 60 - 85 y ) to evaluate whether DNA methylation could be used as a functional indicator of folate status . DESIGN Healthy , postmenopausal women ( n = 33 ) consumed a moderately folate-depleted diet ( 118 microg folate/d ) for 7 wk , followed by 7 wk of folate repletion with 200 or 415 microg/d , each provided as 2 different dietary treatments for a total of 4 treatment groups ( n = 30 ) . Leukocyte DNA methylation was determined on the basis of the ability of DNA to incorporate [(3)H]methyl groups from labeled S:-adenosylmethionine in an in vitro assay . RESULTS Incorporation of [(3)H]methyl groups increased significantly ( P : = 0.0025 ) in response to folate depletion , suggesting undermethylation of DNA . No significant changes were detected in [(3)H]methyl incorporation in any group over the 7-wk repletion period compared with postdepletion values . CONCLUSIONS DNA methylation status may be used as a functional indicator of moderately depleted folate status . The slow response to the repletion diets observed suggests that normalization of DNA methylation after moderate folate depletion may be delayed in older women Based on research demonstrating associations between folate , B-12 and B-6 vitamins and cognition and mood , we investigated the effects of short-term supplementation in 211 healthy younger , middle-aged and older women who took either 750 microg of folate , 15 microg of vitamin B-12 , 75 mg of vitamin B-6 or a placebo daily for 35 d. In addition , we examined associations between dietary intake of these vitamins and cognition and mood . Usual dietary intake status was estimated using a retrospective , self-report , quantified food frequency question naire . Participants completed alternate forms of st and ardized tests of cognitive processing re sources , memory , executive function , verbal ability and self-report mood measures before and after supplementation . Supplementation had a significant positive effect on some measures of memory performance only , and no effect on mood . Dietary intake status was associated with speed of processing , recall and recognition and verbal ability The relationship of folate status and polyphenol intake to thiamin status was studied in 80 r and omly selected elderly and young Irish women , with key variables affecting thiamin nutrition controlled for .  Folate , thiamin , and polyphenol intakes  were measured during a 4-wk baseline ( elderly and young ) and 6-wk double-blind ( elderly ) supplementation period . Only elderly subjects were r and omly assigned to placebo , folic acid ( 400 micrograms ) , thiamin ( 10 mg ) , or folic-acid-plus-thiamin groups .  Thiamin status ( TPP effect ) was not affected by folate status ( plasma and erythrocyte folate ) during the baseline period or with folic acid supplementation alone . Polyphenol intake was not correlated with thiamin status . Only thiamin intake and thiamin supplementation significantly affected thiamin status . Because the majority of subjects ( 102 of 160 ) were initially thiamin deficient , enrichment of Irish grain products with thiamin is recommended INTRODUCTION Observational studies have suggested a causal relationship between hyperhomocysteinemia and cardiovascular complications such as stroke and ischemic heart disease . The Homocysteine Lowering Trialists ' Collaboration has shown that daily administration of folic acid can significantly decrease homocysteine levels up to 25 % . Aim of this study was to investigate the effect of daily supplementation of folic acid ( 5 mg ) on IMT after 18 months of treatment in patients with at least one cardiovascular risk factor . METHODS We enrolled 103 patients with at least one cardiovascular risk factor who were r and omized to receive either a daily dose of 5 mg folic acid ( group I , n=53 ) or placebo ( group II , n=50 ) for 18 months . RESULTS After 18 months of folic acid supplementation , homocysteine levels were significantly reduced in the active treatment group compared to a non-significant increase in the placebo group . Folic acid levels were markedly increased in the former group and non-significantly reduced in the latter . Significant regression of carotid IMT was observed ( 0.961+/-0.092 to 0.933+/-0.077 mm , p<0.001 ) compared to significant IMT progression in the placebo group ( 0.964+/-0.099 to 0.984+/-0.094 mm ) . CONCLUSION Folic acid supplementation results in significant IMT reduction after 18 months in patients with at least one cardiovascular risk OBJECTIVE To measure the prevalence of cobalamin ( vitamin B12 ) deficiency in geriatric out patients as documented by both low serum cobalamin levels and elevations of serum methylmalonic acid and homocysteine and to determine the response to cobalamin treatment . DESIGN Prospect i ve study screening elderly subjects for cobalamin deficiency using radiodilution cobalamin assays as well as stable isotope dilution gas chromatography-mass spectrometry methylmalonic acid and homocysteine assays . In patients with serum cobalamin levels < or = 300 pg/mL , the response to cobalamin treatment in the group with levels of methylmalonic acid and /or homocysteine > 3 st and ard deviations ( SD ) above the mean for normals was compared with that of those without such elevations . SETTING Outpatient geriatric clinics at the VA Medical Center and University Health Sciences Center , Denver , CO . PATIENTS One-hundred and fifty-two consecutive out patients , ages 65 to 99 , were screened . Twenty-nine subjects with serum cobalamin levels < or = 300 pg/mL were prospect ively evaluated and treated with cobalamin . MAIN OUTCOME MEASURES Cobalamin , methylmalonic acid , homocysteine , complete blood counts , neurologic examination , and neuropsychological testing . RESULTS The prevalence of cobalamin deficiency as defined by a serum cobalamin level < or = 300 pg/mL and levels of serum methylmalonic acid and /or homocysteine elevated to > 3 SD was 14.5 % of the screened out patients . A similar proportion of patients with low normal serum cobalamin levels ( between 201 and 300 pg/mL ) demonstrated elevated metabolites > 3 SD ( 56 % ) compared with patients with low serum cobalamin levels ( < or = 200 pg/mL ) ( 62 % ) . Cobalamin therapy caused a marked fall or complete correction of the elevated methylmalonic acid and homocysteine levels in each patient who was treated prospect ively . Results for complete blood count , lactate dehydrogenase , bilirubin , baseline neurologic score , and baseline neuropsychologic scores did not differ in the group of patients with elevated metabolites compared with those with normal metabolites . The mean red cell volume fell significantly in the patients with elevated metabolites after 6 months of cobalamin treatment . One patient with elevated metabolites had marked improvement in his neurologic abnormalities after 6 months of cobalamin treatment . CONCLUSION There was a high ( 14.5 % ) prevalence of cobalamin deficiency as demonstrated by elevations in serum methylmalonic acid and homocysteine in addition to low or low normal serum cobalamin levels in elderly out patients . The serum cobalamin level was insensitive for screening since similar numbers of patients with low normal serum cobalamin levels of 201 - 300 pg/mL compared with patients with low cobalamin levels ( < or = 200 pg/mL ) had markedly elevated metabolites which fell with cobalamin treatment . Additional studies will be required to define the full clinical benefit from treatment with Cbl in elderly subjects A clinical trial of the effect of vitamin B12 therapy was conducted in 39 elderly subjects who had been found , in a community screening survey , to have low levels of serum B12 without a macrocytic anaemia or neuropathy . The study produced no evidence which suggests that in such subjects B12 is superior to placebo in effecting an improvement in psychiatric state or general well-being . There was a clear tendency for all the subjects to show an improvement during the trial , but this probably represents the therapeutic effect of involvement in a research exercise of this kind Cognitive impairment is associated with increased blood concentrations of homocysteine and high blood viscosity . Previous studies have shown that vitamin B supplementation reduces homocysteine and enhances cognitive function in patients with mild dementia and low serum folic acid . However , whether folic acid enhances cognitive function in elderly subjects without dementia and normal serum folic acid is unknown . Twenty-four healthy elderly subjects ( age 73.0+/-5.6 years , mean+/-S.D. ) with normal serum folic acid ( 6.3+/-2.4 microg/l ) and Mini Mental State Examination ( MMSE ) > 27/30 were r and omized to 4-week treatment with folic acid 5mg/day or placebo  in a r and omized , placebo-controlled , parallel-group study . Continuous Attention Test ( CAT ) , Four-Choice Reaction Time ( FCRT ) , Digit-Symbol Substitution ( DSS ) , Scanning Memory Sets ( SMS ) , and blood viscosity for different shear rates were measured before and after treatment . Folic acid supplementation induced a significant increase in serum folic acid levels ( + 13.8 versus + 1.6 microg/l , p<0.001 ) and fall in homocysteine levels ( -1.91 versus -0.41 micromol/l , p=0.05 ) compared to placebo . However , there was no significant change in CAT , FCRT , DSS , SMS , and blood viscosity between the two groups . Short-term folic acid supplementation does not enhance psychomotor performance or reduce blood viscosity in healthy elderly subjects with normal serum folic acid levels and preserved cognitive function Background Evidence regarding the effectiveness of oral vitamin B12 in patients with serum vitamin B12 levels between 125 - 200 pM/l is lacking . We compared the effectiveness of one-month oral vitamin B12 supplementation in patients with a subtle vitamin B12 deficiency to that of a placebo . Methods This multicentre ( 13 general practice s , two nursing homes , and one primary care center in western Switzer 
    Output:
    
agent
The effects did not differ by sex or by age group .
Conclusions Evidence on the effects of supplementation of low concentrations of vitamin B12 and folate on haematological parameters in community-dwelling older people is inconclusive .
***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: Background : Moderate vitamin B-12 deficiency is relatively common in older people . However , there is little robust evidence on the effect of vitamin B-12 supplementation on neurologic and cognitive outcomes in later life . Objective : We investigated whether vitamin B-12 supplementation benefits neurologic and cognitive function in moderately vitamin B-12–deficient older people . Design : We conducted a double-blind , r and omized , placebo-controlled trial in 7 general practice s in South East Engl and , United Kingdom . Study participants were aged ≥75 y and had moderate vitamin B-12 deficiency ( serum vitamin B-12 concentrations : 107–210 pmol/L ) in the absence of anemia and received 1 mg crystalline vitamin B-12 or a matching placebo as a daily oral tablet for 12 mo . Peripheral motor and sensory nerve conduction , central motor conduction , a clinical neurologic examination , and cognitive function were assessed before and after treatment . Results : A total of 201 participants were enrolled in the trial , and 191 subjects provided outcome data . Compared with baseline , allocation to vitamin B-12 was associated with a 177 % increase in serum concentration of vitamin B-12 ( 641 compared with 231 pmol/L ) , a 331 % increase in serum holotranscobalamin ( 240 compared with 56 pmol/L ) , and 17 % lower serum homocysteine ( 14.2 compared with 17.1 μmol/L ) . In intention-to-treat analysis of covariance models , with adjustment for baseline neurologic function , there was no evidence of an effect of supplementation on the primary outcome of the posterior tibial compound muscle action potential amplitude at 12 mo ( mean difference : −0.2 mV ; 95 % CI : –0.8 , 0.3 mV ) . There was also no evidence of an effect on any secondary peripheral nerve or central motor function outcome , or on cognitive function or clinical examination . Conclusion : Results of the trial do not support the hypothesis that the correction of moderate vitamin B-12 deficiency , in the absence of anemia and of neurologic and cognitive signs or symptoms , has beneficial effects on neurologic or cognitive function in later life . This trial was registered at www.is rct n.com as IS RCT N54195799 BACKGROUND Methylation of genomic DNA is dependent on an adequate supply of folate coenzymes . Previous data support the hypothesis that abnormal DNA methylation plays an integral role in carcinogenesis . To date , no studies assessing the effect of inadequate folate status on DNA methylation in older women ( aged > 63 y ) have been reported . OBJECTIVE The effect of moderate folate depletion followed by folate repletion on leukocyte genomic DNA methylation was investigated in elderly women ( aged 60 - 85 y ) to evaluate whether DNA methylation could be used as a functional indicator of folate status . DESIGN Healthy , postmenopausal women ( n = 33 ) consumed a moderately folate-depleted diet ( 118 microg folate/d ) for 7 wk , followed by 7 wk of folate repletion with 200 or 415 microg/d , each provided as 2 different dietary treatments for a total of 4 treatment groups ( n = 30 ) . Leukocyte DNA methylation was determined on the basis of the ability of DNA to incorporate [(3)H]methyl groups from labeled S:-adenosylmethionine in an in vitro assay . RESULTS Incorporation of [(3)H]methyl groups increased significantly ( P : = 0.0025 ) in response to folate depletion , suggesting undermethylation of DNA . No significant changes were detected in [(3)H]methyl incorporation in any group over the 7-wk repletion period compared with postdepletion values . CONCLUSIONS DNA methylation status may be used as a functional indicator of moderately depleted folate status . The slow response to the repletion diets observed suggests that normalization of DNA methylation after moderate folate depletion may be delayed in older women Based on research demonstrating associations between folate , B-12 and B-6 vitamins and cognition and mood , we investigated the effects of short-term supplementation in 211 healthy younger , middle-aged and older women who took either 750 microg of folate , 15 microg of vitamin B-12 , 75 mg of vitamin B-6 or a placebo daily for 35 d. In addition , we examined associations between dietary intake of these vitamins and cognition and mood . Usual dietary intake status was estimated using a retrospective , self-report , quantified food frequency question naire . Participants completed alternate forms of st and ardized tests of cognitive processing re sources , memory , executive function , verbal ability and self-report mood measures before and after supplementation . Supplementation had a significant positive effect on some measures of memory performance only , and no effect on mood . Dietary intake status was associated with speed of processing , recall and recognition and verbal ability The relationship of folate status and polyphenol intake to thiamin status was studied in 80 r and omly selected elderly and young Irish women , with key variables affecting thiamin nutrition controlled for .  Folate , thiamin , and polyphenol intakes  were measured during a 4-wk baseline ( elderly and young ) and 6-wk double-blind ( elderly ) supplementation period . Only elderly subjects were r and omly assigned to placebo , folic acid ( 400 micrograms ) , thiamin ( 10 mg ) , or folic-acid-plus-thiamin groups .  Thiamin status ( TPP effect ) was not affected by folate status ( plasma and erythrocyte folate ) during the baseline period or with folic acid supplementation alone . Polyphenol intake was not correlated with thiamin status . Only thiamin intake and thiamin supplementation significantly affected thiamin status . Because the majority of subjects ( 102 of 160 ) were initially thiamin deficient , enrichment of Irish grain products with thiamin is recommended INTRODUCTION Observational studies have suggested a causal relationship between hyperhomocysteinemia and cardiovascular complications such as stroke and ischemic heart disease . The Homocysteine Lowering Trialists ' Collaboration has shown that daily administration of folic acid can significantly decrease homocysteine levels up to 25 % . Aim of this study was to investigate the effect of daily supplementation of folic acid ( 5 mg ) on IMT after 18 months of treatment in patients with at least one cardiovascular risk factor . METHODS We enrolled 103 patients with at least one cardiovascular risk factor who were r and omized to receive either a daily dose of 5 mg folic acid ( group I , n=53 ) or placebo ( group II , n=50 ) for 18 months . RESULTS After 18 months of folic acid supplementation , homocysteine levels were significantly reduced in the active treatment group compared to a non-significant increase in the placebo group . Folic acid levels were markedly increased in the former group and non-significantly reduced in the latter . Significant regression of carotid IMT was observed ( 0.961+/-0.092 to 0.933+/-0.077 mm , p<0.001 ) compared to significant IMT progression in the placebo group ( 0.964+/-0.099 to 0.984+/-0.094 mm ) . CONCLUSION Folic acid supplementation results in significant IMT reduction after 18 months in patients with at least one cardiovascular risk OBJECTIVE To measure the prevalence of cobalamin ( vitamin B12 ) deficiency in geriatric out patients as documented by both low serum cobalamin levels and elevations of serum methylmalonic acid and homocysteine and to determine the response to cobalamin treatment . DESIGN Prospect i ve study screening elderly subjects for cobalamin deficiency using radiodilution cobalamin assays as well as stable isotope dilution gas chromatography-mass spectrometry methylmalonic acid and homocysteine assays . In patients with serum cobalamin levels < or = 300 pg/mL , the response to cobalamin treatment in the group with levels of methylmalonic acid and /or homocysteine > 3 st and ard deviations ( SD ) above the mean for normals was compared with that of those without such elevations . SETTING Outpatient geriatric clinics at the VA Medical Center and University Health Sciences Center , Denver , CO . PATIENTS One-hundred and fifty-two consecutive out patients , ages 65 to 99 , were screened . Twenty-nine subjects with serum cobalamin levels < or = 300 pg/mL were prospect ively evaluated and treated with cobalamin . MAIN OUTCOME MEASURES Cobalamin , methylmalonic acid , homocysteine , complete blood counts , neurologic examination , and neuropsychological testing . RESULTS The prevalence of cobalamin deficiency as defined by a serum cobalamin level < or = 300 pg/mL and levels of serum methylmalonic acid and /or homocysteine elevated to > 3 SD was 14.5 % of the screened out patients . A similar proportion of patients with low normal serum cobalamin levels ( between 201 and 300 pg/mL ) demonstrated elevated metabolites > 3 SD ( 56 % ) compared with patients with low serum cobalamin levels ( < or = 200 pg/mL ) ( 62 % ) . Cobalamin therapy caused a marked fall or complete correction of the elevated methylmalonic acid and homocysteine levels in each patient who was treated prospect ively . Results for complete blood count , lactate dehydrogenase , bilirubin , baseline neurologic score , and baseline neuropsychologic scores did not differ in the group of patients with elevated metabolites compared with those with normal metabolites . The mean red cell volume fell significantly in the patients with elevated metabolites after 6 months of cobalamin treatment . One patient with elevated metabolites had marked improvement in his neurologic abnormalities after 6 months of cobalamin treatment . CONCLUSION There was a high ( 14.5 % ) prevalence of cobalamin deficiency as demonstrated by elevations in serum methylmalonic acid and homocysteine in addition to low or low normal serum cobalamin levels in elderly out patients . The serum cobalamin level was insensitive for screening since similar numbers of patients with low normal serum cobalamin levels of 201 - 300 pg/mL compared with patients with low cobalamin levels ( < or = 200 pg/mL ) had markedly elevated metabolites which fell with cobalamin treatment . Additional studies will be required to define the full clinical benefit from treatment with Cbl in elderly subjects A clinical trial of the effect of vitamin B12 therapy was conducted in 39 elderly subjects who had been found , in a community screening survey , to have low levels of serum B12 without a macrocytic anaemia or neuropathy . The study produced no evidence which suggests that in such subjects B12 is superior to placebo in effecting an improvement in psychiatric state or general well-being . There was a clear tendency for all the subjects to show an improvement during the trial , but this probably represents the therapeutic effect of involvement in a research exercise of this kind Cognitive impairment is associated with increased blood concentrations of homocysteine and high blood viscosity . Previous studies have shown that vitamin B supplementation reduces homocysteine and enhances cognitive function in patients with mild dementia and low serum folic acid . However , whether folic acid enhances cognitive function in elderly subjects without dementia and normal serum folic acid is unknown . Twenty-four healthy elderly subjects ( age 73.0+/-5.6 years , mean+/-S.D. ) with normal serum folic acid ( 6.3+/-2.4 microg/l ) and Mini Mental State Examination ( MMSE ) > 27/30 were r and omized to 4-week treatment with folic acid 5mg/day or placebo  in a r and omized , placebo-controlled , parallel-group study . Continuous Attention Test ( CAT ) , Four-Choice Reaction Time ( FCRT ) , Digit-Symbol Substitution ( DSS ) , Scanning Memory Sets ( SMS ) , and blood viscosity for different shear rates were measured before and after treatment . Folic acid supplementation induced a significant increase in serum folic acid levels ( + 13.8 versus + 1.6 microg/l , p<0.001 ) and fall in homocysteine levels ( -1.91 versus -0.41 micromol/l , p=0.05 ) compared to placebo . However , there was no significant change in CAT , FCRT , DSS , SMS , and blood viscosity between the two groups . Short-term folic acid supplementation does not enhance psychomotor performance or reduce blood viscosity in healthy elderly subjects with normal serum folic acid levels and preserved cognitive function Background Evidence regarding the effectiveness of oral vitamin B12 in patients with serum vitamin B12 levels between 125 - 200 pM/l is lacking . We compared the effectiveness of one-month oral vitamin B12 supplementation in patients with a subtle vitamin B12 deficiency to that of a placebo . Methods This multicentre ( 13 general practice s , two nursing homes , and one primary care center in western Switzer 
    Output:
    