Dietary folate and vitamin B12 intake and cognitive decline among community-dwelling older persons. Impact of personalized diet and probiotic supplementation on inflammation, nutritional parameters and intestinal microbiota - The "RISTOMED project": Randomized controlled trial in healthy older people. Among vitamin B12 deficient older people, high folate levels are associated with worse cognitive function: combined data from three cohorts. Differences in vitamin D3 dosing regimens in a geriatric community-dwelling population. A randomized, double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations. Homocysteine versus the vitamins folate, B6, and B12 as predictors of cognitive function and decline in older high-functioning adults: MacArthur Studies of Successful Aging. Homocysteine-lowering vitamins do not lower plasma S-adenosylhomocysteine in older people with elevated homocysteine concentrations. A randomized placebo controlled trial of vitamin B12 supplementation to prevent cognitive decline in older diabetic people with borderline low serum vitamin B12. Studies on the effect of folic acid supplement on folate and vitamin B12 status in children. Dietary factors and depression in older people. Serum Vitamin B12, C and Folate Concentrations in the New Mexico Elder Health Survey: Correlations with Cognitive and Affective Functions Rationale and design of the B-PROOF study, a randomized controlled trial on the effect of supplemental intake of vitamin B12 and folic acid on fracture incidence Iron, folate and vitamin B12 status of an elderly South African population Randomized multicenter investigation of folate plus vitamin B12 supplementation in schizophrenia. Effect of Micronutrient Supplementation on Mood in Nursing Home Residents Anemia in older persons: etiology and evaluation. Oral vitamin B12 supplementation reduces plasma total homocysteine concentration in women in India. Vitamins B12, B6, and folic acid for cognition in older men Effect of Vitamin B12 and Folic Acid Supplementation on Bone Mineral Density and Quantitative Ultrasound Parameters in Older People with an Elevated Plasma Homocysteine Level: B-PROOF, a Randomized Controlled Trial Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial. B vitamin supplementation improves cognitive function in the middle aged and elderly with hyperhomocysteinemia Memory improvements in elderly women following 16 weeks treatment with a combined multivitamin, mineral and herbal supplement A cost-utility analysis of multivitamin and multimineral supplements in men and women aged 65 years and over.
BACKGROUND Deficiencies in folate and vitamin B12 have been associated with neurodegenerative disease . OBJECTIVE To examine the association between rates of age-related cognitive change and dietary intakes of folate and vitamin B12 . DESIGN Prospect i ve study performed from 1993 to 2002 . SETTING Geographically defined biracial community in Chicago , Ill. PARTICIPANTS A total of 3718 residents , 65 years and older , who completed 2 to 3 cognitive assessment s and a food frequency question naire .  MAIN OUTCOME MEASURE Change in cognitive function measured at baseline and 3-year and 6-year follow-ups , using the average z score of 4 tests : the East Boston Tests of immediate and delayed recall , the Mini-Mental State Examination , and the Symbol Digit Modalities Test . RESULTS High folate intake was associated with a faster rate of cognitive decline in mixed models adjusted for multiple risk factors . The rate of cognitive decline among persons in the top fifth of total folate intake ( median , 742 microg/d ) was more than twice that of those in the lowest fifth of intake ( median , 186 microg/d ) , a statistically significant difference of 0.02 st and ardized unit per year ( P = .002 ) . A faster rate of cognitive decline was also associated with high folate intake from food ( P for trend = .04 ) and with folate vitamin supplementation of more than 400 microg/d compared with nonusers ( beta = -.03 , P<.001 ) . High total B12 intake was associated with slower cognitive decline only among the oldest participants . CONCLUSIONS High intake of folate may be associated with  cognitive decline in older persons . These unexpected findings call for further study of the cognitive implication s of high levels of dietary folate in older population OBJECTIVES To assess the impact of a personalized diet , with or without addition of VSL#3 preparation , on biomarkers of inflammation , nutrition , oxidative stress and intestinal microbiota in 62 healthy persons aged 65 - 85 years . DESIGN Open label , r and omized , multicenter study . PRIMARY ENDPOINT High-sensitivity C-reactive protein . SETTING Community . INTERVENTIONS Eight week web-based dietary advice ( RISTOMED platform ) alone or with supplementation of VSL#3 ( 2 capsules per day ) . The RISTOMED diet was optimized to reduce inflammation and oxidative stress . MEASUREMENTS Blood and stool sample s were collected on days 1 and 56 . RESULTS Diet alone reduced ESR ( p = 0.02 ) , plasma levels of cholesterol ( p < 0.01 ) and glucose ( p = 0.03 ) . Addition of VSL#3  reduced ESR ( p = 0.05 ) and improved folate ( p = 0.007 ) , vitamin B12 ( p = 0.001 ) and homocysteine ( p < 0.001 ) plasma levels . Neither intervention demonstrated any further effects on inflammation . Subgroup analysis showed 40 participants without signs of low- grade inflammation ( hsCRP<3 mg/l , subgroup 1 ) and 21 participants with low- grade inflammation at baseline ( hsCRP≥3 mg/l , subgroup 2 ) . In subgroup 2 addition of VSL#3  increased bifidobacteria ( p = 0.005 ) in more participants and improved both folate ( p = 0.015 ) and vitamin B12 ( p = 0.035 ) levels compared with subgroup 1 . The increases were positively correlated to the change in the bifidobacteria concentration for folate ( p = 0.023 ) and vitamin B12 ( p = 0.001 ) . As expected change in homocysteine correlated negatively to change in folate ( r = -0.629 , p = 0.002 ) and vitamin B12 ( r = -0.482 , p = 0.026 ) . CONCLUSIONS Addition of VSL#3  increased bifidobacteria and supported adequate folate and vitamin B12 concentrations in subjects with low- grade inflammation . Decrease in homocysteine with VSL#3 was clinical ly relevant . suggesting protective potentials for aging-associated conditions , e.g. cardiovascular or neurological diseases . Clinical Trials.gov : NCT01069445-NCT01179789 BACKGROUND Folate fortification of food aims to reduce the number of babies born with neural tube defects , but has been associated with cognitive impairment when vitamin B12 levels are deficient . Given the prevalence of low vitamin B12 levels among the elderly , and the global deployment of food fortification programs , investigation of the associations between cognitive impairment , vitamin B12 , and folate are needed . OBJECTIVE To investigate the associations of serum vitamin B12 , red cell folate , and cognitive impairment . METHODS Data were collected on 1,354 subjects in two studies investigating cognitive impairment , and from patients attending for assessment or management of memory problems in the Barwon region of south eastern Australia between 2001 and 2011 . Eligible subjects who had blood measurements of vitamin B12 and red cell folate taken within six months of cognitive testing were included . Subjects with stroke or neurodegenerative diseases other than Alzheimer 's disease were excluded . A Mini-Mental State Examination score of < 24 was used to define impaired cognitive function . RESULTS Participants with low serum vitamin B12 ( < 250 pmol/L ) and high red cell folate ( > 1,594 nmol/L ) levels were more likely to have impaired cognitive performance ( adjusted odds ratio ( AOR ) 3.45 , 95 % confidence interval ( CI ) : 1.60 - 7.43 , p = 0.002 ) when compared to participants with biochemical measurements that were within the normal ranges . Participants with high folate levels , but normal serum vitamin B12 , were also more likely to have impaired cognitive performance ( AOR 1.74 , 95 % CI : 1.03 - 2.95 , p = 0.04 ) . CONCLUSIONS High folate or folic acid supplements may be detrimental to cognition in older people with low vitamin B12 levels . This topic is of global significance due to the wide distribution of food fortification programs , so prospect i ve studies should be a high priority OBJECTIVE The adequate dose of vitamin D supplementation for community-dwelling elderly people has not been thoroughly investigated . This study aims to determine the efficacy of a low-dose and a higher dose of vitamin D3 in maintaining 25-hydroxyvitamin D [ 25(OH)D ] levels at or above 30 ng/mL. METHODS This was a single site , double-blind , r and omized exploratory clinical trial that enrolled adults 65 years of age and older . Within strata of baseline 25(OH)D levels ( < 30 versus ≥ 30 ng/mL ) subjects were r and omized in a 1:2 ratio to receive either 400 or 2,000 IU vitamin D3 daily for 6 months . The main outcome measures were changes in serum 25(OH)D levels according to baseline 25(OH)D levels and dose of vitamin D3 . RESULTS At baseline , 41 of 105 participants ( 39 % ) had low 25(OH)D levels ( < 30 ng/mL ) . After 6 months of vitamin D3 supplementation , 21 of 32 participants ( 66 % ) receiving 400 IU and 14 of 59 participants ( 24 % ) receiving 2,000 IU of vitamin D3 still had low 25(OH)D levels . The largest increases in serum 25(OH)D levels were observed in subjects with baseline levels < 30 ng/mL who received 2,000 IU of vitamin D daily . CONCLUSION Regardless of baseline 25(OH)D level , in persons 65 years of age and older , 6-month vitamin D3 supplementation with 400 IU daily result ed in low 25(OH)D in most individuals , while 2,000 IU daily maintained 25(OH)D levels within an acceptable range in most people on this regimen OBJECTIVES To determine the effect of small doses of oral cyanocobalamin supplements in older patients with low or borderline serum vitamin B12 concentrations but no other evidence of pernicious anemia ( PA ) . DESIGN R and omized , double-blind , placebo-controlled study assessing the efficacy of oral cyanocobalamin 10 microg and 50 microg daily for 1 month . SETTING Two geriatric hospitals in the North Western Health Care Network , Melbourne , Australia . PARTICIPANTS Thirty-one in patients with serum vitamin B12 levels between 100 and 150 pmol/L , without PA , other malabsorption disorders , or progressive neurological or terminal illness . The mean age was 81.4 years . INTERVENTION After informed consent , a medical and drug history was taken and the Mini-Mental State Examination ( MMSE ) completed . A dietitian made assessment of oral cobalamin intake . Blood was taken for serum vitamin B12 , serum and red cell folate assay , full blood examination , fasting serum gastrin , parietal and intrinsic factor antibodies , fasting serum homocysteine , and creatinine . Patients were then r and omized to receive 10 microg oral cyanocobalamin , 50 microg oral cyanocobalamin , or placebo treatment for 1 month , after which the investigations and clinical examinations were repeated . MEASUREMENTS Percentage change in the level of vitamin B12 , homocysteine , folate , and red cell parameters and absolute changes in MMSE were calculated and compared between groups . The groups were compared on the number of responders who improved their level of B12 by 20 % . Chi-square calculations on changes in serum vitamin B12 concentration were also performed . RESULTS Mean serum vitamin B12 + /- st and ard deviation improved by 51.7 + /- 47.1 % in the 50-microg group , 40.2 + /- 34.4 % in the 10-microg group , and 11.7 + /- 24.5 % in the placebo group . The change in the 50-microg cyanocobalamin group was significantly greater than that in the placebo group ( P=.044 ) . The change in the 10-microg cyanocobalamin group was not significantly different from that in the placebo group ( P=.186 ) . Eight of 10 subjects in each treatment group were classified as responders , compared with two of 11 in the placebo group ( P=.004 ) . Homocysteine levels fell in patients receiving cyanocobalamin , but this fall failed to reach statistical significance . There were no significant changes in the other parameters measured . CONCLUSION Cyanocobalamin supplementation of 50 microg but not 10 microg daily produced a significant increase in serum vitamin B12 . This result has implication s for the management of patients with subnormal or borderline serum vitamin B12 concentrations and for food fortification with vitamin B12 BACKGROUND Elevated plasma total homocysteine concentration may be a risk factor for cognitive decline and Alzheimer disease , but data from prospect i ve studies are limited . Further , high homocysteine levels are associated with low vitamin status , and it is unknown whether it is homocysteine toxicity or vitamin insufficiency that is responsible for the observed cognitive dysfunction . METHODS We performed cross-sectional and longitudinal analyses of a cohort of 499 high-functioning community-dwelling persons aged 70 to 79 years to determine the effect of homocysteine and related vitamin plasma concentrations on cognitive function and cognitive decline .  Nonfasting plasma concentrations of homocysteine , folate , vitamin B(6 ) , and vitamin B(12 ) were measured at baseline .  Summary measures of cognitive function were created from tests of multiple cognitive domains administered at baseline and again after 7 years . RESULTS In cross-sectional analyses investigating each variable separately , subjects with elevated homocysteine levels , or low levels of folate or vitamin B(6 ) , demonstrated worse baseline cognitive function . In longitudinal analyses , after adjusting for multiple covariates , including homocysteine , those in the bottom quartile of folate had a 1.6-fold increased risk ( 95 % confidence interval : 1.01 to 2.31 ; P = 0.04 ) of being in the worst quartile of 7-year cognitive decline . Low folate levels largely accounted for a trend towards greater cognitive decline with elevated homocysteine level . CONCLUSION In high-functioning older adults , low folate levels appear to be a risk factor for cognitive decline . The risk of developing cognitive decline might be reduced through dietary folate intake Elevated plasma total homocysteine ( tHcy ) is a risk factor for vascular disease but lowering tHcy with B-vitamins , including folate , has generally not reduced vascular events in secondary prevention trials . Elevated plasma S-adenosylhomocysteine ( AdoHcy ) concentration may be a more sensitive indicator of vascular disease than plasma tHcy . However , unlike tHcy , plasma AdoHcy did not correlate with folate concentration in one study indicating that folate supplementation may not lower AdoHcy . Our aim was to determine whether providing B-vitamin supplements to healthy older people with elevated tHcy ( > 13 micromol/l ) affects plasma AdoHcy and S-adenosylmethionine ( AdoMet ) concentrations .  Healthy older participants ( n 276 ; > or = 65 years ) were r and omised to receive a daily supplement containing folate ( 1 mg ) , vitamin B12 ( 500 microg ) and vitamin B6 ( 10 mg ) , or placebo , for 2 years . Of these participants , we selected the first fifty participants in each treatment group and measured plasma AdoHcy and AdoMet . Plasma tHcy was 4.4 ( 95 % CI 3.2 , 5.6 ; P < 0.001 ) micromol/l lower at 2 years in the vitamins group compared with the placebo group . At 2 years , there were no significant differences in plasma AdoMet ( + 4 % ( 95 % CI - 2 , 11 ) ; P = 0.19 ) , AdoHcy ( - 1 % ( 95 % CI - 10 , 8) ; P = 0.61 ) or the AdoMet : AdoHcy ratio ( 0.22 ( 95 % CI - 0.04 , 0.49 ) ; P = 0.10 ) between the two groups . In conclusion , B-vitamin supplementation of older people lowered plasma tHcy but had no effect on plasma AdoMet or AdoHcy concentration . If elevated plasma AdoHcy is detrimental , this may explain why B-vitamins have generally failed to reduce vascular events in clinical trials BACKGROUND & AIMS Older diabetic people are at risk of cognitive decline . Vitamin B12 deficiency in older people is associated with cognitive impairment and Alzheimer 's disease . Vitamin B12 deficiency may therefore contribute to cognitive decline in older diabetic people . We therefore performed a r and omized placebo-controlled trial of vitamin B12 supplementation to prevent cognitive decline in older diabetic people with mild vitamin B12 deficiency . METHODS 271 diabetic non-demented out patients aged 70 years or older with plasma vitamin B12 150 - 300 pmol/L in outpatient clinics were r and omly assigned to take either methylcobalamin 1000 μg or two similar looking placebo tablets once daily for 27 months . All subjects were followed up at 9 monthly intervals . The primary outcome is cognitive decline as defined by an increase in clinical dementia rating scale ( CDR ) global score . The secondary outcomes included Neuropsychological Test Battery ( NTB ) z-scores , serum methymalonic acid ( MMA ) and homocysteine . RESULTS The subjects in the trial groups were well matched in clinical characteristics , except that active intervention group had more smokers . 46.5 % and 74.1 % had elevated serum methymalonic acid ( ≥0.21 μmol/L ) and homocysteine ( ≥13 μmol/L ) respectively . 44 % of the subjects had CDR score of 0.5 suggesting question able dementia . At month 9 and 27 , serum MMA and homocysteine was significantly reduced in the active treatment group , when compared with placebo group . ( P < 0.0001 , student t test ) At month 27 , there was no significant group difference in changes in CDR or NTB z-scores . Exclusion of smokers did not alter the results . Subgroup analysis of high MMSE and serum MMA showed similar results . CONCLUSION Vitamin B12 supplementation did not prevent cognitive decline in older diabetic patients with borderline vitamin B12 status . CLINICAL TRIAL REGISTRATION Clinical Trials.gov : NCT02457507 The effect of folic acid supplement ( 15 mg folic acid per day ) for 5 weeks was studied on a group of 5 children aged 8 - 12 years who were admitted to hospital . The result was compared to a control group of 5 children who were given a placebo .  After supplementation , both serum and red cell folate levels in the experimental group significantly increased , i.e. , 15 fold ( 82.0 ng/ml ) and 4 fold ( 880 ng/ml ) , respectively . Serum UFBP decreased considerably while TFBP showed no significant alteration which result ed in the elevation of the % saturation to its maximum value . These findings indicated that the supplementary folic acid not only increased both serum and red cell folate levels and saturated nearly all serum UFBP but also elevated the % saturation markedly . There were no definite changes of serum vitamin B12 , UBBC , TBBC and TC levels of the experimental group from those of the control group . There were slightly but not significantly increased blood haemoglobin and haematocrit levels in both groups of children . This indicated that folic acid supplement had no definite effect on vitamin B12 and haematological findings in this study Depression is one of the most prevalent mental health conditions and can affect people of all ages , but it is becoming more common among the older population with increasing life expectancy . Observational studies have found poor micronutrient status ( particularly folate and vitamin B12 ) to be associated with an increased risk of  depression in older people .  Supplementation with folic acid has been shown to enhance anti-depressant drug treatment and there is preliminary evidence that supplementation with certain micronutrients may help improve depressive symptoms in older patients . There has also been a lot of interest in the role of long-chain omega-3 fatty acids in depression . However , the evidence from r and omized controlled trials is limited and difficult to evaluate owing to considerable variability between studies . The research highlights the importance of a healthy diet and lifestyle to help maintain good mental health into old age and health professionals should try to support older people in trying to achieve this Objectives : 1 ) To compare serum vitamin B12 , C and folate concentrations in a r and omly selected sample of elderly ( age 65 years or older ) male and female Hispanics and nonHispanic whites ( NHW ) and 2 ) to examine associations between serum B12 , C and folate concentrations compared to measures of cognitive and affective ( depression ) functions . Methods : Equal numbers of male and female Hispanics and NHW were r and omly sample d from the Health Care Financing Administration ( Medicare ) registrant list for Bernalillo County , New Mexico , and asked to volunteer for a paid home interview followed by a paid comprehensive interview/examination covering health and health-related issues . In addition to serum determinations of B12 , C and folate , associations were examined between these vitamins and measures of cognitive and affective functions . Results : Males and Hispanics had lower serum vitamin B12 , C and folate concentrations than females and NHW respectively . Participants taking a multivitamin supplement ( MVI ) had higher serum vitamin concentrations than those not taking MVI . There were significant associations between serum folate concentrations and measures of cognitive function , not seen with B12 or C , nor between any of the vitamins and affective function . Conclusions : Hispanics , even after adjustments for gender , age , vitamin supplementation , vitamin content of dietary foods , education and household income , had lower serum concentrations of B12 , C and folate than NHW . The most significant associations observed were those between serum folate and various measures of cognitive function , even after adjusting for presence of depression Background Osteoporosis is a major health problem , and the economic burden is expected to rise due to an increase in life expectancy throughout the world . Current observational evidence suggests that an elevated homocysteine concentration and poor vitamin B12 and folate status are associated with an increased fracture risk . As vitamin B12 and folate intake and status play a large role in homocysteine metabolism , it is hypothesized that supplementation with these B-vitamins will reduce fracture incidence in elderly people with an elevated homocysteine concentration . Methods / Design The B-PROOF ( B-Vitamins for the PRevention Of Osteoporotic Fractures ) study is a r and omized double-blind placebo-controlled trial . The intervention comprises a period of two years , and includes 2919 subjects , aged 65 years and older , independently living or institutionalized , with an elevated homocysteine concentration ( ≥ 12 μmol/L ) . One group receives daily a tablet with 500 μg vitamin B12 and 400 μg folic acid and the other group receives a placebo tablet . In both tablets 15 μg ( 600 IU ) vitamin D is included . The primary outcome of the study is osteoporotic fractures . Measurements are performed at baseline and after two years and cover bone health i.e. bone mineral density and bone turnover markers , physical performance and physical activity including falls , nutritional intake and status , cognitive function , depression , genetics and quality of life . This large multi-center project is carried out by a consortium from the Erasmus MC ( Rotterdam , the Netherl and s ) , VUmc ( Amsterdam , the Netherl and s ) and Wageningen University , ( Wageningen , the Netherl and s ) , the latter acting as coordinator . Discussion To our best knowledge , the B-PROOF study is the first intervention study in which the effect of vitamin B12 and folic acid supplementation on osteoporotic fractures is studied in a general elderly population . We expect the first longitudinal results of the B-PROOF intervention in the second semester of 2013 . The results of this intervention will provide evidence on the efficacy of vitamin B12 and folate supplementation in the prevention of osteoporotic fractures . Trial Registration The B-PROOF study is registered with the Netherl and s Trial ( NTR NTR1333 ) and with Clinical Trials.gov ( NCT00696514 ) Objectives : To determine the prevalence of anaemia and the haemopoietic nutrient status of older mixed ancestry ( coloured ) South Africans . Design : A cross-sectional analytic study . Subjects : A r and om sample of 200 non-institutionalized subjects aged ≥65 y of age , resident in urban Cape Town , was drawn using a two-stage cluster design . Methods : Trained fieldworkers interviewed subjects to obtain demographic and lifestyle data .  Dietary intake was assessed using a vali date d food frequency question naire . Fasting blood sample s were drawn for the determination of haematological parameters , serum vitamin B12 , serum folate , RBC folate and a full blood count . Results : The prevalence of anaemia was 13.9 % . Eight of the 26 cases of anaemia ( 31 % ) were associated with suboptimal haemopoietic nutrient status ; 2(25 ) and 3(38 ) cases of these 8 anaemic subjects had suboptimal vitamin B12 and folate status , respectively . Iron deficiency anaemia accounted for 5(63)% of the subjects with nutrition-related anaemia . Ten men and two women ( 6.5 % of subjects ) had raised serum ferritin concentrations , half of whom had abnormal biochemical parameters indicative of alcohol abuse . Conclusions : Older coloured South Africans , particularly women , should be encouraged to eat diets with a high nutrient density and to consume adequate amounts of foods high in iron , folate and vitamin B12 . Further investigation regarding the high prevalence of hyperferritinaemia found in the men in this population is indicated . Sponsorship : Financial assistance from the HSRC/UCT Centre for Gerontology , the South African Sugar Association , the Zerilda Steyn Memorial Trust and the Medical Research Council ( DL ) for this project is acknowledged IMPORTANCE More effective treatments are needed for negative symptoms of schizophrenia , which are typically chronic , disabling , and costly . Negative symptoms have previously been associated with reduced blood folate levels , especially among patients with low-functioning variants in genes that regulate folate metabolism , suggesting the potential utility of folate supplementation . OBJECTIVES To determine whether folic acid plus vitamin B12 supplementation reduces negative symptoms of schizophrenia and whether functional variants in folate-related genes influence treatment response . DESIGN Parallel-group , r and omized , double-blind , placebo-controlled clinical trial of 16 weeks of treatment with 2 mg of folic acid and 400 μg of vitamin B12 . SETTING Three community mental health centers affiliated with academic medical centers in the United States . PARTICIPANTS Out patients with chronic schizophrenia who were psychiatrically stable but displayed persistent symptoms despite antipsychotic treatment . Eligible patients were 18 to 68 years old , were treated with an antipsychotic agent for 6 months or more at a stable dose for 6 weeks or more , and scored 60 or more on the Positive and Negative Syndrome Scale . INTERVENTION One hundred forty subjects were r and omized to receive daily oral folic acid plus vitamin B12 or placebo . MAIN OUTCOME MEASURES Change in negative symptoms ( Scale for the Assessment of Negative Symptoms [ SANS ] ) , as well as positive and total symptoms ( Positive and Negative Syndrome Scale ) . RESULTS Folate plus vitamin B12  improved negative symptoms significantly compared with placebo ( group difference , -0.33 change in SANS score per week ; 95 % CI , -0.62 to -0.05 ) when genotype was taken into account but not when genotype was excluded . An interaction of the 484C > T variant of FOLH1 ( rs202676 ) with treatment was observed ( P = .02 ) , where only patients homozygous for the 484 T allele demonstrated significantly greater benefit with active treatment ( -0.59 change in SANS score per week ; 95 % CI , -0.99 to -0.18 ) . In parallel , we observed an inverse relationship between red blood cell folate concentration at baseline and 484C allele load ( P = .03 ) , which persisted until 8 weeks of treatment . Change in positive and total symptoms did not differ between treatment groups . CONCLUSIONS Folate plus vitamin B12 supplementation can improve negative symptoms of schizophrenia , but treatment response is influenced by genetic variation in folate absorption . These findings support a personalized medicine approach for the treatment of negative symptoms . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00611806 One third of older people in nursing and /or residential homes have significant symptoms of depression . In younger people , deficiencies in selenium , vitamin C and folate are associated with depression . This study examines the association between micronutrient status and mood before and after supplementation . The objective was to determine whether the administration of selenium , vitamin C and folate improved mood in frail elderly nursing home residents . Mood was assessed using the Hospital Anxiety and Depression rating scale ( HAD ) , and Montgomery-Åsberg Depression Rating Scale ( MADRS ) . Micronutrient supplementation was provided for 8 weeks in a double-blinded r and omised controlled trial . Significant symptoms of depression ( 29 % ) and anxiety ( 24 % ) were found at baseline . 67 % of patients had low serum concentrations of vitamin C , but no-one was below the reference range for selenium . Depression was significantly associated with selenium levels , but not with folate or vitamin C levels . No individual with a HAD depression score of ≧8 , had selenium levels > 1.2 µM. In those patients with higher HAD depression scores , there was a significant reduction in the score and a significant increase in serum selenium levels after 8 weeks of micronutrient supplementation . Placebo group scores were unchanged . This small study concluded that depression was associated with low levels of selenium in frail older individuals . Following 8 weeks of micronutrient supplementation , there was a significant increase in selenium levels and improved symptoms of depression occurred in a subgroup The aim of this study was to prospect ively determine the etiology of anemia in a cohort of community-dwelling older out patients with a comprehensive hematologic evaluation . Participants were men and women age 65 and older with anemia as defined by World Health Organization criteria recruited from outpatient hematology clinics at Stanford Hospital and Clinics ( SHC ) and Veterans Affairs Palo Alto Health Care System ( VAPAHCS ) . Each participant underwent a history and physical examination , followed by a comprehensive hematologic evaluation  , which in all participants included  complete blood count , red cell indices , review of the blood smear ,  and  assessment of vitamin B12 , folate , iron status and renal function .  Additional evaluation was obtained by clinical providers as per their discretion . 190 participants enrolled and completed the evaluation . Twelve percent of participants had iron deficiency anemia . Of those with iron deficiency in whom there was follow-up information , half normalized their hemoglobin in response to iron repletion , and half did not . Thirty-five percent of participants had unexplained anemia . Those with unexplained anemia had mildly increased inflammatory markers compared to non-anemic controls , and , at the lower hemoglobin ranges had relatively low erythropoietin levels . Sixteen percent of participants were categorized as being " suspicious for myelodysplastic syndrome . " Thus , even with comprehensive hematologic evaluation , unexplained anemia is common in older anemic out patients . Iron deficiency anemia is also common and can be difficult to diagnose , and frequently the anemia is not fully corrected with iron repletion People in India have a high prevalence of low vitamin B12 status and high plasma total homocysteine ( tHcy ) concentrations . In a proof of principle trial , we studied the effect of oral vitamin B12 ( 500 microg ) and /or 100 g cooked green leafy vegetables ( GLV ) every alternate day in a 2x2 factorial design over a 6-week period . Forty-two non-pregnant vegetarian women ( age 20 - 50 years ) were r and omly allocated to four study groups . Clinical measurements were made at the beginning and at the end of the study , and blood sample s were collected before , and 2 and 6 weeks after commencement of intervention . Forty women completed the trial . Twenty-six women had low vitamin B12 status ( < 150 pmol/L ) and 24 had hyperhomocysteinemia ( > 15 micromol/L ) . GLV supplementation did not alter plasma folate or tHcy .  Vitamin B12 supplementation increased plasma vitamin B12 concentration ( 125 to 215 pmol/L , p < 0.05 ) and reduced tHcy concentration ( 18.0 to 13.0 micromol/L , p < 0.05 ) within first 2 weeks , both of which remained stable for the next 4 weeks . Plasma vitamin B12 and tHcy concentrations did not change in those who did not receive vitamin B12 , and there was no change in plasma folate concentration in any of the groups . Blood haemoglobin concentration increased marginally within first two weeks in those women who received vitamin B12 ( by 3 g/L , p < 0.05 ) and the number of women with macrocytosis decreased from 2 to zero . There was no change in vibration sensory threshold during the period of the study . High-dose per oral vitamin B12 supplementation significantly reduced plasma tHcy within 2 weeks but did not achieve normal plasma tHcy concentration even after 6 weeks . People in India have a high prevalence of low vitamin B12 status and high plasma total homocysteine ( tHcy ) concentrations Objective : To investigate whether supplementing older men with vitamins B12 , B6 , and folic acid improves cognitive function . Methods : The investigators recruited 299 community-representative hypertensive men 75 years and older to a r and omized , double-blind controlled clinical trial of folic acid , vitamin B6 , and B12 supplementation vs placebo over 2 years . The primary outcome of interest was the change in the cognitive subscale of the Alzheimer 's Disease Assessment Scale ( ADAS-cog ) . A secondary aim of the study was to determine if supplementation with vitamins decreased the risk of cognitive impairment and dementia over 8 years . Results : The groups were well-balanced for demographic and biochemical parameters . There was no difference in the ADAS-cog change from baseline to 24 months between the placebo ( 0.8 , SD 4.0 ) and vitamins group ( 0.7 , SD 3.4 ) . The adjusted scores in the treatment groups did not differ over time ( placebo 0.2 lower , z = 0.71 , p = 0.478 ) . There was a nonsignificant 28 % decrease in the risk of cognitive impairment ( odds ratio 0.72 , 95 % confidence interval 0.25–2.09 ) and dementia ( hazard ratio 0.72 , 95 % confidence interval 0.29–1.78 ) over 8 years of follow-up . Conclusions : The daily supplementation of vitamins B12 , B6 , and folic acid does not benefit cognitive function in older men , nor does it reduce the risk of cognitive impairment or dementia . Classification of evidence : This study provides Class I evidence that vitamin supplementation with daily doses of 400 μg of B12 , 2 mg of folic acid , and 25 mg of B6 over 2 years does not improve cognitive function in hypertensive men aged 75 and older High plasma homocysteine ( Hcy ) levels are associated with increased osteoporotic fracture incidence . However , the mechanism remains unclear . We investigated the effect of Hcy-lowering vitamin B12 and folic acid treatment on bone mineral density ( BMD ) and calcaneal quantitative ultrasound ( QUS ) parameters . This r and omized , double-blind , placebo-controlled trial included participants aged ≥65 years with plasma Hcy levels between 12 and 50 µmol/L. The intervention comprised 2-year supplementation with either a combination of 500 µg B12 , 400 µg folic acid , and 600 IU vitamin D or placebo with 600 IU vitamin D only . In total , 1111 participants underwent repeated dual-energy X-ray assessment and 1165 participants underwent QUS .  Femoral neck ( FN ) BMD , lumbar spine ( LS ) BMD , calcaneal broadb and ultrasound attenuation ( BUA ) , and calcaneal speed of sound ( SOS ) were assessed . After 2 years , FN-BMD and BUA had significantly decreased , while LS-BMD significantly increased ( all p < 0.01 ) and SOS did not change in either treatment arm . No statistically significant differences between the intervention and placebo group were present for FN-BMD ( p = 0.24 ) , LS-BMD ( p = 0.16 ) , SOS ( p = 0.67 ) , and BUA ( p = 0.96 ) . However , exploratory subgroup analyses revealed a small positive effect of the intervention on BUA at follow-up among compliant persons > 80 years ( estimated marginal mean 64.4 dB/MHz for the intervention group and 61.0 dB/MHz for the placebo group , p = 0.04 for difference ) . In conclusion , this study showed no overall effect of treatment with vitamin B12 and folic acid on BMD or QUS parameters in elderly , mildly hyperhomocysteinemic persons , but suggests a small beneficial effect on BUA in persons > 80 years who were compliant in taking the supplement BACKGROUND Vitamin B-12 deficiency is associated with cognitive impairment in older people . However , evidence from r and omized trials of the effects of vitamin B-12 supplementation on cognitive function is limited and inconclusive . OBJECTIVE The objective was to investigate whether daily supplementation with high doses of oral vitamin B-12 alone or in combination with folic acid has any beneficial effects on cognitive function in persons aged > /=70 y with mild vitamin B-12 deficiency . DESIGN In a double-blind , placebo-controlled trial , 195 subjects were r and omly assigned to receive 1000 microg vitamin B-12 , 1000 microg vitamin B-12 + 400 microg folic acid , or placebo for 24 wk . Vitamin B-12 status was assessed on the basis of methylmalonic acid , total homocysteine ( tHcy ) , and holotranscobalamin ( holoTC ) concentrations before and after 12 and 24 wk of treatment . Cognitive function was assessed before and after 24 wk of treatment with the use of an extensive neuropsychologic test battery that included the domains of attention , construction , sensomotor speed , memory , and executive function . RESULTS Vitamin B-12 status did not change significantly after treatment in the placebo group ; however , oral vitamin B-12 supplementation corrected mild vitamin B-12 deficiency .  Vitamin B-12 + folic acid supplementation increased red blood cell folate concentrations and decreased tHcy concentrations by 36 % . Improvement in memory function was greater in the placebo group than in the group who received vitamin B-12 alone ( P = 0.0036 ) . Neither supplementation with vitamin B-12 alone nor that in combination with folic acid was accompanied by any improvement in other cognitive domains . CONCLUSION Oral supplementation with vitamin B-12 alone or in combination with folic acid for 24 wk does not improve cognitive function Objective : An intervention study was performed to determine if supplement containing folic acid , vitamin B6 , and vitamin B12 could improve cognitive function and lower homocysteine in middle-aged and elderly patients with hyperhomocysteinemia . Methods : One hundred and four participants with hyperhomocysteinemia were recruited in Tianjin , China , aged 55–94 years old . Fifty-seven individuals with hyperhomocysteinemia were included in the intervention group ( vitamin B group , which received 800 µg/day of folate , with 10 mg of vitamin B6 and 25 µg of vitamin B12 ) and 47 patients in the placebo group . The endpoint was the improvement in cognitive function as evaluated by Basic Cognitive Aptitude Tests ( BCATs ) . All parameters were measured before and after the treatment period of 14 weeks . Results : The BCAT total score and four sub-tests scores ( digit copy , Chinese character rotation , digital working memory , and recognition of meaningless figure ) of BCAT at 14 weeks significantly increased only for the vitamin B group . Serum total homocysteine ( tHcy ) levels significantly decreased in the intervention group , while serum concentrations of folate , vitamin B6 , and vitamin B12 significantly increased in the intervention group . Conclusion : The results demonstrated that supplement containing folate , vitamin B6 , and vitamin B12 in middle-aged and elderly patients with hyperhomocysteinemia could improve their cognitive function partly and reduce serum tHcy levels Rationale There is potential for multivitamin supplementation to improve cognition in the elderly . This r and omized , double-blind , placebo-controlled trial was conducted to investigate the effects of 16 weeks multivitamin supplementation ( Swisse Women ’s 50 + Ultivite ® ) on cognition in elderly women . Methods Participants in this study were 56 community dwelling , elderly women , with subjective complaints of memory loss . Cognition was assessed using a computerized battery of memory and attention tasks design ed to be sensitive to age-related declines to fluid intelligence , and a measure of verbal recall . Biochemical measures of selected nutrients , homocysteine , markers of inflammation , oxidative stress , and blood safety parameters were also collected . All cognitive and haematological parameters were assessed at baseline and 16 weeks post-treatment . Results The multivitamin  improved speed of response on a measure of spatial working memory , however benefits to other cognitive processes were not observed . Multivitamin supplementation  decreased levels of homocysteine and increased levels of vitamin B6 and B12 , with a trend for vitamin E to increase . There were no hepatotoxic effects of the multivitamin formula indicating this supplement was safe for everyday usage in the elderly . ConclusionS ixteen weeks ssupplementation with a combined multivitamin , mineral and herbal formula may benefit working memory in elderly women at risk of cognitive decline BACKGROUND & AIMS As people age there is a progressive dysregulation of the immune system that may lead to an increased risk of infections , which may precipitate hospital admission in people with chronic heart or respiratory diseases . Mineral and vitamin supplementation in older people could therefore influence infections in older people . However , the evidence from the available r and omised controlled trials ( RCTs ) is mixed . The aim of the study was to assess the relative efficiency of multivitamin and multimineral supplementation compared with no supplementation . METHODS Cost-utility analysis alongside an RCT . Participants aged 65 years or over from six general practice s in Grampian , Scotl and , were studied . They were r and omised to one tablet daily of either a multivitamin and multimineral supplement or matching placebo . Exclusion criteria were use of mineral , vitamin or fish oil supplements in the previous 3 months ( 1 month for water soluble vitamins ) ,  vitamin B12 injection in the last 3 months . RESULTS Nine hundred and ten participants were recruited ( 454 placebo and 456 supplementation ) .  Use of health service re sources and costs were similar between the two groups . The supplementation arm was more costly although this was not statistically significant ( pound15 per person , 95 % CI-3.75 to 34.95 ) . After adjusting for minimisation and baseline EQ-5D scores supplementation was associated with fewer QALYs per person ( -0.018 , 95 % CI-0.04 to 0.002 ) . It was highly unlikely that supplementation would be considered cost effective . CONCLUSIONS The evidence from this study suggests that it is highly unlikely that supplementation could be considered cost effective
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 .
Background / objectives Low vitamin B12 and folate levels in community-dwelling older people are usually corrected with supplements .
However , the effect of this supplementation on haematological parameters in older persons is not known .