title: Multivitamin supplementation improves nutritional status and bone quality in aged care residents 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. Breakfast cereal fortified with folic acid, vitamin B-6, and vitamin B-12 increases vitamin concentrations and reduces homocysteine concentrations: a randomized trial. Vitamin requirements for the treatment of hyperhomocysteinemia in humans. Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring study. Vitamin and mineral status of trained athletes including the effects of supplementation. Bread cofortified with folic acid and vitamin B-12 improves the folate and vitamin B-12 status of healthy older people: a randomized controlled trial. Effect of supplementation with cobalamin carried either by a milk product or a capsule in mildly cobalamin-deficient elderly Dutch persons. Multivitamin/mineral supplementation improves plasma B-vitamin status and homocysteine concentration in healthy older adults consuming a folate-fortified diet. Lowering homocysteine with B vitamins has no effect on biomarkers of bone turnover in older persons: a 2-y randomized controlled trial. Nutrient-dense foods and exercise in frail elderly: effects on B vitamins, homocysteine, methylmalonic acid, and neuropsychological functioning. Vitamins B6 and B12 and folate status in an adult Mediterranean population Effect of dietary patterns on serum homocysteine: results of a randomized, controlled feeding study. A controlled trial of homocysteine lowering and cognitive performance. Effect of multivitamin supplementation
  on the homocysteine and methylmalonic
  acid blood concentrations in women
  over the age of 60 years Folate, Vitamin B12, and Risk of Ischemic and Hemorrhagic Stroke: A Prospective, Nested Case-Referent Study of Plasma Concentrations and Dietary Intake Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer. Complex Multivitamin Supplementation Improves Homocysteine and Resistance to LDL-C Oxidation Mineral water fortified with folic acid, vitamins B6, B12, D and calcium improves folate status and decreases plasma homocysteine concentration in men and women Low serum vitamin B-12 levels are associated with increased hip bone loss in older women: a prospective study. Iron, folate and vitamin B12 status of an elderly South African population Homocysteine levels and the risk of osteoporotic fracture. Multivitamin-mineral supplementation: effects on blood chemistries of college-age women. Study of the effect of a liquid nutrition supplement on the nutritional status of psycho-geriatric nursing home patients Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia. Reduction of plasma homocysteine and serum methylmalonate concentrations in apparently healthy elderly subjects after treatment with folic acid, vitamin B12 and vitamin B6: a randomised trial Cystatin C levels in plasma and peripheral blood mononuclear cells among hyperhomocysteinaemic subjects: effect of treatment with B-vitamins. A randomized, double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations. Oral vitamin B12 supplementation reduces plasma total homocysteine concentration in women in India. B-vitamins reduce plasma levels of beta amyloid The effect of 7 to 8 months of vitamin/mineral supplementation on the vitamin and mineral status of athletes. The effect of a nutrient dense drink on mental and physical function in institutionalized elderly people Reduction of C-reactive protein levels through use of a multivitamin. Effect of fortified spread on homocysteine concentration in apparently healthy volunteers
abstract: Objectives : To assess the effectiveness of a multivitamin ( MV ) tablet on nutritional status , quantitative heel ultrasound ( QUS ) , mobility , muscle strength and falls . The design comprised two groups matched on mobility levels , r and omized to receive a daily MV or placebo ( P ) tablet for 6 months . The setting was an Australian residential care facility . Subjects : A total of 92 aged care residents . Serum micronutrients , body weight , QUS , rate of falls , h and grip strength , and the timed up and go test were assessed at baseline and 6 months . Results : A total of 49 participants consumed a MV and 43 , a matched P for 6 months . There was a greater increase in the MV vs P group for serum 25(OH)D ( mean difference±st and ard error , 33.4±2.6 nmol l−1 ) , folate ( 13.4±2.8 nmol l−1 ) , and vitamin B12 ( 178.0±40.3 pmol l−1 ) ( all P<0.001 ) . Adequate 25(OH)D concentrations ( ⩾50 nmol l−1 ) were found among 77 % of participants in the MV group vs 10 % taking P ( P<0.001 ) . Adjusting for baseline levels , the increase in QUS was greater in the MV vs P group ( 3.0±2.0 dB MHz−1 vs −2.9±2.1 dB MHz−1 , respectively , P=0.041 ) . There was a trend towards a 63 % lower mean number of falls in the MV vs P group ( 0.3±0.1 falls vs 0.8±0.3 falls , P=0.078 ) . Conclusions : MV  supplementation raised serum vitamin B12 and folate concentrations and increased serum 25(OH)D , which was accompanied by an apparent positive effect on bone density . We also found a trend towards a reduction in falls and this could contribute to a reduction in fractures 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 BACKGROUND High homocysteine and low B vitamin concentrations have been linked to the risk of vascular disease , stroke , and dementia and are relatively common in older adults . OBJECTIVE We assessed the effect of breakfast cereal fortified with folic acid , vitamin B-6 , and vitamin B-12 on vitamin and homocysteine status . DESIGN A r and omized , double-blind trial was conducted in 189 volunteers aged 50 - 85 y. The subjects had no history of hypertension , anemia , asthma , cancer , or cardiovascular or digestive disease and did not regularly consume multiple or B vitamin supplements or highly fortified breakfast cereal . Subjects were r and omly assigned to consume 1 cup ( 0.24 L ) breakfast cereal fortified with 440 microg folic acid , 1.8 mg vitamin B-6 , and 4.8 microg vitamin B-12 or placebo cereal for 12 wk . Blood was drawn at 0 , 2 , 12 , and 14 wk . Methionine-loading tests were conducted at baseline and week 14 . RESULTS Final baseline-adjusted plasma homocysteine concentrations were significantly lower and B vitamin concentrations were significantly higher in the treatment group than in the placebo group ( P < 0.001 ) . The percentage of subjects with plasma folate concentrations < 11 nmol/L decreased from 2 % to 0 % , with vitamin B-12 concentrations < 185 pmol/L from 9 % to 3 % , with vitamin B-6 concentrations < 20 nmol/L from 6 % to 2 % , and with homocysteine concentrations > 10.4 micromol/L ( women ) or > 11.4 micromol/L ( men ) from 6.4 % to 1.6 % . The percentage of control subjects with values beyond these cutoff points remained nearly constant or increased . CONCLUSIONS In this relatively healthy group of volunteers , consumption of 1 cup fortified breakfast cereal daily significantly increased B vitamin and decreased homocysteine concentrations , including post-methionine-load homocysteine concentrations We have previously shown that a modest vitamin supplement containing folic acid , vitamin B-12 and vitamin B-6 is effective in reducing elevated plasma homocysteine concentrations . The effect of supplementation of the individual vitamins on moderate hyperhomocysteinemia has now been investigated in a placebo-controlled study . One hundred men with hyperhomocysteinemia were r and omly assigned to five groups and treated with a daily dose of placebo , folic acid ( 0.65 mg ) , vitamin B-12 ( 0.4 mg ) , vitamin B-6 ( 10 mg ) or a combination of the three vitamins for 6 wk . Folic acid supplementation reduced plasma homocysteine concentrations by 41.7 % ( P < 0.001 ) , whereas the daily vitamin B-12 supplement lowered homocysteine concentrations by 14.8 % ( P < 0.01 ) . The daily pyridoxine dose did not reduce significantly plasma homocysteine concentrations . The combination of the three vitamins reduced circulating homocysteine concentrations by 49.8 % , which was not significantly different ( P = 0.48 ) from the reduction achieved by folate supplementation alone . Our results indicate that folate deficiency may be an important cause of hyperhomocysteinemia in the general population BACKGROUND Low vitamin B-12 status is prevalent among the elderly , but few studies have examined the association between vitamin B-12 status and intake . OBJECTIVE We hypothesized that vitamin B-12 concentrations vary according to intake source . DESIGN Plasma concentrations and dietary intakes were assessed cross-sectionally for 2999 subjects in the Framingham Offspring Study . The prevalence of vitamin B-12 concentrations < 148 , 185 , and 258 pmol/L was examined by age group ( 26 - 49 , 50 - 64 , and 65 - 83 y ) , supplement use , and the following food intake sources : fortified breakfast cereal , dairy products , and meat . RESULTS Thirty-nine percent of subjects had plasma vitamin B-12 concentrations < 258 pmol/L , 17 % had concentrations < 185 pmol/L , and 9 % had concentrations < 148 pmol/L , with little difference between age groups . Supplement users were significantly less likely than non-supplement-users to have concentrations < 185 pmol/L ( 8 % compared with 20 % , respectively ) . Among non-supplement-users , there were significant differences between those who consumed fortified cereal > 4 times/wk ( 12 % ) and those who consumed no fortified cereal ( 23 % ) and between those in the highest and those in the lowest tertile of dairy intake ( 13 % compared with 24 % , respectively ) , but no significant differences by meat tertile . Regression of plasma vitamin B-12 on log of intake , by source , yielded significant slopes for each contributor adjusted for the others . For the total group , b = 40.6 for vitamin B-12 from vitamin supplements . Among non-supplement-users , b = 56.4 for dairy products , 35.2 for cereal , and 16.7 for meat . Only the meat slope differed significantly from the others . CONCLUSIONS In contrast with previous reports , plasma vitamin B-12 concentrations were associated with vitamin B-12 intake . Use of supplements , fortified cereal , and milk appears to protect against lower concentrations . Further research is needed to investigate possible differences in bioavailability We measured serum concentrations of  thiamin , riboflavin  ,  nicotinic acid  ,  pyridoxine , folate , cyanocobalamin , ascorbic acid , retinol , tocopherol , zinc , magnesium , copper , iron , and ferritin as well as hemoglobin , hematocrit , percentage transferrin saturation , and total iron-binding capacity in athletes who ingested a multivitamin and mineral supplement for 3 mo . All blood variables were normal and except for pyridoxine and riboflavin there were no significant changes in the blood concentrations of any other vitamins or minerals measured . This may have been due to variable interactions between the vitamins and minerals in the supplement that prevented their being adequately absorbed . There were no signs or symptoms of serious toxic side effects . We conclude that multivitamin and mineral supplementation was without any measurable ergogenic effect and that such supplementation is unnecessary in athletes ingesting a normal diet BACKGROUND M and atory fortification of flour with folic acid has reduced the number of neural tube defects in North America . Concerns that high intakes of folic acid might mask vitamin B-12 deficiency in older persons have delayed the introduction of fortification in many European countries . Cofortification of flour with folic acid and vitamin B-12 could simultaneously improve folate and vitamin B-12 status . OBJECTIVE The objective was to estimate the effect of the consumption of bread fortified with modest amounts of folic acid and vitamin B-12 on folate and vitamin B-12 status in healthy older persons living in the Netherl and s , where folic acid fortification is not taking place . DESIGN Men and women aged 50 - 75 y were r and omly assigned in this 12-wk double-blind , placebo-controlled trial to consume bread fortified with 138 mug folic acid and 9.6 mug vitamin B-12 daily ( n = 72 ) or unfortified bread ( n = 70 ) . RESULTS The consumption of fortified bread increased serum folate concentrations by 45 % ( mean : 6.3 nmol/L ; 95 % CI : 4.5 , 8.1 nmol/L ) and serum vitamin B-12 concentrations by 49 % ( mean : 102 pmol/L ; 95 % CI : 82 , 122 pmol/L ) relative to the placebo group . Fortified bread increased erythrocyte folate concentrations by 22 % and holotranscobalamin concentrations by 35 % ; it decreased homocysteine concentrations by 13 % and methylmalonic acid concentrations by 10 % . Consumption of fortified bread decreased the proportion of individuals with marginal serum vitamin B-12 concentrations ( < 133 pmol/L ) from 8 % at enrollment to 0 % after 12 wk . CONCLUSION Bread fortified with modest amounts of folic acid and vitamin B-12 will improve folate and vitamin B-12 status and a considerable proportion of vitamin B-12 deficiency in older people . This trial was registered at clinical trials.gov as NCT00353353 BACKGROUND A high prevalence of cobalamin deficiency occurs in the elderly population , which may be treated orally or with injections . Little is known about the relative bioavailability of crystalline cobalamin added to food products . OBJECTIVE The objective was to assess the effect of supplementation with 1000 microg crystalline cobalamin , carried either by a milk product or a capsule , on cobalamin status in mildly cobalamin-deficient elderly Dutch persons . DESIGN Two double-blind r and omized controlled intervention studies , each covering a 12-wk supplementation period , were carried out in parallel . Mildly cobalamin-deficient elderly persons ( n = 112 ) were separately recruited for the milk and capsule trials . Mild cobalamin deficiency was defined as a cobalamin concentration between 100 and 300 pmol/L and a plasma methylmalonic acid ( MMA ) concentration > or = 0.30 micromol/L. Allocation to the placebo or cobalamin carrier was carried out independently in both trials . RESULTS In the fortified-milk group , the mean ( + /-SD ) increase in serum cobalamin was 250 + /- 96 pmol/L , the median ( 5th and 95th percentiles ) decrease in plasma MMA was 0.19 ( -0.76 , -0.04 ) micromol/L , and the median decrease in plasma homocysteine was 4.0 ( -7.3 , 3.0 ) micromol/L. All changes were significantly different from those in the placebo milk group ( P < 0.01 ) . Likewise , in the cobalamin-capsule group , the mean increase in serum cobalamin was 281 + /- 136 pmol/L , the median decrease in plasma MMA was 0.18 ( -2.95 , 0.14 ) micromol/L , and the median decrease in plasma homocysteine was 1.8 ( -10.6 , 2.4 ) micromol/L ; all changes were significantly different from those in the placebo capsule group ( P < 0.01 ) . No significant differences were observed between the fortified-milk and capsule groups ( P > 0.40 ) . CONCLUSION Crystalline cobalamin added to milk is an effective alternative to cobalamin capsules for improving cobalamin status Elevated homocysteine has been identified as an independent risk factor for cardiovascular and cerebrovascular disease . Although multivitamin use has been associated with low plasma homocysteine concentrations in several observational studies , no clinical trials have been conducted using multivitamin/mineral supplements to lower homocysteine . We determined whether a multivitamin/mineral supplement formulated at about 100 % Daily Value will further lower homocysteine concentration and improve B-vitamin status in healthy older adults already consuming a diet fortified with folic acid . In this r and omized , double-blind , placebo-controlled trial , 80 free-living men and women aged 50 - 87 y with total plasma homocysteine concentrations of > or = 8 micromol/L received either a multivitamin/mineral supplement or placebo for 56 d while consuming their usual diet . After the 8-wk treatment , subjects taking the supplement had significantly higher B-vitamin status and lower homocysteine concentration than controls ( P : < 0.01 ) . Plasma folate , pyridoxal phosphate ( PLP ) and vitamin B-12 concentrations were increased 41.6 , 36.5 and 13.8 % , respectively , in the supplemented group , whereas no changes were observed in the placebo group . The mean homocysteine concentration decreased 9.6 % in the supplemented group ( P : < 0.001 ) and was unaffected in the placebo group . There were no significant changes in dietary intake during the intervention . Multivitamin/mineral supplementation can improve B-vitamin status and reduce plasma homocysteine concentration in older adults already consuming a folate-fortified diet BACKGROUND In recent prospect i ve studies , higher homocysteine concentrations were shown to be a risk factor for osteoporotic fractures in older persons . Supplements containing folate and vitamins B-12 and B-6 lower homocysteine concentrations . OBJECTIVE The objective of the study was to determine in healthy older persons whether lowering homocysteine with B vitamins affects plasma biomarkers of bone turnover . DESIGN Healthy older persons ( n = 276 ; aged > or=65 y ) were r and omly assigned to receive either a daily supplement containing folate ( 1 mg ) , vitamin B-12 ( 500 microg ) , and vitamin B-6 ( 10 mg ) or a placebo for 2 y. Of these participants , we selected 135 with baseline homocysteine concentrations > 15.0 micromol/L , and we measured serum bone-specific alkaline phosphatase , a marker of bone formation , and bone-derived collagen fragments , a marker of bone resorption , at baseline and 2 y later . RESULTS At 2 y , plasma homocysteine concentrations were 5.2 mumol/L ( 95 % CI : 3.9 , 6.6 micromol/L ; P < 0.001 ) lower in the vitamin than in the placebo group . No significant differences were found in either serum bone-specific alkaline phosphatase ( -0.3 microg/L ; 95 % CI : -2.8 , 2.1 microg/L ; P = 0.79 ) or bone-derived collagen fragments ( -0.0 microg/L ; 95 % CI : -0.1 , 0.1 microg/L ; P = 0.76 ) between the vitamin and placebo groups , respectively , with 2 y of supplementation . CONCLUSION Supplementation with folate and vitamins B-6 and B-12 lowered plasma homocysteine but had no beneficial effect on bone turnover at the end of 2 y , as assessed by biomarkers of bone formation and resorption BACKGROUND Frail elders are at risk of suboptimal micronutrient status , functional decline , and neurologic disorders . The influence of oral multimicronutrients in physiologic doses and of moderately intense physical exercise on homocysteine ( Hcy ) , methylmalonic acid ( MMA ) , and neurologic functioning have not yet been investigated . OBJECTIVE Our goal was to determine the effects of enriched foods and exercise on blood vitamins , Hcy , MMA , and neuropsychological functioning in the frail . DESIGN A 17-wk r and omized controlled intervention trial was used to study 1 ) enriched foods plus a social program , 2 ) regular foods plus exercise , 3 ) enriched foods plus exercise , and 4 ) regular foods plus a social program . Enriched foods contained multiple micronutrients ( 25 - 100 % of the Dutch recommended dietary allowances ) ; exercises focused on strength , coordination , flexibility , and endurance . Vitamin ( cobalamin , red blood cell folate , and pyridoxal 5'-phosphate ) , Hcy , and MMA concentrations were measured and 2 neuropsychological tests were conducted . RESULTS Vitamin concentrations were higher in the supplemented groups than in the unsupplemented groups ( P < 0.001 ; total n = 130 ) . Compared with baseline , cobalamin in the supplemented groups was increased by 22 % , plasma folate by 101 % , red blood cell folate by 87 % , and pyridoxal 5'-phosphate by 68 % . Concentrations in the unsupplemented groups changed by -2 % , -6 % , 1 % , and -13 % , respectively . Hcy decreased by 25 % and MMA by 30 % in the supplemented groups , compared with a small increase in Hcy ( 2 % ) and decrease in MMA ( 9 % ) in the unsupplemented groups . Exercise did not significantly affect vitamin , Hcy , or MMA concentrations . No significant effect of either intervention was observed on the neuropsychological tests . CONCLUSIONS The decrease in Hcy and MMA in frail elders confirms a sub clinical metabolic deficiency state . Enriched foods containing physiologic amounts of micronutrients have a beneficial effect on these metabolites . No effects of B vitamins on mental health were identified Objective : To assess the nutritional status for vitamins B6 and B12 and folate in an adult Mediterranean population , in order to identify patterns of intake , groups at risk for deficiency , and factors that might influence this risk . Design : A cross-sectional epidemiological survey . Setting : And alusia , a western Mediterranean region in southern Spain . Subjects : The study was carried out with a r and om sample of 3528 subjects ( 1813 men , 1715 women ) who were between 25 and 60 y of age .  Blood sample s were obtained for biochemical assays in a r and om sub sample of 384 subjects ( 183 men , 201 women ) . Interventions :  Food consumption was assessed by 48-h recall .  Vitamin B6 was measured as alpha erythrocyte aspartate aminotransferase activation coefficient ( αEAST ) ; vitamin B12 and folate concentrations were measured in plasma . Results : Energy and vitamin intakes were significantly higher in men than in women . In men , intakes were below two-thirds of the RDA in 10.8 , 2.9 and 22.6 % for B6 , B12 and folate , respectively . The corresponding figures in women were 16.7 , 5.1 and 23.5 % for vitamins B6 , B12 and folate . Age , place of residence and educational level , alcohol use and smoking were also associated with differences in the intake of these nutrients . Biochemical analyses showed that vitamins B6 , B12 and folate status was acceptable in 75.7 , 89.1 and 57.6 % of the population , respectively . Plasma concentration of folate was significantly higher in women . Conclusion : Our results provide a precise estimate of the nutritional status for vitamins B6 , B12 and folate in the adult population of southern Spain . Factors such as age , place of residence , level of education and smoking can increase the risk of inadequate intake of some nutrients . However , these factors did not affect biochemical indexes of nutritional status in the present study .Sponsorship : Dirección General de Salud Pública and the Health Council of the And alusian Regional Government BACKGROUND Elevated blood levels of homocysteine are associated with an increased risk of atherosclerotic cardiovascular disease . Although numerous studies have assessed the impact of vitamin supplements on homocysteine , the effect of dietary patterns on homocysteine has not been well studied . METHODS AND RESULTS During a 3-week run-in , 118 participants were fed a control diet , low in fruits , vegetables , and dairy products , with a fat content typical of US consumption . During an 8-week intervention phase , participants were then fed 1 of 3 r and omly assigned diets : the control diet , a diet rich in fruits and vegetables but otherwise similar to control , or a combination diet rich in fruits , vegetables , and low-fat dairy products and reduced in saturated and total fat . Between the end of run-in and intervention periods , mean change in homocysteine was + 0.46 micromol/L in the control diet , + 0.21 micromol/L in the fruits and vegetables diet ( P=0.47 compared with control ) , and -0.34 micromol/L in the combination diet ( P=0.03 compared with control , P=0.12 compared with the fruits and vegetables diet ) . In multivariable regression models , change in homocysteine was significantly and inversely associated with change in serum folate ( P=0.03 ) but not with change in serum vitamin B(12 ) ( P=0.64 ) or pyridoxal 5 ' phosphate , the coenzyme form of vitamin B(6 ) ( P=0.83 ) . CONCLUSIONS Modification of dietary patterns can have substantial effects on fasting levels of total serum homocysteine . These results provide additional insights into the mechanisms by which diet might influence the occurrence of atherosclerotic cardiovascular disease BACKGROUND The results of observational studies suggest that plasma homocysteine concentrations are inversely related to cognitive function in older people . Our objective was to test the hypothesis that lowering the plasma homocysteine concentration improves cognitive function in healthy older people . METHODS We conducted a two-year , double-blind , placebo-controlled , r and omized clinical trial involving 276 healthy participants , 65 years of age or older , with plasma homocysteine concentrations of at least 13 micromol per liter .  Homocysteine-lowering treatment was a daily supplement containing folate ( 1000 microg ) and vitamins B12 ( 500 microg ) and B6 ( 10 mg ) . Tests of cognition were conducted at baseline and after one and two years of treatment . Treatment effects were adjusted for baseline values , sex , and education . RESULTS On average , during the course of the study , the plasma homocysteine concentration was 4.36 micromol per liter ( 95 percent confidence interval , 3.81 to 4.91 micromol per liter ) lower in the vitamin group than in the placebo group ( P<0.001 ) . Overall , there were no significant differences between the vitamin and placebo groups in the scores on tests of cognition . CONCLUSIONS The results of this trial do not support the hypothesis that homocysteine lowering with B vitamins improves cognitive performance . ( Australian Clinical Trials registry number , ACTR NO 12605000030673 . ) Summary Background Deficiency of folic acid , vitamin B6 and /or vitamin B12 can result in elevated total plasma homocysteine concentrations ( tHcy ) , which are considered to be a risk factor for vascular disease . Studies have shown that supplementation of the three vitamins can lower tHcy even in subjects with tHcy in the normal range . Aim of the study The aim of this study was to evaluate the effect of a 6 month supplementation with vitamin B6 , B12 and folate on the concentrations of total plasma homocysteine and serum methylmalonic acid ( MMA ) of elderly women . Methods The study was design ed as a r and omized placebo controlled doubleblind trial , and 220 healthy women ( aged 60–91 years ) were involved .  The vitamin and mineral capsule contained pyridoxine ( 3.4 mg ) , folic acid ( 400 µg ) and cobalamin ( 9 µg ) in addition to other micronutrients  . Blood concentrations of folate , cobalamin , tHcy , MMA and the activity coefficient of erythrocyte alpha-aspartic aminotransferase ( alpha-EAST ) were measured at baseline and after 6 months of supplementation . Dietary intake was evaluated at the beginning and the end of the intervention by two 3–day diet records . Results Median concentrations of serum cobalamin , serum folate and erythrocyte folate increased significantly and tHcy and alpha – EAST activity ( indicative of improved status of vitamin B6 ) coefficient decreased significantly in the supplemented group . Median MMA concentration of the supplemented group was significantly lower than that of the placebo group after the intervention . The vitamin supplementation had a greater decreasing effect on the tHcy concentration of volunteers with lower vitamin and higher tHcy initial concentrations . In a linear regression model , baseline tHcy , serum folate , age and alpha – EAST activity coefficient were significantly correlated with the change in tHcy . The change in MMA in the supplement group was significantly associated to the baseline MMA values . Conclusions Our results show that a 6 month supplementation including physiological dosages of B vitamins improves the status of these nutrients and reduces tHcy in presumed healthy elderly women Background and Purpose — Folate metabolism has been implicated in stroke . However , the possibility of a role for folate and vitamin B12 , independent of their effects on homocysteine status , remains to be explored . The aim of this prospect i ve , nested case-referent study was to relate plasma and dietary intake levels of folate and vitamin B12 to risk of stroke , taking into consideration plasma homocysteine concentrations and methylenetetrahydrofolate reductase polymorphisms . Methods — Subjects were 334 ischemic and 62 hemorrhagic stroke cases and matched double referents from the population -based Northern Sweden Health and Disease Cohort . Results — Plasma folate was statistically significantly associated with risk of hemorrhagic stroke in an inverse linear manner , both in univariate analysis and after adjustment for conventional risk factors including hypertension ( odds ratio [ OR ] for highest versus lowest quartile 0.21 ( 95 % confidence interval [ CI ] , 0.06 to 0.71 ; P for trend=0.008 ) ) . Risk estimates were attenuated by inclusion of homocysteine in the model ( OR , 0.34 ; 95 % CI , 0.08 to 1.40 ; P for trend=0.088 ) . A similar pattern was observed for increasing folate intake ( multivariate OR , 0.07 ; 95 % CI , 0.01 to 0.55 ; P for trend=0.031 without homocysteine , and OR , 0.16 , 95 % CI , 0.02 to 1.23 ; P for trend=0.118 with homocysteine in the analysis ) . We found little evidence of an association between plasma or dietary folate and risk of ischemic stroke . Neither plasma nor dietary vitamin B12 was associated with risk of either stroke subtype . Conclusions — The results of this study suggest a protective role for folate , possibly in addition to its effects on homocysteine status , in hemorrhagic but not ischemic stroke BACKGROUND In several epidemiologic investigations , folate intake has appeared to reduce the elevated risk of breast cancer associated with moderate alcohol consumption . However , data relating plasma folate levels to breast cancer risk are sparse . We investigated the association between plasma folate and other vitamins with breast cancer in a prospect i ve , nested case-control study . METHODS Blood sample s were obtained during 1989 and 1990 from 32 826 women in the Nurses ' Health Study who were followed through 1996 for the development of breast cancer . We identified 712 breast cancer case patients and selected 712 individually matched control subjects .  Dietary information was obtained using food frequency question naires given in 1980 , 1984 , 1986 , and 1990 . Logistic regression was used to estimate the relative risks ( RRs ) of breast cancer ( after adjustment for potential risk factors ) , and a generalized linear model was used to calculate the Pearson correlation coefficients between plasma estimates of folate , vitamin B(6 ) , vitamin B(12 ) , and homocysteine , and intakes of folate , vitamin B(6 ) , and vitamin B(12 ) . All statistical tests were two-sided . RESULTS The multivariable RR comparing women in the highest quintile of plasma folate with those in the lowest was 0.73 ( 95 % confidence interval [ CI ] = 0.50 to 1.07 ; P(trend ) = .06 ) . The inverse association between plasma folate and breast cancer risk was highly statistically significant among women consuming at least 15 g/day ( i.e. , approximately 1 drink/day ) of alcohol ( multivariable RR = 0.11 , 95 % CI = 0.02 to 0.59 for highest versus lowest quintile ) in contrast with that of women consuming less than 15 g/day ( multivariable RR = 0.72 , 95 % CI = 0.49 to 1.05 ) . The multivariable RR comparing women in the highest quintile of plasma vitamin B(6 ) levels with those in the lowest quintile was 0.70 ( 95 % CI = 0.48 to 1.02 ; P(trend ) = .09 ) . Plasma vitamin B(12 ) levels were inversely associated with breast cancer risk among premenopausal women ( multivariable RR = 0.36 , 95 % CI = 0.15 to 0.86 for highest versus lowest quintile ) but not among postmenopausal women . Plasma homocysteine was not associated with breast cancer risk . CONCLUSIONS Higher plasma levels of folate and possibly vitamin B(6 ) may reduce the risk of developing breast cancer . Achieving adequate circulating levels of folate may be particularly important for women at higher risk of developing breast cancer because of higher alcohol consumption Objective : We previously reported in an open-label pilot trial that a 24-ingredient multivitamin formula favorably influenced homocysteine concentration and LDL-C oxidation indices following 24 weeks of supplementation . Our current aim was to more thoroughly examine this same formula in a r and omized , placebo-controlled , clinical study . Methods : We examined 182 participants for selected plasma vitamin concentrations and clinical ly relevant variables including homocysteine , lipids and LDL-C oxidation indices at baseline and six months . Results : We found no significant differences between groups for any parameter at baseline . Following six months of vitamin supplementation , we observed elevations in plasma concentrations of vitamin B6 ( as pyridoxal 5′-phosphate ; PLP ) , vitamin B12 , folate , vitamin C , vitamin E and β-carotene ( p < 0.0001 ) , all of which were significantly greater than respective placebo group changes ( p < 0.0001 ) . Homocysteine decreased in the treatment ( 8.38 ± 2.9 vs. 6.93 ± 2.5 μmol/L ; p < 0.0001 ) and placebo group ( 8.17 ± 3.0 vs. 7.42 ± 2.2 μmol/L ; p < 0.0001 ) from baseline to six months , respectively , with reductions in the treatment group being greater than placebo ( p < 0.008 ) . LDL-C oxidation indices were also improved as LDL-C oxidation rate was decreased ( −0.39 μmol/min/g protein ; p < 0.0003 ) and LDL-C lag time increased ( 11.3 min ; p < 0.003 ) in supplemented participants . Further analysis also showed that LDL-C oxidation rate was lower ( p < 0.0007 ) and LDL-C lag time longer ( p < 0.0001 ) for the vitamin group than placebo treatment after six months . Conclusion : We conclude that a multi-ingredient vitamin formula with antioxidant properties has measurable effects on homocysteine and LDL-C oxidation indices Objective : We investigated the effects of mineral water fortified with folic acid , vitamins B6 , B12 , D and calcium on folate concentrations in serum and erythrocytes , serum vitamin B12 and plasma homocysteine concentrations in free-living subjects . In addition , we investigated the bioavailability of calcium added to mineral water by measuring urinary calcium excretion and serum alkaline phosphatase activity . Design : R and omized , controlled , double-blinded , parallel design . Setting : Outpatient dietary intervention with free-living subjects in Eastern Finl and .Subjects : Altogether , 66 subjects were recruited for the study . In all , 60 subjects completed the study . Interventions : The study began with a 2-week run-in period followed by an 8-week intervention period . During the intervention study , subjects consumed mineral water fortified with folic acid ( 563 μg/day ) , vitamins B6 ( 1 mg/day ) , B12 ( 7.5 μg/day ) , cholecalciferol ( 0.6 μg/day ) and calcium ( 563 mg/day ) or placebo mineral water . Results : The fortified mineral water increased serum and erythrocyte folate concentrations by 16.1±5.6 nmol/l ( P<0.001 ) and 199±76 nmol/l ( P<0.001 ) , respectively , and decreased plasma homocysteine concentration by 1.6 μmol/l ( P<0.001 ) . Urinary calcium excretion and serum alkaline phosphatase activity for 24 h increased significantly ( P<0.001 and P=0.01 respectively ) in the intervention group . Conclusions : Mineral water fortified with folic acid , vitamins B6 , B12 and D and calcium enhanced folate status and reduced plasma homocysteine concentration in normohomocysteinemic subjects without folate deficiency . Indirect measures of calcium and bone metabolism indicated that the calcium used in the fortification of the mineral water was bioavailable . Sponsorship : Olvi PLC , Iisalmi , Finl and The purpose of this study was to test whether low serum vitamin B-12 levels are associated with more rapid bone loss in elderly women . We archived sera and measured calcaneal bone  mineral density ( BMD ) in community-dwelling white women , aged 65 yr and over , who participated in the Study of Osteoporotic Fractures . BMD of the hip and subregions was measured 2 yr later . Repeat measurements of calcaneal and hip BMD were obtained after 5.9 and 3.5 yr of follow-up , respectively .  Serum vitamin B-12 assays  were performed in 83 r and omly selected participants with initial and repeat measurements of BMD who were not taking estrogen replacement therapy at baseline . After adjusting for age , weight , and clinic site , women with vitamin B-12 levels at or below 280 pg/ml ( 207.2 pmol/liter ; lowest quintile ) experienced an annual change of -1.6 % ( 95 % confidence interval , -2.4 % to -0.8 % ) in total hip BMD , compared with -0.2 % ( -0.5 % to 0.2 % ) in women with levels above 280 pg/ml ( P = 0.003 ) . Results were similar when subregions of the hip were analyzed separately . Serum vitamin B-12 levels were not significantly associated with calcaneal bone loss . We conclude that low serum vitamin B-12 levels are associated with increased rates of hip , but not calcaneal , bone loss in older women 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 BACKGROUND Very high plasma homocysteine levels are characteristic of homocystinuria , a rare autosomal recessive disease accompanied by the early onset of generalized osteoporosis . We therefore hypothesized that mildly elevated homocysteine levels might be related to age-related osteoporotic fractures . METHODS We studied the association between circulating homocysteine levels and the risk of incident osteoporotic fracture in 2406 subjects , 55 years of age or older , who participated in two separate prospect i ve , population -based studies . In the Rotterdam Study , there were two independent cohorts : 562 subjects in cohort 1 , with a mean follow-up period of 8.1 years ; and 553 subjects in cohort 2 , with a mean follow-up period of 5.7 years . In the Longitudinal Aging Study Amsterdam , there was a single cohort of 1291 subjects , with a mean follow-up period of 2.7 years . Multivariate Cox proportional-hazards regression models were used for analysis of the risk of fracture , with adjustment for age , sex , body-mass index , and other characteristics that may be associated with the risk of fracture or with increased homocysteine levels . RESULTS During 11,253 person-years of follow-up , osteoporotic fractures occurred in 191 subjects . The overall multivariable-adjusted relative risk of fracture was 1.4 ( 95 percent confidence interval , 1.2 to 1.6 ) for each increase of 1 SD in the natural-log-transformed homocysteine level . The risk was similar in all three cohorts studied , and it was also similar in men and women . A homocysteine level in the highest age-specific quartile was associated with an increase by a factor of 1.9 in the risk of fracture ( 95 percent confidence interval , 1.4 to 2.6 ) . The associations between homocysteine levels and the risk of fracture appeared to be independent of bone mineral density and other potential risk factors for fracture . CONCLUSIONS An increased homocysteine level appears to be a strong and independent risk factor for osteoporotic fractures in older men and women Forty-two female college students , age 18 - 29 yr . and consuming nutritionally balanced meals in the college cafeteria participated . Subjects discontinued all vitamin-mineral supplements ( VMS ) for 17 days and were r and omly assigned to one of two treatments , either a placebo , or VMS supplying the United States Recommended Daily Allowance ( USRDA ) of all vitamins , zinc , iron , iodine , copper , and 60 % of the USRDA of calcium , 50 % of magnesium and 45 % of phosphorus . Treatments were consumed for 77 days . Fasting pre- and post-treatment blood chemistries were compared . VMS yielded significant increases ( p less than 0.05 ) in serum vitamin B-12 ( + 25.05 pg/ml ) , vitamin C ( + 0.35 mg/dl ) and folate ( + 7.40 ng/ml ) . No significant changes ( p greater than 0.05 ) in hematological or other blood chemistries were observed . Significant decreases in the number of below-normal serum indicators of vitamin status ( p less than 0.05 ) and iron status ( p less than 0.005 ) were seen with VMS . No significant changes were seen with placebo ( p greater than 0.05 ) Objectives : To evaluate the acceptance of a multinutrient liquid nutrition supplement in psycho-geriatric nursing home patients and the effect on weight , plasma nutrients and activities of daily life . Design : Double-blind , placebo-controlled 12-week intervention study . Setting : Two nursing homes in Boxtel , The Netherl and s . Subjects : Forty-two ( body mass index ( BMI ) < 23 kg/m2 for men or < 25 kg/m2 for women ) psycho-geriatric nursing home patients aged 60 y or over . Interventions : Provision with a complete micronutrient-enriched liquid nutrition supplement of 125 ml and 0.6 MJ ( 135 kcal ) or placebo twice daily during daytime between main meals . Study parameters were assessed at 0 , 6 and 12 weeks . Main Outcome for Measures : Weight , Barthel index of daily activities , several plasma values ( albumin , C-reactive protein ( CRP ) , homocysteine , thiamine , thiamine diphosphate ( TDF ) , vitamin B6 , vitamin B12 , folic acid , vitamin D ) , bowel function . Results : The supplement was well accepted . Thirty-five patients completed the intervention period ( 16 control group ; 19 supplement group ) . Baseline daily nutrient intake was low . A statistically significant improvement was observed for body weight ( difference between groups 2.2 kg , P=0.03 ) , and homocysteine , vitamin B1 , TDF , vitamin B6 , vitamin B12 , folate and vitamin D in the supplement group compared to the placebo group . No significant difference was observed in the Barthel index ( mean difference −0.3±1.1 for both groups ) . No difference in occurrence of diarrhoea was observed . Conclusions : The study shows that nutritional supplementation is well accepted and can improve the nutritional status of psycho-geriatric nursing home patients .Sponsorship : Numico Research BV OBJECTIVES To examine the association of cognitive impairment with platelet activation and reactive oxygen species and total homocysteine levels ; and to assess the biochemical efficacy of treatment with aspirin and vitamin supplements in people at high risk of dementia . SUBJECTS People with dementia or mild cognitive impairment . DESIGN AND INTERVENTION In a 2 x 2 x 2 factorial design trial , 149 people at high-risk of dementia were r and omized to receive either low-dose aspirin ( 81 mg ) or placebo ; and folic acid ( 2 mg ) plus vitamin B12 ( 1 mg ) or placebo ; and vitamins E ( 500 mg ) plus C ( 200 mg ) or placebo . Participants were seen twice before and once after 12 weeks of treatment . MAIN OUTCOME MEASURES At each visit , participants had their cognitive function assessed and had blood collected for homocysteine , folate and vitamin B12 determination and urine collected for markers of platelet activation ( 11-dehydro-thromboxane B2 ) and reactive oxygen species ( 8-epi-PGF2 alpha ) . RESULTS Prior to treatment , cognitive function was inversely related with homocysteine and with urinary thromboxane and isoprostane , and these associations were independent of age . Aspirin was associated with a median reduction in 11-dehydrothromboxane B2 of 73 % ( P < 0.001 ) . B-vitamins lowered plasma homocysteine concentration by 30 % ( P < 0.0001 ) and antioxidant vitamins lowered isoprostane excretion by 26 % ( P < 0.1 ) . No effect of treatment on cognitive function was detected . CONCLUSIONS Aspirin and B-vitamins were effective in reducing biochemical factors associated with cognitive impairment in people at risk of dementia . Large-scale trials are now required to assess the relevance of aspirin and B-vitamins for the maintenance of cognitive function in people at risk of dementia Objectives : To investigate , in an elderly population : ( 1 ) the effects of oral B-vitamin therapy on P-tHcys , S-MMA and Hb/MCV , ( 2 ) the appropriate decision limit for ‘ high ’ metabolite concentrations and ( 3 ) the estimated prevalence of vitamin B12/folate deficiency on the basis of different decision limits . Design : Double-blind placebo-controlled intervention study . Setting : Outpatient clinic . Subjects : A total of 209 community-dwelling subjects , median age 76 y ( range 70–93 ) y. Interventions : Four months of oral daily supplementation with 0.5 mg cyanocobalamin , 0.8 mg folic acid and 3 mg vitamin B6 . Results : High P- tHcys was found in 64 % of men and 45 % of women , high S-MMA in 11 % of both . Vitamin B12 deficiency was observed in 7.2 % and folate deficiency in 11 % of all subjects . Health-related upper reference limits for the metabolites at the start were higher than the laboratory 's upper reference limits . The latter were , however , similar to those of the vitamin replete group . There was a significant decrease in P-tHcys ( P<0.001 ) and S-MMA ( P=0.009 ) after 4 months of vitamin treatment . In a multivariate analysis , the P-Hcys change correlated positively with baseline P-tHcys and inversely with baseline P-folate and transferrin saturation ( Fe/TIBC ratio ) . The S-MMA change correlated with baseline S-MMA and inversely with baseline vitamin B12 and age . Conclusions : Suboptimal vitamin status is an important cause of elevated P-tHcys and S-MMA in apparently healthy elderly subjects .  Oral B-vitamin therapy is an effective and convenient way to normalise P-tHcys and S-MMA.Sponsorship : Support — Recip AB Homocysteine has been related to increased risk of CVD . Matrix degradation and inflammation may be involved in this link between hyperhomocysteinaemia and CVD . Recent studies suggest that cystatin C can modulate matrix degradation and inflammation . The present study measured cystatin C at protein ( plasma ) and mRNA levels ( peripheral blood mononuclear cells ( P BMC ) ) in hyperhomocysteinaemic individuals ( n 37 , female seven and male thirty , aged 20 - 70 years ) before and after B-vitamin supplementation for 3 months in a r and omised , placebo-controlled double-blind trial . In a cross-sectional study , seventeen of the hyperhomocysteinaemic subjects were age- and sex-matched to healthy controls ( n 17 ) . Our main findings were : ( i ) as compared with controls , hyperhomocysteinaemic subjects tended to have higher plasma concentrations of cystatin C and lower mRNA levels of cystatin C in P BMC ; ( ii ) compared with placebo , treatment of hyperhomocysteinaemic individuals with B-vitamins significantly increased plasma levels of cystatin C and mRNA levels of cystatin C in P BMC ; ( iii ) while plasma levels of cystatin C were positively correlated with plasma levels of TNF receptor-1 , mRNA levels of cystatin C in P BMC were inversely correlated with this TNF parameter . Taken together , our findings suggest that disturbed cystatin C levels may be a characteristic of hyperhomocysteinaemic individuals , potentially related to low- grade systemic inflammation in hyperhomocysteinaemic subjects , and that B-vitamins may modulate cystatin C levels in these individuals 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 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 Elevated plasma homocysteine ( tHcy ) is a risk factor for Alzheimer 's disease ( AD ) , and thus B vitamins may have a role in the prevention of AD . The objective of this study was to determine if tHcy lowering vitamins decrease the circulating levels of A-beta protein 1 - 40 ( A beta 40 ) . We r and omized 299 older men to treatment with 2 mg of folate , plus 25 mg of B6 and 400 microg of B12 , or placebo . After 2 years of treatment the mean ( S.E. ) increase of A beta 40 was 7.0 pg/ml ( 8.4 ) in the vitamin group ( 4.9 % ) , and 26.8 pg/ml ( 7.7 ) ( 18.5 % ) in the placebo group . We conclude that B vitamins may decrease the plasma level of A beta 40 and have a role in the prevention of AD Blood indicators of eight vitamins ( B1 , B2 , B6 , C , E , A , B12 , folate ) and six minerals ( Cu , Mg , Zn , Ca , P , Al ) were measured in 86 athletes before and after a 7- to 8-month period of training . During this period half consumed a multivitamin/mineral supplement and a matched group took a placebo . Following the supplementation period , blood biochemical indicators of B1 , B6 , B12 , and folate status all increased but there were no significant effects of supplementation on B2 , C , E , and A , or on the blood levels of any of the minerals . The supplementation had no effect on red or white cell counts or on hemoglobin levels . Irrespective of the supplementation , some blood measures varied according to sex , females evidencing significantly higher values than males for vitamins C , E , copper , magnesium , and aluminium , with B2 being higher in males . It is concluded that 7 to 8 months of multivitamin/mineral supplementation increased the blood nutritional status of some vitamins but did not affect any blood mineral levels , and that some blood nutritional indicators may vary according to sex Objectives To determine whether in the current study the supply of a nutrient dense drink has a positive effect on mental and physical function of institutionalized elderly people . Design A 24-week , r and omized , double-blind , placebo-controlled , parallel-group , intervention trial . Setting Homes for the elderly and nursing homes in the Netherl and s. Participants Institutionalized elderly people older than 60 years , with a BMI ≤ 30 kg/m2 , and a Mini-Mental State Examination score of at least 10 points . InterventionIn addition to their usual diet the participants ( n=176 ) received either a nutrient dense drink or a placebo drink twice a day during 24 weeks . Measurements The functionality measures included cognitive function , mood , physical performance and the ability to perform activities of daily living . Results In the supplement group a favorable effect of the intervention drink on body weight ( 1.6 kg difference in change ; P = .035 ) , calf circumference ( 0.9 cm difference in change ; P = .048 ) , and blood values ( e.g. Hcy decreased from 16.8 to 11.2 µmol/L in the supplement group ) was found . In the total group no significant effect was found on functionality outcomes . However , a subgroup of participants with BMI at baseline below 24.4 kg/m2 performed better on the cognitive subscale of Alzheimer ’s Disease Assessment Scale ( P = .09 ) , and its language sub score ( P = .01 ) after 24 weeks of intervention . Conclusion The results in the total group of this trial suggest that the nutritional supplement used in this study improves nutritional status . Furthermore , the results of this trial suggest that it is effective as treatment for decreasing function in a subgroup of institutionalized elderly people with low BMI PURPOSE Elevated C-reactive protein levels are associated with the risk of cardiovascular disease and diabetes . We examined whether multivitamins reduce C-reactive protein levels . METHODS We performed a post hoc subgroup analysis of a 6-month , r and omized , double-blind , placebo-controlled trial . Patients ( n = 87 ; mean age , 53 years ) for whom frozen plasma sample s were available ; who did not have an inflammatory condition at baseline ; and who were not hospitalized , taking antibiotics , smoking , or starting statin therapy during the study were included .  C-reactive protein and plasma vitamin levels  were measured at baseline and 6 months . RESULTS At 6 months , C-reactive protein levels were significantly lower in the multivitamin group than in the placebo group ( between-group difference = -0.91 mg/L ; 95 % confidence interval : -1.52 to -0.30 ; P= 0.005 ) . The reduction in C-reactive protein levels was most evident in patients who had elevated levels ( > or = 1.0 mg/L ) at baseline . Of the six vitamins measured ( C , E , B(6 ) , B(12 ) , folate , and beta carotene ) , only vitamin B(6 ) ( baseline : r = -0.31 , P= 0.003 ; 6 months : r = -0.29 , P= 0.006 ) and vitamin C ( baseline : r = -0.25 , P= 0.02 ) were inversely associated with C-reactive protein level . CONCLUSION In a post hoc analysis of a r and omized , double-blind , placebo-controlled study , multivitamin use was associated with lower C-reactive protein levels . Other similarly formulated multivitamins may yield comparable results Objective : To determine the effect of folic acid , vitamin B6 and B12 fortified spreads on the blood concentrations of these vitamins and homocysteine . Design and setting : A 6-week r and omized , double-blinded , placebo-controlled , parallel trial carried out in a clinical research center . Subjects : One hundred and fifty healthy volunteers ( 50 % males ) . Interventions : For 6 weeks , the subjects consumed the test spreads ( 20 g/day ) : containing per 20 g ( 1 ) 200 μg folic acid , 2 μg vitamin B12 and 1 mg vitamin B6 , or ( 2 ) 400 μg folic acid , 2 μg vitamin B12 and 1 mg vitamin B6 or ( 3 ) no B-vitamins ( control spread ) . Results : The B-vitamin status increased on using the test spreads , with the largest effect on the serum folate concentration : 48 % in men and 58 % in women on spread 1 and 92 and 146 % , respectively , on spread 2 ( P-values all < 0.05 ) . The plasma homocysteine decreased in the groups treated with the fortified spreads as compared to the control group . Average decreases were for males : 0.7±1.5 μmol/l ( 6.8 % ) on spread 1 and 1.7±1.7 μmol/l ( 17.6 % ) on spread 2 and for females : 1.4±1.2 μmol/l ( 14.2 % ) and 2.4±2.0 μmol/l ( 23.3 % ) , respectively ( P-values all < 0.05 ) . Conclusions : Consumption of a spread fortified with folic acid , vitamin B6 and vitamin B12 for 6 weeks significantly increases the blood concentrations of these vitamins and significantly decreases the plasma concentration of homocysteine . Fortified staple foods like spreads can contribute to the lowering of homocysteine concentrations . Sponsorship : Unilever Research and Development , Vlaardingen , The Netherl and
target: RESULTS The meta- analysis of observational studies showed a weaker slope of dose-response relations than the meta- analysis of RCTs .
  The obtained dose-response estimate between vitamin B-12 intake and status provides complementary evidence to underpin recommendations for a vitamin B-12 intake of population
background: BACKGROUND Many r and omized controlled trials ( RCTs ) and observational studies have provided information on the association between vitamin B-12 intake and biomarkers .
  The use of these data to estimate dose-response relations provides a useful means to summarize the body of evidence .
  OBJECTIVE We systematic ally review ed studies that investigated vitamin B-12 intake and biomarkers of vitamin B-12  status and estimated dose-response relations with the use of a meta- analysis .