Effects of vitamin B-12 supplementation on neurologic and cognitive function in older people: a randomized controlled trial12 Longitudinal association of vitamin B-6, folate, and vitamin B-12 with depressive symptoms among older adults over time. Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms--the Beyond Ageing Project: a randomized controlled trial. Randomized controlled trials of vitamin D and cancer incidence: A modeling study Single arm phase II study of oral vitamin B12 for the treatment of musculoskeletal symptoms associated with aromatase inhibitors in women with early stage breast cancer Vitamin Intervention for Stroke Prevention Trial: An Efficacy Analysis Safety of a fat-reduced diet: the Dietary Intervention Study in Children (DISC). 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. Plasma folate, vitamin B-6, vitamin B-12, and risk of breast cancer in women. A parallel group double-blind RCT of vitamin D3 assessing physical function: is the biochemical response to treatment affected by overweight and obesity? Vitamin B-12 supplementation improves arterial function in vegetarians with subnormal vitamin B-12 status Intake of Folate, Vitamin B6 and Vitamin B12 and the Risk of CHD: The Japan Public Health Center-Based Prospective Study Cohort I B-group vitamin supplementation mitigates oxidative damage after acute ischaemic stroke. 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 Impact of a multiple-micronutrient fortified salt on the nutritional status and memory of schoolchildren. Antioxidants and basal cell carcinoma of the skin: A nested case–control study Folate, vitamin B6, multivitamin supplements, and colorectal cancer risk in women.
Background : Moderate vitamin B-12 deficiency is relatively common in older people . However , there is little robust evidence on the effect of vitamin B-12 supplementation on neurologic and cognitive outcomes in later life . Objective : We investigated whether vitamin B-12 supplementation benefits neurologic and cognitive function in moderately vitamin B-12–deficient older people . Design : We conducted a double-blind , r and omized , placebo-controlled trial in 7 general practice s in South East Engl and , United Kingdom . Study participants were aged ≥75 y and had moderate vitamin B-12 deficiency ( serum vitamin B-12 concentrations : 107–210 pmol/L ) in the absence of anemia and received 1 mg crystalline vitamin B-12 or a matching placebo as a daily oral tablet for 12 mo . Peripheral motor and sensory nerve conduction , central motor conduction , a clinical neurologic examination , and cognitive function were assessed before and after treatment . Results : A total of 201 participants were enrolled in the trial , and 191 subjects provided outcome data . Compared with baseline , allocation to vitamin B-12 was associated with a 177 % increase in serum concentration of vitamin B-12 ( 641 compared with 231 pmol/L ) , a 331 % increase in serum holotranscobalamin ( 240 compared with 56 pmol/L ) , and 17 % lower serum homocysteine ( 14.2 compared with 17.1 μmol/L ) . In intention-to-treat analysis of covariance models , with adjustment for baseline neurologic function , there was no evidence of an effect of supplementation on the primary outcome of the posterior tibial compound muscle action potential amplitude at 12 mo ( mean difference : −0.2 mV ; 95 % CI : –0.8 , 0.3 mV ) . There was also no evidence of an effect on any secondary peripheral nerve or central motor function outcome , or on cognitive function or clinical examination . Conclusion : Results of the trial do not support the hypothesis that the correction of moderate vitamin B-12 deficiency , in the absence of anemia and of neurologic and cognitive signs or symptoms , has beneficial effects on neurologic or cognitive function in later life . This trial was registered at www.is rct n.com as IS RCT N54195799 BACKGROUND B-vitamin deficiencies have been associated with depression ; however , there is very little prospect i ve evidence from population -based studies of older adults . OBJECTIVE We examined whether dietary intakes of vitamins B-6 , folate , or vitamin B-12 were predictive of depressive symptoms over an average of 7.2 y in a community-based population of older adults . DESIGN The study sample consisted of 3503 adults from the Chicago Health and Aging project , an ongoing , population -based , biracial ( 59 % African American ) study in adults aged > or = 65 y.  Dietary assessment was made by food-frequency question naire . Incident depression was measured by the presence of > or = 4 depressive symptoms from the 10-item version of the Center for Epidemiologic Studies Depression scale . RESULTS The logistic regression models , which used generalized estimating equations , showed that higher total intakes , which included supplementation , of vitamins B-6 and B-12 were associated with a decreased likelihood of incident depression for up to 12 y of follow-up , after adjustment for age , sex , race , education , income , and antidepressant medication use . For example , each 10 additional milligrams of vitamin B-6 and 10 additional micrograms of vitamin B-12 were associated with 2 % lower odds of depressive symptoms per year . There was no association between depressive symptoms and food intakes of these vitamins or folate . These associations remained after adjustment for smoking , alcohol use , widowhood , caregiving status , cognitive function , physical disability , and medical conditions . CONCLUSION Our results support the hypotheses that high total intakes of vitamins B-6 and B-12 are protective of depressive symptoms over time in community-residing older adults BACKGROUND Evidence remains unclear as to whether folic acid ( FA ) and vitamin B-12 supplementation is effective in reducing depressive symptoms . OBJECTIVES The objective was to determine whether oral FA + vitamin B-12 supplementation prevented cognitive decline in a cohort of community-dwelling older adults with elevated psychological distress . DESIGN A r and omized controlled trial ( RCT ) with a completely crossed 2 × 2 × 2 factorial design comprising daily oral 400 μg FA + 100 μg vitamin B-12 supplementation ( compared with placebo ) , physical activity promotion , and depression literacy with comparator control interventions for reducing depressive symptoms was conducted in 900 adults aged 60 - 74 y with elevated psychological distress ( Kessler Distress 10-Scale ; scores > 15 ) . The 2-y intervention was delivered in 10 modules via mail with concurrent telephone tracking calls . Main outcome measures examined change in cognitive functioning at 12 and 24 mo by using the Telephone Interview for Cognitive Status-Modified ( TICS-M ) and the Brief Test of Adult Cognition by Telephone ( processing speed ) ; the Informant Question naire on Cognitive Decline in the Elderly was administered at 24 mo . RESULTS FA + vitamin B-12  improved the TICS-M total ( P = 0.032 ; effect size d = 0.17 ) , TICS-M immediate ( P = 0.046 ; d = 0.15 ) , and TICS-M delayed recall ( P = 0.013 ; effect size d = 0.18 ) scores at 24 mo in comparison with placebo . No significant changes were evident in orientation , attention , semantic memory , processing speed , or informant reports . CONCLUSION Long-term supplementation of daily oral 400 μg FA + 100 μg vitamin B-12 promotes improvement in cognitive functioning after 24 mo , particularly in immediate and delayed memory performance . This trial was registered at clinical trials.gov as NCT00214682 Although geographic ecological studies and observational studies find that ultraviolet B exposure and 25-hydroxyvitamin D [ 25(OH)D ] concentrations are inversely correlated with 15–20 types of cancer , few r and omized controlled trials ( RCTs ) of vitamin D support those findings . The poor design of some RCTs may account for that lack of support . Most vitamin D RCTs to date have considered the vitamin D dose , rather than initial , final , or changes in , serum 25(OH)D concentrations . Here a model is developed for use in design ing and analyzing vitamin D RCTs with application to cancer incidence . The input variables of the model are  vitamin D dose , baseline and achieved 25(OH)D concentrations , known rates of cancer for the population  , and numbers of participants for the treatment and placebo arms is estimated — vitamin D dosage and numbers of participants are varied to achieve desired hazard ratio significance , using information from two  vitamin D RCTs on cancer incidence conducted in Nebraska with good agreement between the model estimates and reported hazard ratios . Further improvements to the conduct of vitamin D RCTs would be to start the trial with a moderate bolus dose to achieve the desired 25(OH)D concentrations , and bloodspot 25(OH)D assay use in summer and winter annually to monitor seasonal and long-term changes in 25(OH)D concentration and compliance , and to allow dosage adjustment for achievement of desired vitamin D status Breast cancer patients receiving endocrine therapy with aromatase Inhibitors ( AIs ) often experience musculoskeletal and joint-related side effects . The purpose of this study was to evaluate the effect of Vitamin B12 supplements on musculoskeletal symptoms such as pain and arthralgias induced by AIs and to correlate response with serum and inflammatory biomarkers . Upon receiving approval by the Institutional Review Board ( IRB ) , the majority of the patients consented into the study were treated at the Texas Tech Breast Care Center . Included were patients who had a diagnosis of invasive breast cancer ( Stages I-III ) , and were experiencing significant musculoskeletal symptoms associated to AIs . Only patients with an average pain score ≥ 4 , as assessed by the Brief Pain Inventory-Short Form ( BPI-SF ) question naire , were included in the study . Participants received 2500 mcg of sublingual vitamin B12 daily for 90 days . Assessment s at baseline and at 3 months included : BPI-SF pain scores , the impact on quality of life determined by Functional Assessment of Cancer Therapy-Endocrine Symptoms ( FACT-ES ) , and correlative serum markers relative to baseline ( a pre-post study ) . A total of forty-one patients were enrolled . Average pain scores were improved by 34 % ( P < .0001 ) at 3 months compared to baseline . In addition , a 23 % improvement in worst pain was noted ( P = .0003 ) . Analysis of the results for the FACT-ES scoring showed improvement on all scales . No significant adverse events were observed . Decrease in pain score was correlated with increased serum B12 levels . This study suggests that Vitamin B12  reduces pain and improves quality of life for patients taking AIs who experienced AI-related musculoskeletal symptoms . If confirmed in large r and omized prospect i ve trials , Vitamin B12 would be a safe and cost-effective option for the treatment of AI-related musculoskeletal symptoms Background and Purpose — The Vitamin Intervention for Stroke Prevention trial ( VISP ) intention-to-treat analysis did not show efficacy of combined vitamin therapy for recurrent vascular events in patients with nondisabling stroke . Reasons for lack of efficacy may have included folate fortification of grain products , inclusion of the recommended daily intake for B12 in the low-dose arm , treatment with parenteral B12 in patients with low B12 levels in both study arms , a dose of B12 too low for patients with malabsorption , supplementation with non study vitamins , and failure of patients with significant renal impairment to respond to vitamin therapy . We conducted an efficacy analysis limited to patients most likely to benefit from the treatment , based on hypotheses arising from evidence developed since VISP was initiated . The criteria for this subgroup were defined before any data analysis . Methods — For this analysis , we excluded patients with low and very high B12 levels at baseline ( < 250 and > 637 pmol/L , representing the 25th and 95th percentiles ) , to exclude those likely to have B12 malabsorption or to be taking B12 supplements outside the study and patients with significant renal impairment ( glomerular filtration rate < 46.18 ; the 10th percentile ) . Results — This subgroup represents 2155 patients ( 37 % female ) , with a mean age of 66±10.7 years . For the combined end point of ischemic stroke , coronary disease , or death , there was a 21 % reduction in the risk of events in the high-dose group compared with the low-dose group ( unadjusted P=0.049 ; adjusted for age , sex , blood pressure , smoking , and B12 level P=0.056 ) . In Kaplan – Meier survival analysis comparing 4 groups , patients with a baseline B12 level at the median or higher r and omized to high-dose vitamin had the best overall outcome , and those with B12 less than the median assigned to low-dose vitamin had the worst ( P=0.02 for combined stroke , death , and coronary events ; P=0.03 for stroke and coronary events ) . Conclusions — In the era of folate fortification , B12 plays a key role in vitamin therapy for total homocysteine . Higher doses of B12 , and other treatments to lower total homocysteine may be needed for some patients OBJECTIVE To assess the relationship between energy intake from fat and anthropometric , biochemical , and dietary measures of nutritional adequacy and safety . DESIGN Three-year longitudinal study of children participating in a r and omized controlled trial ;  intervention and usual care group data pooled to assess effects of self-reported fat intake ; longitudinal regression analyses of measurements at baseline , year 1 , and year 3 . PARTICIPANTS Six hundred sixty-three children ( 362 boys and 301 girls ) , 8 to 10 years of age at baseline , with elevated low-density lipoprotein cholesterol , who are participants of the Dietary Intervention Study in Children . MEASURES  Energy intake from fat assessed from three 24-hour recalls at each time point was the independent variable . Outcomes were anthropometric measures ( height , weight , body mass index , and sum of skinfolds ) , nutritional biochemical determinations ( serum ferritin , zinc , retinol , albumin , beta-carotene , and vitamin E , red blood cell folate , and hemoglobin ) , and dietary micronutrients ( vitamins A , C , E , thiamin , riboflavin , niacin , vitamins B-6 , B-12 , folate , calcium , iron , zinc , magnesium , and phosphorus )  . RESULTS Lower fat intake was not related to anthropometric measures or serum zinc , retinol , albumin , beta-carotene , or vitamin E. Lower fat intake was related to : 1 ) higher levels of red blood cell folate and hemoglobin , with a trend toward higher serum ferritin ; 2 ) higher intakes of folate , vitamin C , and vitamin A , with a trend toward higher iron intake ; 3 ) lower intakes of calcium , zinc , magnesium , phosphorus , vitamin B-12 , thiamin , niacin  , and riboflavin ;  4 ) increased risk of consuming less than two-thirds of the Recommended Dietary Allowances for calcium in girls at baseline , and zinc and vitamin E in boys and girls at all visits . CONCLUSIONS Lower fat intakes during puberty are nutritionally adequate for growth and for maintenance of normal levels of nutritional biochemical measures , and are associated with beneficial effects on blood folate and hemoglobin . Although lower fat diets were related to lower self-reported intakes of several nutrients , no adverse effects were observed on blood biochemical measures of nutritional status . Current public health recommendations for moderately lower fat intakes in children during puberty may be followed safely 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 B vitamins such as folate , vitamin B-6 , and vitamin B-12 are coenzymes that are important for DNA integrity and stability . Deficiency in these B vitamins may promote tumor carcinogenesis . OBJECTIVE We prospect ively evaluated plasma concentrations of folate , pyridoxal 5-phosphate ( PLP ; the principal active form of vitamin B-6 ) , and vitamin B-12 in relation to breast cancer risk . DESIGN We included 848 incident cases of invasive breast cancer identified as of 31 March 2004 , and 848 individually matched control subjects from 28 345 women in the Women 's Health Study aged > or = 45 y who provided blood sample s and had no history of cancer and cardiovascular disease at baseline in 1993 .  Logistic regression controlling for matching factors and other risk factors for breast cancer was used to estimate relative risks ( RRs ) and 95 % CIs . All statistical tests were 2 sided . RESULTS Plasma concentrations of folate , PLP , and vitamin B-12 were not associated with overall risk of breast cancer . Women in the highest quintile group relative to those in the lowest quintile had multivariate RRs of 1.42 ( 95 % CI : 1.00 , 2.02 ) for plasma folate ( P for trend = 0.21 ) , 0.91 ( 95 % CI : 0.63 , 1.30 ) for plasma PLP ( P for trend = 0.48 ) , and 1.29 ( 95 % CI : 0.92 , 1.82 ) for plasma vitamin B-12 ( P for trend = 0.18 ) . However , higher plasma folate concentrations were moderately associated with an increased risk of developing premenopausal breast cancer ( P for trend = 0.04 ) and for developing estrogen receptor (ER)-positive or progesterone receptor (PR)-positive breast tumors ( P for trend < or = 0.06 ) . Conversely , an inverse association was seen between plasma PLP and postmenopausal breast cancer ( P for trend = 0.04 ) . CONCLUSIONS Data from this study suggest that B vitamins , including folate , vitamin B-6 , and vitamin B-12 , may confer little or no reduction in overall risk of developing breast cancer . The observed positive associations of folate status with risk of developing premenopausal breast cancer and ER-positive or PR-positive tumors are unexpected . Additional research is needed to eluci date the role of folate in breast cancer development Summary Vitamin D may affect skeletal muscle function . In a double-blind , r and omised , placebo-controlled trial , we found that vitamin D3 supplementation ( 400 or 1,000 I.U. vs. placebo daily for 1 year with bimonthly study visits ) does not improve grip strength or reduce falls . Introduction This study aim ed to test the supplementation effects of vitamin D3 on physical function and examine associations between overweight/obesity and the biochemical response to treatment . Methods In a parallel group double-blind RCT , healthy postmenopausal women from North East Scotl and ( latitude—57 ° N ) aged 60–70 years ( body mass index ( BMI ) , 18–45 kg/m2 ) were assigned ( computer r and omisation ) to daily vitamin D3 ( 400 I.U. ( n = 102)/1,000 I.U. ( n = 101 ) ) or matching placebo ( n = 102 ) ( 97 , 96 and 100 participants analysed for outcomes , respectively ) from identical coded containers for 1 year . Grip strength ( primary outcome ) , falls , diet , physical activity and ultraviolet B radiation exposure were measured bimonthly , as were serum 25(OH)D , adjusted calcium ( ACa ) and phosphate . Fat/lean mass ( dual energy X-ray absorptiometry ) , anthropometry , 1,25-dihydroxyvitamin D and parathyroid hormone were measured at baseline and 12 months . Participants and research ers were blinded throughout intervention and analysis . Results Treatment had no effect on grip strength ( mean change (SD)/year = −0.5 ( 2.5 ) , −0.9 ( 2.7 ) and −0.4 ( 3.3 ) kg force for 400/1,000 I.U. vitamin D3 and placebo groups , respectively ( P = .10 , ANOVA ) ) or falls ( P = .65 , chi-squared test ) . Biochemical responses were similar across BMI categories ( < 25.25–29.99 , ≥30 kg/m2 ) with the exception of a small change at 12-months in serum ACa in overweight compared to non-overweight participants ( P = .01 , ANOVA ; 1,000 I.U. group ) . In the  placebo group , 25(OH)D peak concentration change ( winter to summer ) was negatively associated with weight ( r = −.268 ) , BMI ( r = −.198 ) , total ( r = −.278 ) and trunk fat mass ( r = −.251 ) , with total and trunk fat mass predictive of winter to summer 25(OH)D change ( P = .01/.004 respectively , linear regression ) . Conclusion We found no evidence of an improvement in physical function following vitamin D3 supplementation for 1 year Objective Vegetarians are more vascular-healthy but those with subnormal vitamin B-12 status have impaired arterial endothelial function and increased intima-media thickness . We aim ed to study the impact of vitamin B-12 supplementation on these markers , in the vegetarians . Design Double-blind , placebo controlled , r and omised crossover study . Setting Community dwelling vegetarians . Participants Fifty healthy vegetarians ( vegetarian diet for at least 6 years ) were recruited . Intervention : Vitamin B-12 ( 500µg/day ) or identical placebo were given for 12 weeks with 10 weeks of placebo-washout before crossover ( n=43 ) , and then open label vitamin B-12 for additional 24 weeks (n=41).MeasurementHow-mediated dilation of brachial artery ( FMD ) and intima-media thickness ( IMT ) of carotid artery were measured by ultrasound . Results The mean age of the subjects was 45 + 9 years and 22 ( 44 % ) were male . Thirty-five subjects ( 70 % ) had serum B-12 levels < 150pmol/l . Vitamin B-12 supplementation significantly increased serum vitamin B-12 levels ( p<0.0001 ) and lowered plasma homocysteine ( p<0.05 ) . After vitamin B-12 supplementation but not placebo , significant improvement of brachial FMD ( 6.3±1.8 % to 6.9±1.9 % ; p<0.0001 ) and in carotid IMT ( 0.69±0.09 mm to 0.67±0.09 mm , p<0.05 ) were found , with further improvement in FMD ( to 7.4±1.7 % ; p<0.0001 ) and IMT ( to 0.65±0.09 mm ; p<0.001 ) after 24 weeks open label vitamin B-12 . There were no significant changes in blood pressures or lipid profiles . On multivariate analysis , changes in B-12 ( β=0.25 ; p=0.02 ) but not homocysteine were related to changes in FMD , ( R=0.32 ; F value=3.19 ; p=0.028 ) . Conclusions Vitamin B-12 supplementation improved arterial function in vegetarians with subnormal vitamin B-12 levels , proposing a novel strategy for atherosclerosis prevention Objective : To investigate the association of dietary folate , vitamin B6 ( VB6 ) and vitamin B12 ( VB12 ) with the risk of coronary heart disease among middle-aged persons . Methods : A total of 40,803 subjects aged 40–59 years living in the community who were free of prior diagnoses of cardiovascular disease and cancer and who completed a food frequency question naire were followed from 1990–1992 to the end of 2001 in the Japan Public Health Center-based Prospect i ve Study . Results : After 468,472 person-years of follow-up , 251 coronary heart disease incidents were documented . Coronary heart disease and definite myocardial infa rct ion were inversely associated with dietary intake of folate , VB6 and VB12 after adjustment for age and sex , but the associations were attenuated after further adjustment for smoking , dietary and other cardiovascular risk factors . However , among non-multivitamin supplement users , multivariable hazard ratios ( 95 % confidence intervals ) in the highest vs. lowest quintiles of VB6 intake were 0.60 ( 0.37–0.97 ) for total coronary heart disease and 0.52 ( 0.29–0.91 ) for definite myocardial infa rct ion , and the inverse associations with VB12 were marginally significant . The combination of below-median intake of three vitamins or of only B6 conferred a twice excess risk of total coronary heart disease . Conclusions : Dietary intake of VB6 was associated with a reduced risk of coronary heart disease  among middle-aged non-multivitamin supplement users . Dietary folate and VB12 were also suggested to be protective factors for coronary heart disease Evidence shows that there is a rapid increase in the production of markers of oxidative damage immediately following acute stroke and that endogenous antioxidant defences are rapidly depleted , thus permitting further tissue damage . Several studies point to an antioxidant effect of B-group vitamins and a pro-oxidant effect of elevated plasma tHcy ( total homocysteine ) . In the present study , we assessed whether supplementary B-group vitamins during this critical period will enhance antioxidant capacity and mitigate oxidative damage .  Forty-eight patients with acute ischaemic stroke within 12 h of symptom onset were assigned to receive daily oral supplements of B-group vitamins comprising 5 mg of folate , 5 mg of vitamin B2 , 50 mg of vitamin B6 and 0.4 mg of vitamin B12 ( n=24 ) or no supplements ( n=24 ) for 14 days . The treatment group and controls were matched for stroke subtype and age . Blood sample s were obtained before intervention and also at 7 and 14 days post-recruitment for measurement of the following biomarkers : red cell folate ( whole blood folate corrected with haematocrit ) , erythrocyte glutathione reductase activity coefficient ( EGRAC ; measure of vitamin B2 status ) , plasma pyridoxal phosphate ( vitamin B6 status ) , plasma vitamin B12 , plasma alpha-tocopherol , plasma ascorbic acid , plasma TAOC ( total antioxidant capacity ) , plasma MDA ( malondialdehyde ) , plasma tHcy and CRP ( C-reactive protein ) . Supplementation for 14 days with B-group vitamins significantly increased the plasma concentrations of pyridoxal phosphate and red blood cell folate and improved a measure of B2 status compared with the control group ( P<0.05 ) . Plasma tHcy decreased in both groups albeit less in the control group , but differences in cumulative changes were not significant . There was , however , a decrease in plasma MDA concentration in the treatment group , in contrast with the increase seen in the control group and these differences were significant ( P=0.05 ) . CRP concentration , a marker of tissue inflammation , was significantly lower in the treatment group compared with controls ( P<0.05 ) . In conclusion , B-group vitamin supplementation immediately post-infa rct may have antioxidant and anti-inflammatory effects in stroke disease independent of a homocysteine-lowering effect 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 ) OBJECTIVE This study was conducted to test the efficacy of a multiple micronutrient-fortified cooking salt . METHODS A r and omized controlled trial with a pre- and post-test design was used to study children 5 to 18 years of age , with an experimental ( n=213 ) and control group ( n=189 ) . The children were sample d from 3 residential schools and were studied for 9 months . The experimental group received a multiple micronutrient-fortified salt containing vitamins A , B(1 ) , B(2 ) , B(6 ) , B(12 ) , as well as folic acid , niacin , iron , iodine , and zinc . The control group received iodized salt . Biochemical measurements [ hemoglobin , serum ferritin ( SF ) , serum transferrin receptor ( sTfR ) , C-reactive protein ( CRP ) , alpha-1 acid glycoprotein ( AGP ) , serum retinol , serum vitamin B(12 ) , serum folic acid , serum zinc , and urinary iodine ( UI ) ] were measured at baseline and post-intervention . Hemoglobin was measured in all the children three times during the study period , while the remaining biochemical measurements were performed in a sub sample of children . Children between 11 and 18 years of age were given cognitive tests to assess memory and attention . RESULTS There was a significant improvement ( p<0.05 ) in all the biochemical measurements and memory tests in the experimental group when compared with the control group . Post-intervention in the experimental group , the increase in hemoglobin was 0.67 g/dL ( p<0.05 ) . Iron status and body iron stores increased significantly ( p<0.05 ) in the experimental group compared to the control group , while serum zinc increased by 50 mug/dL ( p<0.05 ) , and the prevalence of retinol deficiency decreased from 57.1 % at baseline to 16 % post-intervention ( p<0.05 ) . CONCLUSION The multiple micronutrients from the multiple micronutrient-fortified cooking salt were absorbed in the children and helped in combating micronutrient deficiencies Objective To investigate the relationship between basal cell carcinoma ( BCC ) and antioxidant nutrients , specifically carotenoids , vitamin E and selenium . Methods The Nambour Skin Cancer Study is an ongoing , community-based study of r and omly selected adult residents of a township in sub-tropical Queensl and , Australia . Using a nested case – control design , incident cases of BCC ( n=90 ) were compared with age and sex matched controls ( n=90 ) .  Dietary exposure was measured using food frequency question naire estimates of intake as well as serum biomarkers . Other determinants of skin cancer including sun exposure were also considered . Dietary intakes were adjusted for energy intake , and serum carotenoids and vitamin E were adjusted for serum cholesterol . Odds ratios were calculated across quartiles of dietary intake and serum biomarkers and linear trends were assessed using logistic regression , adjusting for age , sex and supplement use . Results and conclusions In this prospect i ve study no significant associations were found between BCC and  carotenoids , vitamin E or selenium  , as measured by serum biomarkers or dietary intake , although there was a suggestion of a positive association with lutein intake The authors evaluated associations between intakes of folate and vitamin B(6 ) and  colorectal cancer risk among women enrolled in a r and omized trial on aspirin and vitamin E in disease prevention . At baseline ( 1992 - 1995 ) , 37,916 US women aged > or=45 years who were free of cancer and cardiovascular disease provided dietary information . During an average of 10.1 years of follow-up ( through February 20 , 2004 ) , 220 colorectal adenocarcinoma cases were documented . Total folate and vitamin B(6 ) intakes were not significantly associated with the risk of colorectal cancer . However ,  dietary intakes of folate and vitamin B(6 ) were significantly inversely associated with colorectal cancer risk among women who were not taking supplements containing folate and vitamin B(6 ) .  Multivariable relative risks among women in the highest quintiles of intake versus the lowest were 1.16 ( 95 % confidence interval ( CI ) : 0.76 , 1.79 ) for total folate , 1.14 ( 95 % CI : 0.77 , 1.69 ) for total vitamin B(6 ) , 0.46 ( 95 % CI : 0.26 , 0.81 ) for dietary folate , and 0.69 ( 95 % CI : 0.41 , 1.15 ) for dietary vitamin B(6  )  . The use of multivitamin supplements was not related to colorectal cancer risk . These findings suggest that higher dietary intakes of folate and vitamin B(6 ) may reduce  the risk of colorectal cancer in women . An alternative explanation is that other factors related to dietary intakes of folate and vitamin B(6 ) account for the inverse associations
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 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 .