Iron supplements versus placebo during pregnancy: its effects on iron and folate status on mothers and newborns. Antenatal supplementation with micronutrients and biochemical indicators of status and subclinical infection in rural Nepal. Responses of Biomarkers of Folate and Riboflavin Status to Folate and Riboflavin Supplementation in Healthy and Colorectal Polyp Patients (The FAB2 Study) Folic Acid Supplementation in Postpolypectomy Patients in a Randomized Controlled Trial Increases Tissue Folate Concentrations and Reduces Aberrant DNA Biomarkers in Colonic Tissues Adjacent to the Former Polyp Site. Weekly may be as efficacious as daily folic acid supplementation in improving folate status and lowering serum homocysteine concentrations in Guatemalan women. Short-Term Folate Supplementation in Physiological Doses Has No Effect on ESR1 and MLH1 Methylation in Colonic Mucosa of Individuals with Adenoma Subjectively healthy elderly consuming a liquid nutrition supplement maintained body mass index and improved some nutritional parameters and perceived well-being. A prospective study of micronutrient status in adolescent pregnancy. Effect of multivitamin supplementation
on the homocysteine and methylmalonic
acid blood concentrations in women
over the age of 60 years "Folate before pregnancy": the impact on women and health professionals of a population-based health promotion campaign in South Australia. Effects of folate supplementation on two provisional molecular markers of colon cancer: a prospective, randomized trial A randomized trial on folic acid supplementation and risk of recurrent colorectal adenoma. A comparison of iron and folate with folate alone in hematologic recovery of children treated for acute malaria. Folate supplementation in schizophrenia: A possible role for MTHFR genotype The effect of folate and cobalamin on osteoarthritic hands. Influence of folate status and polyphenol intake on thiamin status of Irish women. Genetic and Environmental Risk Assessment and Colorectal Cancer Screening in an Average-Risk Population Effects of extended systemic and topical folate supplementation on gingivitis of pregnancy. Adding zinc to prenatal iron and folate supplements improves maternal and neonatal zinc status in a Peruvian population. Improving autism perinatal risk factors: A systematic review. Cobalamin status modifies the effect of zinc supplementation on the incidence of prolonged diarrhea in 6- to 30-month-old north Indian children. Dietary oligosaccharides increase colonic weight and the amount but not concentration of bacterially synthesized folate in the colon of piglets. Serum Vitamin B12, C and Folate Concentrations in the New Mexico Elder Health Survey: Correlations with Cognitive and Affective Functions
Iron and folate status of 203 pregnant women have been evaluated at 6 months gestation and on the same women and their newborn infants at delivery . The women who had , at 6 months gestation , a Hb level below 11 g/dl were systematic ally given iron supplements . Iron or placebo were r and omly allocated to the other women . At 6 months of pregnancy , one quarter of the women had a Hb level under 11 g/dl but one third had a serum ferritin level below 12 micrograms/l and more than half had low levels of serum and red cell folate . Iron supplements induced an increase both in Hb levels and in serum ferritin values ; however , no significant differences were observed in serum ferritin of the newborn infants , whether their mothers had received iron supplements or not . These results have led us to reconsider the value of ferritin levels at birth as an index of iron stores in the infant . Iron supplements had no effect on the folate status in mothers or infants or on the frequency of obstetrical complications . A significant relationship was found between maternal folate levels and length of gestation . Folate supplementation may reduce the incidence of premature delivery BACKGROUND Previously we showed that women in rural Nepal experience multiple micronutrient deficiencies in early pregnancy . OBJECTIVE This study examined the effects of daily antenatal micronutrient supplementation on changes in the biochemical status of several micronutrients during pregnancy . DESIGN In Nepal , we conducted a r and omized controlled trial in which 4 combinations of micronutrients ( folic acid , folic acid + iron , folic acid + iron + zinc , and a multiple micronutrient supplement containing folic acid , iron , zinc , and 11 other nutrients ) plus vitamin A , or vitamin A alone as a control , were given daily during pregnancy . In a sub sample of subjects ( n = 740 ) , blood was collected both before supplementation and at approximately 32 wk of gestation . RESULTS In the control group , serum concentrations of zinc , riboflavin , and vitamins B-12 and B-6 decreased , whereas those of copper and alpha-tocopherol increased , from the first to the third trimester . Concentrations of serum folate , 25-hydroxyvitamin D , and undercarboxylated prothrombin remained unchanged . Supplementation with folic acid alone or folic acid + iron decreased folate deficiency . However , the addition of zinc failed to increase serum folate , which suggests a negative inhibition ; multiple micronutrient supplementation increased serum folate .  Folic acid + iron + zinc failed to improve zinc status but reduced sub clinical infection .  Multiple micronutrient supplementation decreased the prevalence of serum riboflavin , vitamin B-6 , vitamin B-12 , folate , and vitamin D deficiencies but had no effect on infection . CONCLUSIONS In rural Nepal , antenatal supplementation with multiple micronutrients can ameliorate , to some extent , the burden of deficiency . The implication s of such biochemical improvements in the absence of functional and health benefits remain unclear Epidemiologic data suggest that increasing folate intake may protect against  colorectal cancer .  Riboflavin may interact with folate to modulate the effect . A double-blind r and omized placebo-controlled intervention study ( the FAB2 Study ) was carried out in healthy controls and patients with colorectal polyps ( adenomatous and hyperplastic ) to examine effects of folic acid and riboflavin supplements on biomarkers of nutrient status and on putative biomarkers of colorectal cancer risk ( DNA methylation and DNA damage ; to be reported elsewhere ) . Ninety-eight healthy controls and 106 patients with colorectal polyps were stratified for the thermolabile variant of methylene tetrahydrofolate reductase , MTHFR C677 T , and were r and omized to receive 400 μg of folic acid , 1,200 μg of folic acid , or 400 μg of folic acid plus 5 mg of riboflavin or placebo for 6 to 8 weeks . Blood sample s and colon biopsy sample s were collected for the measurement of biomarkers of folate and riboflavin status . Supplementation with folic acid elicited a significant increase in mucosal 5-methyl tetrahydrofolate , and a marked increase in RBC and plasma , with a dose-response . Measures of riboflavin status improved in response to riboflavin supplementation . Riboflavin supplement enhanced the response to low-dose folate in people carrying at least one T allele and having polyps . The magnitude of the response in mucosal folate was positively related to the increase in plasma 5-methyl tetrahydrofolate but was not different between the healthy group and polyp patients . Colorectal mucosal folate concentration responds to folic acid supplementation to an extent comparable to that seen in plasma , but with a suggestion of an upper limit . ( Cancer Epidemiol Biomarkers Prev 2007;16(10):2128–35 BACKGROUND Low folate status is associated with an increased risk of  colorectal carcinogenesis  . Optimal folate status may be genoprotective by preventing uracil misincorporation into DNA and DNA hypomethylation . Adenomatous polyps have low folate status compared with normal colonic mucosa , and they are surrounded by histologically normal mucosa that also is of low folate status . OBJECTIVE In a r and omized controlled trial conducted at a single Dublin hospital between April 2002 and March 2004 , we assessed the effect of folic acid supplementation on tissue folate , uracil misincorporation into DNA , and global DNA hypomethylation in colonocytes isolated from sites of adenomatous polyps and from histologically normal tissue adjacent and 10 - 15 cm distal to them . METHODS Twenty patients with adenomatous polyps on initial colonoscopy and polypectomy were r and omly assigned to receive either 600 μg folic acid/d [ n = 12 , 38 % men , mean age 64.3 y , and body mass index ( BMI , in kg/m(2 ) ) 26.6 ] or placebo ( n = 8 , 50 % men , mean age 68.4 y , and BMI 27.2 ) for 6 mo , and then repeat the colonoscopy . Blood and colonocyte tissue folate concentrations were measured with the use of a microbiological assay . Uracil misincorporation and global DNA hypomethylation were measured in colonocytes with the use of modified comet assays . RESULTS Over time , folic acid supplementation , compared with placebo , increased tissue folate ( mean ± SEM ) from 15.6 ± 2.62 pg/10(5 ) cells to 18.1 ± 2.12 pg/10(5 ) cells ( P < 0.001 ) and decreased the global DNA hypomethylation ratio from 1.7 ± 0.1 to 1.0 ± 0.1 ( P < 0.001 ) . The uracil misincorporation ratio decreased by 0.5 ± 0.1 for the site adjacent to the polyp over time ( P = 0.05 ) . CONCLUSION A response to folic acid supplementation , which increased colonocyte folate and improved folate-related DNA biomarkers of cancer risk , was seen in the participants studied . Exploratory analysis points toward the area formerly adjacent to polyps as possibly driving the response . That these areas persist after polypectomy in the absence of folate supplementation is consistent with a potentially carcinogenic field 's causing the appearance of the polyp Daily folic acid ( FA ) supplementation improves folate status , lowers circulating homocysteine ( Hcy ) concentrations , and reduces the risk of neural tube defects . Little is known about the efficacy of weekly FA supplementation . The objective of this study was to compare the efficacy of weekly and daily FA supplementations in improving folate and vitamin B-12 status and lowering Hcy concentrations in healthy reproductive-aged women . A r and omized , double-blind supplementation trial was conducted in Guatemala . A total of 459 women were assigned r and omly to 4 groups to receive weekly ( 5000 or 2800 microg ) or daily ( 400 or 200 microg ) FA for 12 wk . Daily and weekly iron , zinc , and vitamin B-12 were also provided . We determined serum and RBC folate by microbiological assays , but the latter was available only at baseline . Serum Hcy and vitamin B-12 were also measured . We used generalized linear regression models to assess the effects of treatment on biochemical indicators . Supplementation improved folate status similarly across all 4 groups . Overall , mean serum folate concentrations increased by 15.4 nmol/L ( 95 % CI : 13.8 , 16.9 ) and the geometric mean serum Hcy concentration decreased by 9.8 % ( 95 % CI : -12.3 , -7.1 ) . Daily supplementation improved serum vitamin B-12 by 20 % ( 95 % CI : 8 , 33.2 ) , whereas weekly supplementation had no effect . In conclusion , weekly FA ( either high or low dose ) plus vitamin B-12 may be as efficacious as daily supplementation in improving serum folate and lowering Hcy concentrations in healthy women of reproductive age Background / Aims : Low folate intake may increase risk of colorectal cancer by altering gene-specific methylation in the colon . We determined whether supplementation with physiological doses of folate could alter methylation in the oestrogen receptor 1 ( ESR1 ) and mutL homolog 1 ( MLH1 ) genes in colonic mucosa of subjects with colorectal adenoma . Methods : This was a r and omised , double-blind , placebo-controlled trial . Subjects received either 400 µg/day folic acid ( n = 15 ) or placebo  ( n = 14 ) for 10 weeks . Blood and colonic tissue sample s were collected at baseline and after intervention to determine biomarkers of folate and vitamin B12 status , MTHFR C677 T and MS A2756 G genotypes , and ESR1 and MLH1 methylation . Results : Although serum and red cell folate increased ( p < 0.001 vs. placebo ) and plasma homocysteine decreased ( p = 0018 vs. placebo ) in the folic acid group , there were no significant changes in ESR1 ( p = 0.649 vs. placebo ) or MLH1 ( p = 0.211 vs. placebo ) methylation . There was a significant effect of gender on ESR1 methylation ( p = 0.004 ) and significant gender and genotype ( MTHFR C677 T and MS A2756 G ) interactions ( p = 0.04 and p = 0.014 , respectively ) that were independent of treatment group allocation . Conclusions : Short-term folate supplementation in physiological doses decreases plasma homocysteine but has no effect on ESR1 and MLH1 methylation in colonic mucosa of individuals with adenoma . Further studies to investigate the interactions between gender , genotype and DNA methylation suggested in this study are warranted OBJECTIVE To evaluate regular use of a liquid nutrition supplement by subjectively healthy elderly persons in terms of body mass index , nutrient intake , selected biochemical parameters , and perceived quality -of-life changes , and to identify advantages and limitations of use . DESIGN A 16-week intervention study in which subjects were assigned r and omly to either a supplemented group or a control group and compared in terms of intergroup and intragroup differences in weight , food intake , blood values , and quality -of-life indexes . Adherence to protocol was monitored by monthly visits with an interviewer and food intake records . SUBJECTS/ SETTING Seventy-one independent living , older Canadian adults ( mean age = 70 + /- 7 years ) consuming on average less than 4 servings of fruit and vegetables daily and a supplement-free diet before the study . Subjects were without functional limitations and did not require therapeutic diets or medical treatments that affect nutritional status . Data were collected in home interviews . Blood for analysis was obtained from a sub sample of 36 subjects . INTERVENTION Inclusion of six 235-mL cans of liquid nutrition supplement weekly into the self-selected dietary patterns of the supplemented group . STATISTICAL ANALYSIS Results were analyzed by Student t tests or Wilcoxon rank sum test , analysis of variance , and multiple stepwise regression . RESULTS Body mass index , energy intake , and consumption of fruit and vegetables did not change throughout the study . In the supplemented group , statistically significant increases occurred from baseline to termination of the study in these nutrients : protein , calcium , iron , magnesium , and folate . Serum albumin , folate , ferritin , hemoglobin , and zinc values were within the normal range for the supplemented and control groups . Scores for the Medical Outcomes Study 36-Item Short-Form Health Status scales increased for the supplemented group from baseline to termination for vitality and general health perception . Values for the General Well-Being Question naire improved for anxiety and general well-being . Of the dietary predictors , folate intake explained the most variance for vitality and for general well-being , 8.6 % and 14.2 % , respectively . APPLICATIONS A liquid nutrition supplement could be recommended to the elderly when energy maintenance and increases in nutrient intake are necessary and convenience is an important consideration . Dietetics professionals should address the issues of affordability of the supplement , the role of food in achieving nutritional adequacy , and overall quality of life of clients . Folate intake as a predictor of perceived general well-being and vitality requires further investigation BACKGROUND Adolescents are more likely than adults to consume energy-dense , micronutrient-poor diets and to experience adverse pregnancy outcomes . OBJECTIVES The objectives were to assess micronutrient intake  and  blood biomarkers  prospect ively in pregnant adolescents recruited to the About Teenage Eating ( ATE ) Study and to determine associations with pregnancy outcome . DESIGN Pregnant adolescents ( n = 500 ) were recruited from 2 UK inner city population s.  Dietary intake was assessed with three 24-h dietary recalls , and micronutrient status was assessed by measurement of third trimester blood biomarkers . Pregnancy outcomes included small-for-gestational age ( SGA ) birth and preterm delivery . RESULTS Median iron and folate intakes were lower than UK and US recommended amounts . Folate and vitamin B-12 status were lower in smokers , despite no differences in dietary intake . Serum folate was < 7.0 nmol/L in 12 % of subjects , and serum total homocysteine ( tHcy ) was elevated ( > 10 micromol/L ) in 20 % of subjects . Fifty-two percent of the subjects had iron deficiency anemia , and 30 % had serum 25-hydroxyvitamin D concentrations < 25 nmol/L. The incidence of SGA birth was higher in subjects with poorer folate status ( red blood cell folate , P = 0.003 ; serum folate , P = 0.02 ; tHcy , P = 0.01 ; simple regression ) and those with low folate intakes , regardless of the inclusion ( P = 0.021 ) or exclusion ( P = 0.049 ) of intake from supplements ( simple regression ) . Adjustment for confounding variables confirmed the independence of these associations . The risk of SGA birth was also higher in subjects with low food iron intake ( P = 0.049 ) , but not when intake included iron from supplements ( P = 0.21 ) . The risk of SGA birth was lower in subjects with iron deficiency anemia ( P = 0.002 ) . CONCLUSION Poor micronutrient intake and status increase the risk of SGA births in pregnant adolescents 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 OBJECTIVES To evaluate a South Australian campaign to promote and implement knowledge that taking adequate folate/folic acid in the periconceptional period can reduce the risk of having a baby with a neural tube defect . DESIGN AND SETTING The campaign , conducted in October 1994 - -August 1995 , targeted women of reproductive age and health professionals . Evaluation was by computer-assisted telephone interviews undertaken by r and om dialling throughout the State before and after the campaign , and by self-administered question naires to health professionals and women in the postnatal period . PARTICIPANTS Women of reproductive age and four groups of health professionals . MAIN OUTCOME MEASURES Knowledge about folate , folate-rich foods and the periconceptional period ; participation of health professionals in advising women about folate ; use of periconceptional folic acid supplements ; sales of folic acid tablets ; and prevalence of neural tube defects . RESULTS Significant increases in knowledge about folate followed the campaign . Health professionals and women in the postnatal period had higher initial levels of knowledge about folate , which also increased significantly . The proportions of women taking periconceptional folic acid supplements  , and of health professionals advising women planning a pregnancy about folate , also increased significantly , and folic acid tablet sales doubled . Total prevalence of neural tube defects declined between 1966 and 1999 from a baseline of 2.0 per 1,000 births to 1.1 per 1,000 births ( Poisson regression , P= 0.03 ; average decline of 1.0 % per year ) . CONCLUSIONS A short educational campaign with a limited budget ( $ 40,000 ) can promote folate successfully , but alternative strategies such as food fortification are likely to be needed to achieve adequate periconceptional folate intake for a very high proportion of women OBJECTIVES : Dietary folate intake is inversely associated with the risk of colorectal cancer . This study investigated the effect of folate supplementation on genomic DNA methylation and DNA str and breaks in exons 5–8 of the p53 gene of the colonic mucosa , two provisional biomarkers of colon cancer . METHODS : Twenty subjects with adenomas were r and omized to receive either folate ( 5 mg/day ) or placebo for 1 yr after polypectomy . At baseline , 6 months and 1 yr , systemic and colonic measures of folate status were determined , as were the biomarkers mentioned earlier . RESULTS : Folate supplementation increased serum , red blood cell and colonic mucosal folate concentrations ( p < 0.02 ) . Folate supplementation also increased the extent of genomic DNA methylation at 6 months and 1 yr ( p = 0.001 ) , whereas placebo administration was associated with an increase in the extent of genomic DNA methylation only at 1 yr . Similarly , folate supplementation decreased the extent of p53 str and breaks in exons 5–8 at 6 months and 1 yr ( p < 0.02 ) , whereas placebo administration was associated with a decrease in the extent of p53 str and breaks only at 1 yr . CONCLUSIONS : Both of these provisional biomarkers of colon cancer underwent accelerated improvement at 6 months with folate supplementation . However , these markers also improved with placebo at 1 yr . Therefore , potential confounding factors that seem to modulate these biomarkers need to be identified and corrected in order for these markers to serve as suitable surrogate endpoints in folate chemoprevention trials BACKGROUND Evidence from observational studies suggests that inadequate folate status enhances colorectal carcinogenesis , but results from some r and omized trials do not support this hypothesis . OBJECTIVE To assess the effect of folic acid supplementation on recurrent colorectal adenoma , we conducted a cost-efficient , double-blind , r and omized trial among participants of 2 large prospect i ve cohorts , the Health Professionals Follow-Up Study and the Nurses ' Health Study . DESIGN Participants were r and omly assigned to receive folic acid ( 1 mg/d ) ( n = 338 ) or placebo ( n = 334 ) for 3 - 6.5 y. The primary endpoint was any new diagnosis of adenoma during the study period ( May 1996-March 2004 ) . Secondary outcomes were adenoma by site and stage and number of recurrent adenomas . Associations were also examined by plasma folate concentrations at baseline . RESULTS Incidence of at least one recurrent adenoma was not significantly associated with folic acid supplementation [ relative risk ( RR ) : 0.82 ; 95 % CI : 0.59,1.13 ; P = 0.22 ] . Among participants with low plasma folate concentrations at baseline ( < or=7.5 ng/mL ) , those r and omly assigned to receive folic acid experienced a significant decrease in adenoma recurrence ( RR : 0.61 ; 95 % CI : 0.42 , 0.90 ; P = 0.01 ) , whereas for subjects with high folate concentrations at baseline ( > 7.5 ng/mL ) , supplemental folic acid had no significant effect ( RR : 1.28 ; 95 % CI : 0.82 , 1.99 ; P = 0.27 , P(interaction ) = 0.01 ) . Contrary to findings from another clinical trial , there was no evidence for an increased risk of advanced or multiple adenomas . CONCLUSIONS Our results do not support an overall protective effect of folic acid supplementation on adenoma recurrence .  Folic acid supplementation may be beneficial among those with lower folate concentrations at baseline . This trial was registered at clinical trials.gov as NCT00512850 Concern has been raised that iron supplementation for treatment of acute malaria may worsen the severity of malaria . We compared the effect of iron and folate with folate alone on hematologic recovery in children treated for acute malaria . We r and omized 82 children 6 - 60 months of age from Nigeria with smear-positive malaria and anemia ( hematocrit < 33 % ) to receive iron ( 2 mg/kg/day ) plus folate ( 5 mg/day ) or folate alone in addition to antimalarial drugs . The mean ± SD hematocrit at baseline was 28.5 % ± 2.9 % . At four weeks , the mean hematocrit increased by 2.5 % ± 1.6 % in the iron plus folate group and by 1.4 % ± 1.0 % in the folate alone group ( P = 0.001 ) . Baseline hematocrit , iron supplementation , weight for height , and weekly meat intake were significant predictors of final hematocrit . The effect of iron was not significantly modified by baseline hematocrit , weekly meat intake , nutritional status , mother 's education , sex , or age of the child . Iron supplementation  improved hematologic recovery in children with malarial anemia BACKGROUND Folate deficiency and the methylenetetrahydrofolate reductase ( MTHFR ) 677C > T polymorphism have been linked to negative symptoms in schizophrenia both independently and synergistically . This study examined the effect of folate supplementation on negative symptoms overall and in relation to MTHFR 677C > T genotype . METHOD Forty-six stable adult schizophrenia out patients were enrolled and 32 were r and omised , double-blind , in a parallel-group , twelve week add-on trial of folate 2mg/d or matching placebo . The primary outcome measure was change from baseline to week 12 on the modified SANS total score using a mixed-model analysis . In addition , we measured the effect of MTHFR genotype on treatment effects and on changes in serum folate by grouping participants with T/T genotype together with C/T genotype and comparing their interactions to patients with C/C genotype . RESULTS Twenty-eight participants completed the trial .  Folate supplementation did not significantly affect negative symptoms compared to placebo across the entire cohort . However , there was a significant genotype × treatment effect on negative symptoms ( F=7.13 , df=1,39 , p=0.01 ) . In addition , MTHFR status significantly moderated the relationship between change in serum folate and change in negative symptoms : among participants with at least one copy of the T allele negative symptoms were more likely to improve with increased serum folate ( p=0.03 ) . CONCLUSION We did not detect a therapeutic benefit of folate supplementation in a sample of patients with residual negative symptoms . However , a possible association between genotypes associated with reduced MTHFR activity and benefit from folate supplementation should be investigated further OBJECTIVE Historically diet and arthritis have been cause/effect associated but the idea is controversial with little evidence that specific diet components are effective treatment . This controlled , double-blinded , crossover study reports the effect of folate and cobalamin supplements in 26 humans diagnosed for an average 5.7 years with idiopathic osteoarthritis of the h and s who had been medicated by prescribed nonsteroidal anti-inflammatory drugs ( NSAID ) . METHODS Subjects entered the study after a 10-day washout period from use of all anti-arthritis drugs , vitamins , and minerals . They were r and omly allocated to consume daily 6400 micrograms folate or 6400 micrograms folate plus 20 micrograms cobalamin or lactose placebo each for 2 months within self-selected diets . Pain was to be medicated by acetaminophen as needed , and at the end of each phase they returned for assessment and dispensing of the next treatment . Serum folate and cobalamin , red blood cell folate , blood smears , diet records , st and ard rheumatology assessment and h and grip measurements were review ed and statistically analyzed . RESULTS For all subjects mean right and left h and grip values were higher with combined cobalamin-folate ingestion than with other " vitamin " supplements and were equivalent to NSAID use . Number of tender h and joints were greater with use of NSAID than with use of cobalamin-folate . Side effects with the vitamin combination were none ; side effects of NSAID are many , and the cost of vitamins and acetaminophen also is lower . CONCLUSION The limited number of subjects in this study demonstrates that ingestion of a prescribed cobalamin-folate supplement and acetaminophen as needed result ed in positive outcomes The relationship of folate status and polyphenol intake to thiamin status was studied in 80 r and omly selected elderly and young Irish women , with key variables affecting thiamin nutrition controlled for .  Folate , thiamin , and polyphenol intakes  were measured during a 4-wk baseline ( elderly and young ) and 6-wk double-blind ( elderly ) supplementation period . Only elderly subjects were r and omly assigned to placebo , folic acid ( 400 micrograms ) , thiamin ( 10 mg ) , or folic-acid-plus-thiamin groups .  Thiamin status ( TPP effect ) was not affected by folate status ( plasma and erythrocyte folate ) during the baseline period or with folic acid supplementation alone . Polyphenol intake was not correlated with thiamin status . Only thiamin intake and thiamin supplementation significantly affected thiamin status . Because the majority of subjects ( 102 of 160 ) were initially thiamin deficient , enrichment of Irish grain products with thiamin is recommended Context Genetic and environmental risk assessment ( GERA ) , in which related genetic and environmental information identifies an individual 's risk for a disease , has been suggested as a means to motivate adherence to recommended cancer screening . Contribution This r and omized trial found that providing 1 specific GERA result to persons who were previously nonadherent to screening recommendations for colorectal cancer did not alter the subsequent rate of screening . Caution The study could assess only 1 set of GERA results and 1 method of communicating these results to patients . Implication Results of GERA can not be assumed to encourage adherence to recommended screening . The Editors Genetic testing for cancer susceptibility is offered most frequently for single-gene disorders . A mutation in the adenomatous polyposis coli gene ( APC ) confers a risk for colorectal cancer ( CRC ) of approximately 90 % ( 1 ) . Identification of this mutation substantially affects clinical practice . However , cancer usually does not arise from single mutations . Instead , susceptibility results from the modest contributions of many genes , usually with environmental interaction . Identification of these genes and their modifiers is an active area of research ( 2 ) . Genetic and environmental risk assessment ( GERA ) for common diseases is anticipated to become a widespread component of health care ( 3 , 4 ) . We assessed polymorphic variants of methylenetetrahydrofolate reductase (MTHFR),an important regulator of cellular folate metabolism . Specific MTHFR polymorphisms are associated with variable susceptibility to CRC ( 58 ) . Epidemiologic data also support a link between serum folate levels and CRC risk ( 9 ) . Assessment of the genetic ( MTHFR ) and environmental ( serum folate levels ) interaction is attractive because data that allow for CRC risk stratification among average-risk persons already exist . Specific polymorphisms in combination with low serum folate levels increase risk for CRC by approximately 1.5 to 2.0 times the baseline risk in white and African American persons in the United States ( 8) . Unlike with genetic testing for high-risk persons , such as those with familial adenomatous polyposis , little is known about the impact on health behaviors or the psychological effects of providing average-risk persons with moderately predictive genetic information ( 4 , 1013 ) . Underst and ing the benefits and harms of such testing in average-risk persons is important because similar testing is marketed directly to the public in an unsupervised manner ( 14 ) . We did a prospect i ve , r and omized , controlled trial to assess the effect of GERA feedback on CRC screening among average-risk persons who did not adhere to screening recommendations at study entry . Prevention of CRC is an optimal area to study the emerging role of moderately predictive genetic testing . Colorectal cancer is the second leading cause of cancer death in the United States ( 15 ) . Screening can reduce disease incidence and mortality ( 16 ) . Our primary hypothesis was that providing personalized GERA information would increase CRC screening uptake compared with usual care . Further , we anticipated that participants characterized as having elevated risk by GERA would undergo screening more than those at average risk . Although MTHFR and serum folate level testing provided personalized risk information , our study did not intend to evaluate the specific predictive value of this combination for colorectal neoplasia . Methods Design Overview We did a r and omized , controlled trial to compare CRC screening utilization in the  GERA group  versus the  usual care ( control ) group and to detect differences in screening proportion between the average- and elevated-risk GERA groups ( 12 ) . To increase the statistical power for comparisons within the GERA group , participants were r and omly assigned in a 2:1 ratio to GERA or usual care , respectively . Participants provided survey data at baseline , 3 weeks , and 6 months and agreed to medical record review to ascertain CRC screening status . Those in the GERA group also participated in GERA counseling and disclosure sessions and had blood drawn for genotyping and measurement of serum folate levels . Setting and Participants Participants in this institutional review boardapproved trial were recruited from 4 internal and family medicine practice s affiliated with Thomas Jefferson University , Philadelphia , Pennsylvania . We search ed scheduling , billing , and medical records data bases and applied filters matching eligibility requirements , including 1 ) age between 50 and 79 years ; 2 ) average-risk status for CRC , defined as being asymptomatic and having no history of colorectal adenomas , cancer , or inflammatory bowel disease or no family history of familial adenomatous polyposis , hereditary nonpolyposis CRC , or CRC in a first-degree relative ; 3 ) nonadherence to CRC screening guidelines at study initiation , defined as not having had home fecal occult blood testing in the past 12 months , barium enema or flexible sigmoidoscopy in the past 5 years , or colonoscopy in the past 10 years ; 4 ) not receiving antibiotics or antifolate medications ( for example , sulfasalazine or methotrexate ) within the past 6 weeks ; and 5 ) the ability to speak English . Potential participants were mailed a letter outlining the study ( Supplement 1 ) , a pamphlet review ing st and ard CRC screening options , a consent form , and information on how to opt out of the study . We telephoned participants who had not opted out , confirmed eligibility , obtained verbal consent , and administered a baseline survey about demographic characteristics and history of medical illnesses and multivitamin use . Participants also responded to previously described question naires about knowledge of CRC screening and the possible role of genes and diet in cancer development ( 17 ) . Finally , they completed the Impact of Event Scale ( IES ) question naire , a well-vali date d assessment tool for psychological distress ( 18 ) . Supplement 1 . Colon Cancer and Genetic and Environmental Risk Assessment R and omization and Intervention Study group allocation was implemented by a secure , Web-based application using r and omization tables generated before the study started . GERA Intervention Group Participants r and omly assigned to GERA  met with specially trained study nurses rather than genetic counselors . This research design reflected an effort to study feasible approaches to disclosure of genetic test results that could be incorporated into primary care setting s , because the number of genetic counselors seems inadequate to meet health service needs even in high-risk setting s ( 19 ) . Study nurses were trained by genetic counselors before study initiation and regularly monitored disclosure sessions to ensure process uniformity . Using a st and ardized study pamphlet describing GERA , the nurse and intervention participants together review ed the purpose of GERA , the potential results from genotyping and serum folate level measurement , and how results would be disclosed . A basic description of genes and their importance in cancer was provided . An average lifetime risk for CRC of 1 in 20 was described . Participants were told that their GERA results would be classified as elevated or average . The study nurse explained that an elevated result did not guarantee disease but was only one potential risk factor for CRC , suggesting modestly increased risk compared with that of a similarly aged person . Conversely , the nurse stated that an average result did not ensure protection against CRC now or in the future but simply indicated the absence of this risk factor . The study nurse emphasized that GERA was a method to stratify CRC risk but was not intended to be a substitute for screening . Venipuncture was done to assess serum folate levels and MTHFR polymorphisms for participants r and omly assigned to GERA .  Serum folate levels were analyzed in a single commercial laboratory using a st and ard 125I RIA kit with controls . All genotyping was done at the Fox Chase Cancer Center Cancer Genomics Facility , Philadelphia , Pennsylvania . After DNA was extracted , separate polymerase chain reaction amplifications of exons 4 and 7 of the MTHFR gene were completed , followed by pyrosequencing specific for codons 677 and 1298 . The GERA-associated CRC risk was characterized by particular combinations of age-specific serum folate levels and MTHFR polymorphisms ( Appendix Table 1 ) ; MTHFR is an important regulator of cellular folate metabolism . Separately , MTHFR polymorphic variant or serum folate level is associated with variable susceptibility to CRC ( 5 , 6 , 9 , 20 , 21 ) . Most persons with compound genotype combinations have a modestly elevated CRC risk in the setting of low serum folate levels compared with carriers of these same genotypes with normal serum folate levels or persons with less common combinations ( TT/AA and CC/CC ) , regardless of serum folate levels ( 8 , 22 , 23 ) . Low serum folate level status was conventionally assigned to any person in the 25th percentile or below for age-based population normal values , according to data from NHANES ( National Health and Nutrition Examination Survey ) at study commencement ( 24 ) . Appendix Table 1 . Compound Genotype Frequencies Within 2 weeks of blood collection , GERA results were disclosed and explained to every participant , first by telephone and then by mail ( Supplement 2 ) . In the disclosure session , the same points about multiple potential risk factors ( GERA being only one ) were emphasized , as was the importance of screening regardless of GERA result . Supplement 2 . Results Mailing Usual Care ( Control ) Group Usual care recipients completed the same baseline question naire as GERA recipients ; however , they did not meet with a study nurse , discuss GERA , participate in decision counseling , or provide a blood sample . Regardless of study group or risk , all participants were encouraged to have screening . Outcomes and Follow-up Control and intervention recipients subsequently received a A former double-blind study evaluated the effect of a 14-day period of systemic and topical folate supplementation on  gingival inflammation during pregnancy ( Pack & Thomson 1980 ) . The current experiment was similar to the earlier one except that supplementation was for 28 days during the eighth month only . Thirty women during their 32nd week of pregnancy were r and omly divided into three equal groups . Control Group A received placebo mouthwash ( MW ) and placebo tablets ; Group B received placebo MW and one 5 mg folate tablet daily ; Group C received placebo tablets and rinsed with folate MW twice daily for 1 min . At the beginning and end of the experimental period , oral status was determined using a plaque index ( PlI ) and a gingival index ( GI ) . Each subject furnished a 1-week diet record which was analysed for dietary folate . No differences in parameters existed between groups at the commencement of the study except for folate levels which were lower in Group B. Results confirmed the findings of the former experiment . Group C showed highly significant improvement in GI despite no significant changes in PlI ( 0.001 less than P less than 0.01 ) , whilst in Group B , changes in gingival health were not statistically significant ( 0.05 less than P less than 0.10 ) . No significant changes were demonstrated in Group A. Folate levels increased significantly in Groups B and C. Dietary folate was similar in all groups BACKGROUND Maternal zinc deficiency during pregnancy may be widespread among women in developing countries , but few data are available on whether prenatal zinc supplementation improves maternal and neonatal zinc status . OBJECTIVE We studied whether maternal zinc supplementation improved the zinc status of mothers and neonates participating in a supplementation trial in a shantytown in Lima , Peru . DESIGN Beginning at gestation week 10 - 24 , 1295 mothers were r and omly assigned to receive prenatal supplements containing 60 mg Fe and 250 microg folate , with or without 15 mg Zn .  Venous blood and urine sample s were collected at enrollment , at gestation week 28 - 30 , and at gestation week 37 - 38 . At birth , a sample of cord vein blood was collected . We measured serum zinc concentrations in 538 women , urinary zinc concentrations in 521 women , and cord zinc concentrations in 252 neonates . RESULTS At 28 - 30 and 37 - 38 wk , mothers receiving zinc supplements had higher serum zinc concentrations than mothers who did not receive zinc ( 8.8 + /- 1.9 compared with 8.4 + /- 1.5 micromol/L and 8.6 + /- 1.5 compared with 8.3 + /- 1.4 micromol/L , respectively ) . Urinary zinc concentrations were also higher in mothers who received supplemental zinc ( P < 0.05 ) . After adjustment for covariates and confounding factors , neonates of mothers receiving zinc supplements had higher cord zinc concentrations than neonates of mothers who did not receive zinc ( 12.7 + /- 2.3 compared with 12.1 + /- 2.1 micromol/L ) . Despite supplementation , maternal and neonatal zinc concentrations remained lower than values reported for well-nourished population s. CONCLUSION Adding zinc to prenatal iron and folate tablets improved maternal and neonatal zinc status , but higher doses of zinc are likely needed to further improve maternal and neonatal zinc status in this population BACKGROUND Current underst and ing of the etiology of autism is based on the interaction of multiple genes with each other and with environmental factors , leading to a neurodevelopmental process that results in the expression of autism spectrum disorder ( ASD ) in the child . This suggests that it might be possible to strengthen resilience to environmental stressors during the perinatal period to improve outcomes and possibly prevent the development of ASD . METHODS We search ed the MEDLINE data base for multiple perinatal factors associated with the development of ASD published between January 1 , 2005 and July 1 , 2018 . The search terms used were " autism " crossed with either " perinatal , " " prenatal , " " gestational , " or " pregnancy , " and crossed again with each perinatal risk factor highlighted in this review including topics on parental health , infections , medications , and environmental stressors . We then search ed interventions that may improve neurodevelopmental outcome before and during pregnancy , including supplements , breastfeeding , and postpartum stress reduction . We identified recent or unique metanalyses and systematic review s of the identified focus and on r and omized controlled trials and summarized these using the most recent and comprehensive review s. RESULTS Folate , omega-3 , vitamin D3 , environmental toxin avoidance , correcting deficiencies , immune boosting , and prolonged breast feeding are all reported to be linked to the possible reduction of adverse pregnancy outcomes including ASD . CONCLUSIONS Studies of individual components for improving pregnancy outcomes and several uncontrolled preconception to infancy medical practice s suggest that multiple interventions might improve the outcomes of pregnancies where there is risk for developing ASD The observed effect of zinc supplementation on  diarrheal morbidity  varies between trials and there is a need to identify subgroups most likely to benefit from improved zinc nutriture . In a r and omized , double-blind trial in 2296 children in New Delhi , India , we assessed whether baseline cobalamin or folate status modified the effect of zinc supplementation on the incidence of  prolonged ( ≥ 7 d duration ) and acute diarrhea . Children aged 6 - 30 mo  received zinc or placebo daily for 4 mo . We measured plasma concentrations of folate , cobalamin , total homocysteine ( tHcy ) , and methylmalonic acid ( MMA ) at enrollment and assessed the efficacy of zinc supplementation in subgroups based on these variables . The efficacy of zinc on reducing the risk of prolonged diarrhea was higher in those with plasma cobalamin concentrations below the 25th percentile and in those with tHcy and MMA concentrations above the 75th percentile . The OR ( 95 % CI ) for children below and above the 25th percentile for cobalamin were 0.53 ( 0.35 - 0.78 ) and 0.90 ( 0.73 - 1.11 ) , respectively ( P-interaction = 0.015 ) . There were similar differences for the OR when comparing efficacy in those above and below the 75th percentile for tHcy and MMA ( P-interaction = 0.045 and 0.188 , respectively ) . Baseline folate status did not modify the effect of zinc on prolonged diarrhea . Neither cobalamin nor folate status influenced the effect of zinc on acute diarrhea . Children with poor cobalamin status benefited more from zinc supplementation for the prevention of prolonged diarrhea Recently , we demonstrated that the large pool of folate present in the colon of humans can be absorbed . Here , we investigated whether the net amount of folate synthesized by bacteria in the colon of piglets can be modified by feeding prebiotics to alter their microbial milieu . Male piglets ( age 5 d , n = 12 ) were r and omized to a milk-based formula containing either 5 g/L inulin + 5 g/L galactooligosaccharides ( IN-GOS ) or 5 g/L maltodextrin ( control ) .  Body weight did not differ between groups during the 28-d feeding intervention . However , the mean weight of colonic tissue ( 38 % ) and their contents ( 238 % ) was higher in the IN-GOS than in the control group ( P = 0.004 , P = 0.0001 , respectively ) . Total bacterial load in the colon of piglets fed IN-GOS was 531 % greater and the total amount of folate found in the colon contents was 53 % greater than that of controls ( P = 0.002 , P = 0.02 , respectively ) . Indices of blood folate status ( plasma and RBC folate and plasma homocysteine ) and folate concentrations in liver and kidneys were unaffected . Both groups exhibited low RBC folate ( 56 ± 23 nmol/L ) and elevated homocysteine ( 24 ± 7 μmol/L ) concentrations , evidence of deficiency if present in humans . In conclusion , dietary supplementation with 5 g of inulin + 5 g of galactooligosaccharides increased the weight , bacterial load , and total folate content in the piglet colon ; however , these changes were insufficient to modify indices of whole body folate status . Future studies investigating the impact of feeding prebiotics on localized folate status at the level of the colonocyte are warranted Objectives : 1 ) To compare serum vitamin B12 , C and folate concentrations in a r and omly selected sample of elderly ( age 65 years or older ) male and female Hispanics and nonHispanic whites ( NHW ) and 2 ) to examine associations between serum B12 , C and folate concentrations compared to measures of cognitive and affective ( depression ) functions . Methods : Equal numbers of male and female Hispanics and NHW were r and omly sample d from the Health Care Financing Administration ( Medicare ) registrant list for Bernalillo County , New Mexico , and asked to volunteer for a paid home interview followed by a paid comprehensive interview/examination covering health and health-related issues . In addition to serum determinations of B12 , C and folate , associations were examined between these vitamins and measures of cognitive and affective functions . Results : Males and Hispanics had lower serum vitamin B12 , C and folate concentrations than females and NHW respectively . Participants taking a multivitamin supplement ( MVI ) had higher serum vitamin concentrations than those not taking MVI . There were significant associations between serum folate concentrations and measures of cognitive function , not seen with B12 or C , nor between any of the vitamins and affective function . Conclusions : Hispanics , even after adjustments for gender , age , vitamin supplementation , vitamin content of dietary foods , education and household income , had lower serum concentrations of B12 , C and folate than NHW . The most significant associations observed were those between serum folate and various measures of cognitive function , even after adjusting for presence of depression
We conclude that both serum and erythrocyte folate values reflect folate intake ; however , serum folate reacts more rapidly to folate intake than erythrocyte folate .
As to health outcomes , we found no evidence indicating that additional intake of folate can influence haematological parameters in non-anaemic paediatric patients .
We were unable to find evidence of a favourable effect of folate supplementation on the growth of infants .
However , the limited data available suggest that supplementing the diet of low-birth-weight infants with folic acid may moderate the rapid fall of serum and red cell folate in the first months of life
The aim of this systematic review was to collect all available r and omized controlled trials on the effect of folate supplementation on folate status and health outcomes within the paediatric age group .