Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls The effect of iron deficiency and mental stimulation on Indonesian children's cognitive performance and development. Iron treatment normalizes cognitive functioning in young women. A Study of the Effects of Latent Iron Deficiency on Measures of Cognition: A Pilot Randomised Controlled Trial of Iron Supplementation in Young Women Effects of iron supplementation and anthelmintic treatment on motor and language development of preschool children in Zanzibar: double blind, placebo controlled study Iron and zinc supplementation improved iron and zinc status, but not physical growth, of apparently healthy, breast-fed infants in rural communities of northeast Thailand. Iron fortified follow on formula from 9 to 18 months improves iron status but not development or growth: a randomised trial Efficacy of Iron and/or Zinc Supplementation on Cognitive Performance of Lead-Exposed Mexican Schoolchildren: A Randomized, Placebo-Controlled Trial Effects of iron supplementation of low-birth-weight infants on cognition and behavior at 7 years: a randomized controlled trial Randomized, double-blind, placebo-controlled trial of iron supplementation in female soldiers during military training: effects on iron status, physical performance, and mood. Long-term effects of iron and zinc supplementation during infancy on cognitive function at 9 y of age in northeast Thai children: a follow-up study. Improvements in Iron Status and Cognitive Function in Young Women Consuming Beef or Non-Beef Lunches Once-weekly and 5-days a week iron supplementation differentially affect cognitive function but not school performance in Thai children. Effects of Iron Supplementation of LBW Infants on Cognition and Behavior at 3 Years
BACKGROUND Up to 25 % of adolescent girls in the USA are iron deficient . This double-blind , placebo-controlled clinical trial assessed the effects of iron supplementation on cognitive function in adolescent girls with non-anaemic iron deficiency . METHODS 716 girls who enrolled at four Baltimore high schools were screened for non-anaemic iron deficiency ( serum ferritin < or = 12 micrograms/L with normal haemoglobin ) . 98 ( 13.7 % ) girls had non-anaemic iron deficiency of whom 81 were enrolled in the trial . Participants were r and omly assigned oral ferrous sulphate ( 650 mg twice daily ) or placebo for 8 weeks . The effect of iron treatment was assessed by question naires and haematological and cognitive tests , which were done before treatment started and repeated after the intervention . We used four tests of attention and memory to measure cognitive functioning . Intention-to-treat and per- protocol analyses were done . FINDINGS Of the 81 enrolled girls with non-anaemic iron deficiency , 78 ( 96 % ) completed the study ( 39 in each group ) . Five girls ( three control , two treatment ) developed anaemia during the intervention and were excluded from the analyses . Thus , 73 girls were included in the per- protocol analysis . Ethnic distribution , mean age , serum ferritin concentrations , haemoglobin concentrations , and cognitive test scores of the groups did not differ significantly at baseline . Postintervention haematological measures of iron status were significantly improved in the treatment group ( serum ferritin 27.3 vs 12.1 micrograms/L , p < 0.001 ) . Regression analysis showed that girls who received iron performed better on a test of verbal learning and memory than girls in the control group ( p < 0.02 ) . INTERPRETATION In this urban population of non-anaemic iron-deficient adolescent girls , iron supplementation improved verbal learning and memory Three studies conducted in Indonesia will be described . Soewondo ( 12 ) investigated the relation of iron deficiency and cognitive function and impact of iron supplementation on verbal intelligence , attention and concept learning among iron deficient children without anemia and iron deficient anemic children . Half of 176 children , aged 3 - 6 years , received elemental Fe for 8 weeks and the other half received  placebo . There were significant changes from pre to post intervention evaluations in ferritin , transferrin saturation , free erythrocyte protoporphyrin , and hemoglobin in the iron deficient anemic children . Pre and post treatment psychological test data showed that iron deficiency anemia produced alterations in cognitive processes related to visual attention and concept acquisition . These alterations can be reversed with iron treatment . Idjradinata ( 4 ) assessed the impact of iron supplementation on iron deficient infant 's mental and psychomotor development . Hundred twenty six subjects aged 12 to 18 month were r and omly assigned to either iron treatment or placebo intervention . After 4 months of iron supplementation , the hemoglobin , ferritin and transferrin saturation changed significantly in the iron deficient infants . A developmental delay was observed in the iron deficient anemic infants before intervention and the conditions were reversed after 4 months of iron treatment . Soemiarti ( 8) examined the effectiveness of a  training course  given to mothers of children aged 12 to 24 month on the rearing environment and consequently to the child 's development .  The subjects were 69 mothers of 20 - 35 years old . The training lasted for 21 days by giving mothers training using the program " Ibu Maju Anak Bermutu " . The rearing environment improved , also the child 's mental and psychomotor development BACKGROUND Evidence suggests that brain iron deficiency at any time in life may disrupt metabolic processes and subsequently change cognitive and behavioral functioning . Women of reproductive age are among those most vulnerable to iron deficiency and may be at high risk for cognitive alterations due to iron deficiency . OBJECTIVE We aim ed to examine the relation between iron status and cognitive abilities in young women . DESIGN A blinded , placebo-controlled , stratified intervention study was conducted in women aged 18 - 35 y of varied iron status who were r and omly assigned to receive iron supplements or a placebo .  Cognition was assessed by using 8  cognitive performance tasks  ( from Detterman 's Cognitive Abilities Test ) at baseline ( n = 149 ) and after 16 wk of treatment ( n = 113 ) . RESULTS At baseline , the iron-sufficient women ( n = 42 ) performed better on cognitive tasks ( P = 0.011 ) and completed them faster ( P = 0.038 ) than did the women with iron deficiency anemia ( n = 34 ) . Factors representing performance accuracy and the time needed to complete the tasks by the iron-deficient but nonanemic women ( n = 73 ) were intermediate between the 2 extremes of iron status . After treatment , a significant improvement in serum ferritin was associated with a 5 - 7-fold improvement in cognitive performance , whereas a significant improvement in hemoglobin was related to improved speed in completing the cognitive tasks . CONCLUSIONS Iron status is a significant factor in cognitive performance in women of reproductive age . Severity of anemia primarily affects processing speed , and severity of iron deficiency affects accuracy of cognitive function over a broad range of tasks . Thus , the effects of iron deficiency on cognition are not limited to the developing brain Rates of iron deficiency are high amongst healthy young women .  Cognitive impairment occurs secondary to iron deficiency in infants and children , but evaluation of the impact on cognition among young women is inconsistent . The aim was to determine the suitability of the IntegNeuro test battery for assessing cognitive function in iron-deficient and iron-sufficient young women . A pilot double-blinded , placebo-controlled intervention trial was conducted in iron-deficient ( serum ferritin ≤ 20 μg/L and haemoglobin > 120 g/L ) and iron-sufficient young women ( 18–35 years ) . Cognitive function and haematological markers of iron status were measured at baseline and follow-up . Iron-deficient participants ( n = 24 ) were r and omised to receive placebo , 60 mg or 80 mg elemental iron daily supplements for 16 weeks . A control group of iron-sufficient participants ( n = 8) was allocated to placebo . Change scores for Impulsivity and Attention were significantly greater in plasma ferritin improvers than in non-improvers ( p = 0.004 , p = 0.026 ) . IntegNeuro was easy to administer and acceptable to young women . Based on the differences in Memory and Attention scores between iron-deficient participants on iron treatment and those on placebo , it was decided that between 26 and 84 participants would be required in each iron treatment group for an adequately powered extension of this pilot RCT Abstract Objective : To measure the effects of iron supplementation and anthelmintic treatment on iron status , anaemia , growth , morbidity , and development of children aged 6–59 months . Design : Double blind , placebo controlled r and omised factorial trial of iron supplementation and anthelmintic treatment . Setting : Community in Pemba Isl and , Zanzibar . Participants : 614 preschool children aged 6–59 months . Main outcome measures : Development of language and motor skills assessed by parental interview before and after treatment in age appropriate subgroups . Results : Before intervention , anaemia was prevalent and severe , and geohelminth infections were prevalent and light — Plasmodium falciparum infection was nearly universal . Iron supplementation significantly improved iron status , but not haemoglobin status . Iron supplementation improved language development by 0.8 ( 95 % confidence interval 0.2 to 1.4 ) points on the 20 point scale . Iron supplementation also improved motor development , but this effect was modified by baseline haemoglobin concentrations ( P=0.015 for interaction term ) and was apparent only in children with baseline haemoglobin concentrations < 90 g/l . In children with a baseline haemoglobin concentration of 68 g/l ( one st and ard deviation below the mean value ) , iron treatment increased scores by 1.1 ( 0.1 to 2.1 ) points on the 18 point motor scale . Mebendazole significantly reduced the number and severity of infections caused by Ascaris lumbricoides and Trichuris trichiura , but not by hookworms . Mebendazole  increased development scores by 0.4 ( −0.3 to 1.1 ) points on the motor scale and 0.3 ( −0.3 to 0.9 ) points on the language scale . Conclusions : Iron supplementation improved motor and language development of preschool children in rural Africa . The effects of iron on motor development were limited to children with more severe anaemia ( baseline haemoglobin concentration < 90 g/l ) . Mebendazole had a positive effect on motor and language development , but this was not statistically significant . What is already known on this topic Iron is needed for development and functioning of the human brain Anaemic children show developmental delays , but it is not yet clear whether iron deficiency causes these deficits or whether iron supplementation can reverse them Helminth infections in schoolchildren are associated with cognitive deficits , but few studies have been made of helminth infection and early child development What this study adds Low doses of oral iron supplementation given daily improved language development in children aged 1–4 years in Zanzibar Iron supplementation improved motor development , but only in children with initial haemoglobin concentrations below 90 g/l The effects of routine anthelmintic treatment on motor and language milestones were positive , but non-significant , with our sample Iron deficiency is prevalent in children and infants worldwide . Zinc deficiency may be prevalent , but data are lacking . Both iron and zinc deficiency negatively affect growth and psychomotor development . Combined iron and zinc supplementation might be beneficial , but the potential interactions need to be verified . In a r and omized , placebo-controlled trial using 2 x 2 factorial design , 609 Thai infants aged 4 - 6 mo were supplemented daily with 10 mg of iron and /or 10 mg of zinc for 6 mo to investigate effects and interactions on micronutrient status and growth . Iron supplementation alone increased hemoglobin and ferritin concentrations more than iron and zinc combined . Anemia prevalence was significantly lower in infants receiving only iron than in infants receiving iron and zinc combined .  Baseline iron deficiency was very low , and iron deficiency anemia was almost nil . After supplementation , prevalence of iron deficiency and iron deficiency anemia were significantly higher in infants receiving placebo and zinc than in those receiving iron or iron and zinc .  Serum zinc was higher in infants receiving zinc ( 16.7 + /- 5.2 micromol/L ) , iron and zinc ( 12.1 + /- 3.8 micromol/L ) or iron alone ( 11.5 + /- 2.5 micromol/L ) than in the placebo group ( 9.8 + /- 1.9 micromol/L ) . Iron and zinc interacted to affect iron and zinc status , but not hemoglobin . Iron supplementation had a small but significant effect on ponderal growth , whereas zinc supplementation did not . To conclude , in Thai infants , iron supplementation improved hemoglobin , iron status , and ponderal growth , whereas zinc supplementation improved zinc status . Overall , for infants , combined iron and zinc supplementation is preferable to iron or zinc supplementation alone AIMS Iron deficiency anaemia is associated , in observational studies , with developmental disadvantage . This study tested the hypothesis that feeding iron supplemented formula from 9 to 18 months of age would improve developmental performance . SUBJECTS AND METHODS 493 healthy children aged 9 months being fed pasteurised cows ’ milk were recruited from three UK centres . They were r and omised to : cows ’ milk as before , formula containing 0.9 mg/litre iron , or formula containing 1.2 mg/litre iron , until 18 months of age . Bayley mental and psychomotor developmental indices were measured at 18 months , as were growth and haematological indices . RESULTS Children fed iron fortified formula had higher plasma ferritin concentrations , but there were no significant intergroup differences in development or growth . CONCLUSIONS There are no developmental or growth advantages in children given iron supplemented formula , but a benefit for a minority who were anaemic , or the possibility that a benefit may emerge at a later age , can not be excluded OBJECTIVE . Lead exposure in children has been associated with both global and specific cognitive deficits . Although chelation therapy is advised for children with blood lead concentrations of > 44 μg/dL , treatment options for children with lower blood lead values are limited . Because lead absorption is related to children 's nutritional status , micronutrient supplements may be 1 strategy for combating low-level , chronic lead exposure . This study was design ed to test the efficacy of iron and zinc supplementation for lowering blood lead concentrations and improving cognitive performance in schoolchildren who live in a lead-contaminated city . METHODS . This r and omized , double-blind , placebo-controlled field trial was conducted in public elementary schools in Torreón , an industrialized city in northern Mexico . A metal foundry , located close to the city center and within 3.5 km of 9 schools , was the main source of lead exposure . A total of 602 children who were aged 6 to 8 years and regularly attending first grade in the study schools were enrolled . Children were given 30 mg of iron , 30 mg of zinc , both , or a placebo daily for 6 months . A total of 527 completed the treatment , and 515 were available for long-term follow-up , after another 6 months without supplementation . Eleven cognitive tests of memory , attention , visual-spatial abilities , and learning were administered at baseline and each follow-up . RESULTS . There were no consistent or lasting differences in cognitive performance among treatment groups . CONCLUSIONS . Daily supplementation with iron and /or zinc may be of limited usefulness for improving cognition in lead-exposed schoolchildren . However , these treatments may be effective in setting s with higher prevalence of nutritional deficiencies or in younger children Background Low-birth-weight infants ( LBW ) are at an increased risk of iron deficiency that has been associated with impaired neurodevelopment . We hypothesized that iron supplementation of LBW infants improves cognitive scores and reduces behavioral problems until school age . Methods We r and omized 285 marginally LBW ( 2,000–2,500 g ) infants to receive 0 , 1 , or 2 mg/kg/day of iron supplements from 6 weeks to 6 months of age . At 7 years of age , 205 participants were assessed regarding cognition using Wechsler Intelligence Scale for Children ( WISC-IV ) and behavior using the parental question naires Child Behavior Checklist ( CBCL ) and Five  to Fifteen  ( FTF ) . Results There were no significant differences between the intervention groups in WISC-IV or FTF . However , the CBCL scores for externalizing problems were significantly different , in favor of supplemented children ( P=0.045 ) . When combining the supplemented groups , they had significantly lower scores for externalizing behavior compared with placebo ( median ( interquartile range ) : 44 [ 34;51 ] vs. 48.5 [ 41;56 ] P=0.013 ) , and their risk ratio ( 95 % confidence interval ) for a total behavioral score above the cutoff for clinical problems was 0.31 ( 0.09–1.0 ) , P=0.054 . Conclusion Lower scores of externalizing behavior in supplemented children support our previous findings at 3 years , and suggest that iron supplementation may have long-lasting effects on behavioral functions BACKGROUND Decrements in iron status have been reported in female soldiers during military training . Diminished iron status adversely affects physical and cognitive performance . OBJECTIVE We wanted to determine whether iron supplementation could prevent decrements in iron status and improve measures of physical performance and cognitive status in female soldiers during basic combat training ( BCT ) . DESIGN In this 8-wk r and omized , double-blind , placebo-controlled trial , soldier volunteers ( n = 219 ) were provided with capsules containing either 100 mg ferrous sulfate or a placebo . Iron status indicator assays were performed pre- and post-BCT . Two-mile running time was assessed post-BCT ; mood was assessed by using the Profile of Mood States question naire pre- and post-BCT . RESULTS The BCT course affected iron status : red blood cell distribution width and soluble transferrin receptor were elevated ( P < 0.05 ) , and serum ferritin was lowered ( P < 0.05 ) post-BCT . Iron supplementation attenuated the decrement in iron status ; group-by-time interactions ( P < 0.01 ) were observed for serum ferritin and soluble transferrin receptor . Iron supplementation result ed in improved ( P < 0.05 ) vigor scores on the Profile of Mood States post-BCT and in faster running time ( P < 0.05 ) in volunteers reporting to BCT with iron deficiency anemia . CONCLUSIONS Iron status is affected by BCT , and iron supplementation attenuates the decrement in indicators of iron status in female soldiers . Furthermore , iron supplementation may prove to be beneficial for mood and physical performance during the training period . Future efforts should identify and treat female soldiers or athletes who begin training regimens with iron deficiency or iron deficiency anemia BACKGROUND Iron and zinc are important micronutrients for child growth and development . One would expect that iron and zinc supplementation in infancy would affect long-term cognitive development and school achievement , but this has not been evaluated . OBJECTIVE We investigated the effect of iron or zinc supplementation or both during infancy on cognitive performance 8 y later . DESIGN A follow-up study was performed in 560 children aged 9 y or 92 % of those who had participated in a r and omized controlled trial involving 4 groups who received daily iron , zinc , iron plus zinc , or a placebo at 4 - 6 mo of age for 6 mo .  Cognitive performance was assessed by using the Wechsler Intelligence Scale for Children-Third Edition ( Thai version ) , the Raven 's Colored Progressive Matrices ( CPM ) , and school performance tests . General linear mixed models were used to assess long-term effects . RESULTS No significant differences in any of the outcomes at 9 y of age were observed at follow-up between the 4 groups . Mean intelligence quotients ranged across groups from 92.9 to 93.7 for full scale , 93.9 - 95.4 for verbal , and 93.1 - 94.0 for performance . The Raven 's CPM score ranged from 21.4 to 22.4 . CONCLUSION Supplementation with iron or zinc or both during infancy does not lead to long-term cognitive improvement in 9-y-old children . This trial was registered at clinical trials.gov as NCT00824304 Iron status is associated with cognitive performance and intervention trials show that iron supplementation improves mental function in iron-deficient adults . However , no studies have tested the efficacy of naturally iron-rich food in this context . This investigation measured the hematologic and cognitive responses to moderate beef consumption in young women . Participants ( n = 43 ; age 21.1 ± 0.4 years ) were r and omly assigned to a beef or non-beef protein lunch group [ 3-oz ( 85 g ) , 3 times weekly ] for 16 weeks . Blood was sample d at baseline , and weeks 8 and 16 , and cognitive performance was measured at baseline and week 16 . Body iron increased in both lunch groups ( p < 0.0001 ) , with greater improvement demonstrated in women with lower baseline body iron ( p < 0.0001 ) . Body iron had significant beneficial effects on spatial working memory and planning speed ( p < 0.05 ) , and ferritin responders ( n = 17 ) vs. non-responders ( n = 26 ) showed significantly greater improvements in planning speed , spatial working memory strategy , and attention ( p < 0.05 ) . Lunch group had neither significant interactions with iron status nor consistent main effects on test performance . These findings support a relationship between iron status and cognition , but do not show a particular benefit of beef over non-beef protein consumption on either measure in young women Many studies have reported comparable hemoglobin response in subjects given intermittent and daily iron supplements .  However , the effect of intermittent iron supplementation on impaired cognitive function , one of the serious consequences of iron deficiency among children , has not been studied . We investigated the effects of 1 d/wk ( weekly ) and 5 d/wk ( daily ) iron supplementation on changes in results of intelligence quotient ( IQ ) , Thai language , and mathematics tests among Thai primary schoolchildren . A double-blind , r and omized , placebo-controlled trial was conducted . Primary schoolchildren ( n = 397 ) were r and omly assigned to receive iron supplements daily or weekly or placebo . Ferrous sulfate ( 300 mg ) or placebo tablets were given under direct observation by the research er for 16 wk . Changes in IQ , and Thai language and mathematics scores were then compared . The increases in hemoglobin concentration were comparable in the weekly and daily iron supplementation groups but serum ferritin increased more in the children supplemented daily . Children receiving daily iron supplements , however , had a significantly lower increase in IQ ( 3 + /- 12 points ) than those receiving the supplement weekly ( 6 + /- 12 points ) or placebo ( 6 + /- 12 points ) , whereas the last-mentioned two groups did not differ . Z-scores of Thai language and mathematics test results did not differ among the groups . We conclude that weekly iron supplementation is the regimen of choice in this study community OBJECTIVE : Low birth weight ( LBW ) infants are at increased risk of cognitive and behavioral problems and at risk for iron deficiency , which is associated with impaired neurodevelopment . We hypothesized that iron supplementation of LBW infants would improve cognitive scores and reduce behavioral problems . METHODS : In a r and omized controlled trial , 285 marginally LBW ( 2000–2500 g ) infants received 0 , 1 , or 2 mg/kg/day of iron supplements from 6 weeks to 6 months of age . At 3.5 years of age , these infants and 95 normal birth weight controls were assessed with a psychometric test ( Wechsler Preschool and Primary Scale of Intelligence ) and a question naire of behavioral problems ( Child Behavior Checklist ; CBCL ) . RESULTS : There were no significant differences in IQ between the LBW groups or LBW infants versus controls  .  Mean ( SD ) full-scale IQ was 105.2 ( 14.5 ) , 104.2 ( 14.7 ) , and 104.5 ( 12.7 ) in the placebo , 1 mg , and 2 mg groups , respectively ( P = .924 ) . However , for behavioral problems , there was a significant effect of intervention . The prevalence of children with CBCL scores above the US sub clinical cutoff was 12.7 % , 2.9 % , and 2.7 % in the placebo , 1-mg , and 2-mg groups , respectively ( P = .027 ) , compared with 3.2 % in controls . Relative risk ( 95 % confidence interval ) for CBCL score above cutoff in placebo-treated children versus supplemented was 4.5 ( 1.4–14.2 ) . CONCLUSIONS : Early iron supplementation of marginally LBW infants does not affect cognitive functions at 3.5 years of age but significantly reduces the prevalence of behavioral problems . The study suggests a causal relation between infant iron deficiency and later behavioral problems
In anaemic groups supplementation improved intelligence quotient ( IQ ) by 2.5 points ( 95 % CI 1.24 to 3.76 ) , but had no effect on non-anaemic participants , or on memory , psychomotor skills or scholastic achievement .
Background In observational studies anaemia and iron deficiency are associated with cognitive deficits , suggesting that iron supplementation may improve cognitive function .
However , due to the potential for confounding by socio-economic status in observational studies , this needs to be verified in data from r and omised controlled trials ( RCTs ) .
Aim To assess whether iron supplementation improved cognitive domains : concentration , intelligence , memory , psychomotor skills and scholastic achievement .