title: EFA supplementation in children with inattention, hyperactivity, and other disruptive behaviors Omega 3/6 fatty acids for reading in children: a randomized, double‐blind, placebo‐controlled trial in 9‐year‐old mainstream schoolchildren in Sweden CONSORT 2010 Explanation and Elaboration: Updated guidelines for reporting parallel group randomised trials. Increased Erythrocyte Eicosapentaenoic Acid and Docosahexaenoic Acid Are Associated With Improved Attention and Behavior in Children With ADHD in a Randomized Controlled Three-Way Crossover Trial Diet-induced changes in iron and n-3 fatty acid status and associations with cognitive performance in 8-11-year-old Danish children: secondary analyses of the Optimal Well-Being, Development and Health for Danish Children through a Healthy New Nordic Diet School Meal Study. Docosahexaenoic Acid for Reading, Cognition and Behavior in Children Aged 7–9 Years: A Randomized, Controlled Trial (The DOLAB Study) A double-blind placebo-controlled randomised trial of omega-3 supplementation in children with moderate ADHD symptoms Side effects of methylphenidate in children with attention deficit hyperactivity disorder: a systemic, placebo-controlled evaluation. Effects of fish oil supplementation on learning and behaviour of children from Australian Indigenous remote community schools: a randomised controlled trial. Driving up the Quality and Relevance of Research Through the Use of Agreed Core Outcomes Eicosapentaenoic and docosahexaenoic acids, cognition, and behavior in children with attention-deficit/hyperactivity disorder: a randomized controlled trial.
abstract: This pilot study evaluated the effects of supplementation with PUFA on blood FA composition and behavior in children with Attention-Deficit/Hyperactivity Disorder (AD/HD)-like symptoms also reporting thirst and skin problems . Fifty children were r and omized to treatment groups receiving either a PUFA supplement providing a daily dose of 480 mg DHA , 80 mg EPA , 40 mg arachidonic acid ( AA ) , 96 mg GLA , and 24 mg α-tocopheryl acetate , or an olive oil placebo for 4 mon of doubleblind parallel treatment . Supplementation with the PUFA led to a substantial increase in the proportions of EPA , DHA , and α-tocopherol in the plasma phospholipids and red blood cell ( RBC ) total lipids , but an increase was noted in the plasma phospholipid proportions of 18∶3n-3 with olive oil as well . Significant improvements in multiple but outcomes ( as rated by parents ) were noted in both groups , but a clear benefit from PUFA supplementation for all behaviors characteristic of AD/HD was not observed . For most outcomes , improvement of the PUFA group was consistently nominally better than that of the olive oil group ; but the treatment difference was significantly , by secondary intent-to-treat analysis on only 2 out of 16 outcome measures : conduct problems rated by parents ( −42.7 vs. −9.9 % , n=47 , P=0.05 ) , and attention symptoms rated by teachers ( −14.8 vs. + 3.4 % , n=47 , P=0.03 ) . PUFA supplementation led to a greater number of participants showing improvement in oppositional defiant behavior from a clinical to a non clinical range compared with olive oil supplementation ( 8 out of 12 vs. 3 out of 11 , n=33 , P=0.02 ) . Also , significant correlations were observed when comparing the magnitude of change between increasing proportions of EPA in the RBC and decreasing disruptive behavior as assessed by the Abbreviated Symptom Question naire ( ASQ ) for parents ( r=−0.38 , n=31 , P<0.05 ) , and for EPA and DHA in the RBC and the teachers ' Disruptive Behavior Disorders ( DBD ) Rating Scale for Attention ( r=−0.49 , n=24 , P<0.05 ) . Interestingly , significant correlations were observed between the magnitude of increase in α-tocopherol concentrations in the RBC and a decrease in scores for all four subscales of the teacher 's DBD ( Hyperactivity , r=−0.45 ; Attention , r=−0.60 ; Conduct , r=−0.41 ; Oppositional/Defiant Disorder , r=−0.54 ; n=24 , P<0.05 ) as well as the ASQ for teachers ( r=−0.51 , n=24 , P<0.05 ) . Thus , the results of this pilot study suggest the need for further research with both n−3 FA and vitamin E in children with behavioral disorders BACKGROUND Previous research has shown positive effects of Omega 3/6 fatty acids in children with inattention and reading difficulties .  We aim ed to investigate if Omega 3/6 improved reading ability  in mainstream schoolchildren . METHODS We performed a 3-month parallel , r and omized , double-blind , placebo-controlled trial followed by 3-month active treatment for all subjects . Mainstream schoolchildren aged 9 - 10 years were r and omized 1:1 to receive three Omega 3/6 capsules twice daily or identical placebo . Assessment s were made at baseline , 3 months , and 6 months . The primary outcome measure was the Logos test battery for evaluating reading abilities . The trial is registered with Clinical Trials.gov , number NCT02557477 . RESULTS The study enrolled 154 children ( active n = 78 ; placebo n = 76 ) , of whom 122 completed the first 3 months ( active n = 64 ; placebo n = 58 ) and 105 completed the whole study ( active/active n = 55 ; placebo/active n = 50 ) . Outcomes were assessed by per protocol ( PP ) and intention-to-treat ( ITT ) analyses . Active treatment was superior to placebo at 3 months for improvement in phonologic decoding time ( PP active/placebo difference -0.16 ; 95 % CI -0.03 , -0.29 ; effect size ( ES ) .44 ; p = .005 ; and ITT ES .37 ; p = .036 ) , in visual analysis time ( PP active/placebo difference -0.19 ; 95 % CI -0.05 , -0.33 ; ES .49 ; p = .013 ; and ITT ES .40 ; p = .01 ) , and for boys in phonologic decoding time ( PP -0.22 ; 95 % CI -0.03 , -0.41 ; ES .62 ; p = .004 ) . Children with ADHD-RS scores above the median showed treatment benefits in visual analysis time ( PP ES .8 , p = .009 ) , reading speed per word ( PP ES .61 , p = .008 ) , and phonologic decoding time per word ( PP ES .85 , p = .006 ) . Adverse events were rare and mild , mainly stomach pain/diarrhea ( active n = 9 , placebo n = 2 ) . CONCLUSIONS Compared with placebo , 3 months of Omega 3/6 treatment improved reading ability - specifically the clinical ly relevant ' phonologic decoding time ' and ' visual analysis  time ' - in mainstream schoolchildren . In particular , children with attention problems showed treatment benefits Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials Objective : To investigate effects of omega-3 polyunsaturated fatty acids ( n-3 PUFA ) docosahexaenoic acid ( DHA ) and eicosapentaenoic acid ( EPA ) on attention , literacy , and behavior in children with ADHD . Method : Ninety children were r and omized to consume supplements high in EPA , DHA , or linoleic acid ( control ) for 4 months each in a crossover design . Erythrocyte fatty acids , attention , cognition , literacy , and Conners ’ Parent Rating Scales ( CPRS ) were measured at 0 , 4 , 8 , 12 months . Results : Fifty-three children completed the treatment . Outcome measures showed no significant differences between the three treatments . However , in children with blood sample s ( n = 76 - 46 ) , increased erythrocyte EPA + DHA was associated with improved spelling ( r = .365 , p < .001 ) and attention ( r = −.540 , p < .001 ) and reduced oppositional behavior ( r = −.301 , p < .003 ) , hyperactivity ( r = −.310 , p < .001 ) , cognitive problems ( r = −.326 , p < .001 ) , Diagnostic and Statistical Manual of Mental Disorders ( 4th ed . ; DSM-IV ) hyperactivity ( r = −.270 , p = .002 ) and DSM-IV inattention ( r = −.343 , p < .001 ) . Conclusion : Increasing erythrocyte DHA and EPA via dietary supplementation may improve behavior , attention , and literacy in children with ADHD Fe and n-3 long-chain PUFA ( n-3 LCPUFA ) have both been associated with cognition , but evidence remains inconclusive in well-nourished school-aged children . In the Optimal Well-Being , Development and Health for Danish Children through a Healthy New Nordic Diet ( OPUS ) School Meal Study , the 3-month intervention increased reading performance , inattention , impulsivity and dietary intake of fish and Fe . This study investigated whether the intervention influenced n-3 LCPUFA and Fe status and , if so , explored how these changes correlated with the changes in cognitive performance . The study was a cluster-r and omised cross-over trial comparing school meals with packed lunch ( control ) . At baseline and after each treatment , we measured serum ferritin , whole-blood n-3 LCPUFA and Hb , and performance in reading , mathematics and d2-test of attention . Data were analysed using mixed models ( n 726 ) and principal component analysis of test performances ( n 644 ) , which showed two main patterns : ' school performance ' and ' reading comprehension ' . The latter indicated that children with good reading comprehension were also more inattentive and impulsive ( i.e. higher d2-test error% ) . The intervention improved ' school performance ' ( P=0·015 ) , ' reading comprehension ' ( P=0·043 ) and EPA+DHA status 0·21 ( 95 % CI 0·15 , 0·27 ) w/w % ( P<0·001 ) , but it did not affect serum ferritin or Hb . At baseline , having small Fe stores was associated with poorer ' school performance ' in girls , but with better ' reading comprehension ' in both boys and girls . Both baseline EPA+DHA status and the intervention-induced increase in EPA+DHA status was positively associated with ' school performance ' , suggesting that n-3 LCPUFA could potentially explain approximately 20 % of the intervention effect . These exploratory associations indicate that increased fish intake might explain some of the increase in reading performance and inattention in the study Background Omega-3 fatty acids are dietary essentials , and the current low intakes in most modern developed countries are believed to contribute to a wide variety of physical and mental health problems . Evidence from clinical trials indicates that dietary supplementation with long-chain omega-3 may improve child behavior and learning , although most previous trials have involved children with neurodevelopmental disorders such as attention-deficit/hyperactivity disorder ( ADHD ) or developmental coordination disorder ( DCD ) . Here we investigated whether such benefits might extend to the general child population . Objectives To determine the effects of dietary supplementation with the long-chain omega-3 docosahexaenoic acid ( DHA ) on the reading , working memory , and behavior of healthy schoolchildren . Design Parallel group , fixed-dose , r and omized , double-blind , placebo-controlled trial ( RCT ) . Setting Mainstream primary schools in Oxfordshire , UK ( n = 74 ) . Participants Healthy children aged 7–9 years initially underperforming in reading ( ≤33rd centile ) . 1376 invited , 362 met study criteria .  Intervention 600 mg/day DHA ( from algal oil ) , or taste/color matched corn/soybean oil placebo . Main Outcome Measures Age-st and ardized measures of reading , working memory , and parent- and teacher-rated behavior . Results ITT analyses showed no effect of DHA on reading in the full sample , but significant effects in the pre-planned subgroup of 224 children whose initial reading performance was ≤20th centile ( the target population in our original study design ) . Parent-rated behavior problems ( ADHD-type symptoms ) were significantly reduced by active treatment , but little or no effects were seen for either teacher-rated behaviour or working memory . Conclusions DHA supplementation appears to offer a safe and effective way to improve reading and behavior in healthy but underperforming children from mainstream schools . Replication studies are clearly warranted , as such children are known to be at risk of low educational and occupational outcomes in later life . Trial Registration Clinical Trials.gov NCT01066182 and Controlled-Trials.com IS RCT Objective Clinical trials and inconclusive meta-analyses have investigated the effects of omega-3 supplements in children with Attention-Deficit Hyperactivity Disorder ( ADHD ) . We performed a r and omised placebo-controlled trial to evaluate the efficacy of omega-3 fatty acids . Methods Children aged 6–15 years with established diagnosis of ADHD were r and omised 1:1 to receive either supplements containing docosahexaenoic acid ( DHA ) and eicosapentaenoic acid ( EPA ) or a placebo for 3 months . Psychotropic or omega-3-containing treatments were not authorised during the study . The primary outcome was the change in the Attention-Deficit Hyperactivity Disorder Rating Scale version 4 ( ADHD-RS-IV ) . Other outcomes included safety , lexical level ( Alouette test ) , attention ( Test of Attentional Performance for Children — KiTAP ) , anxiety ( 48-item Conners Parent Rating Scale-Revised — CPRS-R ) , and depression ( Children ’s Depression Inventory — CDI ) . Results Between 2009 and 2011 , 162 children were included in five French child psychiatry centres . The mean age was 9.90 ( SD 2.62 ) years and 78.4 % were boys . The inclusion ADHD-RS-IV at was 37.31 ( SD 8.40 ) . The total ADHD-RS-IV score reduction was greater in the placebo group than in the DHA – EPA group : −19 ( −26 , −12 ) % and −9.7 ( −16.6 , −2.9 ) % , respectively , p = 0.039 . The other components of the Conners score had a similar variation but the differences between groups were not significant . Two patients in the DHA – EPA group and none in the placebo group experienced a severe adverse event ( hospitalisation for worsening ADHD symptoms ) . Conclusion This study did not show any beneficial effect of omega-3 supplement in children with mild ADHD symptoms The frequency and severity of 17 side effects presumably associated with stimulant medication were assessed during a rigorous , triple-blind , placebo-controlled , crossover evaluation of methylpheni date , 0.3 and 0.5 mg/kg twice a day , in 83 children with attention deficit hyperactivity disorder . Side effects were rated by parents and teachers at the end of each weekly drug condition . Three children ( 3.6 % ) had side effects that were sufficiently serious to warrant immediate discontinuation of medication . Parent ratings indicated that only the side effects of decreased appetite , insomnia , stomachaches , and headaches increased significantly in frequency and severity during the two active medication doses as compared with the placebo condition . Fewer than half of the children experienced these side effects and among those who did , ratings of mean severity remained in the mild range . Teacher ratings showed little change over drug conditions , except on ratings of staring , sadness , and anxiety , which declined with increasing dose of medication . Parent ratings indicated that only the side effects of decreased appetite , insomnia , stomachaches , and headaches increased significantly in frequency and severity during the two active medication doses as compared with the placebo condition . Fewer than half of the children experienced these side effects and among those who did , ratings of mean severity remained in the mild range . Teacher ratings showed little change over drug conditions , except on ratings of staring , sadness , and anxiety , which declined with increasing dose of medication . Surprisingly , a high frequency of these behavior side effects were reported during the placebo condition . Stimulant medication within this therapeutic range , therefore , results in few , generally mild side effects . ( ABSTRACT TRUNCATED AT 250 WORDS Omega-3 fatty acids are essential for brain function . We recruited 409 children aged 3 - 13 years ( M=8.27 , SD=2.17 ) for a r and omised controlled trial supplementing with placebo or fish oil capsules ( providing 750 mg docosahexaenoic plus eicosapentaenoic acids , and 60 mg gamma linolenic acid/school day ) for 20 school weeks ( Phase 1 ) followed by one-way crossover to fish oil ( Phase 2 ) . Children undertook assessment s of reading , spelling and non-verbal cognitive development ( Draw-A-Person ) at baseline , 20 and 40 weeks . Teachers completed Conners Behaviour Rating Scales ( CBRS ) . The treatment group showed improvements in Draw-A-Person compared with the placebo during Phase 1 ( p=0.029 ) , with strongest effects in Indigenous 7 - 12 year olds ( p=0.008 ) . The placebo group showed significant within-group improvements after switching to treatment ( p<0.001 ) . There was no treatment effect for reading or spelling , and CBRS data were unable to be analysed . These findings may be understood in the context that sustained school attendance and nutrition interact to produce school-related achievement There is a growing recognition that insufficient attention has been paid to the selection of the outcomes to measure in clinical trials and clinical audit . Outcomes need to be relevant to patients , clinicians , purchasers and policy-makers if the findings of research are to influence practice and future research . In addition , st and ardization of outcomes is needed to combine data from different studies to allow evidence synthesis and to compare data sets . Inconsistent choice of outcome measures means that many meta-analyses are unable to include data from all the relevant studies . For example , the five most accessed Cochrane review s in 2009 , together with the top cited review in that year , all described inconsistencies in the outcomes reported in eligible trials . A call for the st and ardization of outcomes is a regular conclusion of systematic review s. Furthermore , outcome reporting bias , defined as the bias arising from selecting outcomes for publication based on the results , affects many r and omized trials and ‘ is an under-recognized problem that affects the conclusions in a substantial proportion of Cochrane review s ’ . That bias is likely to affect systematic review s more widely as well as affecting individual studies when considered on their own . Similar problems occur with clinical audit , highlighting the importance of establishing national audits that use and report the same outcomes for all participants . All these issues could be addressed with the development and application of agreed st and ardized sets of outcomes that have been termed ‘ core outcome sets ’ . These should be measured and reported , as a minimum , in all relevant clinical trials and national clinical audits for a specific condition . Adopting a core outcome set does not imply that a particular study , review or audit should be restricted to only those outcomes . Rather , the expectation is that , as a minimum , core outcomes will always be collected and reported to allow the results of trials to be compared , contrasted and combined as appropriate . The adoption of core outcomes would have implication s across all areas of research in health and health care , reduce heterogeneity between trials , and lead to research that is more likely to have measured relevant outcomes . Importantly , they would enhance the value of evidence synthesis by reducing the risk of outcome reporting bias and ensuring that all trials contribute usable information . In addition , they will increase the efficiency and value of research . An important rationale for core outcome sets is that outcomes currently reported for trials do not consistently reflect endpoints that are meaningful for patients . Examples exist where trials failed to include all outcomes important to patients and where involvement of patients has identified an outcome that might not have been considered by practitioners on their own . Despite increasing recognition of the importance of incorporating patients ’ opinions , their involvement has been limited . Recent regulatory guidance in the USA requires documented evidence of patient input during the development of instruments to measure  patient reported outcomes ( PROs ) . However , measurement of PROs in clinical trials is hampered by the multiplicity and heterogeneity of tools currently available . Many generic , disease and domain-specific instruments have been developed and vali date d , each containing multiple scales and items . As a result , synthesis of PRO data from trials is difficult and review s aim ing to summarize treatment effect according to PROs may fail . There is synergy between the development of core outcome sets for trials and work to select up to seven outcomes that are important to patients for inclusion in Summary of Findings tables in systematic review s. Developed by the GRADE group ( http://www . grade workinggroup.org ) , Cochrane review s have featured such tables since 2008 , and they play a key role in presenting research in guidelines , such as those produced by the World Health Organization ( WHO ) . The development of core outcome sets needs to be accelerated and undertaken in ways that maximize efficiency . The COMET ( Core Outcome Measures in Effectiveness Trials , http://www.comet-initiative.org ) Initiative in the UK brings together research ers interested in the development and application of core outcome sets . These include key participants in a collaboration of research ers in rheumatology who have done the most notable work to date in this area . The COMET Initiative was launched in January 2010 , with a second meeting in July 2011 . Attendees included trialists , systematic review ers , patients , clinicians , journal editors , research funders , policy-makers , people responsible for trials registries and regulators . Data on individual studies , both published and ongoing , are being included in a free , publically available internet-based re source . This will be up date d periodically , to minimize the risk of duplication . Seventy-eight published or ongoing studies have already been entered into the repository . In addition , published review s of outcomes used in clinical trials or studies examining patients ’ views , will be entered OBJECTIVE To determine the effects of an eicosapentaenoic acid (EPA)-rich oil and a docosahexaenoic acid (DHA)-rich oil versus an ω-6 polyunsaturated fatty acid-rich safflower oil ( control ) on literacy and behavior in children with attention-deficit/hyperactivity disorder ( ADHD ) in a r and omized controlled trial . METHODS Supplements rich in EPA , DHA , or safflower oil were r and omly allocated for 4 mo to 90 Australian children 7 to 12 y old with ADHD symptoms higher than the 90th percentile on the Conners Rating Scales . The effect of supplementation on cognition , literacy , and parent-rated behavior was assessed by linear mixed modeling . Pearson correlations determined associations between the changes in outcome measurements and the erythrocyte fatty acid content ( percentage of total ) from baseline to 4 mo . RESULTS There were no significant differences between the supplement groups in the primary outcomes after 4 mo . However , the erythrocyte fatty acid profiles indicated that an increased proportion of DHA was associated with improved word reading ( r = 0.394 ) and lower parent ratings of oppositional behavior ( r = 0.392 ) . These effects were more evident in a subgroup of 17 children with learning difficulties : an increased erythrocyte DHA was associated with improved word reading ( r = 0.683 ) , improved spelling ( r = 0.556 ) , an improved ability to divide attention ( r = 0.676 ) , and lower parent ratings of oppositional behavior ( r = 0.777 ) , hyperactivity ( r = 0.702 ) , restlessness ( r = 0.705 ) , and overall ADHD symptoms ( r = 0.665 ) . CONCLUSION Increases in erythrocyte ω-3 polyunsaturated fatty acids , specifically DHA , may improve literacy and behavior in children with ADHD . The greatest benefit may be observed in children who have comorbid learning difficulties
target: Reading , working memory , and behavior change scores showed no consistent differences between intervention and placebo group .
  Some behavioral subscales showed minor group differences .
  Conclusions This RCT did not replicate results of the earlier DOLAB 1 study on the effectiveness of nutritional supplementation with DHA for learning and behavior .
background: Background Omega-3 fatty acids are central to brain-development of children .
  Evidence from clinical trials and systematic review s demonstrates the potential of long-chain Omega-3 supplementation for learning and behavior .
  However , findings are inconclusive and in need of robust replication studies since such work is lacking .
  Objectives Replication of the 2012 DOLAB 1 study findings that a dietary supplementation with the long-chain omega-3 docosahexaenoic acid ( DHA ) had beneficial effects on the reading , working memory , and behavior of healthy schoolchildren .