Docosahexaenoic acid for reading, working memory and behavior in UK children aged 7-9: A randomized controlled trial for replication (the DOLAB II study) Docosahexaenoic Acid for Reading, Cognition and Behavior in Children Aged 7–9 Years: A Randomized, Controlled Trial (The DOLAB Study) Effect of supplementation with long-chain ω-3 polyunsaturated fatty acids on behavior and cognition in children with attention deficit/hyperactivity disorder (ADHD): a randomized placebo-controlled intervention trial. Randomized controlled trial of maternal omega-3 long-chain PUFA supplementation during pregnancy and early childhood development of attention, working memory, and inhibitory control. Supplementation of polyunsaturated fatty acids, magnesium and zinc in children seeking medical advice for attention-deficit/hyperactivity problems - an observational cohort study Effect of supplementation of arachidonic acid (AA) or a combination of AA plus docosahexaenoic acid on breastmilk fatty acid composition. Preliminary evidence that acute long-chain omega-3 supplementation reduces cardiovascular reactivity to mental stress: A randomized and placebo controlled trial The relationship of dietary omega-3 long-chain polyunsaturated fatty acid intake with incident age-related macular degeneration: AREDS report no. 23. Dietary Omega-3 Fatty Acid Supplementation Reduces Inflammation in Obese Pregnant Women: A Randomized Double-Blind Controlled Clinical Trial Oral supplementation of lutein/zeaxanthin and omega-3 long chain polyunsaturated fatty acids in persons aged 60 years or older, with or without AMD. [Effect of long-chain polyunsaturated fatty acids on arachidonate and docosahexaeonic acid in healthy infants in the first four months of life].
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 . Design Parallel group , fixed-dose , r and omized ( minimization , 30 % r and om element ) , double-blind , placebo-controlled trial ( RCT ) . Setting Mainstream primary schools ( n = 84 ) from five counties in the UK in 2012–2015 . Participants Healthy children aged 7–9 underperforming in reading ( < 20th centile ) . 1230 invited , 376 met study criteria . Intervention 600 mg/day DHA ( from algal oil ) , placebo : taste/color matched corn/soybean oil ; for 16 weeks . Main outcome measures Age-st and ardized measures of reading , working memory , and behavior , parent-rated and as secondary outcome teacher-rated . Results 376 children were r and omized . 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 . Possible reasons are discussed , particularly regarding the replication of complex interventions . Trial registration and protocol www.controlled-trials.com ( IS RCT N48803273 ) and protocol s.io ( https://dx.doi.org/10.17504/ protocol s.io.k8kczuw 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 To determine whether supplementation with the long-chain omega-3 polyunsaturated fatty acids eicosapentaenoic ( EPA ) and docosahexaenoic acid ( DHA ) affects behavioral symptoms and cognitive impairments in children 6 - 12 years of age diagnosed with attention-deficit/hyperactivity disorder ( ADHD ) . STUDY DESIGN The r and omized , double-blind placebo-controlled 16 weeks trial was conducted with 95 children diagnosed with ADHD according to DSM-IV criteria . Behavior was assessed by parents , teachers and investigators using st and ardized rating scales and question naires . Further outcome variables were working memory , speed of information processing and various measures of attention . For a subgroup of 81 participants , erythrocyte membrane fatty acid composition was analyzed before and after the intervention . RESULTS Supplementation with the omega-3 fatty acid mix increased EPA and DHA concentrations in erythrocyte membranes and improved working memory function , but had no effect on other cognitive measures and parent- and teacher-rated behavior in the study population . Improved working memory correlated significantly with increased EPA , DHA and decreased AA ( arachidonic acid ) BACKGROUND Docosahexaenoic acid ( DHA ) accumulates in the hippocampus and frontal lobes of the fetal brain during the last trimester of pregnancy . These areas of the brain contribute to attention and working memory and inhibitory control ( WMIC ) . OBJECTIVE We evaluated the effect of maternal omega-3 ( n-3 ) long-chain polyunsaturated fatty acid supplementation in pregnancy on child attention and WMIC . DESIGN A total of 185 term-born children of mothers who were r and omly allocated to consume 800 mg DHA/d ( treatment ) or a placebo ( control )  from ∼20 wk of gestation until birth were assessed with multiple measures of attention and WMIC at a mean ( ± SD ) of 27 ± 2 mo . Primary outcomes were the average time it took to be distracted when playing with a toy ( distractibility ) and the accuracy of remembering a new hiding location while inhibiting a learned response to search in the previous location ( WMIC ) . RESULTS Assessment s were completed by 81 children in the treatment group ( mean ± SD age : 835 ± 50.4 d ) and 77 children in the control group ( 839 ± 65.6 d ) . There was no effect of supplementation on primary outcomes [ distractibility mean difference : -0.2 s ( 95 % CI : -0.7 , 0.4 s ) ; WMIC mean difference : 8.9 mm ( 95 % CI : -10.6 , 28.3 mm ) ] . There was no difference between DHA-supplemented and control groups except that treatment-group children looked away from the toys fewer times than controls when presented with multiple toys competing for attention but less accurately remembered a repeated hiding location . These secondary effects were not consistent with any other outcomes and may have been a result of chance . Cord plasma DHA was not consistently associated with attention and WMIC . CONCLUSION Maternal DHA supplementation during pregnancy does not enhance attention or WMIC in term-born preschoolers . The DHA for Maternal and Infant Outcomes trial was registered at www.anzctr.org.au as ACTRN1260500056906 Background Polyunsaturated fatty acids are essential nutrients for humans . They are structural and functional components of cell membranes and pre-stages of the hormonally and immunologically active eicosanoids . Recent discoveries have shown that the long-chained omega-3 fatty acids eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) also play an important role in the central nervous system . They are essential for normal brain functioning including attention and other neuropsychological skills . Material s and methods In our large observational study we monitored 810 children from 5 to 12 years of age referred for medical help and recommended for consuming polyunsaturated fatty acids ( PUFA ) in combination with zinc and magnesium by a physician over a period of at least 3 months . The food supplement ESPRICO ® ( further on referred to as the food supplement ) is developed on the basis of current nutritional science and containing a combination of omega-3 and omega-6 fatty acids as well as magnesium and zinc . Study objective was to evaluate the nutritional effects of the PUFA-zinc-magnesium combination on symptoms of attention deficit , impulsivity , and hyperactivity as well as on emotional problems and sleep related parameters . Assessment was performed by internationally st and ardised evaluation scales , i.e. SNAP-IV and SDQ . Tolerance ( adverse events ) and acceptance ( compliance ) of the dietary therapy were documented . Results After 12 weeks of consumption of a combination of omega-3 and omega-6 fatty acids as well as magnesium and zinc most subjects showed a considerable reduction in symptoms of attention deficit and hyperactivity/impulsivity assessed by SNAP-IV . Further , the assessment by SDQ revealed fewer emotional problems at the end of the study period compared to baseline and also sleeping disorders . Mainly problems to fall asleep , decreased during the 12 week nutritional therapy . Regarding safety , no serious adverse events occurred . A total of 16 adverse events with a possible causal relationship to the study medication were reported by 14 children ( 1.7 % ) and only 5.2 % of the children discontinued the study due to acceptance problems . Continuation of consumption of the food supplement was recommended by the paediatricians for 61.1 % of the children . Conclusion Our results suggest a beneficial effect of a combination of omega-3 and omega-6 fatty acids as well as magnesium and zinc consumption on attentional , behavioural , and emotional problems of children and adolescents . Thus , considering the behavioural benefit in combination with the low risk due to a good safety profile , the dietary supplementation with PUFA in combination with zinc and magnesium can be recommended We investigated whether supplementation with arachidonic acid ( 20:4 omega 6 ; AA ) , or a combination of AA and docosahexaenoic acid ( 22:6 omega 3 ; DHA ) would affect  human milk polyunsaturated fatty acid ( PUFA ) composition . Ten women were daily supplemented with 300 mg AA  , eight with 300 mg AA , 110 mg eicosapentaenoic acid ( 20:5 omega 3 ; EPA ) and 400 mg DHA , for one week and eight women served as unsupplemented controls . Milk sample s were collected on days 0 , 1 and 7 . The fatty acid composition of the milk was analyzed by capillary gas chromatography with flame ionisation detection . Supplementation with AA alone had no effect on breastmilk AA , but tended to reduce EPA and DHA levels . Administration of a combination of AA , EPA and DHA tended to increase both milk AA and long chain PUFA (LCPUFA)omega 3 content . A larger simultaneous increase of milk AA , DHA and EPA than observed in the present study can probably be accomplished by the use of a combination of a lower LCPUFA omega 6/LCPUFA omega 3 ratio and higher AA , EPA and DHA dosages OBJECTIVE Exaggerated cardiovascular reactivity predicts cardiovascular morbidity and mortality . Some evidence suggests that omega-3 fatty acids improve cardiovascular function . The objective of this study was to examine the influence of an acute low dose of long-chain omega-3 fatty acids on young , healthy individuals . METHODS Participants ( n=34 ) were r and omly assigned to either 21-days of omega-3 fatty acids ( 1.4 g EPA and DHA ) or matched placebo .  Cardiovascular measurements were obtained in the laboratory during baseline and during a st and ard mental arithmetic task , where participants were instructed to engage in serial subtractions by 17s from a four-digit number and cardiovascular reactivity to the task was calculated . RESULTS Mean arterial pressure reactivity was significantly reduced by supplementation ( F(1,32)=5 . 12 , p=.03 , η(2)=.144 ) but not by placebo . CONCLUSION Supplementation of omega-3 fatty acids may reduce cardiovascular reactivity to stress OBJECTIVE To examine the association of dietary omega-3 long-chain polyunsaturated fatty acid and fish intake with incident neovascular age-related macular degeneration ( AMD ) and central geographic atrophy ( CGA ) . METHODS Multicenter clinic-based prospect i ve cohort study from a clinical trial including Age-Related Eye Disease Study ( AREDS ) participants with bilateral drusen at enrollment . Main outcome measures were incident neovascular AMD and CGA , ascertained from annual stereoscopic color fundus photographs ( median follow-up , 6.3 years ) . We estimated nutrient and food intake from a vali date d food frequency question naire ( FFQ ) at baseline , with intake of docosahexaenoic acid ( DHA ) , eicosapentaenoic acid ( EPA ) , combined EPA and DHA , and fish as primary exposures . RESULTS After controlling for known covariates , we observed a reduced likelihood of progression from bilateral drusen to CGA among people who reported the highest levels of EPA ( odds ratio [ OR ] , 0.44 ; 95 % confidence interval [ CI ] , 0.23 - 0.87 ) and EPA+DHA ( OR , 0.45 ; 95 % CI , 0.23 - 0.90 ) consumption . Levels of DHA  were associated with CGA in age- , sex- , and calorie-adjusted models ( OR , 0.51 ; 95 % CI , 0.26 - 1.00 ) ; however , this statistical relationship did not persist in multivariable models . CONCLUSIONS Dietary lipid intake is a modifiable factor that may influence the likelihood of developing sight-threatening forms of AMD . Our findings suggest that dietary omega-3 long-chain polyunsaturated fatty acid intake is associated with a decreased risk of progression from bilateral drusen to CGA Objective Long-chain omega 3 fatty acids , eicosapentaenoic acid ( EPA , 20:5n-3 ) and docosahexaenoic acid ( DHA , 22:6n-3 ) exert potent anti-inflammatory properties in humans . This study characterized the effects of omega-3 ω-3 fatty acids supplements ( ω-3 FA ) on the inflammatory status in the placenta and adipose tissue of overweight/obese pregnant women . Study Design A r and omized , double-masked controlled trial was conducted in overweight/obese pregnant women that were r and omly assigned to receive DHA plus EPA ( 2g/day ) or the equivalent of a placebo twice a day from week 10–16 to term . Inflammatory pathways were characterized in : 1 ) adipose tissue and placenta of treated vs. untreated women ; and 2 ) adipose and trophoblast cells cultured with long chain FAs . Results The sum of plasma DHA and EPA increased by 5.8 fold and ω-3 FA/ ω-6 FA ratio was 1.5 in treated vs. untreated women ( p < 0.005 ) . Plasma CRP concentrations were reduced ( p<0.001 ) . The adipose tissue and placenta of treated women exhibited a significant decrease in TLR4 adipose and placental expression as well as IL6 , IL8 , and TNFα In vitro , EPA and DHA suppressed the activation of TLR4 , IL6 , IL8 induced by palmitate in culture of adipose and trophoblast cells . Conclusion Supplementation of overweight/obese pregnant women with dietary ω-3 FAs for > 25 weeks reduced inflammation in maternal adipose and the placental tissue . TLR4 appears as a central target of the anti-inflammatory effects at the cellular level . Trial Registration Clinical Trials.gov PURPOSE Increased dietary intake of lutein/zeaxanthin and omega-long-chain polyunsaturated fatty acids ( omega-3 LCPUFA ) was found to be associated with reduced risk of advanced age-related macular degeneration ( AMD ) . The purpose of the study was to examine the effect of oral supplementation of omega-3 LCPUFA on changes in serum levels of lutein/zeaxanthin  during supplementation in persons 60 years of age and older , with or without AMD . METHODS Forty participants with AMD of various degrees of severity received lutein ( 10 mg ) and zeaxanthin ( 2 mg ) daily and were equally r and omized to receive omega-3 LCPUFA ( 350 mg docosahexaenoic acid [ DHA ] and 650 mg eicosapentaenoic acid [ EPA ] ) or placebo for 6 months . Serum levels of lutein , zeaxanthin , and omega-3 LCPUFAs and macular pigment optical densities were measured at baseline , 1 week , and 1 , 3 , 6 , and 9 months . RESULTS By month 6 , the median serum levels of lutein/zeaxanthin increased by two- to threefold compared with baseline . Increases in serum levels of lutein/zeaxanthin did not differ by omega-3 LCPUFA treatment ( P > 0.5 ) . After 1 month , in the omega-3 LCPUFA-treated group , the median levels of DHA and EPA increased and the placebo group had no changes . At month 6 , participants with AMD had a lower increase in serum lutein concentration than did those without AMD ( P < 0.05 ) . CONCLUSIONS The addition of omega-3 LCPUFA to oral supplementation of lutein/zeaxanthin did not change the serum levels of lutein and zeaxanthin . A long-term large clinical trial is necessary to investigate the benefits and adverse effects of these factors for the treatment of AMD Fatty acid compositions of plasma phospholipids ( PL ) , triglycerides ( TG ) and sterol esters ( STE ) were measured by high resolution capillary gas-liquid chromatography in formula fed healthy infants at the ages of 5 days and 1 , 2 , 3 and 4 months . The infants were r and omly assigned to receive either conventional infant formula ( F , n = 10 ) without long-chain polyunsaturates ( LCP ) or the same formula supplemented with LCP ( LCP-F , n = 12 ) in amounts and ratios similar to those characteristic to human milk . From the age of 1 month onwards , percentage contributions of the principal omega-6 LCP , arachidonic acid were significantly higher in plasma lipids of infants fed LCP-F than in those receiving conventional formula without dietary LCP . Values of the principal omega-3 LCP , docosahexaenoic acid were also significantly lower in the infants fed conventional formula than in those receiving LCP-F throughout the study . The data obtained indicate that from the formula supplemented with LCP both arachidonic and docosahexaenoic acids were effectively absorbed and incorporated into infantile plasma lipids . Recent data of the literature suggest that supplementation of infant formula with LCP may beneficially influence visual and psychomotor development also in healthy , term infants
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 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 .