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]. Reduced Symptoms of Inattention after Dietary Omega-3 Fatty Acid Supplementation in Boys with and without Attention Deficit/Hyperactivity Disorder A randomised controlled trial of vitamin D and omega-3 long chain polyunsaturated fatty acids in the treatment of irritability and hyperactivity among children with autism spectrum disorder The Effects of Long-Chain Omega-3 Fish Oils and Multivitamins on Cognitive and Cardiovascular Function: A Randomized, Controlled Clinical Trial Retinal development in very-low-birth-weight infants fed diets differing in omega-3 fatty acids. Biochemical and Psychological Effects of Omega-3/6 Supplements in Male Adolescents with Attention-Deficit/Hyperactivity Disorder: A Randomized, Placebo-Controlled, Clinical Trial. Dietary supplementation with fish oil rich in omega-3 polyunsaturated fatty acids in children with bronchial asthma. Baseline characteristics of participants in the VITamin D and OmegA-3 TriaL (VITAL). Fish oil supplementation increases event-related posterior cingulate activation in older adults with subjective memory impairment Effect of 2-y n-3 long-chain polyunsaturated fatty acid supplementation on cognitive function in older people: a randomized, double-blind, controlled trial. Omega-3 fatty acids and cognitive decline: modulation by ApoEε4 allele and depression Improved Working Memory but No Effect on Striatal Vesicular Monoamine Transporter Type 2 after Omega-3 Polyunsaturated Fatty Acid Supplementation The influence of a formula supplemented with dairy lipids and plant oils on the erythrocyte membrane omega-3 fatty acid profile in healthy full-term infants: a double-blind randomized controlled trial
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 Attention deficit/hyperactivity disorder ( ADHD ) is one of the most common child psychiatric disorders , and is often treated with stimulant medication . Nonpharmacological treatments include dietary supplementation with omega-3 fatty acids , although their effectiveness remains to be shown conclusively . In this study , we investigated the effects of dietary omega-3 fatty acid supplementation on ADHD symptoms and cognitive control in young boys with and without ADHD . A total of 40 boys with ADHD , aged 8–14 years , and 39 matched , typically developing controls participated in a 16-week double-blind r and omized placebo-controlled trial . Participants consumed 10 g of margarine daily , enriched with either 650 mg of eicosapentaenoic acid (EPA)/docosahexaenoic acid ( DHA ) each or placebo . Baseline and follow-up assessment s addressed ADHD symptoms , fMRI of cognitive control , urine homovanillic acid , and cheek cell phospholipid sampling . EPA/DHA supplementation improved parent-rated attention in both children with ADHD and typically developing children . Phospholipid DHA level at follow-up was higher for children receiving EPA/DHA supplements than placebo . There was no effect of EPA/DHA supplementation on cognitive control or on fMRI measures of brain activity . This study shows that dietary supplementation with omega-3 fatty acids  reduces symptoms of ADHD , both for individuals with ADHD and typically developing children . This effect does not appear to be mediated by cognitive control systems in the brain , as no effect of supplementation was found here . Nonetheless , this study offers support that omega-3 supplementation may be an effective augmentation for pharmacological treatments of ADHD ( NCT01554462 : The Effects of EPA/DHA Supplementation on Cognitive Control in Children with ADHD ; http:// clinical trials.gov/show/NCT01554462 ) Irritability and hyperactivity are common in children with Autism Spectrum Disorder ( ASD ) . Because pharmacological treatments may have adverse effects , and despite limited evidence , caregivers/parents often use dietary supplements such as vitamin D and omega-3 fatty acids to address these behavioural symptoms . As a secondary objective of the VIDOMA ( Vitamin D and Omega-3 in ASD ) trial , we evaluated the efficacy of vitamin D , omega-3 long chain polyunsaturated fatty acid [ omega-3 LCPUFA ; docosahexaenoic acid ( DHA ) ] , or both on irritability and hyperactivity .  New Zeal and children with ASD ( aged 2.5 - 8 years ) participated in a 12-month r and omized , double-blind , placebo-controlled trial of vitamin D ( 2000 IU/day , VID ) , omega-3 LCPUFA ( 722 mg/day DHA , OM ) , or both ( 2000 IU/day vitamin D + 722 mg/day DHA , VIDOM ) . The primary outcomes were the Aberrant Behaviour Checklist ( ABC ) domains of irritability and hyperactivity . Biomarkers ( serum 25-hydroxyvitamin D [ 25(OH)D ] and omega-3 index ) and primary outcomes were measured at baseline and 12-months . Out of 111 children who completed baseline data collection , 66 % completed the study ( VID = 19 , OM = 23 , VIDOM = 15 , placebo = 16 ) . After 12 months , children receiving OM ( -5.0 ± 5.0 , P = 0.001 ) and VID ( -4.0±4.9 , P = 0.01 ) had greater reduction in irritability than placebo ( 0.8±6.1 ) . Compared to placebo , children on VID also had greater reduction in hyperactivity ( -5.2±6.3 vs. -0.8±5.6 , P = 0.047 ) . Serum 25(OH)D concentration ( nmol/L , mean±SD ) increased by 27±14 in VID and by 36±17 in VIDOM groups ( P < 0.0001 ) , and omega-3 index ( % , median ( 25th , 75th percentiles ) ) by 4.4 ( 3.3 , 5.9 ) in OM and by 4.0 ( 2.0 , 6.0 ) in VIDOM groups ( P < 0.0001 ) , indicating a good compliance rate . The results indicate that vitamin D and omega-3 LCPUFA reduced irritability symptoms in children with ASD . Vitamin D also reduced hyperactivity symptoms in these children Objective : Fish oils and multivitamins are two of the most commonly used dietary supplements . Fish oil use may reduce vascular risk factors associated with cognitive decline , thus providing benefits to both heart and brain health . Multivitamins may also have direct effects on brain function . The present study investigated the effects of fish oil , with and without the addition of a multivitamin , on cognitive and cardiovascular function . Methods : In a r and omized ,  placebo-controlled  , double-blind fashion , 160 healthy adults aged 50–70 years were r and omized to receive either 3 g of fish oil ( 240 mg eicosapentaenoic acid [ EPA ] + 240 mg docosahexaenoic acid [ DHA ] ) with a multivitamin , 6 g of fish oil ( 480 mg EPA + 480 mg DHA ) with a multivitamin , or 6 g of fish oil without a multivitamin or a placebo . Cognitive performance , brachial blood pressure , and aortic ( central ) blood pressure were measured at baseline , 6 weeks , and 16 weeks . Results : Treatment allocation had no effect on the primary cognitive outcomes at endpoint . Absolute increases in the red blood cell omega-3/6 ratio were associated with improvements in spatial working memory . The group receiving 6 g fish oil without the multivitamin displayed a significant decrease in aortic pulse pressure and aortic augmentation pressure , two measures of aortic blood pressure and aortic stiffness . Conclusions : Fish oil decreased aortic pulse pressure and augmentation pressure . Reductions in aortic blood pressure were not accompanied by consistent improvements in cognition Full-field electroretinograms ( ERGs ) were obtained from very-low-birth-weight ( VLBW ) neonates to determine whether omega-3 ( omega-3 ) fatty acids are essential for normal human retinal development . Eighty-one infants born at 30.4 ( st and ard deviation , + /- 1.5 ) wk gestation were , within 10 d of birth , either enrolled to receive mother 's milk ( naturally containing both omega-6 and omega-3 essential fatty acids ) or  r and omized to receive one of the infant formulas . Corn oil-based Formula A contained mainly linoleic acid ( 18:2 omega-6 ) and was low in all omega-3 fatty acids . Soy oil-based Formula B contained ample alpha-linolenic acid ( 18:3 omega-3 ) but no long-chain omega-3 . Formula C , supplemented with both alpha-linolenic acid and marine oils , was comparable to human milk in long-chain omega-3 . Full-field ERGs were obtained in the special care nursery from infants aged 36 and 57 wk postconception . Ten healthy preterm infants born at 35 wk gestation were tested at 36 wk postconception . Significant differences were found among groups in rod ERG function . Post hoc comparisons showed that infants fed Formula A had significantly higher rod thresholds than infants receiving long-chain omega-3 ( human milk , Formula C , and intrauterine ) . Infants receiving Formula B had intermediate thresholds that were significantly higher than those of infants receiving intrauterine nutrition . Analysis of the leading edge of the a-wave showed that b-wave differences originated at the photoreceptor level . Differences were not present in infants at 57 wk postconception . No significant differences among groups were found in cone b-waves at 36 or 57 wk postconception . Oscillatory potentials had significantly longer implicit times at 57 wk postconception in infants fed Formula A than in infants receiving human milk . These findings suggest that retinal function varies with the dietary supply of omega-3 fatty acids in VLBW infants BACKGROUND An abnormality in long chain-polyunsaturated fatty acid ( LC-PUFA ) levels has been implicated in attention-deficit/hyperactivity disorder ( ADHD ) . Studies evaluating LC-PUFA supplementation for therapeutic efficacy in ADHD have shown mixed and , therefore , inconclusive results . METHODS Seventy-six male adolescents ( age 12 - 16 years , mean = 13.7 ) with ADHD were assessed for the effects of 12 weeks omega-3 and omega-6 supplements on biochemical and psychological outcomes in a r and omized , placebo-controlled , clinical trial . The primary outcome measure was change in the Conners ' Teacher Rating Scales ( CTRS ) following 12 weeks of supplementation of LC-PUFA or placebo . At baseline , the placebo and treatment groups had comparable levels of LC-PUFA as measured by red blood cell phosphatidylcholine . In the treatment group , supplementation enhanced eicosapentaenoic acid ( EPA ) , docosahexaenoic acid ( DHA ) , and total omega-3 fatty acid levels . RESULTS No superiority of LC-PUFAs to placebo was observed on the primary outcome . Further , there were no reliable treatment effects on aggression , impulsivity , depression , and anxiety . CONCLUSIONS Future studies should use larger sample sizes and longer supplementation period to detect small-modest effects for clinical recommendations in ADHD Omega-3 polyunsaturated fatty acids have anti-inflammatory effects in vitro , and high dietary levels are associated with a lower incidence of inflammatory diseases . However , only limited effects have been demonstrated in asthma . The effects of dietary supplementation with fish oil for 10 months in 29 children with bronchial asthma was investigated in a r and omized controlled fashion . In order to minimize the effects of environmental inhaled allergens and diet , this study was performed in a long-term treatment hospital . Subjects received fish oil capsules containing 84 mg eicosapentaenoic acid ( EPA ) and 36 mg docosahexaenoic acid ( DHA ) or control capsules containing 300 mg olive oil . The daily dosages of EPA and DHA were 17.0 - 26.8 and 7.3 - 11.5 mg x kg body weight(-1 ) , respectively . Asthma symptom scores decreased and responsiveness to acetylcholine decreased in the fish oil group but not in the control group . In addition , plasma EPA levels increased significantly only in the fish oil group ( p<0.0088 ) . No significant side-effects were observed . The present results suggest that dietary supplementation with fish oil rich in the omega-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid is beneficial for children with bronchial asthma in a strictly controlled environment in terms of inhalant allergens and diet Evidence for a role of supplemental vitamin D and marine omega-3 fatty acids in preventing cancer and cardiovascular disease ( CVD ) remains inconclusive and insufficient to inform nutritional recommendations for primary prevention . The VITamin D and Omega-A 3 TriaL ( VITAL ) is an ongoing nationwide , r and omized , double-blind , placebo-controlled clinical trial design ed to fill this knowledge gap . The study population consists of 25,874 U.S. adults without cancer or CVD at baseline , who were selected only on age ( men aged ≥50 and women aged ≥55 ) , with an oversampling of African Americans ( n=5,107 ) . In a 2 × 2 factorial design , participants were r and omized to one of four supplement groups : [ 1 ] active vitamin D3 ( cholecalciferol ; 2000 IU/d ) and active marine omega-3 fatty acids ( Omacor ® fish oil , eicosapentaenoic acid [ EPA ] and docosahexaenoic acid [ DHA ] , 1g/d ) ; [ 2 ] active vitamin D and omega-3 placebo ; [ 3 ] vitamin D placebo and active marine omega-3 fatty acids ; or [ 4 ] vitamin D placebo and omega-3 placebo . The mean length of the r and omized treatment period will be 5 years . The r and omization was successful , as evidence d by similar distributions of baseline demographic , health , and behavioral characteristics across treatment groups . The similar distribution of known potential confounders across treatment groups strongly suggests that unmeasured or unknown potential confounders are also equally distributed . VITAL is expected to provide important information on the benefit-risk balance of vitamin D and omega-3 fatty acid supplementation when taken for the primary prevention of cancer and CVD Objective To determine the effects of long-chain omega-3 ( LCn-3 ) fatty acids found in fish oil , including eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , on cortical blood oxygen level-dependent ( BOLD ) activity during a working memory task in older adults with subjective memory impairment . Design R and omized , double-blind , placebo-controlled study . Setting Academic medical center . Participants Healthy older adults ( 62–80 years ) with subjective memory impairment , but not meeting criteria for mild cognitive impairment or dementia . InterventionFish oil ( EPA+DHA : 2.4 g/d , n=11 ) or placebo ( corn oil , n=10 ) for 24 weeks . Measurements Cortical BOLD response patterns during performance of a sequential letter n-back working memory task were determined at baseline and week 24 by functional magnetic resonance imaging ( fMRI ) . Results At 24 weeks erythrocyte membrane EPA+DHA composition increased significantly from baseline in participants receiving fish oil ( + 31 % , p≤0.0001 ) but not placebo ( −17 % , p=0.06 ) . Multivariate modeling of fMRI data identified a significant interaction among treatment , visit , and memory loading in the right cingulate ( BA 23/24 ) , and in the right sensorimotor area ( BA 3/4 ) . In the fish oil group , BOLD increases at 24 weeks were observed in the right posterior cingulate and left superior frontal regions during memory loading . A region-of-interest analysis indicated that the baseline to endpoint change in posterior cingulate cortex BOLD activity signal was significantly greater in the fish oil group compared with the placebo group during the 1-back ( p=0.0003 ) and 2-back ( p=0.0005 ) conditions . Among all participants , the change in erythrocyte EPA+DHA during the intervention was associated with performance in the 2-back working memory task ( p = 0.01 ) , and with cingulate BOLD signal during the 1-back ( p = 0.005 ) with a trend during the 2-back ( p = 0.09 ) . Further , cingulate BOLD activity was related to performance in the 2-back condition . Conclusions Dietary fish oil supplementation increases red blood cell omega-3 content , working memory performance , and BOLD signal in the posterior cingulate cortex during greater working memory load in older adults with subjective memory impairment suggesting enhanced neuronal response to working memory challenge BACKGROUND Increased consumption of n-3 ( omega-3 ) long-chain polyunsaturated fatty acids ( LC PUFAs ) , especially eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , may maintain cognitive function in later life . OBJECTIVE We tested the hypothesis that n-3 LC PUFA supplementation would benefit cognitive function in cognitively healthy older people . DESIGN At total of 867 cognitively healthy adults , aged 70 - 79 y , from 20 general practice s in Engl and and Wales were r and omly assigned into a double-blind controlled trial of daily capsules providing 200 mg EPA plus 500 mg DHA or olive oil for 24 mo . Treatment-allocation codes were obtained from a central computerized r and omization service . Trained research nurses administered a battery of cognitive tests , including the primary outcome , the California Verbal Learning Test ( CVLT ) , at baseline and 24 mo . Intention-to-treat analysis of covariance , with adjustment for baseline cognitive scores , age , sex , and age at leaving full-time education , included 748 ( 86 % ) individuals who completed the study . RESULTS The mean age of participants was 75 y ; 55 % of the participants were men .  Withdrawals and deaths were similar in active ( n = 49 and n = 9 , respectively ) and placebo ( n = 53 and n = 8 , respectively ) arms . Mean ( + /-SD ) serum EPA and DHA concentrations were significantly higher in the active arm than in the placebo arm at 24 mo ( 49.9 + /- 2.7 mg EPA/L in the active arm compared with 39.1 + /- 3.1 mg EPA/L in the placebo arm ; 95.6 + /- 3.1 mg DHA/L in the active arm compared with 70.7 + /- 2.9 mg DHA/L in the placebo arm ) . There was no change in cognitive function scores over 24 mo , and intention-to-treat analysis showed no significant differences between trial arms at 24 mo in the CVLT or any secondary cognitive outcome . CONCLUSIONS Cognitive function did not decline in either study arm over 24 mo . The lack of decline in the control arm and the relatively short intervention period may have limited our ability to detect any potential beneficial effect of fish oil on cognitive function in this study . The Older People And n-3 Long-chain polyunsaturated fatty acids ( OPAL ) Study was registered at www.controlled-trials.com as IS RCT N 72331636 Long-chain omega-3 fatty acids eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) may slow cognitive decline . The ε4 allele of the ApolipoproteinE ( ApoE ) , the main genetic risk factor for Alzheimer 's disease , and depressive symptoms , which are frequently associated with cognitive impairment in older persons , may modify this relationship . We estimated the associations between EPA and DHA  plasma levels and subsequent cognitive decline over 7 years , taking into account ApoE-ε4 status and depressive symptoms , in a prospect i ve population -based cohort . Participants ( ≥ 65 years , n = 1,228 nondemented at baseline ) were evaluated at least once over three follow-up visits using four cognitive tests . Plasma EPA was associated with slower decline on Benton Visual Retention Test ( BVRT ) performances in ApoE-ε4 carriers , or in subjects with high depressive symptoms at baseline . Plasma DHA was associated with slower decline on BVRT performances in ApoE-ε4 carriers only . EPA and DHA may contribute to delaying decline in visual working memory in ApoE-ε4 carriers . In older depressed subjects  , EPA , but not DHA , may slow cognitive decline Studies in rodents indicate that diets deficient in omega-3 polyunsaturated fatty acids ( n–3 PUFA ) lower dopamine neurotransmission as measured by striatal vesicular monoamine transporter type 2 ( VMAT2 ) density and amphetamine-induced dopamine release . This suggests that dietary supplementation with fish oil might increase VMAT2 availability , enhance dopamine storage and release , and improve dopamine-dependent cognitive functions such as working memory . To investigate this mechanism in humans , positron emission tomography ( PET ) was used to measure VMAT2 availability pre- and post-supplementation of n–3 PUFA in healthy individuals . Healthy young adult subjects were scanned with PET using [11C]-(+)-α-dihydrotetrabenzine ( DTBZ ) before and after six months of n–3 PUFA supplementation ( Lovaza , 2 g/day containing docosahexaenonic acid , DHA 750 mg/d and eicosapentaenoic acid , EPA 930 mg/d ) . In addition , subjects underwent a working memory task ( n-back ) and red blood cell membrane ( RBC ) fatty acid composition analysis pre- and post-supplementation . RBC analysis showed a significant increase in both DHA and EPA post-supplementation . In contrast , no significant change in [11C]DTBZ binding potential ( BPND ) in striatum and its subdivisions were observed after supplementation with n–3 PUFA . No correlation was evident between n–3 PUFA induced change in RBC DHA or EPA levels and change in [11C]DTBZ BPND in striatal subdivisions . However , pre-supplementation RBC DHA levels was predictive of baseline performance ( i.e. , adjusted hit rate , AHR on 3-back ) on the n-back task ( y = 0.19 + 0.07 , r2 = 0.55 , p = 0.009 ) . In addition , subjects AHR performance improved on 3-back post-supplementation ( pre 0.65±0.27 , post 0.80±0.15 , p = 0.04 ) . The correlation between n-back performance , and DHA levels are consistent with reports in which higher DHA levels is related to improved cognitive performance . However , the lack of change in [11C]DBTZ BPND indicates that striatal VMAT2 regulation is not the mechanism of action by which n–3 PUFA improves cognitive performance Background Human milk is the optimal nutrition for infants . When breastfeeding is not possible , supplementation of infant formula with long chain polyunsaturated fatty acids appears to promote neurodevelopmental outcome and visual function .  Plant oils , that are the only source of fat in most of infant formulas , do not contain specific fatty acids that are present in human and cow milk and do not encounter milk fat triglyceride structure . Experimental data suggest that a mix of dairy lipids and plant oils can potentiate endogenous synthesis of n-3 long chain polyunsaturated fatty acids . This trial aims to determine the effect of an infant formula supplemented with a mixture of dairy lipids and plant oils on the erythrocyte membrane omega-3 fatty acid profile in full-term infants ( primary outcome ) . Erythrocyte membrane long chain polyunsaturated fatty acids and fatty acids content , the plasma lipid profile and the insulin-growth factor 1 level , the gastrointestinal tolerance , the changes throughout the study in blood fatty acids content , in growth and body composition are evaluated as secondary outcomes . Methods / Design In a double-blind controlled r and omized trial , 75 healthy full-term infants are r and omly allocated to receive for four months a formula supplemented with a mixture of dairy lipids and plant oils or a formula containing only plant oils or a formula containing plant oils supplemented with arachidonic acid and docosahexaenoic acid .  Twenty-five breast-fed infants constitute the reference group .  Erythrocyte membrane omega-3 fatty acid profile , long chain polyunsaturated fatty acids and the other fatty acids content , the plasma lipid profile and the insulin-growth factor 1 level are measured after four months of intervention . Gastrointestinal tolerance , the changes in blood fatty acids content , in growth and body composition , assessed by means of an air displacement plethysmography system , are also evaluated throughout the study . Discussion The achievement of an appropriate long chain polyunsaturated fatty acids status represents an important goal in neonatal nutrition . Gaining further insight in the effects of the supplementation of a formula with dairy lipids and plant oils in healthy full-term infants could help to produce a formula whose fat content , composition and structure is more similar to human milk . Trial registration Clinical Trials.gov Identifier
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 .