However, given evidence of modest efficacy of omega-3 fatty acid supplementation and given its relatively benign side-effect profile, omega-3 fatty acid supplementation, particularly with higher doses of EPA, is a reasonable treatment strategy as augmentation to traditional pharmacotherapy or for those families reticent to use psychopharmacological agents. Figure 3 is a scatterplot that depicts the relationship between EPA dose and effect size of supplementation for individual trials. We conducted a sensitivity analysis to examine our decision to use a random-effects rather than fixed effects model for meta-analysis. Cheng JY, Chen RY, Ko JS, Ng EM.
The most significant results are encouraging: When the quantity of EPA +DHA was increased in the blood stream, these patients were better able to concentrate and, according to their parents, their ADHD symptoms were better controlled. We additionally searched for unpublished or ongoing trials on the cinicaltrials.gov website using search terms fatty acid, omega-3 OR omega-6 and ADHD. Heterogeneity of treatment response was assessed visually from the forest plot of weighted mean differences and relative risk of individual studies.
alpha-linolenic acid).14 A high omega-6 to omega-3 ratio can alter cell membrane properties and increase production of inflammatory mediators because arachidonic acid, an omega 6 fatty acid found in cell membranes, is the precursor of inflammatory eicosanoids, such as prostaglandins and thromboxanes.15 By contrast, omega-3 fatty acids are anti-inflammatory.15 Therefore, a high dietary omega-6 to omega-3 fatty ratio could promote neuroinflammation Increased omega-3 fatty acid concentration in the diet may also act by altering central nervous system cell membrane fluidity and phospholipid composition which may alter the structure and function of the proteins embedded in it.16 By this mechanism, increased omega-3 fatty acid concentrations in cell membranes have been shown to affect serotonin and dopamine neurotransmission especially in the frontal cortex.17, Through these mechanisms omega-3 fatty acid consumption has been hypothesized to alter risk for a variety of psychiatric conditions including psychosis, depression, dementia and ADHD.18, 19 Several studies have demonstrated differences in omega-3 fatty acid composition in plasma and in erythrocyte membranes in ADHD patients compared to unaffected controls.2026 Furthermore, omega-3 fatty acid supplementation has been consistently demonstrated to alter cell membrane composition in vivo.25, 27, Several double-blind, placebo-controlled trials have been conducted to assess the efficacy of omega-3 fatty acid supplementation in the treatment of children with ADHD. Arnold LE, Kleykamp D, Votolato NA, Taylor WA, Kontras SB, Tobin K. Gamma-linolenic acid for attention-deficit hyperactivity disorder: placebo-controlled comparison to D-amphetamine. Int J Mol Sci 2017; 18(12). Higher doses of EPA within omega-3 fatty acids supplements were significantly associated with increased efficacy in treating ADHD symptoms (=0.36 (95% CI: 0.010.72), t=2.30, p=0.04, R2=0.37). Although we reported a significant effect of omega-3 fatty acid supplementation in treating ADHD symptomatology, there are several weaknesses and limitations to the current meta-analysis. In ADHD, certain areas of the brain are less used, and these areas are also 10% smaller in volume.
Any significant findings should be regarded as exploratory because we did not adjust for inflation of false-positive error from our 13 secondary analyses. about navigating our updated article layout. Effect size (SMD) of trials was entered as the dependent variable with the variables of interest being the independent variable. The effect of fish oil on physical aggression in schoolchildren--a randomized, double-blind, placebo-controlled trial.
Doses of other omega-3 fatty acids within supplements such as DHA (=0.24 (95% CI: 0.541.02), t=0.70, p=0.50) and ALA (=1.71 (95% CI: 4.621.19), t=1.33, p=0.22) were not significantly associated with the measured efficacy of supplements. More than 70% of children with ADHD respond to psychostimulant medications (i.e. We found no significant difference in the efficacy of omega-3 fatty acid supplementation based on whether they were given as monotherapy versus as augmentation to other traditional ADHD medications (Test for subgroup differences: Chi2 = 0.45, df = 1 (P = 0.50, I2 = 0%). Chan E, Gardiner P, Kemper KJ. Note: Scatterplot of measured efficacy of omega-3 fatty acid supplementation in trials as a function of Eicosapentaenoic acid (EPA) dose utilized. The outcome measure selected from each included trial was the difference in mean improvement between omega-3 fatty acid supplementation and placebo group in a clinical rating scale measuring ADHD severity over the course of the trial. 
Klein RG, Landa B, Mattes JA, Klein DF. Spencer T, Biederman J, Wilens T, Harding M, O'Donnell D, Griffin S. Pharmacotherapy of attention-deficit hyperactivity disorder across the life cycle. Simopoulos AP. ketogenic As many rating scales have excellent psychometric properties in evaluating ADHD, this hierarchy of preferred rating scales for ADHD is not meant to reflect the relative merit of these measures. We identified 4 potentially eligible trials from the references of relevant reviews.
Raz R, Carasso RL, Yehuda S. The influence of short-chain essential fatty acids on children with attention-deficit/hyperactivity disorder: a double-blind placebo-controlled study. Publication bias was assessed by plotting the effect size against sample size for each trial (funnel plot).30 Publication bias was also statistically tested by testing the association between sample size and effect size in meta-regression.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. However, given its relatively benign side-effect profile and evidence of modest efficacy, it may be reasonable to use omega-3 fatty supplementation to augment traditional pharmacological interventions or for families who decline all other psychopharmacological options. Because of poor quality and potential issues of blinding in many of the included trials, further clinical trials are needed to replicate the results of this meta-analysis. adhd dha ratio oilswelove Cochrane Handbook for Systematic Reviews of Interventions 4.2.5. Combining forces leads to a good result. Eicosapentaenoic acid (EPA) dose within supplements was significantly correlated with supplement efficacy. Diagnostic and statistical manual of mental disorders. Young GS, Maharaj NJ, Conquer JA. and transmitted securely. Trials that relied on completers' analysis (SMD=0.32 (95%CI: 0.120.52) z=3.09, p=0.002) did not demonstrate a significantly greater efficacy (Test for subgroup differences: Chi2 = 0, df = 1 (P = 0.98), I2 = 0%) of omega-3 fatty acid supplementation than trials that utilized ITT or modified ITT analysis methods (SMD=0.31 (95%CI: 0.080.55), z=2.6, p=0.009).
Meta-regression also demonstrated a significant association between efficacy and dose of EPA given in supplements. This product is not intended to diagnose, treat, cure, or prevent any disease. In this meta-analysis we report a small but significant benefit of omega-3 fatty acid supplementation. Likely some evidence of each of these phenomena would be present if any of these types of bias were driving our results. Given the considerable heterogeneity expected in the literature, we also wanted to use meta-regression to examine how the use of different omega-3 fatty acid compositions in supplementation affected treatment efficacy. Of course every child who is on occasion particularly careless, easily distracted, noisy or energetic does not earn this label. For all subgroup analyses and meta-regression we used the same threshold for statistical significance. SMD was favored over weighted mean difference because rating scales differed across studies. Figure 1 demonstrates a flow diagram depicting our selection procedure for this meta-analysis. A fixed effects model was chosen for meta-analysis because this method is favored when testing for subgroup differences in stratified meta-analysis. Yes, and in fact the combination is beneficial. In the Western diet omega-6 fatty acids or their precursors (e.g. However, given its relatively benign side-effect profile and evidence of modest efficacy, it may be reasonable to use omega-3 fatty supplementation to augment traditional pharmacological interventions or for families who decline other psychopharmacological options. Gustafsson PA, Birberg-Thornberg U, Duchen K, Landgren M, Malmberg K, Pelling H, et al. methylphenidate and dextroamphetamine derivatives).4 Other medications such as atomoxetine, alpha-2 agonists and desipramine have also demonstrated efficacy in treating ADHD.57 However, many families elect not to use traditional pharmacotherapies to treat ADHD. Despite these limitations of individual trials, overall meta-analysis demonstrates no evidence of publication bias, heterogeneity between trials and effect of subject dropout or poor study quality. For secondary analysis, we used the same methodology as above to examine the effect of omega-3 supplementation for the symptoms of inattention and hyperactivity/impulsivity separately. Connor DF, Fletcher KE, Swanson JM. Several studies have demonstrated differences in omega-3 fatty acid composition in plasma and in erythrocyte membranes in patients with ADHD compared to unaffected controls.
Freeman MP, Hibbeln JR, Wisner KL, Davis JM, Mischoulon D, Peet M, et al. We found no significant effect of type of placebo on the measured effect of omega-3 supplementation in trials (Test for subgroup differences: Chi2 = 2.26, df = 4 (P = 0.69), I2 = 0%). Belanger SA, Vanasse M, Spahis S, Sylvestre MP, Lippe S, L'Heureux F, et al. Note: ADHD = attention-deficit/hyperactivity disorder. The site is secure. Overall this meta-analysis demonstrates a small but statistically significant benefit of omega-3 fatty acid supplementation in the treatment of ADHD.
International Journal of Methods in Psychiatric Research. Effect of supplementation with polyunsaturated fatty acids and micronutrients on learning and behavior problems associated with child ADHD. Stevens L, Zhang W, Peck L, Kuczek T, Grevstad N, Mahon A, et al. Ten studies involving 699 participants contributed to this analysis. The new PMC design is here! Methylphenidate is the medication used in ADHD, but there are some drawbacks. Note: Twelve trials involving 735 children with attention-deficit/hyperactivity disorder (ADHD) were included in this meta-analysis. Standard mean difference (SMD) was chosen as the summary statistic for meta-analysis and calculated by pooling the standardized mean improvement of each study using RevMan 5. Peet M, Stokes C. Omega-3 fatty acids in the treatment of psychiatric disorders. Schachter HM, Pham B, King J, Langford S, Moher D. How efficacious and safe is short-acting methylphenidate for the treatment of attention-deficit disorder in children and adolescents? Chen JR, Hsu SF, Hsu CD, Hwang LH, Yang SC.
We found no significant effect of study quality on the measured efficacy of omega-3 fatty acid supplementation in the treatment of ADHD (Test for subgroup differences: Chi2 = 0.41, df = 1 (P = 0.52), I2 = 0%). Some children and young people can be treated with Omega 3 alone, others can reduce their medication if it is taken in combination with Omega 3. Methylphenidate and growth in hyperactive children. For instance, one recent systematic review published in the last year described the results of current trials in the area very disappointing with most randomized trials have clearly demonstrated lack of superiority or arbitrary findings (which may be a result of multiple analyses without appropriate statistical correction) compared with placebo.13 Another recent review, evaluating the same literature stated that the administration of specific combinations of long chain- polyunsaturated fatty acids (LC-PUFAs) can have a positive effect in children with ADHD but that the optimum LC-PUFA composition and dose needs to be established.28. At least its natural: herbs and dietary supplements in ADHD. The https:// ensures that you are connecting to the The value of Omega 3 in children and young people with ADHD. There is second advantage to the combination with Omega 3, because the same clinical effect can be obtained from the combination in a lower dose than when methylphenidate is used alone. We also performed several subgroup analyses and meta-regression. Clinical practice guideline: diagnosis and evaluation of the child with attention-deficit/hyperactivity disorder. will also be available for a limited time. Meta-analysis found no evidence of publication bias or of significant heterogeneity between trials. A randomized, double-blind, placebo-controlled trial of docosahexaenoic acid supplementation in children with attention-deficit/hyperactivity disorder. In order to have sufficient power (=80%, 2-sided =0.05) to detect a significant benefit of omega-3 fatty acid supplementation compared to placebo assuming the effect size observed in this meta-analysis, clinical trials would require a sample size of approximately 330 children.
Prostaglandins Leukot Essent Fatty Acids. EFA supplementation in children with inattention, hyperactivity, and other disruptive behaviors. We used a meta-regression techniques to examine the association between omega-3 and naturally continuous variables such as (1) trial duration, (2) proportion of dropouts in trials using completers analysis and (3) doses of omega-3 fatty acids in supplementation preparations. When it was combined with Omega 3, insomnia was no longer found. Correlation between changes in blood fatty acid composition and visual sustained attention performance in children with inattention: effect of dietary n-3 fatty acids containing phospholipids. Lastly, questions have been raised regarding the adequacy of blinding in early trials using fish oil because of a fishy aftertaste present when the active formulations are refluxed.50 Based on the data presented in manuscripts it is not possible to evaluate the effectiveness of blinding in these trials. The efficacy of omega-3 fatty acid supplementation did not significantly (Test for subgroup differences: Chi2 = 0.12, df = 1 (P = 0.73), I2 = 0%) differ whether ADHD was the subjects' primary diagnoses (SMD=0.30 (95% CI: 0.130.47, z=3.42, p=0.0006) or whether ADHD symptoms were being targeted in another psychiatric condition (SMD=0.36 (95% CI: 0.040.69, z=2.18, p=0.03). Omega-3 fatty acids have anti-inflammatory properties.15 Omega-3 fatty acids are also known to alter cell membrane fluidity in the CNS which affects dopamine and serotonin neurotransmission.17 It remains unclear why supplementation with EPA may improve ADHD symptoms while supplementation with DHA may not to the same degree. There was no significant heterogeneity or publication bias evident for these measures. A hierarchy of preferred ADHD rating scale for our primary outcome was established a priori (as opposed to utilizing the ADHD rating scale indentified as primary by the trial investigator) in order to avoid any possible inflation of treatment effects caused by possible reporting bias towards measures that showed the greatest efficacy. Careers, Yale Child Study Center and Yale University, Yale Child Study Center and the Child Institute at Al-Quds University, Correspondence to: Michael H. Bloch, MD, MS, Child Study Center, Yale University School of Medicine, PO Box 2070900, New Haven, CT 06520 or, The publisher's final edited version of this article is available at, Attention-Deficit Disorder with Hyperactivity, polyunsaturated fatty acids, omega-3 fatty acids, Eicosapentaenoic acid (EPA), meta-analysis.