Meta-Analysis August 30, 2023

Omega-3 Polyunsaturated Fatty Acids for Core Symptoms of Attention-Deficit/Hyperactivity Disorder: A Meta-Analysis of Randomized Controlled Trials

J Clin Psychiatry 2023;84(5):22r14772

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ABSTRACT

Objective: Previous studies have shown conflicting results for the effectiveness of omega-3 polyunsaturated fatty acids (PUFAs) in improving attention-deficit/hyperactivity disorder (ADHD) symptoms. This inconsistency may be due to differences in dosage, composition, and treatment duration. The current meta-analysis aims to address this inconsistency by improving subtype analyses and focusing on heterogeneity in treatment duration, omega-3 PUFA composition, and eicosapentaenoic acid (EPA) dose.

Data Sources and Study Selection: We searched PubMed, EMBASE, PsycINFO, and Cochrane Library for randomized controlled trials of omega-3 PUFAs for ADHD, without publication year or language limitations, up to November 27, 2022. The primary outcome was the improvement of ADHD core symptoms. Subgroup analyses were conducted based on the formula, dosages, and composition ratios of omega-3 PUFAs. To ensure methodological quality, the Cochrane Risk-of-Bias Tool 1.0 was utilized to assess the risk of bias for each study included in the analysis. The pooled data were then analyzed using the random-effect meta-analysis, and the inverse variance method was employed.

Data Extraction: The outcomes of interest were extracted using a data extraction form developed for this study.

Results: Twenty-two studies with 1,789 participants were included in the analysis. Overall, omega-3 PUFAs did not significantly improve ADHD core symptoms compared to placebo (standardized mean difference [SMD]: −0.16; 95% CI, −0.34 to 0.01; P = .07). However, in the subgroup of studies with a treatment duration of at least 4 months, omega-3 PUFAs were significantly more effective than placebo (SMD: −0.35; 95% CI,−0.61 to −0.09; P = .007). Neither high eicosapentaenoic acid (EPA) dosage nor high EPA/docosahexaenoic acid (DHA) ratio was found to improve ADHD symptoms.

Conclusions: Our findings indicate that omega-3 PUFAs did not improve ADHD core symptoms, but long-term supplementation may have potential benefits. The main limitation of the study was the moderate heterogeneity and small sample sizes in subgroup analyses and the lack of dietary pattern information.

J Clin Psychiatry 2023;84(5):22r14772

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  1. Epstein JN, Loren RE. Changes in the definition of ADHD in DSM-5: subtle but important. Neuropsychiatry (London). 2013;3(5):455–458. PubMed CrossRef
  2. Polanczyk GV, Willcutt EG, Salum GA, et al. ADHD prevalence estimates across three decades: an updated systematic review and meta-regression analysis. Int J Epidemiol. 2014;43(2):434–442. PubMed CrossRef
  3. Subcommittee on Attention-Deficit/Hyperactivity Disorder SCoQI. Management. ADHD: Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents. IL, USA: American Academy of Pediatrics Elk Grove Village; 2011:1007–1022.
  4. Sokoła-Wysoczańska E, Wysoczański T, Wagner J, et al. Polyunsaturated fatty acids and their potential therapeutic role in cardiovascular system disorders: a review. Nutrients. 2018;10(10):1561. PubMed CrossRef
  5. Calder PC. Polyunsaturated fatty acids and inflammation. Prostaglandins Leukot Essent Fatty Acids. 2006;75(3):197–202. PubMed CrossRef
  6. Hawkey E, Nigg JT. Omega-3 fatty acid and ADHD: blood level analysis and meta-analytic extension of supplementation trials. Clin Psychol Rev. 2014;34(6):496–505. PubMed CrossRef
  7. LaChance L, McKenzie K, Taylor VH, et al. Omega-6 to omega-3 fatty acid ratio in patients with ADHD: a meta-analysis. J Can Acad Child Adolesc Psychiatry. 2016;25(2):87–96. PubMed
  8. Carucci S, Romaniello R, Demuru G, et al. Omega-3/6 supplementation for mild to moderate inattentive ADHD: a randomised, double-blind, placebo-controlled efficacy study in Italian children. Eur Arch Psychiatry Clin Neurosci. 2022;272:1453–1467. PubMed CrossRef
  9. Chang JP-C, Su K-P, Mondelli V, et al. High-dose eicosapentaenoic acid (EPA) improves attention and vigilance in children and adolescents with attention deficit hyperactivity disorder (ADHD) and low endogenous EPA levels. Transl Psychiatry. 2019;9(1):303. PubMed CrossRef
  10. Assareh M, Davari Ashtiani R, Khademi M, et al. Efficacy of polyunsaturated fatty acids (PUFA) in the treatment of attention deficit hyperactivity disorder: a randomized, double-blind, placebo-controlled clinical trial. J Atten Disord. 2017;21(1):78–85. PubMed CrossRef
  11. Bos DJ, Oranje B, Veerhoek ES, et al. Reduced symptoms of inattention after dietary omega-3 fatty acid supplementation in boys with and without attention deficit hyperactivity disorder. Neuropsychopharmacology. 2015;40(10):2298–2306. PubMed CrossRef
  12. Cornu C, Mercier C, Ginhoux T, et al. A double-blind placebo-controlled randomised trial of omega-3 supplementation in children with moderate ADHD symptoms. Eur Child Adolesc Psychiatry. 2018;27(3):377–384. PubMed CrossRef
  13. Crippa A, Tesei A, Sangiorgio F, et al. Behavioral and cognitive effects of docosahexaenoic acid in drug-naïve children with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled clinical trial. Eur Child Adolesc Psychiatry. 2019;28(4):571–583. PubMed CrossRef
  14. Dashti N, Hekmat H, Soltani HR, et al. Comparison of therapeutic effects of omega-3 and methylphenidate (Ritalin) in treating children with attention deficit hyperactivity disorder. Iran J Psychiatry Behav Sci. 2014;8(4):7–11. PubMed
  15. Döpfner M, Dose C, Breuer D, et al. Efficacy of omega-3/omega-6 fatty acids in preschool children at risk of ADHD: a randomized placebo-controlled trial. J Atten Disord. 2021;25(8):1096–1106. PubMed CrossRef
  16. Gustafsson PA, Birberg-Thornberg U, Duchén K, et al. EPA supplementation improves teacher-rated behaviour and oppositional symptoms in children with ADHD. Acta Paediatr. 2010;99(10):1540–1549. PubMed CrossRef
  17. Kean JD, Sarris J, Scholey A, et al. Reduced inattention and hyperactivity and improved cognition after marine oil extract (PCSO-524) supplementation in children and adolescents with clinical and subclinical symptoms of attention-deficit hyperactivity disorder (ADHD): a randomised, double-blind, placebo-controlled trial. Psychopharmacology (Berl). 2017;234(3):403–420. PubMed CrossRef
  18. Manor I, Magen A, Keidar D, et al. The effect of phosphatidylserine containing Omega3 fatty-acids on attention-deficit hyperactivity disorder symptoms in children: a double-blind placebo-controlled trial, followed by an open-label extension. Eur Psychiatry. 2012;27(5):335–342. PubMed CrossRef
  19. Milte CM, Parletta N, Buckley JD, et al. 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. J Atten Disord. 2015;19(11):954–964. PubMed CrossRef
  20. Moghaddam MF, Shamekhi M, Rakhshani T. Effectiveness of methylphenidate and PUFA for the treatment of patients with ADHD: a double-blinded randomized clinical trial. Electron Physician. 2017;9(5):4412–4418. PubMed CrossRef
  21. Mohammadzadeh S, Baghi N, Yousefi F, et al. Effect of omega-3 plus methylphenidate as an alternative therapy to reduce attention deficit hyperactivity disorder in children. Korean J Pediatr. 2019;62(9):360–366. PubMed CrossRef
  22. Perera H, Jeewandara KC, Seneviratne S, et al. Combined ω3 and ω6 supplementation in children with attention-deficit hyperactivity disorder (ADHD) refractory to methylphenidate treatment: a double-blind, placebo-controlled study. J Child Neurol. 2012;27(6):747–753. PubMed CrossRef
  23. Rodríguez C, García T, Areces D, et al. Supplementation with high-content docosahexaenoic acid triglyceride in attention-deficit hyperactivity disorder: a randomized double-blind placebo-controlled trial. Neuropsychiatr Dis Treat. 2019;15:1193–1209. PubMed CrossRef
  24. Salehi B, Mohammadbeigi A, Sheykholeslam H, et al. Omega-3 and Zinc supplementation as complementary therapies in children with attention-deficit/hyperactivity disorder. J Res Pharm Pract. 2016;5(1):22–26. PubMed CrossRef
  25. Sinn N, Bryan J. Effect of supplementation with polyunsaturated fatty acids and micronutrients on learning and behavior problems associated with child ADHD. J Dev Behav Pediatr. 2007;28(2):82–91. PubMed CrossRef
  26. Stevens L, Zhang W, Peck L, et al. EFA supplementation in children with inattention, hyperactivity, and other disruptive behaviors. Lipids. 2003;38(10):1007–1021. PubMed CrossRef
  27. Vaisman N, Kaysar N, Zaruk-Adasha Y, et al. 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. Am J Clin Nutr. 2008;87(5):1170–1180. PubMed CrossRef
  28. Widenhorn-Müller K, Schwanda S, Scholz E, et al. 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. Prostaglandins Leukot Essent Fatty Acids. 2014;91(1–2):49–60. PubMed CrossRef
  29. Anand P, Sachdeva A. Effect of poly unsaturated fatty acids administration on children with attention deficit hyperactivity disorder: a randomized controlled trial. J Clin Diagn Res. 2016;10(9):OC01–OC05. PubMed CrossRef
  30. Behdani F, Hebrani P, Naseraee A, et al. Does omega-3 supplement enhance the therapeutic results of methylphenidate in attention deficit hyperactivity disorder patients? J Res Med Sci. 2013;18(8):653–658. PubMed
  31. Chang JP-C, Su K-P, Mondelli V, et al. Omega-3 polyunsaturated fatty acids in youths with attention deficit hyperactivity disorder: a systematic review and meta-analysis of clinical trials and biological studies. Neuropsychopharmacology. 2018;43(3):534–545. PubMed CrossRef
  32. Händel MN, Rohde JF, Rimestad ML, et al. Efficacy and safety of polyunsaturated fatty acids supplementation in the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents: a systematic review and meta-analysis of clinical trials. Nutrients. 2021;13(4):1226. PubMed CrossRef
  33. Matsudaira T, Gow RV, Kelly J, et al. Biochemical and psychological effects of omega-3/6 supplements in male adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, clinical trial. J Child Adolesc Psychopharmacol. 2015;25(10):775–782. PubMed CrossRef
  34. Gillies D, Sinn JKh, Lad SS, et al. Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database Syst Rev. 2012;2012(7):CD007986. PubMed CrossRef
  35. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Int J Surg. 2021;88:105906. PubMed CrossRef
  36. Higgins JP, Altman DG, Gøtzsche PC, et al; Cochrane Bias Methods Group; Cochrane Statistical Methods Group. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. PubMed CrossRef
  37. Guyatt GH, Oxman AD, Vist GE, et al; GRADE Working Group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924–926. PubMed CrossRef
  38. Higgins JP, Thomas J, Chandler J, et al. Cochrane Handbook for Systematic Reviews of Interventions. John Wiley & Sons; 2019.
  39. Hedges LV, Olkin I. Statistical Methods for Meta-Analysis. Academic Press; 2014.
  40. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–1558. PubMed CrossRef
  41. Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–560. PubMed CrossRef
  42. Derbyshire E. Do omega-3/6 fatty acids have a therapeutic role in children and young people with ADHD? J Lipids. 2017;2017:6285218. PubMed CrossRef
  43. Heilskov Rytter MJ, Andersen LBB, Houmann T, et al. Diet in the treatment of ADHD in children—a systematic review of the literature. Nord J Psychiatry. 2015;69(1):1–18. PubMed CrossRef
  44. Hooijmans CR, Pasker-de Jong PC, de Vries RB, et al. The effects of long-term omega-3 fatty acid supplementation on cognition and Alzheimer’s pathology in animal models of Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis. 2012;28(1):191–209. PubMed CrossRef
  45. Casula M, Soranna D, Catapano AL, et al. Long-term effect of high dose omega-3 fatty acid supplementation for secondary prevention of cardiovascular outcomes: a meta-analysis of randomized, double blind, placebo controlled trials. Atheroscler suppl. 2013;14(2):243–251. PubMed CrossRef
  46. Voigt RG, Llorente AM, Jensen CL, et al. A randomized, double-blind, placebo-controlled trial of docosahexaenoic acid supplementation in children with attention-deficit/hyperactivity disorder. J Pediatr. 2001;139(2):189–196. PubMed CrossRef
  47. Kang H. Trial sequential analysis: novel approach for meta-analysis. Anesth Pain Med (Seoul). 2021;16(2):138–150. PubMed CrossRef