European Child & Adolescent Psychiatry

, Volume 27, Issue 3, pp 377–384 | Cite as

A double-blind placebo-controlled randomised trial of omega-3 supplementation in children with moderate ADHD symptoms

  • Catherine Cornu
  • Catherine Mercier
  • Tiphanie Ginhoux
  • Sandrine Masson
  • Julie Mouchet
  • Patrice Nony
  • Behrouz Kassai
  • Valérie Laudy
  • Patrick Berquin
  • Nathalie Franc
  • Marie-France Le Heuzey
  • Hugues Desombre
  • Olivier Revol
Original Contribution



Clinical trials and inconclusive meta-analyses have investigated the effects of omega-3 supplements in children with Attention-Deficit Hyperactivity Disorder (ADHD). We performed a randomised placebo-controlled trial to evaluate the efficacy of omega-3 fatty acids.


Children aged 6–15 years with established diagnosis of ADHD were randomised 1:1 to receive either supplements containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or a placebo for 3 months. Psychotropic or omega-3-containing treatments were not authorised during the study. The primary outcome was the change in the Attention-Deficit Hyperactivity Disorder Rating Scale version 4 (ADHD-RS-IV). Other outcomes included safety, lexical level (Alouette test), attention (Test of Attentional Performance for Children—KiTAP), anxiety (48-item Conners Parent Rating Scale-Revised—CPRS-R), and depression (Children’s Depression Inventory—CDI).


Between 2009 and 2011, 162 children were included in five French child psychiatry centres. The mean age was 9.90 (SD 2.62) years and 78.4% were boys. The inclusion ADHD-RS-IV at was 37.31 (SD 8.40). The total ADHD-RS-IV score reduction was greater in the placebo group than in the DHA–EPA group: −19 (−26, −12)  % and −9.7 (−16.6, −2.9) %, respectively, p = 0.039. The other components of the Conners score had a similar variation but the differences between groups were not significant. Two patients in the DHA–EPA group and none in the placebo group experienced a severe adverse event (hospitalisation for worsening ADHD symptoms).


This study did not show any beneficial effect of omega-3 supplement in children with mild ADHD symptoms.


Child ADHD Omega-3 rich fatty acid supplementation Randomized controlled trial 


Compliance with ethical standards

Conflict of Interest

The authors declare they have no conflicts of interest to disclose.


  1. 1.
    APA (2010) Diagnostic and statistical manual of mental disorders, 4th edn, text revision (DSM-IV-TR). American Psychiatric Association. 943 ppGoogle Scholar
  2. 2.
    American Psychiatric Association (1996) DSM4 V, Manuel diagnostique et statistique des troubles mentaux. Traduction française, Paris, Masson, 1056 ppGoogle Scholar
  3. 3.
    Cantwell DP (1996) Attention deficit disorder: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry 35(8):978–987CrossRefPubMedGoogle Scholar
  4. 4.
    Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA (2007) The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry 164(6):942–948CrossRefPubMedGoogle Scholar
  5. 5.
    Faraone SV, Sergeant J, Gillberg C, Biederman J (2003) The worldwide prevalence of ADHD: is it an American condition? World Psychiatry 2(2):104–113PubMedPubMedCentralGoogle Scholar
  6. 6.
    Schachter HM, Pham B, King J, Langford S, Moher D (2001) How efficacious and safe is short-acting methylphenidate for the treatment of attention-deficit disorder in children and adolescents? A meta-analysis. CAMJ 165(11):1475–1488Google Scholar
  7. 7.
  8. 8.
    Attention deficit hyperactivity disorder: diagnosis and management. NICE guidelines [CG72] Published date: September 2008 Last updated: February 2016Google Scholar
  9. 9.
    Storebø OJ, Krogh HB, Ramstad E, Moreira-Maia CR, Holmskov M, Skoog M, Nilausen TD, Magnusson FL, Zwi M, Gillies D, Rosendal S, Groth C, Rasmussen KB, Gauci D, Kirubakaran R, Forsbøl B, Simonsen E, Gluud C (2015) Methylphenidate for attention-deficit/hyperactivity disorder in children and adolescents: cochrane systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. BMJ 25(351):h5203CrossRefGoogle Scholar
  10. 10.
    Kidwell KM, Van Dyk TR, Lundahl A, Nelson TD (2015) Stimulant medications and sleep for youth with ADHD: a meta-analysis. Pediatrics 136(6):1144–1153CrossRefPubMedGoogle Scholar
  11. 11.
  12. 12.
    Burgess JR, Stevens L, Zhang W, Peck L (2000) Long-chain polyunsaturated fatty acids in children with attention-deficit hyperactivity disorder. Am J Clin Nutr 71:327–330CrossRefGoogle Scholar
  13. 13.
    Mitchell EA, Aman MG, Turbott SH, Manku M (1987) Clinical characteristics and serum essential fatty acid levels in hyperactive children. Clin Pediatr (Phila) 26(8):406–411CrossRefGoogle Scholar
  14. 14.
    Burgess JR, Stevens L, Zhang W, Peck L (2000) Long-chain polyunsaturated fatty acids in children with attention-deficit hyperactivity disorder. Am J Clin Nutr 71(1 Suppl):327S–330SCrossRefPubMedGoogle Scholar
  15. 15.
    Parletta N, Niyonsenga T, Duff J (2016) Omega-3 and omega-6 polyunsaturated fatty acid levels and correlations with symptoms in children with attention deficit hyperactivity disorder, autistic spectrum disorder and typically developing controls. PLoS ONE 11(5):e0156432CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Richardson AJ, Puri BK (2000) The potential role of fatty acids in attention-deficit/hyperactivity disorder. Prostaglandins Leukot Essent Fatty Acids 63(1–2):79–87CrossRefPubMedGoogle Scholar
  17. 17.
    Lange KW, Hauser J, Lange KM, Makulska-Gertruda E, Nakamura Y, Reissmann A, Sakaue Y, Takeuchi Y (2017) The role of nutritional supplements in the treatment of ADHD: what the evidence says. Curr Psychiatry Rep 19(2):8Google Scholar
  18. 18.
    Gillies D, Sinn JKh, Lad SS, Leach MJ, Ross MJ (2012) Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database Syst Rev, 7: p. CD007986Google Scholar
  19. 19.
    Sonuga-Barke EJ, Brandeis D, Cortese S, Daley D, Ferrin M, Holtmann M, Stevenson J, Danckaerts M, van der Oord S, Döpfner M, Dittmann RW, Simonoff E, Zuddas A, Banaschewski T, Buitelaar J, Coghill D, Hollis C, Konofal E, Lecendreux M, Wong IC, Sergeant J, European ADHD Guidelines Group (2013) Nonpharmacological interventions for ADHD: systematic review and meta-analyses of randomized controlled trials of dietary and psychological treatments. Am J Psychiatry 170(3):275–289CrossRefPubMedGoogle Scholar
  20. 20.
    Bloch MH, Qawasmi A (2011) Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: systematic review and meta-analysis. J Am Acad Child Adolesc Psychiatry 50(10):991–1000CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    DuPaul GJ, Power TJ, Anastopoulos AD (1998) ADHD Rating Scale IV: checklists, norms, and clinical interpretations. Guilford Press, New York (NY)Google Scholar
  22. 22.
    Mercier C, Roche S, Gaillard S et al (2016) Partial validation of a French version of the ADHD-rating scale IV on a French population of children with ADHD and epilepsy. Factorial structure, reliability, and responsiveness. Epilepsy Behav 58:1–6CrossRefPubMedGoogle Scholar
  23. 23.
    Conners CK (1969) A teacher rating scale for use in drug studies with children. Am J Psychiatry 126(6):884–888CrossRefPubMedGoogle Scholar
  24. 24.
    Lefavrais P. Test de l’Alouette, Éditions du Centre de Psychologie Appliquée. 2ème édition ed. 1967, ParisGoogle Scholar
  25. 25.
  26. 26.
    Finch AJ Jr, Saylor CF, Edwards GL (1985) Children’s depression inventory: sex and grade norms for normal children. J Consult Clin Psychol 53(3):424–425CrossRefPubMedGoogle Scholar
  27. 27.
    Michelson D, Allen AJ, Busner J et al (2002) Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: a randomized, placebo-controlled study. Am J Psychiatry 159(11):1896–1901CrossRefPubMedGoogle Scholar
  28. 28.
    Michelson D, Faries D, Wernicke J et al (2001) Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study. Pediatrics 108(5):E83CrossRefPubMedGoogle Scholar
  29. 29.
    Staquet Maurice J, Hays Ron D (1998) Peter M. Methods and Practice, Fayers. Quality of Life Assessment in Clinical TrialsGoogle Scholar
  30. 30.
    Goodman D, Faraone SV, Adler LA et al (2010) Interpreting ADHD rating scale scores: linking ADHD rating scale scores and CGI levels in two randomized controlled trials of Lisdexamfetamine Dimesylate in ADHD. Primary Psychiatry 17(3):44–52Google Scholar
  31. 31.
    Hawkey E, Nigg JT (2014) Omega-3 fatty acid and ADHD: blood level analysis and meta-analytic extension of supplementation trials. Clin Psychol Rev 34(6):496–505CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Stevens L, Zhang W, Peck L et al (2003) EFA supplementation in children with inattention, hyperactivity, and other disruptive behaviors. Lipids 38(10):1007–1021CrossRefPubMedGoogle Scholar
  33. 33.
    Gustafsson PA, Birberg-Thornberg U, Duchén K et al (2010) EPA supplementation improves teacher-rated behaviour and oppositional symptoms in children with ADHD. Acta Paediatr 99(10):1540–1549CrossRefPubMedGoogle Scholar
  34. 34.
    Itomura M, Hamazaki K, Sawazaki S et al (2005) The effect of fish oil on physical aggression in schoolchildren—a randomized, double-blind, placebo-controlled trial. J Nutr Biochem 16(3):163–171CrossRefPubMedGoogle Scholar
  35. 35.
    Kirby A, Woodward A, Jackson S, Wang Y, Crawford MA (2010) A double-blind, placebo-controlled study investigating the effects of omega-3 supplementation in children aged 8–10 years from a mainstream school population. Res Dev Disabil 31(3):718–730CrossRefPubMedGoogle Scholar
  36. 36.
    Richardson AJ, Burton JR, Sewell RP, Spreckelsen TF, Montgomery P (2012) Docosahexaenoic acid for reading, cognition and behavior in children aged 7–9 years: a randomized, controlled trial (the DOLAB Study). PLoS One 7(9):e43909. doi: 10.1371/journal.pone.0043909. Epub 2012 Sep 6
  37. 37.
    Bos DJ, van Montfort SJ, Oranje B, Durston S, Smeets PA (2016) Effects of omega-3 polyunsaturated fatty acids on human brain morphology and function: what is the evidence? Eur Neuropsychopharmacol 26(3):546–561. doi: 10.1016/j.euroneuro.2015.12.031. Epub 2015 Dec 21. Review
  38. 38.
    Vyncke KE, Libuda L, De Vriendt T, Moreno LA, Van Winckel M, Manios Y, Gottrand F, Molnar D, Vanaelst B, Sjöström M, González-Gross M, Censi L, Widhalm K, Michels N, Gilbert CC, Xatzis C, Cuenca García M, de Heredia FP, De Henauw S, Huybrechts I; HELENA consortium (2012) Dietary fatty acid intake, its food sources and determinants in European adolescents: the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Study. Br J Nutr 108(12):2261–273. doi: 10.1017/S000711451200030X. Epub 2012 Feb 28
  39. 39.
    Koletzko B, Uauy R, Palou A, Kok F, Hornstra G, Eilander A, Moretti D, Osendarp S, Zock P, Innis S (2010) Dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in children—a workshop report. Br J Nutr 103(6):923–928CrossRefPubMedGoogle Scholar
  40. 40.
    Voigt RG, Llorente AM, Jensen CL, Fraley JK, Berretta MC, Heird WC (2001) A randomized, double-blind, placebo-controlled trial of docosahexaenoic acid supplementation in children with attention-deficit/hyperactivity disorder. J Pediatr 139(2):189–196CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Catherine Cornu
    • 1
    • 2
    • 3
    • 12
  • Catherine Mercier
    • 4
    • 5
    • 6
  • Tiphanie Ginhoux
    • 1
  • Sandrine Masson
    • 1
  • Julie Mouchet
    • 4
  • Patrice Nony
    • 2
    • 3
  • Behrouz Kassai
    • 1
    • 2
    • 3
  • Valérie Laudy
    • 1
  • Patrick Berquin
    • 7
  • Nathalie Franc
    • 8
  • Marie-France Le Heuzey
    • 9
  • Hugues Desombre
    • 10
  • Olivier Revol
    • 11
  1. 1.INSERM, CIC1407BronFrance
  2. 2.Laboratoire de Biométrie et Biologie EvolutiveCNRS, UMR 5558LyonFrance
  3. 3.Service de Pharmacologie CliniqueHospices Civils de LyonBronFrance
  4. 4.Université Claude Bernard Lyon 1LyonFrance
  5. 5.Service de Biostatistique-BioinformatiqueHospices Civils de LyonLyonFrance
  6. 6.Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-SantéCNRS, UMR 5558VilleurbanneFrance
  7. 7.Service de Neurologie PédiatriqueHôpital NordAmiensFrance
  8. 8.Service de Médecine Psychologique Enfants et AdolescentsHôpital Saint-EloiMontpellierFrance
  9. 9.Service de psychiatrie de l’enfant et de l’adolescentHôpital Robert DebréParisFrance
  10. 10.Unité de Psychologie Médicale et de LiaisonHôpital femme-Mère-EnfantBronFrance
  11. 11.Service de Psychopathologie de l’enfant et de l’adolescentHôpital Pierre WertheimerBronFrance
  12. 12.Centre d’Investigation Clinique - Hôpital Louis PradelBronFrance

Personalised recommendations