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Cited by 52Autism Spectrum Disorder ResearchFatty Acid Research and HealthChild Nutrition and Feeding Issues

Impact of polyunsaturated fatty acids on patient-important outcomes in children and adolescents with autism spectrum disorder: a systematic review

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on behalf of the ISACA guideline working group, De Crescenzo, Franco, D’Alò, Gian Loreto, Morgano, Gian Paolo, Minozzi, Silvia, Mitrova, Zuzana, Saulle, Rosella, Cruciani, Fabio +6 more·2020·Health and Quality of Life Outcomes
DOI 10.1186/s12955-020-01284-5PMC PMC7026962
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Abstract

Background: Recent randomized controlled trials (RCTs) claimed PUFAs to be effective for autism spectrum disorder (ASD) but international guidelines have not considered yet this body of evidence. Our aim was to assess the effectiveness of PUFAs in children and adolescents with ASD, for the Italian national guidelines on the management of ASD in children and adolescents. Methods: We performed a systematic review and meta-analysis of RCTs comparing PUFAs versus placebo or a healthy diet for the treatment of ASD in children and adolescents. The outcomes considered were deemed by the guideline panel to be highly relevant to children and adolescents with ASD and to their caregivers. The outcomes included hyperactivity, quality of sleep, self-harm, aggression, irritability, anxiety, attention, adaptive functioning, social interaction, restricted and repetitive interests and behavior, communication, hyperactivity and disruptive behaviors coexistent with core symptoms. The risk of bias of the included studies was assessed with the Cochrane tool, and the rating of the confidence in the effect estimates according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: We included 9 studies with 405 participants. The strength of evidence ranged from low to very low. Six studies included preschoolers and school-age children, three studies included both children and adolescents. The majority of participants were males (83.8%), with a mean age of 6.7 years. PUFAs were superior compared to placebo in reducing anxiety in individuals with ASD (SMD -1.01, 95% CI − 1.86 to − 0.17; very low certainty of evidence). Moreover, PUFAs worsened quality of sleep compared to a healthy diet (SMD 1.11, 95% CI 0.21 to 2.00; very low certainty of evidence). PUFAs were not better than placebo in reducing aggression, hyperactivity, adaptive functioning, irritability, restricted and repetitive interests and behaviors and communication. Effects on some critical outcomes such as sleep, self-harm and disruptive behavior are currently unknown. The main limitations were the small number of participants included in the RCTs and the dosage which varied greatly (from 200 mg/day to 1540 mg/day), making it difficult to address causal inference. Conclusions: PUFAs did not show evidence of effect in children and adolescents with ASD and the certainty of evidence as measured with the GRADE was low to very low. Further research is needed on this topic because the available evidence is inconclusive.

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  • Several clinical trials have shown beneficial effects of n-3 PUFA supplementation in ASD and ADHD, but not all results are consistent.

    “Several clinical trials have shown beneficial effects of n-3 PUFA supplementation in ASD and ADHD, but not all results are consistent and the ratio of EPA and DHA in n-3 PUFA supplements and the overall dietary intake of FAs may affect the clinical outcome62–65.”

    From An iPSC-derived astrocyte model of fragile X syndrome exhibits dysregulated cholesterol homeostasis (2023) · cites this paper as [62]

    The Results report reduced anxiety in children and adolescents with ASD, while the Discussion describes mixed trial findings and low to very low certainty of evidence. The Introduction says EPA and DHA have been studied for ADHD, but our copy does not report beneficial ADHD trial results. (LLM, conf=0.87)

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Research works printed but not linked: 44

  1. [2]Narzisi A Posada M Barbieri F Chericoni N Ciuffolini D Pinzino M Prevalence of autism Spectrum disorder in a large Italian catchment area: a school-based population study within the ASDEU project Epidemiol Psychiatr Sci 2018 29 e5 10.1017/S2045796018000483 30187843 PMC8061252 · DOI
  2. [5]Postorino V Fatta LM Sanges V Giovagnoli G De Peppo L Vicari S Intellectual disability in autism Spectrum disorder: investigation of prevalence in an Italian sample of children and adolescents Res Dev Disabil 2016 48 193 201 10.1016/j.ridd.2015.10.020 26619372 · DOI
  3. [6]Lai MC Lombardo MV Baron-Cohen S Autism Lancet 2014 383 9920 896 910 10.1016/S0140-6736(13)61539-1 24074734 · DOI · Paper page
  4. [7]Abdelhamid AS Martin N Bridges C Brainard JS Wang X Brown TJ Polyunsaturated fatty acids for the primary and secondary prevention of cardiovascular disease Cochrane Database Syst Rev 2018 7 CD012345 30019767 PMC6513571
  5. [8]Bozzatello Paola Brignolo Elena De Grandi Elisa Bellino Silvio Supplementation with Omega-3 Fatty Acids in Psychiatric Disorders: A Review of Literature Data Journal of Clinical Medicine 2016 5 8 67 10.3390/jcm5080067 PMC4999787 27472373 · DOI
  6. [10]ASCEND Study Collaborative Group Bowman L Mafham M Wallendszus K Stevens W Buck G Barton J Murphy K Effects of n-3 fatty acid supplements in diabetes mellitus N Engl J Med 2018 379 16 1540 1550 10.1056/NEJMoa1804989 30146932 · DOI · Paper page
  7. [11]Foti F De Crescenzo F Vivanti G Menghini D Vicari S Implicit learning in individuals with autism spectrum disorders: a meta-analysis Psychol Med 2015 45 5 897 910 10.1017/S0033291714001950 25126858 · DOI
  8. [12]Yui K Koshiba M Nakamura S Kobayashi Y Effects of large doses of arachidonic acid added to docosahexaenoic acid on social impairment in individuals with autism spectrum disorders: a double-blind, placebo-controlled, randomized trial J Clin Psychopharmacol 2012 32 2 200 206 10.1097/JCP.0b013e3182485791 22370992 · DOI
  9. [13]De Giorgi R, De Crescenzo F, D'Alò GL, Rizzo Pesci N, Di Franco V, Sandini C, et al. Prevalence of Non-Affective Psychoses in Individuals with Autism Spectrum Disorders: A Systematic Review. J Clin Med. 2019;8(9). PMC6780908 31450601
  10. [15]Lee J-H Polyunsaturated fatty acids in children Pediatr Gastroenterol Hepatol Nutr 2013 16 3 153 161 10.5223/pghn.2013.16.3.153 24224148 PMC3819697 · DOI
  11. [16]IOM (Institute of Medicine). Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press, 2011.
  12. [17]Qaseem A Forland F Macbeth F Ollenschläger G Phillips S Van der Wees P Board of Trustees of the guidelines international network. Guidelines international network: toward international standards for clinical practice guidelines Ann Intern Med 2012 156 7 525 531 10.7326/0003-4819-156-7-201204030-00009 22473437 · DOI · Paper page
  13. [20]DerSimonian R Laird N Meta-analysis in clinical trials Control Clin Trials 1986 7 3 177 188 10.1016/0197-2456(86)90046-2 3802833 · DOI · Paper page
  14. [22]Schünemann HJ, Oxman AD, Higgins JPT, Vist GE, Glasziou P, Guyatt GH, et al. Presenting results and “Summary of findings” tables. In: Higgins JPT, Green S, eds. Cochrane handbook for systematic reviews of interventions. Chichester: Wiley; 2008. p. 335–8.
  15. [24]Guyatt GH Oxman AD Santesso N Helfand M Vist G Kunz R GRADE guidelines: 12. Preparing summary of findings tables-binary outcomes J Clin Epidemiol 2013 66 2 158 172 10.1016/j.jclinepi.2012.01.012 22609141 · DOI · Paper page
  16. [25]Guyatt GH Thorlund K Oxman AD Walter SD Patrick D Furukawa TA GRADE guidelines: 13. Preparing summary of findings tables and evidence profiles-continuous outcomes J Clin Epidemiol 2013 66 2 173 183 10.1016/j.jclinepi.2012.08.001 23116689 · DOI · Paper page
  17. [26]Johnson SM Hollander E Evidence that eicosapentaenoic acid is effective in treating autism J Clin Psychiatry 2003 64 848 849 10.4088/JCP.v64n0718c 12934990 · DOI
  18. [27]Meguid NA Atta HM Gouda AS Khalil RO Role of polyunsaturated fatty acids in the management of Egyptian children with autism Clin Biochem 2008 41 1044 1048 10.1016/j.clinbiochem.2008.05.013 18582451 · DOI
  19. [28]Meiri G Bichovsky Y Belmaker RH Omega 3 fatty acid treatment in autism J Child Adolesc Psychopharm 2009 19 4 449 451 10.1089/cap.2008.0123 19702497 · DOI
  20. [30]Politi P Cena H Comelli M Marrone G Allegri C Emanuele E Behavioral effects of omega-3 fatty acid supplementation in young adults with severe autism: an open label study Arch Med Res 2008 39 7 682 685 10.1016/j.arcmed.2008.06.005 18760197 · DOI
  21. [31]Ooi YP Weng SJ Jang LY Low L Seah J Teo S Omega-3 fatty acids in the management of autism spectrum disorders: findings from an open-label pilot study in Singapore Eur J Clin Nutr 2015 69 8 969 971 10.1038/ejcn.2015.28 25804268 · DOI
  22. [32]Boone KM Gracious B Klebanoff MA Rogers LK Rausch J Coury DL Omega-3 and -6 fatty acid supplementation and sensory processing in toddlers with ASD symptomology born preterm: a randomized controlled trial Early HumDev 2017 115 64 70 10.1016/j.earlhumdev.2017.09.015 PMC9530960 28941976 · DOI
  23. [33]Boone KM Gracious B Klebanoff MA Rogers LK Rausch J Coury DL Corrigendum to "Omega-3 and -6 fatty acid supplementation and sensory processing in toddlers with ASD symptomology born preterm: a randomized controlled trial" Early Hum Dev 2018 128 120 10.1016/j.earlhumdev.2017.11.005 28941976 PMC9530960 · DOI
  24. [34]Keim SA Gracious B Boone KM Klebanoff MA Rogers LK Rausch J ω-3 and ω-6 fatty acid supplementation may reduce autism symptoms based on parent report in preterm toddlers J Nutr 2018 148 2 227 235 10.1093/jn/nxx047 29490101 PMC6251698 · DOI
  25. [35]Sheppard KW Boone KM Gracious B Klebanoff MA Rogers LK Rausch J Effect of Omega-3 and -6 supplementation on language in preterm toddlers exhibiting autism Spectrum disorder symptoms J Autism Dev Disord 2017 47 11 3358 3369 10.1007/s10803-017-3249-3 28748334 PMC9540981 · DOI
  26. [47]Bent S Hendren RL Zandi T Law K Choi JE Widjaja F Internet-based, randomized, controlled trial of omega-3 fatty acids for hyperactivity in autism J Am Acad Child Adolesc Psychiatry 2014 53 6 658 666 10.1016/j.jaac.2014.01.018 24839884 PMC4076340 · DOI
  27. [48]Amminger GP Berger GE Schafer MR Klier C Friedrich MH Feucht M Omega-3 fatty acids supplementation in children with autism: a double-blind randomized, placebo-controlled pilot study Biol Psychiatry 2007 61 551 553 10.1016/j.biopsych.2006.05.007 16920077 · DOI · Paper page
  28. [49]Bent S Bertoglio K Ashwood P Bostrom A Hendren RL A pilot randomized controlled trial of omega-3 fatty acids for autism spectrum disorder J Autism Dev Disord 2011 41 5 545 554 10.1007/s10803-010-1078-8 20683766 PMC3076562 · DOI · Paper page
  29. [50]Mankad D Dupuis A Smile S Roberts W Brian J Lui T A randomized, placebo controlled trial ofomega-3 fatty acids in the treatment of young children with autism Mol Autism 2015 6 18 10.1186/s13229-015-0010-7 25798215 PMC4367852 · DOI
  30. [51]Parellada M Llorente C Calvo R Gutierrez S Lázaro L Graell M Randomized trial of omega-3 for autism spectrum disorders: effect on cell membrane composition and behavior Eur Neuropsychopharmacol 2017 27 12 1319 1330 10.1016/j.euroneuro.2017.08.426 28935269 · DOI · Paper page
  31. [52]Voigt RG Mellon MW Katusic SK Weaver AL Matern D Mellon B Dietary docosahexaenoic acid supplementation in children with autism J Pediatr Gastroenterol Nutr 2014 58 6 715 722 24345834
  32. [53]Johnson CR Handen BL Zimmer M Sacco K Polyunsaturated fatty acid supplementation in young children with autism J Dev Phys Disabil 2010 22 1 10 10.1007/s10882-009-9152-x · DOI
  33. [54]Sterne JAC, Egger M, Moher D; Cochrane Bias Method Group. Addressing reporting biases. In: Higgins JPT, Green S, editors. Cochrane Handbook of Systematic Reviews of Interventions. Chichester, UK: Wiley, 2008. p. 297–333.
  34. [58]Bays HE Safety considerations with omega-3 fatty acid therapy Am J Cardiol 2007 99 6A 35C 43C 10.1016/j.amjcard.2006.11.020 17368277 · DOI
  35. [59]Institute of Medicine, Food and Nutrition Board. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids (macronutrients). Washington, DC: National Academy Press; 2005.
  36. [60]EFSA Panel on Dietetic Products NaA Scientific opinion on the tolerable upper intake level of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) EFSA J 2012 10 2815 PMC13093066 42016086
  37. [61]Hilleman D Smer A Prescription Omega-3 fatty acid products and dietary supplements are not interchangeable Manag Care 2016 25 1 46 52 26882630
  38. [62]Santini A Cammarata SM Capone G Ianaro A Tenore GC Pani L Nutraceuticals: opening the debate for a regulatory framework Br J Clin Pharmacol 2018 84 4 659 672 10.1111/bcp.13496 29433155 PMC5867125 · DOI
  39. [63]Morgano GP, Fulceri F, Nardocci F, Barbui C, Ostuzzi G, Papola D, et al. Introduction and methods of the evidence-based guidelines for the diagnosis and management of autism Spectrum disorder by the Italian National Institute of health. Submitted to Health Qual Life Outcomes. PMC7098105 32216833
  40. [64]James S Montgomery P Williams K Omega-3 fatty acids supplementation for autism spectrum disorders (ASD) Cochrane Database Syst Rev 2011 11 CD007992 PMC13606348 22071839
  41. [65]Mazahery Hajar Stonehouse Welma Delshad Maryam Kruger Marlena Conlon Cathryn Beck Kathryn von Hurst Pamela Relationship between Long Chain n-3 Polyunsaturated Fatty Acids and Autism Spectrum Disorder: Systematic Review and Meta-Analysis of Case-Control and Randomised Controlled Trials Nutrients 2017 9 2 155 10.3390/nu9020155 PMC5331586 28218722 · DOI
  42. [66]Horvath A Łukasik J Szajewska H ω-3 fatty acid supplementation does not affect autism Spectrum disorder in children: a systematic review and meta-analysis J Nutr 2017 147 3 367 376 10.3945/jn.116.242354 28077731 · DOI
  43. [68]Huang A Seshadri K Matthews TA Ostfeld BM Parental perspectives on use, benefits, and physician knowledge of complementary and alternative medicine in children with autistic disorder and attention-deficit/hyperactivity disorder J Altern Complement Med 2013 19 9 746 750 10.1089/acm.2012.0640 23621389 PMC3768225 · DOI
  44. [69]D’Alò GL, De Crescenzo F, Minozzi S, Morgano GP, Mitrova Z, Scattoni ML, et al. Equity, acceptability and feasibility of using polyunsaturated fatty acids in children and adolescents with autism spectrum disorder: a rapid systematic review. Submitted to Health Qual Life Outcomes. PMC7164335 32299432

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Authors
on behalf of the ISACA guideline working group, De Crescenzo, F., D’Alò, G. L., Morgano, G. P., Minozzi, S., Mitrova, Z., Saulle, R., Cruciani, F., Fulceri, F., Davoli, M., Scattoni, M. L., Nardocci, F., Schünemann, H. J., & Amato, L.
Affiliations
  • University of Rome Tor Vergata (IT)
  • McMaster University (CA)
  • Istituto Superiore di Sanità (IT)
  • Michael G. DeGroote Cochrane Canada Centre (CA)
ORCID
Venue
Health and Quality of Life Outcomes
Publisher
Springer Science and Business Media LLC
Published
2020-02-17
Volume
18
Issue
1
Pages
28-28
ISSN
1477-7525 (ISSN-L)
DOI
10.1186/s12955-020-01284-5
PMC
PMC7026962
OpenAlex
W3009195529
Cited by
52
References
7
Citations by year
2026: 5 · 2025: 3 · 2024: 5 · 2023: 5 · 2022: 3 · 2021: 15 · 2020: 16
FWCI
1.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Health and Quality of Life Outcomes (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institute for Health and Care Research (RP-2017-08-ST2-006)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
Keywords
polyunsaturated fatty acids, autism spectrum disorder, children and adolescents, dietary supplementation, anxiety, sleep quality, aggression, hyperactivity, irritability, restricted and repetitive behaviors, adaptive behavior, social interaction, communication, treatment guidelines, quality of evidence, omega-3 fatty acids, omega-6 fatty acids, n-6/n-3 ratio, omega-3 index
MeSH terms
Autism Spectrum Disorder, Diet, Healthy, Child, Fatty Acids, Unsaturated, Female, Humans, Male, Quality of Life, Randomized Controlled Trials as Topic, Treatment Outcome

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