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Journal of Autism and Developmental Disorders

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11-01-2022 | Original Paper

Randomized Controlled Trial of Omega-3 and -6 Fatty Acid Supplementation to Reduce Inflammatory Markers in Children with Autism Spectrum Disorder

Auteurs: Sarah A. Keim, Abigail Jude, Katie Smith, Aiman Q. Khan, Daniel L. Coury, Joseph Rausch, Shivika Udaipuria, Megan Norris, Lindsay R. Bartram, Anita R. Narayanan, Lynette K. Rogers

Gepubliceerd in: Journal of Autism and Developmental Disorders | Uitgave 12/2022

Abstract

This double-blind, randomized controlled trial, tested fatty acid (FA) supplementation in children (ages 2- < 6 years) recently diagnosed with Autism Spectrum Disorder (ASD). Participants received daily oral FA supplement containing omega-3 and omega-6 FA, or a placebo for 90 days based on participant weight. Erythrocyte FAs and the cytokines, IL-1β, IL-2, IFNγ, were measured in plasma obtained from serial blood collections. Treatment increased omega-3 and omega-6 FA levels (1.40 mol% for EPA and 1.62 mol% for DHA) and reduced IL-2 levels compared to placebo (− 0.17 pg/mL, 95% CI − 0.31, − 0.02, d = − 0.62). Omega 3–6 treatment was tolerable and adherence was greater than 70%. Future research will assess the effects of Omega 3–6 treatment on ASD symptoms. Registered on 06/08/2018 with ClinicalTrials.gov: NCT03550209.

vorige artikel A Randomized, Community-Based Feasibility Trial of Modified ESDM for Toddlers with Suspected Autism

volgende artikel Theory of Mind Development in Italian Children with Specific Language Impairment and Autism Spectrum Disorder: Delay, Deficit, or Neither?

Amminger, G. P., Berger, G. E., Schäfer, M. R., Klier, C., Friedrich, M. H., & Feucht, M. (2007). Omega-3 Fatty Acids Supplementation in Children with Autism: A Double-blind Randomized, Placebo-controlled Pilot Study. Biological Psychiatry, 61, 551–553. https://doi.org/10.1016/j.biopsych.2006.05.007CrossRefPubMed

Anisman, H., Hayley, S., Turrin, N., & Merali, Z. (2002). Cytokines as a stressor: Implications for depressive illness. International Journal of Neuropsychopharmacology, 5(4), 357–373. https://doi.org/10.1017/S1461145702003097CrossRefPubMed

Arnold, L., Young, A., Belury, M., Cole, R., Gracious, B., Seidenfeld, A., Wolfson, H., & Fristad, M. (2017). Omega-3 Fatty Acid Plasma Levels Before and After Supplementation: Correlations with Mood and Clinical Outcomes in the Omega 3 and Therapy Studies (OATS). Journal of Child and Adolescent Psychopharmacology, 27(3), 223–233. https://doi.org/10.1089/cap.2016.0123CrossRefPubMedPubMedCentral

Bazan, N. G. (2006). Cell survival matters: Docosahexaenoic acid signaling, neuroprotection and photoreceptors. Trends in Neurosciences, 29(5), 263–271. https://doi.org/10.1016/j.tins.2006.03.005CrossRefPubMed

Bent, S., Bertoglio, K., Ashwood, P., Bostrom, A., & Hendren, R. L. (2011). A pilot randomized controlled trial of omega-3 fatty acids for autism spectrum disorder. Journal of Autism and Developmental Disorders, 41(5), 545–554. https://doi.org/10.1007/s10803-010-1078-8CrossRefPubMed

Bent, S., Hendren, R. L., Zandi, T., Law, K., Choi, J. E., Widjaja, F., Kalb, L., Nestle, J., & Law, P. (2014). Internet-based, randomized, controlled trial of omega-3 fatty acids for hyperactivity in autism. Journal of the American Academy of Child and Adolescent Psychiatry, 53(6), 658–666. https://doi.org/10.1016/j.jaac.2014.01.018CrossRefPubMedPubMedCentral

Bloch, M. H., & Qawasmi, A. (2011). Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: Systematic review and meta-analysis. Journal of the American Academy of Child and Adolescent Psychiatry, 50(10), 991–1000. https://doi.org/10.1016/j.jaac.2011.06.008CrossRefPubMedPubMedCentral

Boone, K. M., Pattison, K., Pelak, G., Sheppard, K. W., Rausch, J., Yeates, K. O., Nelin, M. A., Klebanoff, M. A., Norris Turner, A., & Rogers, L. K. (2021). Docosahexaenoic and arachidonic acid supplementation at 1 year has mixed effects on development and behavior at age 2 for preterm children. Acta Paediatrica. https://doi.org/10.1111/apa.15858CrossRefPubMed

Brigandi, S. A., Shao, H., Qian, S. Y., Shen, Y. P., Wu, B. L., & Kang, J. X. (2015). Autistic Children Exhibit Decreased Levels of Essential Fatty Acids in Red Blood Cells. International Journal of Molecular Sciences, 16(5), 10061–10076. https://doi.org/10.3390/ijms160510061CrossRefPubMedPubMedCentral

Briggs-Gowan, M. J., Carter, A. S., Irwin, J. R., Wachtel, K., & Cicchetti, D. V. (2004). The Brief Infant-Toddler Social and Emotional Assessment: Screening for social-emotional problems and delays in competence. Journal of Pediatric Psychology, 29(2), 143–155. https://doi.org/10.1093/jpepsy/jsh017CrossRefPubMed

Chalon, S. (2006). Omega-3 fatty acids and monoamine neurotransmission. Prostaglandins, Leukotrienes, and Essential Fatty Acids, 75(4–5), 259–269. https://doi.org/10.1016/j.plefa.2006.07.005CrossRefPubMed

Christian, L. M., Young, A. S., Mitchell, A. M., Belury, M. A., Gracious, B. L., Arnold, L. E., & Fristad, M. A. (2017). Body weight affects ω-3 polyunsaturated fatty acid (PUFA) accumulation in youth following supplementation in post-hoc analyses of a randomized controlled trial. PLoS ONE, 12(4), e0173087. https://doi.org/10.1371/journal.pone.0173087CrossRefPubMedPubMedCentral

Coffman, C. J., Edelman, D., & Woolson, R. F. (2016). To condition or not condition? Analysing “change” in longitudinal randomised controlled trials. British Medical Journal Open, 6(12), e013096. https://doi.org/10.1136/bmjopen-2016-013096CrossRef

Coti Bertrand, P., O’Kusky, J. R., & Innis, S. M. (2006). Maternal dietary (n-3) fatty acid deficiency alters neurogenesis in the embryonic rat brain. Journal of Nutrition, 136(6), 1570–1575. https://doi.org/10.1093/jn/136.6.1570CrossRefPubMed

Dawson, G., Rogers, S., Munson, J., Smith, M., Winter, J., Greenson, J., Donaldson, A., & Varley, J. (2010). Randomized, controlled trial of an intervention for toddlers with autism: The Early Start Denver Model. Pediatrics, 125(1), e17-23. https://doi.org/10.1542/peds.2009-0958CrossRefPubMed

de Vinck-Baroody, O., Shui, A., Macklin, E. A., Hyman, S. L., Leventhal, J. M., & Weitzman, C. (2015). Overweight and obesity in a sample of children with autism spectrum disorder. Academic Pediatrics, 15(4), 396–404. https://doi.org/10.1016/j.acap.2015.03.008CrossRefPubMed

Eder, K. (1995). Gas chromatographic analysis of fatty acid methyl esters. Journal of Chromatography B: Biomedical Applications, 671(1–2), 113–131.CrossRefPubMed

Granpeesheh, D., Dixon, D. R., Tarbox, J., Kaplan, A. M., & Wilke, A. E. (2009). The effects of age and treatment intensity on behavioral intervention outcomes for children with autism spectrum disorders. Research in Autism Spectrum Disorders, 3(4), 1014–1022. https://doi.org/10.1016/j.rasd.2009.06.007CrossRef

Greenhill, L. L., Vitiello, B., Fisher, P., Levine, J., Davies, M., Abikoff, H., Chrisman, A. K., Chuang, S., Findling, R. L., March, J., Scahill, L., Walkup, J., & Riddle, M. A. (2004). Comparison of increasingly detailed elicitation methods for the assessment of adverse events in pediatric psychopharmacology. Journal of the American Academy of Child and Adolescent Psychiatry, 43(12), 1488–1496. https://doi.org/10.1097/01.chi.0000142668.29191.13CrossRefPubMed

Grosse, S. D., Ji, X., Nichols, P., Zuvekas, S. H., Rice, C. E., & Yeargin-Allsopp, M. (2021). Spending on young children with autism spectrum disorder in employer-sponsored plans, 2011–2017. Psychiatric Services, 72(1), 16–22. https://doi.org/10.1176/appi.ps.202000099CrossRefPubMed

Ibrahim, S. H., Voigt, R. G., Katusic, S. K., Weaver, A. L., & Barbaresi, W. J. (2009). Incidence of gastrointestinal symptoms in children with autism: A population-based study. Pediatrics, 124(2), 680–686. https://doi.org/10.1542/peds.2008-2933CrossRefPubMed

Innis, S. M. (2008). Dietary omega 3 fatty acids and the developing brain. Brain Research, 1237, 35–43. https://doi.org/10.1016/j.brainres.2008.08.078CrossRefPubMed

Johnson, C. R., Handen, B. L., Zimmer, M., & Sacco, K. (2010). Polyunsaturated fatty acid supplementation in young children with autism. Journal of Developmental and Physical Disabilities, 22(1), 1–10. https://doi.org/10.1007/s10882-009-9152-xCrossRef

Keim, S. A., Gracious, B., Boone, K. M., Klebanoff, M. A., Rogers, L. K., Rausch, J., Coury, D. L., Sheppard, K. W., Husk, J., & Rhoda, D. A. (2018). ω-3 and ω-6 fatty acid supplementation may reduce autism symptoms based on parent report in preterm toddlers. The Journal of Nutrition, 148(2), 227–235. https://doi.org/10.1093/jn/nxx047CrossRefPubMedPubMedCentral

Kitajka, K., Puskas, L. G., Zvara, A., Hackler, L., Jr., Barcelo-Coblijn, G., Yeo, Y. K., & Farkas, T. (2002). The role of n-3 polyunsaturated fatty acids in brain: Modulation of rat brain gene expression by dietary n-3 fatty acids. Proceedings of the National Academy of Sciences of the United States of America, 99(5), 2619–2624. https://doi.org/10.1073/pnas.042698699CrossRefPubMedPubMedCentral

Kuratko, C. (2013). Food-frequency questionnaire for assessing long-chain ω-3 fatty-acid intake: Re: Assessing long-chain ω-3 polyunsaturated fatty acids: A tailored food-frequency questionnaire is better. Nutrition, 29(5), 807–808. https://doi.org/10.1016/j.nut.2012.10.013CrossRefPubMed

Lai, K., & Kelley, K. (2012). Accuracy in parameter estimation for ANCOVA and ANOVA contrasts: Sample size planning via narrow confidence intervals. British Journal of Mathematical and Statistical Psychology, 65(2), 350–370. https://doi.org/10.1111/j.2044-8317.2011.02029.xCrossRefPubMed

Lazear, H. M., Nice, T. J., & Diamond, M. S. (2015). Interferon-lambda: Immune functions at barrier surfaces and beyond. Immunity, 43(1), 15–28. https://doi.org/10.1016/j.immuni.2015.07.001CrossRefPubMedPubMedCentral

Lord, C., Rutter, M., Dilavore, P. C., Risi, S., Gotham, K., & Bishop, S. L. (2012). Autism Diagnostic Observation Schedule, Second Edition (ADOS-2). WPS.

Maenner, M. J., Shaw, K. A., Baio, J., Washington, A., Patrick, M., DiRienzo, M., Christensen, D. L., Wiggins, L. D., Pettygrove, S., Andrews, J. G., Lopez, M., Hudson, A., Baroud, T., Schwenk, Y., White, T., Rosenberg, C. R., Lee, L. C., Harrington, R. A., Huston, M., … Dietz, P. M. (2020). Prevalence of autism spectrum disorder among children aged 8 years—Autism and developmental disabilities monitoring network, 11 sites, United States, 2016. MMWR: Surveillance Summaries, 69(4), 1–12. https://doi.org/10.15585/mmwr.ss6904a1CrossRefPubMedPubMedCentral

Mankad, D., Dupuis, A., Smile, S., Roberts, W., Brian, J., Lui, T., Genore, L., Zaghloul, D., Iaboni, A., Marcon, P. M., & Anagnostou, E. (2015). A randomized, placebo controlled trial of omega-3 fatty acids in the treatment of young children with autism. Molecular Autism, 6, 18. https://doi.org/10.1186/s13229-015-0010-7CrossRefPubMedPubMedCentral

Martinez, M. (1994). Polyunsaturated fatty acids in the developing human brain, red cells and plasma—Influence of nutrition and peroxisomal disease. Fatty Acids and Lipids: Biological Aspects, 75, 70–78. https://doi.org/10.1159/000423553CrossRef

Masi, A., Glozier, N., Dale, R., & Guastella, A. J. (2017). The immune system, cytokines, and biomarkers in autism spectrum disorder. Neuroscience Bulletin, 33(2), 194–204. https://doi.org/10.1007/s12264-017-0103-8CrossRefPubMedPubMedCentral

Masi, A., Quintana, D. S., Glozier, N., Lloyd, A. R., Hickie, I. B., & Guastella, A. J. (2015). Cytokine aberrations in autism spectrum disorder: A systematic review and meta-analysis. Molecular Psychiatry, 20(4), 440–446. https://doi.org/10.1038/mp.2014.59CrossRefPubMed

Mazahery, H., Conlon, C. A., Beck, K. L., Mugridge, O., Kruger, M. C., Stonehouse, W., Camargo, C. A., Meyer, B. J., Tsang, B., & von Hurst, P. R. (2020). Inflammation (IL-1β) modifies the effect of vitamin D and omega-3 long chain polyunsaturated fatty acids on core symptoms of autism spectrum disorder—An exploratory pilot study. Nutrients, 12(3), 661. https://doi.org/10.3390/nu12030661CrossRefPubMedCentral

McPheeters, M. L., Warren, Z., Sathe, N., Bruzek, J. L., Krishnaswami, S., Jerome, R. N., & Veenstra-Vanderweele, J. (2011). A systematic review of medical treatments for children with autism spectrum disorders. Pediatrics, 127(5), e1312-1321. https://doi.org/10.1542/peds.2011-0427CrossRefPubMed

Mozaffarian, D., & Wu, J. H. (2012). (n-3) fatty acids and cardiovascular health: Are effects of EPA and DHA shared or complementary? Journal of Nutrition, 142(3), 614S-625S. https://doi.org/10.3945/jn.111.149633CrossRefPubMedPubMedCentral

Ooi, Y. P., Weng, S. J., Jang, L. Y., Low, L., Seah, J., Teo, S., Ang, R. P., Lim, C. G., Liew, A., Fung, D. S., & Sung, M. (2015). Omega-3 fatty acids in the management of autism spectrum disorders: Findings from an open-label pilot study in Singapore. European Journal of Clinical Nutrition, 69(8), 969–971. https://doi.org/10.1038/ejcn.2015.28CrossRefPubMed

Petitto, J. M., Meola, D., & Huang, Z. (2012). Interleukin-2 and the brain: Dissecting central versus peripheral contributions using unique mouse models. Methods in Molecular Biology, 934, 301–311. https://doi.org/10.1007/978-1-62703-071-7_15CrossRefPubMed

Puri, B. K., & Martins, J. G. (2014). Which polyunsaturated fatty acids are active in children with attention-deficit hyperactivity disorder receiving PUFA supplementation? A fatty acid validated meta-regression analysis of randomized controlled trials. Prostaglandins, Leukotrienes, and Essential Fatty Acids, 90(5), 179–189. https://doi.org/10.1016/j.plefa.2014.01.004CrossRefPubMed

Reichow, B., & Wolery, M. (2009). Comprehensive synthesis of early intensive behavioral interventions for young children with autism based on the UCLA young autism project model. Journal of Autism and Developmental Disorders, 39(1), 23–41. https://doi.org/10.1007/s10803-008-0596-0CrossRefPubMed

Salem, N., Litman, B., Kim, H. Y., & Gawrisch, K. (2001). Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids, 36(9), 945–959. https://doi.org/10.1007/s11745-001-0805-6CrossRefPubMed

Sergeant, S., Rahbar, E., & Chilton, F. H. (2016). Gamma-linolenic acid, dihommo-gamma linolenic, eicosanoids and inflammatory processes. European Journal of Pharmacology, 785, 77–86. https://doi.org/10.1016/j.ejphar.2016.04.020CrossRefPubMedPubMedCentral

Sheppard, K. W., Gracious, B. K., Klebanoff, M. A., Rogers, L. K., Rausch, J., Bartlett, C., Coury, D. L., & Keim, S. A. (2017). Effect of Omega-3 and -6 Supplementation on Language in Preterm Toddlers Exhibiting Autism Spectrum Disorder Symptoms. Journal of Autism and Developmental Disorders, 47(11), 3358–3369. https://doi.org/10.1007/s10803-017-3249-3CrossRefPubMedPubMedCentral

Simopoulos, A. P. (2002). Omega-3 fatty acids in inflammation and autoimmune diseases. Journal of the American College of Nutrition, 21(6), 495–505. https://doi.org/10.1080/07315724.2002.10719248CrossRefPubMed

Sweeten, T. L., Posey, D. J., Shankar, S., & McDougle, C. J. (2004). High nitric oxide production in autistic disorder: A possible role for interferon-gamma. Biological Psychiatry, 55(4), 434–437. https://doi.org/10.1016/j.biopsych.2003.09.001CrossRefPubMed

Theoharides, T. C., Tsilioni, I., Patel, A. B., & Doyle, R. (2016). Atopic diseases and inflammation of the brain in the pathogenesis of autism spectrum disorders. Translational Psychiatry, 6(6), e844. https://doi.org/10.1038/tp.2016.77CrossRefPubMedPubMedCentral

Tostes, M. H., Teixeira, H. C., Gattaz, W. F., Brandao, M. A., & Raposo, N. R. (2012). Altered neurotrophin, neuropeptide, cytokines and nitric oxide levels in autism. Pharmacopsychiatry, 45(6), 241–243. https://doi.org/10.1055/s-0032-1301914CrossRefPubMed

Vancassel, S., Durand, G., Barthelemy, C., Lejeune, B., Martineau, J., Guilloteau, D., Andres, C., & Chalon, S. (2001). Plasma fatty acid levels in autistic children. Prostaglandins, Leukotrienes, and Essential Fatty Acids, 65(1), 1–7. https://doi.org/10.1054/plef.2001.0281CrossRefPubMed

Vezzani, A., & Viviani, B. (2015). Neuromodulatory properties of inflammatory cytokines and their impact on neuronal excitability. Neuropharmacology, 96(Pt A), 70–82. https://doi.org/10.1016/j.neuropharm.2014.10.027CrossRefPubMed

Wei, M. Y., & Jacobson, T. A. (2011). Effects of eicosapentaenoic acid versus docosahexaenoic acid on serum lipids: A systematic review and meta-analysis. Current Atherosclerosis Reports, 13(6), 474–483. https://doi.org/10.1007/s11883-011-0210-3CrossRefPubMed

Whitehouse, A. J. (2013). Complementary and alternative medicine for autism spectrum disorders: Rationale, safety and efficacy. Journal of Paediatrics and Child Health, 49(9), E438–E442. https://doi.org/10.1111/jpc.12242 quiz E442.CrossRefPubMed

Winkens, B., van Breukelen, G. J., Schouten, H. J., & Berger, M. P. (2007). Randomized clinical trials with a pre- and a post-treatment measurement: Repeated measures versus ANCOVA models. Contemporary Clinical Trials, 28(6), 713–719. https://doi.org/10.1016/j.cct.2007.04.002CrossRefPubMed

Xu, N., Li, X., & Zhong, Y. (2015). Inflammatory cytokines: Potential biomarkers of immunologic dysfunction in autism spectrum disorders. Mediators of Inflammation, 2015, 531518. https://doi.org/10.1155/2015/531518CrossRefPubMedPubMedCentral

Yui, K., Imataka, G., Kawasak, Y., & Yamada, H. (2016). Increased omega-3 polyunsaturated fatty acid/arachidonic acid ratios and upregulation of signaling mediator in individuals with autism spectrum disorders. Life Sciences, 145, 205–212. https://doi.org/10.1016/j.lfs.2015.12.039CrossRefPubMed

Titel: Randomized Controlled Trial of Omega-3 and -6 Fatty Acid Supplementation to Reduce Inflammatory Markers in Children with Autism Spectrum Disorder
Auteurs: Sarah A. Keim
Abigail Jude
Katie Smith
Aiman Q. Khan
Daniel L. Coury
Joseph Rausch
Shivika Udaipuria
Megan Norris
Lindsay R. Bartram
Anita R. Narayanan
Lynette K. Rogers
Publicatiedatum: 11-01-2022
Uitgeverij: Springer US
Gepubliceerd in: Journal of Autism and Developmental Disorders / Uitgave 12/2022
Print ISSN: 0162-3257
Elektronisch ISSN: 1573-3432
DOI: https://doi.org/10.1007/s10803-021-05396-9

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