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A Randomised-Controlled Trial of Vitamin D and Omega-3 Long Chain Polyunsaturated Fatty Acids in the Treatment of Core Symptoms of Autism Spectrum Disorder in Children

  • Hajar Mazahery
  • Cathryn A. Conlon
  • Kathryn L. Beck
  • Owen Mugridge
  • Marlena C. Kruger
  • Welma Stonehouse
  • Carlos A. CamargoJr.
  • Barbara J. Meyer
  • Bobby Tsang
  • Beatrix Jones
  • Pamela R. von HurstEmail author
Original Paper

Abstract

We evaluated the efficacy of vitamin D (VID), omega-3 long chain polyunsaturated fatty acids (omega-3 LCPUFA, OM), or both (VIDOM) on core symptoms of ASD. New Zealand children with ASD (n = 73; aged 2.5–8.0 years) received daily 2000 IU vitamin D3, 722 mg docosahexaenoic acid, both, or placebo. Outcome measures were Social Responsiveness Scale (SRS) and Sensory Processing Measure (SPM). Of 42 outcome measures comparisons (interventions vs. placebo), two showed greater improvements (P = 0.03, OM and VIDOM for SRS-social awareness) and four showed trends for greater improvements (P < 0.1, VIDOM for SRS-social communicative functioning, OM for SRS-total, VIDOM for SPM-taste/smell and OM for SPM-balance/motion). Omega-3 LCPUFA with and without vitamin D may improve some core symptoms of ASD but no definitive conclusions can be made.

Keywords

Vitamin D Omega-3 Autism Intervention Children Supplement Core symptoms 

Notes

Author Contributions

PRvH: conceived and designed the study, acquired funding and ethics approval, and supervised the study; HM and OM: coordinated recruitment, participant management, and data collection; HM: conducted the data-analysis with supervision from BJ; HM: prepared the manuscript; CC, KLB, and MK: supervised the trial; WS: advised on the omega-3 fatty acid section and statistical analysis; CACJr: advised on the vitamin D section; BM: advised on the RBC fatty acids laboratory protocol; BT: advised on the autism section. All authors read and approved the final manuscript.

Funding

Partial funding for the study was provided by Massey University Strategic Innovation Fund, Massey University, New Zealand. Additional support was provided by Douglas Nutrition, Pty. Ltd., NZ who were supplying the active supplement and identical-appearing placebo, but who had no input into study design, implementation, data management, statistical analysis or reporting of results.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Supplementary material 1 (DOCX 23 KB)
10803_2018_3860_MOESM2_ESM.docx (13 kb)
Supplementary material 2 (DOCX 13 KB)
10803_2018_3860_MOESM3_ESM.docx (18 kb)
Supplementary material 3 (DOCX 18 KB)
10803_2018_3860_MOESM4_ESM.docx (15 kb)
Supplementary material 4 (DOCX 14 KB)

References

  1. Al-Haidar, F. A. (2008). Parental attitudes toward the prescription of psychotropic medications for their children. Journal of Family & Community Medicine, 15(1), 35–42.Google Scholar
  2. Allaire, J., Harris, W. S., Vors, C., Charest, A., Marin, J., Jackson, K. H., & Lamarche, B. (2017). Supplementation with high-dose docosahexaenoic acid increases the Omega-3 Index more than high-dose eicosapentaenoic acid. Prostaglandins, Leukotrienes and Essential Fatty Acids, 120, 8–14.  https://doi.org/10.1016/j.plefa.2017.03.008.CrossRefGoogle Scholar
  3. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, D.C.: American Psychiatric AssociationCrossRefGoogle Scholar
  4. Amminger, G. P., Berger, G. E., Schafer, 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(4), 551–553.  https://doi.org/10.1016/j.biopsych.2006.05.007.CrossRefPubMedGoogle Scholar
  5. Azzam, H. M. E., Sayyah, H., Youssef, S., Lotfy, H., Abdelhamid, I. A., Elhamed, A., & Maher, S. (2015). Autism and vitamin D: An intervention study. Middle East Current Psychiatry, 22(1), 9–14.  https://doi.org/10.1097/01.xme.0000457269.05570.78.CrossRefGoogle Scholar
  6. Bandini, L. G., Anderson, S. E., Curtin, C., Cermak, S., Evans, E. W., Scampini, R., & Must, A. (2010). Food selectivity in children with autism spectrum disorders and typically developing children. Journal of Pediatrics, 157(2), 259–264.  https://doi.org/10.1016/j.jpeds.2010.02.013.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Bender, B. G., Ellison, M. C., Gleason, M., Murphy, J. R., Sundstrom, D. A., & Szefler, S. J. (2003). Minimizing attrition in a long-term clinical trial of pediatric asthma. Annals of Allergy Asthma and Immunology, 91(2), 168–176.  https://doi.org/10.1016/s1081-1206(10)62173-4.CrossRefGoogle Scholar
  8. 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 Devevlopmental Disorder, 41(5), 545–554.  https://doi.org/10.1007/s10803-010-1078-8.CrossRefGoogle Scholar
  9. Bent, S., Hendren, R. L., Zandi, T., Law, K., Choi, J. E., Widjaja, F., & 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.2014.01.018.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Bolte, S., Poustka, F., & Constantino, J. N. (2008). Assessing autistic traits: cross-cultural validation of the social responsiveness scale (SRS). Autism Research, 1(6), 354–363.  https://doi.org/10.1002/aur.49.CrossRefPubMedGoogle Scholar
  11. Boone, K. M., Gracious, B., Klebanoff, M. A., Rogers, L. K., Rausch, J., Coury, D. L., & Keim, S. A. (2017). Omega-3 and -6 fatty acid supplementation and sensory processing in toddlers with ASD symptomology born preterm: A randomized controlled trial. Early Human Development, 115, 64–70.  https://doi.org/10.1016/j.earlhumdev.2017.09.015.CrossRefPubMedGoogle Scholar
  12. Brown, T., Morrison, I. C., & Stagnitti, K. (2010). The reliability of two sensory processing scales used with school-age children: Comparing the response consistency of mothers, fathers, and classroom teachers rating the same child. Journal of Occupational Therapy, Schools, & Early Intervention, 3(4), 331–347.  https://doi.org/10.1080/19411243.2010.541775.CrossRefGoogle Scholar
  13. Brown, T., & Subel, C. (2013). Known-group validity of the infant toddler sensory profile and the sensory processing measure-preschool. Journal of Occupational Therapy, Schools, & Early Intervention, 6(1), 54–72.  https://doi.org/10.1080/19411243.2013.771101.CrossRefGoogle Scholar
  14. Cass, W. A., Smith, M. P., & Peters, L. E. (2006). Calcitriol protects against the dopamine- and serotonin-depleting effects of neurotoxic doses of methamphetamine. Annals of New York Academy of Sciences, 1074, 261–271.  https://doi.org/10.1196/annals.1369.023.CrossRefGoogle Scholar
  15. Cheng, Y. S., Tseng, P. T., Chen, Y. W., Stubbs, B., Yang, W.-C., Chen, T. Y., & Lin, P. Y. (2017). Supplementation of omega 3 fatty acids may improve hyperactivity, lethargy, and stereotypy in children with autism spectrum disorders: A meta-analysis of randomized controlled trials. Neuropsychiatric Disease and Treatment, 13, 2531–2543.  https://doi.org/10.2147/NDT.S147305.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Cholemkery, H., Kitzerow, J., Rohrmann, S., & Freitag, C. (2014). Validity of the social responsiveness scale to differentiate between autism spectrum disorders and disruptive behaviour disorders. European Child and Adolescent Psychiatry, 23(2), 81–93.  https://doi.org/10.1007/s00787-013-0427-5.CrossRefPubMedGoogle Scholar
  17. Constantino, J., & Gruber, C. (2012). The social responsiveness scale, Second Edition (SRS-2). Los Angeles: Western Psychological Services.Google Scholar
  18. Dugas, C., Simard, M.-N., Fombonne, E., & Couture, M. (2017). Comparison of two tools to assess sensory features in children with autism spectrum disorder. American Journal of Occupational Therapy, 72(1), 1–9.  https://doi.org/10.5014/ajot.2018.024604.CrossRefGoogle Scholar
  19. Emond, A., Emmett, P., Steer, C., & Golding, J. (2010). Feeding symptoms, dietary patterns, and growth in young children with autism spectrum disorders. Pediatrics, 126(2), e337–e342.  https://doi.org/10.1542/peds.2009-2391.CrossRefPubMedGoogle Scholar
  20. Enko, D., Fridrich, L., Rezanka, E., Stolba, R., Ernst, J., Wendler, I., & Halwachs-Baumann, G. (2014). 25-Hydroxy-vitamin D status: Limitations in comparison and clinical interpretation of serum-levels across different assay methods. Clinica y Laboratorio, 60(9), 1541–1550.  https://doi.org/10.7754/Clin.Lab.2014.131114.CrossRefGoogle Scholar
  21. Fedorova, I., Alvheim, A. R., Hussein, N., & Salem, N. Jr.. (2009). Deficit in prepulse inhibition in mice caused by dietary n–3 fatty acid deficiency. Behavioral Neuroscience. 123(6), 1218–1225.  https://doi.org/10.1037/a0017446.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Feng, J., Shan, L., Du, L., Wang, B., Li, H., Wang, W., & Jia, F. (2017). Clinical improvement following vitamin D3 supplementation in autism spectrum disorder. Nutritional Neuroscience, 20(5), 284–290.  https://doi.org/10.1080/1028415x.2015.1123847.CrossRefPubMedGoogle Scholar
  23. Flock, M. R., Skulas-Ray, A. C., Harris, W. S., Etherton, T. D., Fleming, J. A., & Kris-Etherton, P. M. (2013). Determinants of erythrocyte omega-3 fatty acid content in response to fish oil supplementation: A dose-response randomized controlled trial. Journal of American Heart Association, 2(6), e000513.  https://doi.org/10.1161/jaha.113.000513.CrossRefGoogle Scholar
  24. Fortunato, J. J., da Rosa, N., Laurentino, M., Goulart, A. O., Michalak, M., Borges, C., & Petronilho, F. (2017). Effects of ω-3 fatty acids on stereotypical behavior and social interactions in Wistar rats prenatally exposed to lipopolysaccarides. Nutrition, 35, 119–127.  https://doi.org/10.1016/j.nut.2016.10.019.CrossRefPubMedGoogle Scholar
  25. Fox, N., Hunn, A., & Mather, N. (1998). Sampling. Trent Focus for Research and Development in Primary Health Care.Google Scholar
  26. Graf-Myles, J., Farmer, C., Thurm, A., Royster, C., Kahn, P., Soskey, L., & Swedo, S. (2013). Dietary adequacy of children with autism compared with controls and the impact of restricted diet. Journal of Developmental and Behavioral Pediatrics, 34(7), 449–459.  https://doi.org/10.1097/DBP.0b013e3182a00d17.CrossRefPubMedGoogle Scholar
  27. Harris, W. S., & Von Schacky, C. (2004). The Omega-3 Index: A new risk factor for death from coronary heart disease? Preventive Medicine, 39(1), 212–220.  https://doi.org/10.1016/j.ypmed.2004.02.030.CrossRefPubMedGoogle Scholar
  28. Hendren, R. L. (2013). Autism: biomedical complementary treatment approaches. Child and Adolescent Psychiatry Clinics of North America, 22(3), 443–456.  https://doi.org/10.1016/j.chc.2013.03.002. vi.CrossRefGoogle Scholar
  29. Hertz-Picciotto, I., Green, P. G., Delwiche, L., Hansen, R., Walker, C., & Pessah, I. N. (2010). Blood mercury concentrations in CHARGE Study children with and without autism. Environmental Health Perspectives, 118(1), 161–166.  https://doi.org/10.1289/ehp.0900736.CrossRefPubMedGoogle Scholar
  30. Holick, M. F., Binkley, N. C., Bischoff-Ferrari, H. A., Gordon, C. M., Hanley, D. A., Heaney, R. P., & Weaver, C. M. (2011). Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. The Journal of Clinical Endocrinology & Metabolism, 96(7), 1911–1930.  https://doi.org/10.1210/jc.2011-0385.CrossRefGoogle Scholar
  31. Horvath, A., Lukasik, J., & Szajewska, H. (2017). Omega-3 fatty acid supplementation does not affect autism spectrum disorder in children: A systematic review and meta-analysis. Journal of Nutrition, 147(3), 367–376.  https://doi.org/10.3945/jn.116.242354.CrossRefPubMedGoogle Scholar
  32. Humble, M. B., Gustafsson, S., & Bejerot, S. (2010). Low serum levels of 25-hydroxyvitamin D (25-OHD) among psychiatric out-patients in Sweden: relations with season, age, ethnic origin and psychiatric diagnosis. Journal of Steroid Biochemistry and Molecular Biology, 121(1–2), 467–470.  https://doi.org/10.1016/j.jsbmb.2010.03.013.CrossRefPubMedGoogle Scholar
  33. Institute of Medicine. (2011). Dietary reference intakes for calcium and vitamin D. Washington, DC, USA: The National Academies Press.Google Scholar
  34. Jia, F., Wang, B., Shan, L., Xu, Z., Staal, W. G., & Du, L. (2015). Core symptoms of autism improved after vitamin D supplementation. Pediatrics, 135(1), e196–e198.  https://doi.org/10.1542/peds.2014-2121.CrossRefGoogle Scholar
  35. 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-x.CrossRefGoogle Scholar
  36. Johnson, S. M., & Hollander, E. (2003). Evidence that eicosapentaenoic acid is effective in treating autism. Journal of Clinical Psychiatry, 64(7), 848–849.  https://doi.org/10.4088/JCP.v64n0718c.CrossRefPubMedGoogle Scholar
  37. Karlson, C. W., & Rapoff, M. A. (2009). Attrition in randomized controlled trials for pediatric chronic conditions. Journal of Pediatric Psychology, 34(7), 782–793.  https://doi.org/10.1093/jpepsy/jsn122.CrossRefPubMedGoogle Scholar
  38. Katan, M. B., Deslypere, J. P., van Birgelen, A. P., Penders, M., & Zegwaard, M. (1997). Kinetics of the incorporation of dietary fatty acids into serum cholesteryl esters, erythrocyte membranes, and adipose tissue: An 18-month controlled study. Journal of Lipid Research, 38(10), 2012–2022.PubMedGoogle Scholar
  39. Kerley, C. P., Power, C., Gallagher, L., & Coghlan, D. (2017). Lack of effect of vitamin D3 supplementation in autism: A 20-week, placebo-controlled RCT. Archives of Disease in Childhood, 102(11), 1030–1036.  https://doi.org/10.1136/archdischild-2017-312783.CrossRefPubMedGoogle Scholar
  40. Lewis, R. D., Laing, E. M., Hill Gallant, K. M., Hall, D. B., McCabe, G. P., Hausman, D. B., & Weaver, C. M. (2013). A randomized trial of vitamin D3 supplementation in children: Dose-response effects on vitamin D metabolites and calcium absorption. The Journal of Clinical Endocrinology & Metabolism, 98(12), 4816–4825.  https://doi.org/10.1210/jc.2013-2728.CrossRefGoogle Scholar
  41. Logan, V. F., Gray, A. R., Peddie, M. C., Harper, M. J., & Houghton, L. A. (2013). Long-term vitamin D3 supplementation is more effective than vitamin D2 in maintaining serum 25-hydroxyvitamin D status over the winter months. British Journal of Nutrition, 109(6), 1082–1088.  https://doi.org/10.1017/S0007114512002851.CrossRefPubMedGoogle Scholar
  42. Mankad, D., Dupuis, A., Smile, S., Roberts, W., Brian, J., Lui, T., & 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/s13229-015-0010-7.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Marí-Bauset, S., Llopis-González, A., Zazpe-García, I., Marí-Sanchis, A., & Morales-Suárez-Varela, M. (2015). Nutritional status of children with autism spectrum disorders (ASDs): A case–control study. Journal of Autism and Developmental Disordorder, 45(1), 203–212.  https://doi.org/10.1007/s10803-014-2205-8.CrossRefGoogle Scholar
  44. Mazahery, H., Camargo, C. A. Jr., Conlon, C., Beck, K. L., Kruger, M. C., & von Hurst, P. R. (2016a). Vitamin D and autism spectrum disorder: A literature review. Nutrients, 8(4), 236.  https://doi.org/10.3390/nu8040236.CrossRefPubMedPubMedCentralGoogle Scholar
  45. Mazahery, H., Conlon, C., Beck, K. L., Kruger, M. C., Stonehouse, W., Camargo, C. A. Jr., & von Hurst, P. R. (2016b). Vitamin D and omega-3 fatty acid supplements in children with autism spectrum disorder: A study protocol for a factorial randomised, double-blind, placebo-controlled trial. Trials, 17(1), 295.  https://doi.org/10.1186/s13063-016-1428-8.CrossRefPubMedPubMedCentralGoogle Scholar
  46. Mazahery, H., Stonehouse, W., Delshad, M., Kruger, M. C., Conlon, C. A., Beck, K. L., & von Hurst, P. R. (2017). 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, 9(2), 28.  https://doi.org/10.3390/nu9020155.CrossRefGoogle Scholar
  47. Mazahery, H., Stonehouse, W., & von Hurst, P. R. (2015). The effect of monthly 50,000 IU or 100,000 IU vitamin D supplements on vitamin D status in premenopausal Middle Eastern women living in Auckland. European Journal of Clinical Nutrition, 69(3), 367–372.  https://doi.org/10.1038/ejcn.2014.264.CrossRefPubMedGoogle Scholar
  48. Mazahery, H., & von Hurst, P. R. (2015). Factors affecting 25-Hydroxyvitamin D concentration in response to vitamin D supplementation. Nutrients, 7(7), 5111–5142.  https://doi.org/10.3390/nu7075111.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 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–e1321.  https://doi.org/10.1542/peds.2011-0427.CrossRefPubMedGoogle Scholar
  50. Meguid, N. A., Atta, H. M., Gouda, A. S., & Khalil, R. O. (2008). Role of polyunsaturated fatty acids in the management of Egyptian children with autism. Clinical Biochemistry, 41(13), 1044–1048.  https://doi.org/10.1016/j.clinbiochem.2008.05.013.CrossRefPubMedGoogle Scholar
  51. Meiri, G., Bichovsky, Y., & Belmaker, R. H. (2009). Omega 3 fatty acid treatment in autism. Journal of Child and Adolescent Psychopharmacology, 19(4), 449–451.  https://doi.org/10.1089/cap.2008.0123.CrossRefPubMedGoogle Scholar
  52. Milte, C. M., Parletta, N., Buckley, J. D., Coates, A. M., Young, R. M., & Howe, P. R. (2012). Eicosapentaenoic and docosahexaenoic acids, cognition, and behavior in children with attention-deficit/hyperactivity disorder: A randomized controlled trial. Nutrition, 28(6), 670–677.  https://doi.org/10.1016/j.nut.2011.12.009.CrossRefPubMedGoogle Scholar
  53. Ministry of Health and Cancer Society of New Zealand. (2012). Consensus Statement on Vitamin D and Sun Exposure in New Zealand. Wellington: Ministry of Health and Cancer Society of New Zealand.Google Scholar
  54. Ooi, Y. P., Weng, S. J., Jang, L. Y., Low, L., Seah, J., Teo, 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.2015.28.CrossRefPubMedGoogle Scholar
  55. Parham, L. D., Ecker, C., Miller-Kuhaneck, H., Henry, D. A., & Glennon, T. (2007). Sensory processing measure (SPM) manual. Los Angeles: Western Psychological Services.Google Scholar
  56. 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), e0156432.  https://doi.org/10.1371/journal.pone.0156432.CrossRefPubMedPubMedCentralGoogle Scholar
  57. Patrick, L., & Salik, R. (2005). The effect of essential fatty acid supplementation on language development and learning skills in autism and Asperger’s syndrome. Autism Asperger’s Digestion, 39, 36–37.Google Scholar
  58. Patrick, R. P., & Ames, B. N. (2015). Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: Relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior. FASEB Journal, 29(6), 2207–2222.  https://doi.org/10.1096/fj.14-268342.CrossRefPubMedGoogle Scholar
  59. Raine, A., Portnoy, J., Liu, J., Mahoomed, T., & Hibbeln, J. R. (2015). Reduction in behavior problems with omega-3 supplementation in children aged 8–16 years: A randomized, double-blind, placebo-controlled, stratified, parallel-group trial. Journal of Child Psychology and Psychiatry, 56(5), 509–520.  https://doi.org/10.1111/jcpp.12314.CrossRefPubMedGoogle Scholar
  60. Robson, L. G., Dyall, S., Sidloff, D., & Michael-Titus, A. T. (2010). Omega-3 polyunsaturated fatty acids increase the neurite outgrowth of rat sensory neurones throughout development and in aged animals. Neurobiology of Aging, 31(4), 678–687.  https://doi.org/10.1016/j.neurobiolaging.2008.05.027.CrossRefPubMedGoogle Scholar
  61. Rockell, J. E. P., Skeaff, C. M., Venn, B. J., Williams, S. M., & Green, T. J. (2008). Vitamin D insufficiency in New Zealanders during the winter is associated with higher parathyroid hormone concentrations: Implications for bone health? New Zealand Medical Journal, 121(1286), 75–84.PubMedGoogle Scholar
  62. Rothman, K. J. (1990). No adjustments are needed for multiple comparisons. Epidemiology, 1(1), 43–46.CrossRefGoogle Scholar
  63. Saad, K., Abdel-Rahman, A. A., Elserogy, Y. M., Al-Atram, A. A., Cannell, J. J., Bjorklund, G., & Ali, A. M. (2015). Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children. Nutritional Neuroscience., 19(8), 346–351.  https://doi.org/10.1179/1476830515y.0000000019.CrossRefPubMedGoogle Scholar
  64. Saad, K., Abdel-Rahman, A. A., Elserogy, Y. M., Al-Atram, A. A., El-Houfey, A. A., Othman, H. A., & Abdel-Salam, A. M. (2018). Randomized controlled trial of vitamin D supplementation in children with autism spectrum disorder. Journal of Child Psychology and Psychiatry, 59(1), 20–29.  https://doi.org/10.1111/jcpp.12652.CrossRefPubMedGoogle Scholar
  65. Salas, A. A., Woodfin, T., Phillips, V., Peralta-Carcelen, M., Carlo, W. A., & Ambalavanan, N. (2018). Dose–response effects of early vitamin D supplementation on neurodevelopmental and respiratory outcomes of extremely preterm infants at 2 years of age: A randomized trial. Neonatology, 113(3), 256–262.  https://doi.org/10.1159/000484399.CrossRefPubMedGoogle Scholar
  66. Sifers, S. K., Puddy, R. W., Warren, J. S., & Roberts, M. C. (2002). Reporting of demographics, methodology, and ethical procedures in journals in pediatric and child psychology. Journal of Pediatric Psychology, 27(1), 19–25.  https://doi.org/10.1093/jpepsy/27.1.19.CrossRefPubMedGoogle Scholar
  67. Singh, K., Connors, S. L., Macklin, E. A., Smith, K. D., Fahey, J. W., Talalay, P., & Zimmerman, A. W. (2014). Sulforaphane treatment of autism spectrum disorder (ASD). Proceedings of the National Academy of Sciences, 111(43), 15550–15555.  https://doi.org/10.1073/pnas.1416940111.CrossRefGoogle Scholar
  68. Tang, M., Zhang, M., Cai, H., Li, H., Jiang, P., Dang, R., & Wu, Y. (2016). Maternal diet of polyunsaturated fatty acid altered the cell proliferation in the dentate gyrus of hippocampus and influenced glutamatergic and serotoninergic systems of neonatal female rats. Lipids in Health and Disease, 15(1), 71.  https://doi.org/10.1186/s12944-016-0236-1.CrossRefPubMedPubMedCentralGoogle Scholar
  69. Ucuz, I. I., Dursun, O. B., Esin, İS., Özgeriş, F. B., Kurt, N., Kiziltunç, A., & Orbak, Z. (2015). The relationship between Vitamin D, autistic spectrum disorders, and cognitive development: Do glial cell line-derived neurotrophic factor and nerve growth factor play a role in this relationship? International Journal of Developmental Disabilities, 61(4), 222–230.  https://doi.org/10.1179/2047387714Y.0000000054.CrossRefGoogle Scholar
  70. van der Wurff, I. S. M., Meyer, B. J., & de Groot, R. H. M. (2017). A review of recruitment, adherence and drop-out rates in omega-3 polyunsaturated fatty acid supplementation trials in children and adolescents. Nutrients. 9(5), 474.  https://doi.org/10.3390/nu9050474.CrossRefPubMedCentralGoogle Scholar
  71. Vieth, R., Kimball, S., Hu, A., & Walfish, P. G. (2004). Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients. Nutrition Journal, 3, 8.  https://doi.org/10.1186/1475-2891-3-8.CrossRefPubMedPubMedCentralGoogle Scholar
  72. Voigt, R. G., Mellon, M. W., Katusic, S. K., Weaver, A. L., Matern, D., Mellon, B., & Barbaresi, W. J. (2014). Dietary docosahexaenoic acid supplementation in children with autism. Journal of Pediatric Gastroenterology and Nutrition, 58(6), 715–722.  https://doi.org/10.1097/mpg.0000000000000260.CrossRefPubMedGoogle Scholar
  73. Wang, T., Shan, L., Du, L., Feng, J., Xu, Z., Staal, W. G., & Jia, F. (2016). Serum concentration of 25-hydroxyvitamin D in autism spectrum disorder: A systematic review and meta-analysis. European Child & Adolescent Psychiatry, 25(4), 341–350.  https://doi.org/10.1007/s00787-015-0786-1.CrossRefGoogle Scholar
  74. Yui, K., Koshiba, M., Nakamura, S., & Kobayashi, Y. (2012). 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. Journal of Clinincal Psychopharmacology, 32(2), 200–206.  https://doi.org/10.1097/JCP.0b013e3182485791.CrossRefGoogle Scholar

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Authors and Affiliations

  • Hajar Mazahery
    • 1
  • Cathryn A. Conlon
    • 1
  • Kathryn L. Beck
    • 1
  • Owen Mugridge
    • 1
  • Marlena C. Kruger
    • 1
  • Welma Stonehouse
    • 2
  • Carlos A. CamargoJr.
    • 3
  • Barbara J. Meyer
    • 4
  • Bobby Tsang
    • 5
  • Beatrix Jones
    • 5
  • Pamela R. von Hurst
    • 1
    Email author
  1. 1.College of HealthMassey UniversityAucklandNew Zealand
  2. 2.Commonwealth Scientific Industrial Research Organisation, Food and Nutrition FlagshipAdeliadeAustralia
  3. 3.Department of Emergency Medicine, Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  4. 4.School of Medicine, Lipid Research Centre, Illawarra Health & Medical Research InstituteUniversity of WollongongWollongongAustralia
  5. 5.University of AucklandAucklandNew Zealand

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