{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:46:04Z","timestamp":1790808364922,"version":"4.1.0"},"reference-count":97,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T00:00:00Z","timestamp":1636761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Attention-deficit\/hyperactivity disorder (ADHD) is a neurodevelopmental disorder common from childhood to adulthood, affecting 5% to 12% among the general population in developed countries. Potential etiological factors have been identified, including genetic causes, environmental elements and epigenetic components. Nutrition is currently considered an influencing factor, and several studies have explored the contribution of restriction and dietary supplements in ADHD treatments. Iron is an essential cofactor required for a number of functions, such as transport of oxygen, immune function, cellular respiration, neurotransmitter metabolism (dopamine production), and DNA synthesis. Zinc is also an essential trace element, required for cellular functions related to the metabolism of neurotransmitters, melatonin, and prostaglandins. Epidemiological studies have found that iron and zinc deficiencies are common nutritional deficits worldwide, with important roles on neurologic functions (poor memory, inattentiveness, and impulsiveness), finicky appetite, and mood changes (sadness and irritability). Altered levels of iron and zinc have been related with the aggravation and progression of ADHD. Objective: This is a systematic review focused on the contribution of iron and zinc in the progression of ADHD among children and adolescents, and how therapies including these elements are tolerated along with its effectiveness (according to PRISMA guidelines). Method: The scientific literature was screened for randomized controlled trials published between January 2000 to July 2021. The databases consulted were Medline, PsycINFO, Web of Science, and Google Scholar. Two independent reviewers screened studies, extracted data, and assessed quality and risk of bias (CONSORT, NICE, and Cochrane checklists used). Conclusion: Nine studies met the eligibility criteria and were selected. Evidence was obtained regarding the contribution of iron-zinc supplementation in the treatment of ADHD among young individuals. The discussion was focused on how the deficits of these elements contribute to affectation on multiple ADHD correlates, and potential mechanisms explaining the mediational pathways. Evidence also suggested that treating ADHD with diet interventions might be particularly useful for specific subgroups of children and adolescents, but further investigations of the effects of these diet interventions are needed.<\/jats:p>","DOI":"10.3390\/nu13114059","type":"journal-article","created":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T20:51:53Z","timestamp":1636923113000},"page":"4059","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["The Role of Iron and Zinc in the Treatment of ADHD among Children and Adolescents: A Systematic Review of Randomized Clinical Trials"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6308-3198","authenticated-orcid":false,"given":"Roser","family":"Granero","sequence":"first","affiliation":[{"name":"Department of Psychobiology and Methodology, Autonomous University of Barcelona, 08193 Barcelona, Spain"},{"name":"Ciber Fisiopatolog\u00eda Obesidad y Nutrici\u00f3n (CIBERobn), Instituto Salud Carlos III, 28029 Madrid, Spain"},{"name":"Basic Psychology, Behavioral Analysis and Programmatic Development PAD-Group, Catholic University of Cuenca, Cuenca 010107, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"Pardo-Garrido","sequence":"additional","affiliation":[{"name":"Department of Psychobiology and Methodology, Autonomous University of Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivonne Lorena","family":"Carpio-Toro","sequence":"additional","affiliation":[{"name":"Laboratory of Basic Psychology, Behavioral Analysis and Programmatic Development PAD-Lab, Catholic University of Cuenca, Cuenca 010107, Ecuador"},{"name":"Laboratory of Psychometry, Comparative Psychology and Ethology, Catholic University of Cuenca, Cuenca 010107, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s Alexis","family":"Ram\u00edrez-Coronel","sequence":"additional","affiliation":[{"name":"Laboratory of Basic Psychology, Behavioral Analysis and Programmatic Development PAD-Lab, Catholic University of Cuenca, Cuenca 010107, Ecuador"},{"name":"Health and Behavior Research Group (HBR), Catholic University of Cuenca, Cuenca 010107, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Carlos","family":"Mart\u00ednez-Su\u00e1rez","sequence":"additional","affiliation":[{"name":"Laboratory of Basic Psychology, Behavioral Analysis and Programmatic Development PAD-Lab, Catholic University of Cuenca, Cuenca 010107, Ecuador"},{"name":"Health and Behavior Research Group (HBR), Catholic University of Cuenca, Cuenca 010107, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geovanny Genaro","family":"Reivan-Ortiz","sequence":"additional","affiliation":[{"name":"Basic Psychology, Behavioral Analysis and Programmatic Development PAD-Group, Catholic University of Cuenca, Cuenca 010107, Ecuador"},{"name":"Laboratory of Basic Psychology, Behavioral Analysis and Programmatic Development PAD-Lab, Catholic University of Cuenca, Cuenca 010107, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Di Lorenzo, R., Balducci, J., Poppi, C., Arcolin, E., Cutino, A., Ferri, P., D\u2019Amico, R., and Filippini, T. (2021). Children and adolescents with ADHD followed up to adulthood: A systematic review of long-term outcomes. Acta Neuropsychiatr., 1\u201342.","DOI":"10.1017\/neu.2021.23"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders: DSM-5, American Psychiatric Association. [5th ed.].","DOI":"10.1176\/appi.books.9780890425596"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.ijpam.2021.04.002","article-title":"Child and adolescent mental health disorders in the GCC: A systematic review and meta-analysis","volume":"8","author":"Chan","year":"2021","journal-title":"Int. J. Pediatr. Adolesc. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1111\/jcpp.12381","article-title":"Annual Research Review: A meta-analysis of the worldwide prevalence of mental disorders in children and adolescents","volume":"56","author":"Polanczyk","year":"2015","journal-title":"J. Child Psychol. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S2215-0366(17)30167-0","article-title":"ADHD in children and young people: Prevalence, care pathways, and service provision","volume":"5","author":"Sayal","year":"2018","journal-title":"Lancet Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1007\/s40474-017-0116-z","article-title":"Attention-Deficit\/Hyperactivity Disorder in Looked-After Children: A Systematic Review of the Literature","volume":"4","author":"Willis","year":"2017","journal-title":"Curr. Dev. Disord. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.neubiorev.2020.07.042","article-title":"Prevalence of attention-deficit\/hyperactivity disorder in older adults: A systematic review and meta-analysis","volume":"118","author":"Dobrosavljevic","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"04009","DOI":"10.7189\/jogh.11.04009","article-title":"The prevalence of adult attention-deficit hyperactivity disorder: A global systematic review and meta-analysis","volume":"11","author":"Song","year":"2021","journal-title":"J. Glob. Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"102036","DOI":"10.1016\/j.cpr.2021.102036","article-title":"A systematic review of transdiagnostic risk and protective factors for general and specific psychopathology in young people","volume":"87","author":"Lynch","year":"2021","journal-title":"Clin. Psychol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1038\/s41380-020-0673-0","article-title":"Meta-analysis and systematic review of ADGRL3 (LPHN3) polymorphisms in ADHD susceptibility","volume":"26","author":"Bruxel","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e23400","DOI":"10.1097\/MD.0000000000023400","article-title":"Association of Val158Met polymorphism in COMT gene with attention-deficit hyperactive disorder: An updated meta-analysis","volume":"99","author":"Kang","year":"2020","journal-title":"Medicine"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1007\/s00702-020-02197-9","article-title":"Mental health dished up\u2014the use of iPSC models in neuropsychiatric research","volume":"127","author":"McNeill","year":"2020","journal-title":"J. Neural Transm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1016\/j.jaac.2021.01.019","article-title":"Systematic Review: How the Attention-Deficit\/Hyperactivity Disorder Polygenic Risk Score Adds to Our Understanding of ADHD and Associated Traits","volume":"60","author":"Ronald","year":"2021","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"126","DOI":"10.3389\/fpsyt.2015.00126","article-title":"Attention Deficit Hyperactivity Disorder in the Light of the Epigenetic Paradigm","volume":"6","author":"Schuch","year":"2015","journal-title":"Front. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/mp.2016.85","article-title":"Epigenetic profiling of ADHD symptoms trajectories: A prospective, methylome-wide study","volume":"22","author":"Walton","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41398-021-01198-w","article-title":"Maternal acute and chronic inflammation in pregnancy is associated with common neurodevelopmental disorders: A systematic review","volume":"11","author":"Han","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1093\/ije\/dyaa040","article-title":"Maternal pre-pregnancy overweight\/obesity and the risk of attention-deficit\/hyperactivity disorder in offspring: A systematic review, meta-analysis and quasi-experimental family-based study","volume":"49","author":"Li","year":"2020","journal-title":"Int. J. Epidemiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Qu, A., Cao, T., Li, Z., Wang, W., Liu, R., Wang, X., Nie, Y., Sun, S., Liu, X., and Zhang, X. (2021). The association between maternal perfluoroalkyl substances exposure and early attention deficit hyperactivity disorder in children: A systematic review and meta-analysis. Environ. Sci. Pollut. Res., 1\u201316.","DOI":"10.21203\/rs.3.rs-437360\/v1"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1093\/jpepsy\/jsaa038","article-title":"Distinct Profiles of Attention in Children Born Moderate-to-Late Preterm at 6 Years","volume":"45","author":"Verhoeven","year":"2020","journal-title":"J. Pediatr. Psychol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1037\/dev0000865","article-title":"Attentional system of very prematurely born preschoolers","volume":"56","author":"Harciarek","year":"2020","journal-title":"Dev. Psychol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1017\/S0954579420000620","article-title":"Early environmental risk factors for neurodevelopmental disorders\u2014A systematic review of twin and sibling studies","volume":"33","author":"Carlsson","year":"2020","journal-title":"Dev. Psychopathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1111\/aogs.13644","article-title":"Long-term cognition and behavior in children born at early term gestation: A systematic review","volume":"98","author":"Nielsen","year":"2019","journal-title":"Acta Obstet. Et Gynecol. Scand."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rivollier, F., Krebs, M.-O., and Kebir, O. (2019). Perinatal Exposure to Environmental Endocrine Disruptors in the Emergence of Neurodevelopmental Psychiatric Diseases: A Systematic Review. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16081318"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1111\/jcpp.12779","article-title":"Research Review: The role of obstetric and neonatal complications in childhood attention deficit and hyperactivity disorder\u2014A systematic review","volume":"58","author":"Serati","year":"2017","journal-title":"J. Child Psychol. Psychiatry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11531","DOI":"10.1007\/s11356-020-08134-3","article-title":"Association between exposure to polycyclic aromatic hydrocarbons and attention deficit hyperactivity disorder in children: A systematic review and meta-analysis","volume":"27","author":"Kalantary","year":"2020","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1111\/jcpp.12480","article-title":"Fever and infections in pregnancy and risk of attention deficit\/hyperactivity disorder in the offspring","volume":"57","author":"Dreier","year":"2015","journal-title":"J. Child Psychol. Psychiatry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s10802-014-9904-7","article-title":"Moderators of Neuropsychological Mechanism in Attention-Deficit Hyperactivity Disorder","volume":"43","author":"Nikolas","year":"2014","journal-title":"J. Abnorm. Child Psychol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.neubiorev.2018.09.009","article-title":"Motor dysfunction as research domain across bipolar, obsessive-compulsive and neurodevelopmental disorders","volume":"95","author":"Hirjak","year":"2018","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"519840","DOI":"10.3389\/fpsyt.2021.519840","article-title":"Disentangling ADHD\u2019s Presentation-Related Decision-Making\u2014A Meta-Analytic Approach on Predominant Presentations","volume":"12","author":"Schulze","year":"2021","journal-title":"Front. Psychiatry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1089\/acm.2007.0610","article-title":"Nutritional and Environmental Approaches to Preventing and Treating Autism and Attention Deficit Hyperactivity Disorder (ADHD): A Review","volume":"14","author":"Curtis","year":"2008","journal-title":"J. Altern. Complement. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"83","DOI":"10.4103\/2008-7802.164313","article-title":"Magnesium, iron, and zinc supplementation for the treatment of attention deficit hyperactivity disorder: A systematic review on the recent literature","volume":"6","author":"Azadbakht","year":"2015","journal-title":"Int. J. Prev. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1192\/bjp.bp.113.132126","article-title":"Vitamin\u2013mineral treatment of attention-deficit hyperactivity disorder in adults: Double-blind randomised placebo-controlled trial","volume":"204","author":"Rucklidge","year":"2014","journal-title":"Br. J. Psychiatry"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1037\/fsh0000356","article-title":"Integrated care models for ADHD in children and adolescents: A systematic review","volume":"36","author":"Shahidullah","year":"2018","journal-title":"Fam. Syst. Health"},{"key":"ref_34","first-page":"1","article-title":"Shared Care Models in the Treatment of Pediatric Attention-Deficit\/Hyperactivity Disorder (ADHD): Are They Effective?","volume":"5","author":"Sultan","year":"2018","journal-title":"Health Serv. Res. Manag. Epidemiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jpsychires.2020.01.006","article-title":"A literature review and meta-analysis on the effects of ADHD medications on functional outcomes","volume":"123","author":"Boland","year":"2020","journal-title":"J. Psychiatr. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"223","DOI":"10.2147\/PRBM.S47013","article-title":"Pharmacological interventions for adolescents and adults with ADHD: Stimulant and nonstimulant medications and misuse of prescription stimulants","volume":"7","author":"Weyandt","year":"2014","journal-title":"Psychol. Res. Behav. Manag."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"19r13015","DOI":"10.4088\/JCP.19r13015","article-title":"Effect of Continuing and Discontinuing Medications on Quality of Life After Symptomatic Remission in Attention-Deficit\/Hyperactivity Disorder: A Systematic Review and Meta-Analysis","volume":"81","author":"Tsujii","year":"2020","journal-title":"J. Clin. Psychiatry"},{"key":"ref_38","first-page":"62","article-title":"Treatment of Children with Attention-Deficit\/Hyperactivity Disorder (ADHD) and Irritability: Results from the Multimodal Treatment Study of Children with ADHD (MTA)","volume":"54","author":"Simonoff","year":"2014","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"811","DOI":"10.2165\/11538990-000000000-00000","article-title":"Sleep Problems in the Child with Attention-Deficit Hyperactivity Disorder: Defining Aetiology and Appropriate Treatments","volume":"24","author":"Weiss","year":"2010","journal-title":"CNS Drugs"},{"key":"ref_40","first-page":"413","article-title":"Evaluacion y tratamiento de los problemas de sue\u00f1o en ni\u00f1os diagnosticados de trastorno por deficit de atencion\/hiperactividad: Actualizacion de la evidencia [Evaluation and treatment of sleep problems in children diagnosed with attention deficit hyperactivity disorder: An update of the evidence]","volume":"64","author":"Chamorro","year":"2017","journal-title":"Rev. Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.chc.2020.08.010","article-title":"Restless Legs Syndrome in Children and Adolescents","volume":"30","author":"DelRosso","year":"2020","journal-title":"Child Adolesc. Psychiatr. Clin. North Am."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Baxter, A.J., Patton, G., Scott, K.M., Degenhardt, L., and Whiteford, H.A. (2013). Global Epidemiology of Mental Disorders: What Are We Missing?. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065514"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1093\/ije\/dyt261","article-title":"ADHD prevalence estimates across three decades: An updated systematic review and meta-regression analysis","volume":"43","author":"Polanczyk","year":"2014","journal-title":"Int. J. Epidemiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e994","DOI":"10.1542\/peds.2014-3482","article-title":"Prevalence of Attention-Deficit\/Hyperactivity Disorder: A Systematic Review and Meta-analysis","volume":"135","author":"Thomas","year":"2015","journal-title":"Pediatrics"},{"key":"ref_45","first-page":"1","article-title":"Nutritional psychiatry research: An emerging discipline and its intersection with global urbanization, environmental challenges and the evolutionary mismatch","volume":"33","author":"Logan","year":"2014","journal-title":"J. Physiol. Anthr."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Agostoni, C., Nobile, M., Ciappolino, V., DelVecchio, G., Tesei, A., Turolo, S., Crippa, A., Mazzocchi, A., Altamura, C.A., and Brambilla, P. (2017). The Role of Omega-3 Fatty Acids in Developmental Psychopathology: A Systematic Review on Early Psychosis, Autism, and ADHD. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122608"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.jaac.2011.10.015","article-title":"Meta-Analysis of Attention-Deficit\/Hyperactivity Disorder or Attention-Deficit\/Hyperactivity Disorder Symptoms, Restriction Diet, and Synthetic Food Color Additives","volume":"51","author":"Nigg","year":"2012","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1080\/08039488.2020.1769187","article-title":"The use of diet interventions to treat symptoms of ADHD in children and adolescents\u2014A systematic review of randomized controlled trials","volume":"74","author":"Torp","year":"2020","journal-title":"Nord. J. Psychiatry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/08039488.2014.921933","article-title":"Diet in the treatment of ADHD in children\u2014A systematic review of the literature","volume":"69","author":"Rytter","year":"2014","journal-title":"Nord. J. Psychiatry"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.chc.2014.05.002","article-title":"Nutritional Supplements for the Treatment of ADHD","volume":"23","author":"Bloch","year":"2014","journal-title":"Child Adolesc. Psychiatr. Clin. N. Am."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Verlaet, A.A.J., Maasakkers, C.M., Hermans, N., and Savelkoul, H.F.J. (2018). Rationale for Dietary Antioxidant Treatment of ADHD. Nutrients, 10.","DOI":"10.3390\/nu10040405"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.jad.2019.04.061","article-title":"Dietary patterns and attention deficit\/hyperactivity disorder (ADHD): A systematic review and meta-analysis","volume":"252","author":"Quinte","year":"2019","journal-title":"J. Affect. Disord."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jtemb.2006.01.006","article-title":"Zinc requirements and the risks and benefits of zinc supplementation","volume":"20","author":"Maret","year":"2006","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1177\/1087054719829816","article-title":"Elevated Melatonin Levels in Children With Attention Deficit Hyperactivity Disorder: Relationship to Oxidative and Nitrosative Stress","volume":"25","author":"Avcil","year":"2019","journal-title":"J. Atten. Disord."},{"key":"ref_55","first-page":"164","article-title":"Review on iron and its importance for human health","volume":"19","author":"Abbaspour","year":"2014","journal-title":"J. Res. Med Sci. Isfahan Univ. Med Sci."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Robberecht, H., Verlaet, A.A.J., Breynaert, A., De Bruyne, T., and Hermans, N. (2020). Magnesium, Iron, Zinc, Copper and Selenium Status in Attention-Deficit\/Hyperactivity Disorder (ADHD). Molecules, 25.","DOI":"10.3390\/molecules25194440"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.pnpbp.2018.09.007","article-title":"Can we predict treatment response in children with ADHD to a vitamin-mineral supplement? An investigation into pre-treatment nutrient serum levels, MTHFR status, clinical correlates and demographic variables","volume":"89","author":"Rucklidge","year":"2018","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1177\/1087054719886363","article-title":"Do Changes in Blood Nutrient Levels Mediate Treatment Response in Children and Adults with ADHD Consuming a Vitamin\u2013Mineral Supplement?","volume":"25","author":"Rucklidge","year":"2019","journal-title":"J. Atten. Disord."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1097\/MCO.0b013e3280523a9e","article-title":"Nutrition and performance in children","volume":"10","author":"Fanjiang","year":"2007","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1586\/ern.09.7","article-title":"Nutrient supplementation approaches in the treatment of ADHD","volume":"9","author":"Rucklidge","year":"2009","journal-title":"Expert Rev. Neurother."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Page, M.J., McKenzie, J.E., Bossuyt, P.M., Boutron, I., Hoffmann, T.C., Mulrow, C.D., Shamseer, L., Tetzlaff, J.M., Akl, E.A., and Brennan, S.E. (2021). The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. PLoS Med., 18.","DOI":"10.1371\/journal.pmed.1003583"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2288-7-10","article-title":"Development of AMSTAR: A measurement tool to assess the methodological quality of systematic reviews","volume":"7","author":"Shea","year":"2007","journal-title":"BMC Med Res. Methodol."},{"key":"ref_63","unstructured":"Higgins, J.P., and Green, S. (2021, July 15). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration. Available online: https:\/\/handbook.cochrane.org."},{"key":"ref_64","unstructured":"American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-R, American Psychiatric Association."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1017\/S0007114511003606","article-title":"Guidelines for the design, conduct and reporting of human intervention studies to evaluate the health benefits of foods","volume":"106","author":"Welch","year":"2011","journal-title":"Br. J. Nutr."},{"key":"ref_66","unstructured":"(2021, July 15). National Institute for Health and Care Excellence, NICE. Methods for the Development of NICE Public Health Guidance. Available online: https:\/\/www.nice.org.uk\/process\/pmg4\/resources\/methods-for-the-development-of-nice-public-health-guidance-third-edition-pdf-2007967445701."},{"key":"ref_67","unstructured":"Critical Appraisal Skills Programme, CASP (2021, July 15). Randomized Controlled Trials Checklist. Available online: https:\/\/casp-uk.net\/casp-tools-checklists."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: A revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"101868","DOI":"10.1016\/j.ajp.2019.101868","article-title":"The efficacy of zinc augmentation in children with attention deficit hyperactivity disorder under treatment with methylphenidate: A randomized controlled trial","volume":"48","author":"Noorazar","year":"2019","journal-title":"Asian J. Psychiatry"},{"key":"ref_70","first-page":"242","article-title":"Zinc en la terapia del sindrome de d\u00e9ficit de atenci\u00f3n e hiperactividad en ni\u00f1os. Un estudio controlado aleatorio preliminar [Zinc in the therapy of the atten-tion-deficit\/hyperactivity disorder in children. A preliminar randomized controlled trial]","volume":"61","author":"Zamora","year":"2011","journal-title":"Arch. Latinoam. Nutr."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/cap.2010.0073","article-title":"Zinc for Attention-Deficit\/Hyperactivity Disorder: Placebo-Controlled Double-Blind Pilot Trial Alone and Combined with Amphetamine","volume":"21","author":"Arnold","year":"2011","journal-title":"J. Child Adolesc. Psychopharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-244X-4-9","article-title":"Zinc sulfate as an adjunct to methylphenidate for the treatment of attention deficit hyperactivity disorder in children: A double blind and randomized trial [ISRCTN64132371]","volume":"4","author":"Akhondzadeh","year":"2004","journal-title":"BMC Psychiatry"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.pnpbp.2003.09.034","article-title":"Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder","volume":"28","author":"Bilici","year":"2004","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.pediatrneurol.2007.08.014","article-title":"Effects of iron supplementation on attention deficit hyperactivity disorder in children","volume":"38","author":"Konofal","year":"2008","journal-title":"Pediatr. Neurol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"138","DOI":"10.4103\/japtr.JAPTR_45_17","article-title":"The effect of adding ferrous sulfate to methylphenidate on attention-deficit\/hyperactivity disorder in children","volume":"8","author":"Safavi","year":"2017","journal-title":"J. Adv. Pharm. Technol. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/jcpp.12817","article-title":"Vitamin-mineral treatment improves aggression and emotional regulation in children with ADHD: A fully blinded, randomized, placebo-controlled trial","volume":"59","author":"Rucklidge","year":"2017","journal-title":"J. Child Psychol. Psychiatry"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"223","DOI":"10.3109\/15622975.2011.570376","article-title":"Brain iron levels in attention-deficit\/hyperactivity disorder: A pilot MRI study","volume":"13","author":"Cortese","year":"2011","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"740S","DOI":"10.3945\/jn.110.131169","article-title":"Early Iron Deficiency Has Brain and Behavior Effects Consistent with Dopaminergic Dysfunction","volume":"141","author":"Lozoff","year":"2011","journal-title":"J. Nutr."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Kennedy, D.O. (2016). B Vitamins and the Brain: Mechanisms, Dose and Efficacy\u2014A Review. Nutrients, 8.","DOI":"10.3390\/nu8020068"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"668","DOI":"10.4088\/JCP.15m10166","article-title":"Correlation of Clinical Response with Homocysteine Reduction During Therapy with Reduced B Vitamins in Patients with MDD Who Are Positive for MTHFR C677T or A1298C Polymorphism: A randomized, double-blind, place-bo-controlled study","volume":"77","author":"Mech","year":"2016","journal-title":"J. Clin. Psychiatry"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Smith, A.D., Smith, S., De Jager, C.A., Whitbread, P., Johnston, C., Agacinski, G., Oulhaj, A., Bradley, K.M., Jacoby, R., and Refsum, H. (2010). Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012244"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.1016\/j.nut.2004.07.021","article-title":"Effect of micronutrient supplement on health and nutritional status of schoolchildren: Mental function","volume":"22","author":"Vazir","year":"2006","journal-title":"Nutrition"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1089\/cap.2005.15.628","article-title":"Serum Zinc Correlates with Parent- and Teacher- Rated Inattention in Children with Attention-Deficit\/Hyperactivity Disorder","volume":"15","author":"Arnold","year":"2005","journal-title":"J. Child Adolesc. Psychopharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s00787-009-0746-8","article-title":"Sleep disturbances and serum ferritin levels in children with attention-deficit\/hyperactivity disorder","volume":"18","author":"Cortese","year":"2009","journal-title":"Eur. Child Adolesc. Psychiatry"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1007\/s00415-017-8431-1","article-title":"Iron, dopamine, genetics, and hormones in the pathophysiology of restless legs syndrome","volume":"264","author":"Khan","year":"2017","journal-title":"J. Neurol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s10578-010-0178-1","article-title":"Effects of Zinc and Ferritin Levels on Parent and Teacher Reported Symptom Scores in Attention Deficit Hyperactivity Disorder","volume":"41","author":"Oner","year":"2010","journal-title":"Child Psychiatry Hum. Dev."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s11065-007-9019-9","article-title":"Etiologic Subtypes of Attention-Deficit\/Hyperactivity Disorder: Brain Imaging, Molecular Genetic and Environmental Factors and the Dopamine Hypothesis","volume":"17","author":"Swanson","year":"2007","journal-title":"Neuropsychol. Rev."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1001\/archpsyc.64.8.932","article-title":"Depressed Dopamine Activity in Caudate and Preliminary Evidence of Limbic Involvement in Adults With Attention-Deficit\/Hyperactivity Disorder","volume":"64","author":"Volkow","year":"2007","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e1601631","DOI":"10.1126\/sciadv.1601631","article-title":"Key role of the dopamine D 4 receptor in the modulation of corticostriatal glutamatergic neurotransmission","volume":"3","author":"Bonaventura","year":"2017","journal-title":"Sci. Adv."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.expneurol.2014.06.023","article-title":"Low brain iron effects and reversibility on striatal dopamine dynamics","volume":"261","author":"Unger","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1476-511X-9-105","article-title":"Supplementation of polyunsaturated fatty acids, magnesium and zinc in children seeking medical advice for attention-deficit\/hyperactivity problems\u2014An observational cohort study","volume":"9","author":"Huss","year":"2010","journal-title":"Lipids Health Dis."},{"key":"ref_92","first-page":"377","article-title":"Effects of nutrients (in food) on the structure and function of the nervous system: Update on dietary requirements for brain. Part 1: Micronutrients","volume":"10","author":"Bourre","year":"2006","journal-title":"J. Nutr. Health Aging"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Sinn, N., and Wilson, C. (2006). Dietary Supplementation with Highly Unsaturated Fatty Acids: Implications for Interventions with Persons with Mental Retardation from Research on Infant Cognitive Development, ADHD, and Other Developmental Disabilities. Int. Rev. Res. Ment. Retard., 159\u2013196.","DOI":"10.1016\/S0074-7750(06)32006-X"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1089\/cap.2000.10.111","article-title":"Does Zinc Moderate Essential Fatty Acid and Amphetamine Treatment of Attention-Deficit\/Hyperactivity Disorder?","volume":"10","author":"Arnold","year":"2000","journal-title":"J. Child Adolesc. Psychopharmacol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1089\/cap.2010.0053","article-title":"Serum Ferritin and Amphetamine Response in Youth with Attention-Deficit\/Hyperactivity Disorder","volume":"20","author":"Calarge","year":"2010","journal-title":"J. Child Adolesc. Psychopharmacol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1177\/1087054710385067","article-title":"Iron Status in Toddlerhood Predicts Sensitivity to Psychostimulants in Children","volume":"16","author":"Turner","year":"2010","journal-title":"J. Atten. Disord."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"l6890","DOI":"10.1136\/bmj.l6890","article-title":"Synthesis without meta-analysis (SWiM) in systematic reviews: Reporting guideline","volume":"368","author":"Campbell","year":"2020","journal-title":"BMJ"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/11\/4059\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:29:42Z","timestamp":1760167782000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/11\/4059"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,13]]},"references-count":97,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["nu13114059"],"URL":"https:\/\/doi.org\/10.3390\/nu13114059","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,13]]}}}