*Review* **The Role of Iron and Zinc in the Treatment of ADHD among Children and Adolescents: A Systematic Review of Randomized Clinical Trials**

**Roser Granero 1,2,3,\*, Alfred Pardo-Garrido 1, Ivonne Lorena Carpio-Toro 4,5, Andrés Alexis Ramírez-Coronel 4,6, Pedro Carlos Martínez-Suárez 4,6 and Geovanny Genaro Reivan-Ortiz 3,4**


**Abstract:** 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.

**Keywords:** ADHD; zinc; iron; treatment; children

**Citation:** Granero, R.; Pardo-Garrido, A.; Carpio-Toro, I.L.; Ramírez-Coronel, A.A.; Martínez-Suárez, P.C.; Reivan-Ortiz, G.G. The Role of Iron and Zinc in the Treatment of ADHD among Children and Adolescents: A Systematic Review of Randomized Clinical Trials. *Nutrients* **2021**, *13*, 4059. https://doi.org/10.3390/ nu13114059

Academic Editor: Ann-Sofie Sandberg

Received: 17 September 2021 Accepted: 11 November 2021 Published: 13 November 2021

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