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

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.

Associations between Dietary Intake and Attention Deficit Hyperactivity Disorder (ADHD) Scores by Repeated Measurements in School-Age Children

“…In a recent systematic review of randomized clinical trials of the role of iron and zinc in the treatment of ADHD in children and adolescents, it is unclear whether changes in nutritional levels in blood tests mediate treatment outcomes in children with ADHD taking mineral supplements, but lower levels of iron and zinc have been observed in children diagnosed with ADHD compared to healthy controls. Importantly, consistent with our findings, the results of this systematic review support the existence of a subgroup that may particularly benefit from treatments that include dietary zinc and iron supplements [40,56].…”

Eating Patterns and Dietary Interventions in ADHD: A Narrative Review

“…Zinc is also an essential trace element, required for cellular functions related to the metabolism of neurotransmitters, melatonin, and prostaglandins. Altered levels of iron and zinc have been related with the aggravation and progression of ADHD [ 54 ].…”

Do Children with Attention-Deficit/Hyperactivity Disorder Follow a Different Dietary Pattern than That of Their Control Peers?

“…Some studies found altered levels of certain oligo elements such as magnesium, iron, and zinc in serum in children with ADHD [ 11 , 12 , 13 , 14 , 15 ]. For these reasons, several studies attempted to find a more natural, as opposed to pharmacological, treatment for ADHD; hence, various systematic reviews analyzed the effect of different nutritional interventions on behavioral symptomatology [ 13 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ], but were unable to find clear supporting evidence. Furthermore, other authors studied the relationship between diet and ADHD versus non-ADHD.…”