Iron deficiency linked to restless sleep in ADHD and autism

By Dr. Priyom Bose, Ph.D.Reviewed by Benedette Cuffari, M.Sc.Sep 17 2024

New study links iron deficiency to sleep disorders in children with ADHD and autism: exploring the critical role of iron in sleep regulation.

Study: Iron Deficiency and Restless Sleep/Wake Behaviors in Neurodevelopmental Disorders and Mental Health Conditions. Image Credit: Dragana Gordic / Shutterstock.com

A recent Nutrients study examines the relationship iron deficiency (ID) and sleep-related disorders.

Iron and sleep/wake disorders

Iron is a trace element present in neurons, astrocytes, oligodendrocytes, and microglia. Iron is also an essential component for both the synthesis of neurotransmitters that regulate the sleep/wake cycle, as well as the dopamine synthesis pathway.

These observations indicate that ID could significantly influence sleep and wake patterns; however, iron levels are rarely considered in the clinical management of sleep/wake disorders.

The most frequent causes of sleep/wake disorders are hyper-arousability, restless leg syndrome (RLS), hyper-motor restlessness, restless sleep disorder (RSD), and periodic limb movements in sleep (PLMS).

About the study

Prospective data were obtained between 2021 and 2023 through clinical assessments and structured intake forms. Subsequently, a retrospective analysis was conducted.

Data on the most recent iron status and parental ID history, as well as covariate factors, including comorbidities, demographics, and medications, were recorded. Patients with hematologic comorbidities were excluded. The mean patient age was about 11 years.

Study findings

Of the 250 patients referred to the Sleep/Wake-Behavior clinic in Vancouver, British Columbia, 80% met the inclusion criteria, 188 of whom fulfilled the criteria for non-anemic or anemic ID. A family history of ID was reported in several participants, many of whom indicated that their mothers experienced some form of ID in their teenage years and/or during pregnancy.

Approximately half of the study cohort reported disruptive behaviors, with attention deficit hyperactivity disorder (ADHD) being the most common diagnosis. Anxiety disorder was the most frequently reported internalizing disorder among 84 participants.

Autism spectrum disorder (ASD), global developmental delay/intellectual disability, neurologic conditions, and genetic conditions were the most commonly reported neurodevelopmental presentations.

About 74% of patients exhibited RLS, 52% reported a family history of RLS, and 11% had painful RLS. In 30% of patients, PLMS/restless sleep was noted.

A total of 92 patients had ADHD, among whom the risk of having familial RLS, insomnia, and RLS was significantly increased with a family history of ID. No evidence of an increased risk of painful RLS was observed.

A family history of ID significantly increased the likelihood of having RLS/PLMS/restlessness, insomnia/DIMS, RLS, and familial RLS in a subsample of patients with ASD.

As compared to patients without ID, a family history of ID was associated with a significantly higher risk of RLS. ADHD patients were almost twice as likely to have RLS as compared to patients without ADHD. No association was observed between RLS and ASD, nor bedtime resistance or restlessness, in multivariate logistic regression analyses.

Familial RLS analysis indicated that a family history of ID was associated with a four-fold increased risk of familial RLS as compared to those without a family history of ID. RLS and ADHD were not associated; however, a 70% increased risk of familial RLS was observed in ASD patients. No association was reported between bedtime resistance and restlessness and familial RLS.

Insignificant results were obtained regarding the association between a family history of ID and probable painful RLS. Bedtime resistance or restlessness, ADHD, and ASD were not associated with probable painful RLS.

These findings highlight the need to integrate comprehensive blood work and family history to capture ID in children and adolescents with restless behaviors.”

Strengths and limitations

The high prevalence and family history of ID, coupled with a possible association between ID and self-injurious behaviors, are key strengths of the present study. Nevertheless, there remained a lack of information on the possible causes of ID. Thus, future studies are needed to elucidate the mechanisms involved ID, as this nutrient deficit could be due to multiple factors, such as inflammation or inadequate nutrition.

The current study is a retrospective analysis, which lacks a structured categorization for certain data. For example, no distinction was made between anemic and nonanemic ID in the electronic intake forms, whereas data on mother and father ID was not separated. The statistical power in logistic regression analyses was also reduced due to relatively small sample sizes.