ADHD affects 5% of children. Etiological and pathophysiological factors of this disorder is still not completely understood.Iron deficiency, which is a common disorder, has been suggested as having some role in ADHD. Iron is a co-factor of enzymes necessary for the mono aminergic neurotransmitter system. Iron deficiency is associated with a decrease in dopamine transporter expression. It may lead to dysfunction in the basal ganglia and changes in basal ganglia are believed to play a role in ADHD. ADHD could be co morbid with restless legs syndrome (RLS) ( an urge to move the legs, often accompanied by unpleasant sensations which appear during periods of rest or inactivity and usually relieved by movement) where Iron deficiency is thought to be an etiological factor.
This meta analysis by Samuele Cortese, Marco Angriman, Michel Lecendreux and Eric Konofal included studies that used formal criteria to diagnose ADHD and compared various iron indices between ADHD and non ADHD groups. A comprehensive search was done to include literature up to July 2012. Total of 22 studies met the strict inclusion criteria.
Several studies found evidence supporting a possible iron deficiency in ADHD. Correlations with Conner’s Parent Rating Score and serum ferritin was also reported in many studies. ( Eg: Konofal et al,2004, Oner et al, 2008 Juneja et al 2010, Mahmoud et al 2011.Lahat et al.2011 etc). However Chen et al.2004 found increased serum iron in their study. Many studies did not find any relationship between ADHD and ferritin levels ( eg: Millichap et al 2006, Menegassi et al 2010, Karakurt et al 2011. Donfrancesco et al 2012 ).
The results are clearly mixed. This could be due to various factors. If patients are on psychostimulants , this may affect appetite and, consequently, alter serum ferritin levels. Weight loss associated with psychostimulant treatment might lead to increased ferritin levels due to reduced iron utilisation. Also, studies have adopted different methods for serum ferritin measurement.
Some authors suggest that with ADHD with sleep disorders, in particular RLS, may be a subgroup particularly at risk for having Iron deficiency. In studies that looked at this subgroup, ADHD with RLS had significantly lower serum ferritin levels.
It is unclear whether serum ferritin levels correlate with brain iron .The only published study (brain MRI), found significantly lower iron levels in the thalamus (bilaterally) in children with ADHD (n = 18) versus non-ADHD comparisons (n = 18) (Cortese et al.2012). Reviewers caution that since T2 scans are usually used to assess brain iron overload and this finding should be interpreted with caution.
Any benefits with Iron supplementation?
In a short-term (one month) open-label trial of iron supplementation in 14 boys with ADHD (7–11 years), Sever et al. (1997) found a significant decrease in the Conners Parent Rating Scale index score (CPRS) but not in the measures of ADHD symptom severity provided by the teachers. In the only RCT in this area, (Konofal al 2008) 23 children with ADHD and serum ferritin levels <30 ng/ml were randomized to oral iron or placebo. After 12 weeks, a significant decrease in the clinical global impression severity scale was found. However, there was no significant reduction on the teacher or parent reported scores.
1.Most studies have focused on serum ferritin measures and the results are mixed with regard to the role of iron deficiency in ADHD. Only one study assessed brain iron levels,and this suggest brain iron deficiency in ADHD.
2. ADHD with sleep disorders, in particular RLS, may be a subgroup to have iron deficiency.
3.Iron supplementation studies have small sample sizes and evidence is not conclusive of benefits.
4.Given the role of iron in dopamine synthesis, it might have some role as an adjunctive agent to psycho stimulants in ADHD.
Summary of the article:
Iron and attention deficit/hyperactivity disorder: what is the empirical evidence so far? A systematic review of the literature. Cortese S, Angriman M, Lecendreux M, Konofal E. Expert Rev Neurother. 2012 Oct;12(10):1227-40