Iron deficiency and sleep - A scoping review.

Iron deficiency (ID) is associated with sleep disorders, but standardized assessment of iron status in the diagnostic work-up and iron supplementation as treatment have not been considered in clinical practice. We investigated associations of ID with type and severity of sleep disorders and whether iron supplementation improves sleep-related symptoms. In 2017, we conducted a scoping review for the period 1972-2016 using the terms "iron deficiency anemia" and "sleep" on biomedical database search engines, and in 2019, we updated our review with an ad-hoc search. Among the 93 articles meeting our inclusion criteria, 74/93 studies investigated restless legs syndrome (RLS), 8/93 periodic limb movements in sleep (PLMs), 3/93 sleep disordered breathing (SDB), 6/93 general sleep disturbances (GSD), and 2/93 attention-deficit/ hyperactivity disorder related sleep disorders (ADHD-SDs). A statistically supported positive association with ID was found in 22/42 RLS, 3/8 PLMs, 1/2 SDB, 3/4 GSD, and 1/2 ADHD-SDs association studies. The ad-hoc literature search revealed eight additional association studies with a statistically supported positive association in 2/5 RLS, 1/1 SDB, 1/1 ADHD-SDs, and 1/1 restless sleep disorder (RSD) studies. Iron supplementation was beneficial in 29/30 RLS (including five randomized controlled trials [RCTs]), 1/1 SDB, and 2/2 GSD treatment studies. Iron supplementation was also beneficial in 2/2 RLS (including two RCTs), 1/1 GSD (RCT), and 1/1 RSD studies identified in the ad-hoc search. In pediatric populations, 1/1 RLS, 1/1 SDB, 2/5 PLMs, 2/3 GSD and 1/2 ADHD-SDs studies found positive associations, and 6/6 RLS and 2/2 GSD studies demonstrated a benefit with iron supplementation. In conclusion, iron investigation and supplementation should be considered in patients presenting with sleep disorders. To investigate the role of ID in sleep in the future, a harmonization of study designs, including outcome measures and standardized iron and inflammation status is necessary.