Association between homocysteine and periodic limb movement during sleep in samples from the São Paulo epidemiological sleep study (EPISONO): Homocysteine and PLMS in the EPISONO study.

Periodic limb movement in sleep (PLMS) involves repetitive, involuntary limb movements and is central to diagnosing periodic limb movement disorder (PLMD). Although distinct, PLMS frequently co-occurs with restless legs syndrome (RLS) and shares common pathophysiological factors, including deficiencies in brain dopamine, blood iron, and possibly cobalamin. Our aim was to investigate associations between blood concentrations of cobalamin, folic acid, homocysteine (Hcy), hemoglobin, iron, ferritin, and PLMS. Data from the 2007 and 2018 editions of the São Paulo Epidemiologic Sleep Study (EPISONO) were used. Elevated Hcy concentrations were identified as a risk factor for PLMS, with each 1 µmol/L increase in Hcy being associated with a 1.09-fold increase in the odds of PLMS, particularly in males. Conversely, hemoglobin concentrations were inversely associated with PLMS risk in males. Our findings suggest that Hcy may serve as a biochemical marker of PLMS risk, especially in men, while also highlighting a protective role of hemoglobin in this context. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-026-00637-9.