Oxidative stress and autonomic nervous system functions in restless legs syndrome

Eur J Clin Invest. 2011 Jul;41(7):734-42. doi: 10.1111/j.1365-2362.2010.02461.x. Epub 2011 Jan 20.


Background: Oxidative stress has been implicated in over 100 disorders in recent years; however, the situation in restless legs syndrome (RLS) has not been studied yet.

Methods: Fifty patients with RLS not medicated for RLS and 50 sex- and age-matched, healthy controls and controls with no pathology except mild iron deficiency or iron deficiency anaemia were enrolled. Patients with secondary RLS other than iron deficiency were excluded. Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), arylesterase (ARE), paraoxonase (PON), stimulated paraoxonase (stim-PON), lipid hydroperoxides (LOOHs), acetyl cholinesterase (AChE) and butyryl cholinesterase (BuChE) were measured. Heart rate variability (HRV) analysis was performed.

Results: TOS, ARE and AChE were increased (P = 0·018, P < 0·001 and P < 0·001, respectively), whereas LOOHs were decreased (P < 0·001) in RLS group. TAS, OSI, PON and stim-PON were comparable. Erythrocyte sedimentation rate (ESR) and mean platelet volume (MPV) were increased (P = 0·021 and P = 0·037, respectively) in RLS group. HRV triangular index (HRVi) was lower (P = 0·012) in RLS group. Other HRV parameters were similar.

Conclusions: Increased AChE and decreased LOOHs, which were influenced by increased PON1, were considered as indicators of efforts towards the protection of dopaminergic activity in central nervous system in RLS group. Increased ESR, MPV and low HRVi indicate elevated sympathetic activity in RLS group. Elevated sympathetic activity might be beneficial in relieving RLS symptoms, also causing increases in TOS. The evidence we found regarding oxidative stress and autonomic nervous system might be seminal in RLS treatment.

MeSH terms

  • Acetylcholinesterase / blood
  • Adult
  • Aging / blood
  • Anemia, Iron-Deficiency / complications
  • Aryldialkylphosphatase / blood
  • Autonomic Nervous System / physiopathology*
  • Blood Sedimentation
  • Carboxylic Ester Hydrolases / blood
  • Case-Control Studies
  • Female
  • Heart Rate / physiology
  • Humans
  • Iron Deficiencies
  • Lipid Peroxides / blood
  • Lipids / blood
  • Male
  • Middle Aged
  • Oxidative Stress / physiology*
  • Restless Legs Syndrome / blood
  • Restless Legs Syndrome / physiopathology*


  • Lipid Peroxides
  • Lipids
  • Carboxylic Ester Hydrolases
  • arylesterase
  • Acetylcholinesterase
  • Aryldialkylphosphatase
  • PON1 protein, human