title: A meta-analysis of biomarkers related to oxidative stress and nitric oxide pathway in migraine.
abstract: BACKGROUND
  Oxidative and nitrosative stress are considered key events in the still unclear pathophysiology of migraine.
  
  
  METHODS
  Studies comparing the level of biomarkers related to nitric oxide (NO) pathway/oxidative stress in the blood/urine of migraineurs vs. unaffected controls were extracted from the PubMed database. Summary estimates of mean ratios (MR) were carried out whenever a minimum of three papers were available. Nineteen studies were included in the meta-analyses, accounting for more than 1000 patients and controls, and compared with existing literature.
  
  
  RESULTS
  Most studies measuring superoxide dismutase (SOD) showed lower activity in cases, although the meta-analysis in erythrocytes gave null results. On the contrary, plasma levels of thiobarbituric acid reactive substances (TBARS), an aspecific biomarker of oxidative damage, showed a meta-MR of 2.20 (95% CI: 1.65-2.93). As for NOs, no significant results were found in plasma, serum and urine. However, higher levels were shown during attacks, in patients with aura, and an effect of diet was found. The analysis of glutathione precursor homocysteine and asymmetric dimethylarginine (ADMA), an NO synthase inhibitor, gave inconclusive results.
  
  
  CONCLUSIONS
  The role of the oxidative pathway in migraine is still uncertain. Interesting evidence emerged for TBARS and SOD, and concerning the possible role of diet in the control of NOx levels.
authors.affiliation: Clinical and Molecular Epidemiology, Area of Systems Approaches and Non-Communicable Diseases, IRCCS San Raffaele Pisana, Italy monicaneri2008@gmail.com.
authors.forename: Monica
authors.initials: M
authors.lastname: Neri
authors.affiliation: Clinical and Molecular Epidemiology, Area of Systems Approaches and Non-Communicable Diseases, IRCCS San Raffaele Pisana, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Frustaci
authors.affiliation: Clinical and Molecular Epidemiology, Area of Systems Approaches and Non-Communicable Diseases, IRCCS San Raffaele Pisana, Italy Institute for Medical Research and Occupational Health, Mutagenesis Unit, Croatia.
authors.forename: Mirta
authors.initials: M
authors.lastname: Milic
authors.affiliation: Clinical and Molecular Epidemiology, Area of Systems Approaches and Non-Communicable Diseases, IRCCS San Raffaele Pisana, Italy.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Valdiglesias
authors.affiliation: IRCCS San Raffaele Pisana, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Fini
authors.affiliation: Clinical and Molecular Epidemiology, Area of Systems Approaches and Non-Communicable Diseases, IRCCS San Raffaele Pisana, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonassi
authors.affiliation: Headache and Pain Unit, Department of Neurological, Motor and Sensorial Sciences, IRCCS San Raffaele Pisana, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Barbanti
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000378:metabolism / Q000652:urine; D003430:Cross-Sectional Studies; D006801:Humans; D008881:Migraine Disorders / Q000175:diagnosis* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide
keywords: Biological markers; blood; case-control studies; meta-analysis; migraine; nitric oxide; oxidative stress; superoxide dismutase