title: Arachidonic Acid and Cerebral Ischemia Risk: A Systematic Review of Observational Studies.
abstract: BACKGROUND
  Arachidonic acid (ARA) is a precursor of various lipid mediators. ARA metabolites such as thromboxane A2 cause platelet aggregation and vasoconstriction, thus may lead to atherosclerotic disease. It is unclear whether dietary ARA influences the ARA-derived lipid mediator balance and the risk for atherosclerotic diseases, such as cerebral ischemia. Considering the function of ARA in atherosclerosis, it is reasonable to focus on the atherothrombotic type of cerebral ischemia risk. However, no systematic reviews or meta-analyses have been conducted to evaluate the effect of habitual ARA exposure on cerebral ischemia risk. We aimed to systematically evaluate observational studies available on the relationship between ARA exposure and the atherothrombotic type of cerebral ischemia risk in free-living populations.
  
  
  CONCLUSIONS
  The PubMed database was searched for articles registered up to June 24, 2014. We designed a PubMed search formula as follows: key words for humans AND brain ischemia AND study designs AND ARA exposure. Thirty-three articles were reviewed against predefined criteria. There were 695 bibliographies assessed from the articles that included both ARA and cerebral ischemia descriptions. Finally, we identified 11 eligible articles and categorized them according to their reporting and methodological quality. We used the Strengthening the Reporting of Observational Studies in Epidemiology Statement (STROBE) checklist to score the reporting quality. The methodological quality was qualitatively assessed based on the following aspects: subject selection, ARA exposure assessment, outcome diagnosis, methods for controlling confounders, and statistical analysis. We did not conduct a meta-analysis due to the heterogeneity among the studies. All eligible studies measured blood ARA levels as an indicator of exposure. Our literature search did not identify any articles that evaluated dietary ARA intake and tissue ARA as assessments of exposure. Seven of the 11 eligible articles were considered to be of low quality. No articles reported a dose-dependent positive association between an increased cerebral ischemia risk and ARA exposure. However, most studies did not assess the risk in each subtype of cerebral ischemia, thus various etiological types of cerebral ischemia risk were involved in their results.
  
  
  CONCLUSIONS
  We did not find a positive association between ARA exposure and cerebral ischemia risk. Eligible studies reported inconsistent findings: cerebral ischemia risk did not change or significantly decreased. We could not draw any conclusions due to the limited number of eligible high-quality studies. Further evidence from well-designed observational studies is required. Simultaneously, in order to develop effective preventive measures against cerebral ischemia, it is imperative to establish standardized definitions, nomenclatures, classifications, and diagnostic procedures.
authors.affiliation: Department of Social and Preventive Epidemiology, School of Public Health, The University of Tokyo, Japan ; Quality Assurance Department, Suntory Wellness Limited, Tokyo, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Sakai
authors.affiliation: Department of Social and Preventive Epidemiology, School of Public Health, The University of Tokyo, Japan ; Institute for Health Care Science, Suntory Wellness Limited, Osaka, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Kakutani
authors.affiliation: Institute for Health Care Science, Suntory Wellness Limited, Osaka, Japan.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Tokuda
authors.affiliation: Institute for Health Care Science, Suntory Wellness Limited, Osaka, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Institute for Health Care Science, Suntory Wellness Limited, Osaka, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Kominami
authors.affiliation: Institute for Health Care Science, Suntory Wellness Limited, Osaka, Japan.
authors.forename: Kahori
authors.initials: K
authors.lastname: Egawa
authors.affiliation: Research Institute, Suntory Global Innovation Center Limited, Osaka, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Saito
authors.affiliation: Institute for Health Care Science, Suntory Wellness Limited, Osaka, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Rogi
authors.affiliation: Institute for Health Care Science, Suntory Wellness Limited, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawashima
authors.affiliation: Institute for Health Care Science, Suntory Wellness Limited, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shibata
authors.affiliation: Department of Social and Preventive Epidemiology, School of Public Health, The University of Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sasaki
keywords: Arachidonic acid; Case-control studies; Cerebral ischemia; Cohort studies; Cross-sectional studies; Dietary fatty acids; Epidemiology; Free-living populations; Nested case-control studies; Systematic review