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. Summary: 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. Key Messages: 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.

Associations of serum n-3 and n-6 PUFA and hair mercury with the risk of incident stroke in men: the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD)

“…However, as in our cohort, this has not been observed in all studies (6,15,18) . Our results on the lack of association with AA, GLA and dihomo-γ-linolenic acid are consistent with other findings from other observational studies (6,14,17,19,21) . In the KIHD cohort, high hair Hg content was associated with a higher risk of CVD and with attenuation of the inverse association between n-3 PUFA and these events (22,23) .…”

“…Circulating fatty acids provide an objective measure of exposure, and are thus less subject to random error. However, previous studies that have used circulating PUFA as exposure have not produced consistent findings (6)(7)(8)(14)(15)(16)(17)(18)(19)(20)(21) . Therefore, the aim of our study was to investigate the associations between serum n-3 and n-6 PUFA and risk of stroke in men.…”

Comparison of Fatty Acid Profiles in a Group of Female Patients with Chronic Kidney Diseases (CKD) and Metabolic Syndrome (MetS)–Similar Trends of Changes, Different Pathophysiology

“…In addition, a more intensive synthesis of arachidonic acid (C20:4n6) was observed from essential fatty acids (EFAs), which probably includes linoleic acid (C18:2n6). These derivatives are responsible for the formation of blood clots, atherosclerotic changes, inflammatory and allergic reactions, cell proliferation, and the development of tumor tissue [21]. An increased percentage of C22:4n6 and omega-3-family acids, including C22:5n3 and C22:6n3 (EPA and DHA), were observed as well.…”

Associations between whole peripheral blood fatty acids and DNA methylation in humans

“…As for AA, this PUFA has complex biological functions, ranging from the participation in inflammation resolution mentioned above, to being a precursor of inflammatory mediators. The impact of AA on cardiovascular health and other inflammation-related disorders has not yet been conclusively established 62 . We showed that AA induces global DNA hypermethylation in human THP-1 monocytes (Silva-Martínez et al ., in press), in accordance with the positive association detected in the present study.…”