The Relationship of Omega(n)–3 Long–chain Polyunsaturated Fatty Acid (LCPUFA) Intake and Regular Aspirin (ASA) Use With Prevalent Neovascular Age–Related Macular Degeneration (NV AMD)

Abstract

Abstract: : Purpose: To investigate the relationship of n–3 LCPUFA intake and regular ASA use with prevalent NV AMD in the Age–Related Eye Disease Study. Background: The likelihood of having NV AMD is lower among people who report consuming higher amounts of n–3 LCPUFAs. Dietary and retinal LCPUFAs are the source of vasoregulatory eicosanoids. LCPUFAs also are capable of reacting through ASA–driven pathways to generate a family of bioactive molecules (lipoxins) with potent immunoregulatory properties. Methods: In this case–control study of 657 people with NV AMD and 1112 people without AMD (few or no drusen) we administered a validated food frequency questionnaire and a standardized drug use questionnaire to obtain estimates of habitual LCPUFA intake and resgular ASA use. Results: Subjects reporting the highest n–3 LCPUFA intake and the longest duration of ASA use were also the least likely to have NV AMD, as based on multivariable logistic regression models adjusted with all measured nutrient– and non–nutrient–based covariates. Docosahexaenoic acid (DHA) is the major n–3 LCPUFA of the neural and vascular retina. The likelihood of NV AMD associated with highest v. lowest reported levels of DHA intake was reduced among subjects who reported never regularly using ASA (OR= 0.6; 95%CI = 0.3–0.9). The likelihood also was reduced among those who regularly used ASA for at least 3 months (OR = 0.4; 95%CI = 0.2–0.8) or at least 5 years (OR=0.2; 95%CI = 0.1–0.7). Eicosapentaenoic acid (EPA) is the primary n–3 substrate of COX and LOX pathways involved in eicosanoid biosynthesis. Higher intake of EPA was protective of NV AMD only in regular ASA users. For subjects who reported never regularly using ASA, the OR was 1.0 (95%CI = 0.6–1.5). Values were 0.4 (95%CI = 0.2–0.8) and 0.2 (95%CI = 0.1–0.8) for subjects who reported regular use of ASA for at least 3 months and at least 5 years, respectively. Conclusions: The relationship of n–3 LCPUFA intake with NV AMD may be modified by regular ASA use. While the constraints of our experimental design do not allow us to conclusively rule out the possibility that results may be explained by unmeasured covariates, these novel findings provide a reasonable basis for investigating mechanisms driving LCPUFA–ASA–NV AMD relationships.

Keywords: age-related macular degeneration • nutritional factors • neovascularization