Omega-3s May Modify Genetic Susceptibility to Dry AMD

Omega-3 Fats & Advanced AMD Development

The omega-3 long-chain polyunsaturated fatty acids have anti-inflammatory and anti-oxidative properties, and increased dietary intake of these fats has been shown to slow or reduce development of advanced stages of age-related macular degeneration (AMD) in a number of studies.

AMD has a strong genetic component, and several genes are associated with advanced AMD including CFH, ARMS2/HTRA1, C3, C2, CFB, CFI and LIPC. The exact mechanisms by which some people never progress beyond the early or intermediate stages and others go on to develop geographic (GA) or neo-vascular (NV) AMD are not completely understood. 

Together, these factors led a team from Tufts Medical Center and New England Eye Center to investigate the impact of specific types of fat on GA and, controlling for genetic susceptibility, whether their intake could affect progression to GA.

Study Design and Methods

This study was an observational analysis of a prospective cohort: 2531 participants from the Age-related Eye Disease Study (AREDS). Among these participants, 525 eyes progressed to GA while 4,165 did not.

Eyes without advanced AMD at baseline were evaluated for progression to GA. Behavioral data were collected at baseline using questionnaires.

Food frequency questionnaires were used to calculate omega-3 (EPA and DHA), omega-6 fatty acids, monounsaturated, saturated, polyunsaturated and total fat, which were adjusted for sex and calories and divided into quintiles.

Eight single nucleotide polymorphisms in 7 genes (listed previously) were genotyped.

Cox proportional hazards models were used to test for associations between incident GA and intake of

dietary lipids, and interaction between dietary fat and genetic variation on GA risk. 

Two models were used: Model A was adjusted for baseline grade, as well as demographic and environmental characteristics (age, sex, education, smoking, whether or not they were assigned to the antioxidants group in AREDS, and body mass index or BMI).  Model B was adjusted for all the covariates in Model A plus all genes.

Results

Higher DHA intake was significantly associated with a lower risk of progression to GA in model A that controlled for behavioral risk factors and Model B that controlled for behavioral and genetic risk factors (P trend = 0.01 and 0.03 respectively).

EPA + DHA was significantly associated with reduced risk of GA progression in the model controlling for both genetic and behavioral factors (P trend = 0.02).

Total fat and saturated fat did not affect risk of progression, while there was a trend toward higher monounsaturated intake and risk in Model A.

Most notably, DHA had a protective effect among people with the ARMS2/HTRA1 homozygous risk genotype (P = 0.002).

Comments

Based on this study, the authors conclude that eating at least one or more 3 oz. portion of omega-3 rich fish weekly may reduce the risk of developing the GA form of AMD, even among those with genetic vulnerability to progression.

Reference

Reynolds R et al. Dietary omega-3 fatty acids, other fat intake, genetic susceptibility, and progression to incident geographic atrophy. Ophthalmol [ePub ahead of print March 4, 2013].