Several large studies have found that increased intake of nutrients such as zinc, omega-3 fatty acids and antioxidants can protect against AMD. However, studies investigating interaction between these nutrients and genetic risk have been relatively small and their results inconsistent. To further investigate this issue, investigators assessed the intake of antioxidants, zinc, and ω-3 fatty acids in daily foods among 2,167 individuals 55 years or older who were at risk for AMD and enrolled in the Rotterdam Study.
Participants completed a semiquantitative food frequency questionnaire at baseline and underwent genetic testing. They were followed for about eight years. Biological interaction between risk factors was identified with the synergy index. Among subgroups based on levels of nutrient intake and genotypes, the risk for early AMD was estimated with hazard ratios (HRs).
They found a possible biological interaction between the CFH Y402H genotype and intakes of zinc, β-carotene, lutein/zeaxanthin, and eicosapentaenoic/docosahexaenoic acid (EPA/DHA), and between the LOC387715 A69S genotype and zinc and EPA/DHA, based on significant synergy indices (P < .05 for all).
Participants who were homozygous for CFH Y402H and had dietary zinc intake in the highest tertile reduced their hazard ratio of early AMD from 2.25 to 1.27. Similar risk reductions were found among those in the highest tertile for β-carotene, lutein/zeaxanthin, and eicosapentaenoic/docosahexaenoic acid (EPA/DHA). Carriers of LOC387715 A69S with the highest intake of zinc and EPA/DHA reduced their risk from 1.70 to 1.17 and 1.59 to 0.95, respectively (all P trends <0.05).
Several biological mechanisms can explain diet's antagonistic effect in CFH Y402H carriers. However, the precise mechanism of the increased risk of AMD conferred by the A69S variant is unclear. One hypothesis is that the A69S variant may jeopardize mitochondrial function and consequently lead to the formation of reactive oxygen species, apoptosis, and AMD.
What diet is recommended? Fortified cereals, meats, dairy products, nuts, and seeds are a good source of zinc; dark-green leafy vegetables such as spinach and kale and orange vegetables including carrots and pumpkin are rich in β-carotene and lutein/zeaxanthin; and oily fish such as herring, salmon, sardines, trout, and tuna provide EPA/DHA. It does not appear necessary to consume excessive amounts of these nutrients. Consuming the recommended dietary allowance will suffice.
The authors write that physicians should provide dietary advice to young susceptible individuals to postpone or prevent the devastating effects of AMD.