Fish and Vitamin D Linked to Lower Risk of Macular Degeneration

ROCKVILLE, Md., May 14 -- Eating fatty fish and drinking milk may reduce the risk of age-related macular degeneration, researchers reported.

The findings emerged from two studies reported in the May issue of the Archives of Ophthalmology. One was the Age-Related Eye Diseases Study (AREDS), which looked at patients at 11 retinal specialty clinics.

It found that higher dietary levels of omega-3 fatty acids, mainly from fatty fish, reduced the risk of age-related macular degeneration.

In the case-control study, eating more than two medium servings a week of fatty fish, a food rich in omega-3 long-chain polyunsaturated fatty acids, was associated with a 39% reduced risk of neovascular age-related macular degeneration.

The primary focus of the other study was that higher serum levels of vitamin D, mainly from milk, reduced the risk of early disease, relegating protection from fatty fish to advanced disease.

Julie Mares, Ph.D., of the University of Wisconsin in Madison, and colleagues, reported that levels of serum vitamin D were inversely associated with early macular degeneration but not advanced disease.

The AREDS researchers compared lipid intake with the baseline severity of age-related macular degeneration in 4,519 participants, ages 60 to 80 at enrollment. A self-administered food-frequency questionnaire and fundus photographs were used to divide individuals into four severity groups and a control group (those with less than 15 small drusen).

Participants were recruited through various sources, including medical records at AREDS clinics, referrals, HMO groups, senior centers fairs, other gathering places, and public advertisements.

Comparing the highest versus lowest quintile of intake, after adjustment for total energy intake and covariates, dietary total omega-3 long-chain polyunsaturated fatty acid intake was inversely associated with age-related macular degeneration (odds ratio 0.61; 95% confidence interval 0.41-0.90), as was potentially protective docosahexaenoic acid, a retinal omega-3 fatty acid (OR, 0.54; 95% CI, 0.36-0.80).

Higher fish consumption, both total and broiled or baked, including shellfish, was also inversely associated with macular degeneration (OR, 0.61; CI, 0.37-1.00 and OR, 0.65; CI, 0.45-0.93, respectively).

Dietary arachidonic acid, an omega-6 fatty acid, was directly associated with the prevalence of macular degeneration (OR, 1.54; 95% CI, 1.04-2.29), the researchers reported. Participants with the highest intakes were 1.5 times more likely to be in the advanced macular degeneration group than those in the lowest quintile level.

Because of this direct association, the researchers said, it is important to consider the balance and composition of dietary long-chain polyunsaturated fatty acids from the omega-3 and the omega-6 families.

Finally, the investigators said, they found no statistically significant relationships for the other lipids or macular degeneration groups.

There are inherent limitations in the case-control design of this study, the authors wrote. Because all nonnutritional factors associated with the disease were reported in previous studies, they assumed that they were unlikely to model factors from spurious relationships. Nevertheless, the possibility of consistent bias across studies cannot be excluded, they said.

Also, they noted the sampling scheme for the clinic-based case-control design may have misclassified some of the subjects. The possible effect of selection bias must also be considered, they said. Participants in AREDS classified with no macular degeneration or lower levels of severity, were more likely than those with more severe disease to volunteer in response to public advertisements.

These results and those from other observational analytic investigations suggest that adding more foods rich in omega-3 polyunsaturated fatty acids could reduces the risk of age-related macular degeneration, the investigators said.

In addition to carefully designed observational analytic studies, they added, clinical trials would provide unique information on whether dietary intervention or supplementation would help prevent the development of advanced age-related macular degeneration.

In the Wisconsin study, the researchers evaluated serum vitamin D and early and advanced macular degeneration in individuals from the National Health and Nutrition Examination Survey III (NHANES III).

The study included 7,752 individuals, 11% with age-related macular degeneration.

The risk of early age-related macular degeneration among participants in the highest versus the lowest quintile of serum vitamin D was reduced by 36% (OR, 0.64 (95% CI, 0.5-0.8; P trend

No associations were found between serum vitamin D levels and the risk for pigmentary abnormalities or advanced macular degeneration, the researchers reported.

Exploratory analyses to evaluate associations with important food and supplemental sources of vitamin D found that milk intake was protective and inversely associated with early disease (OR, 0.75; CI, 0.6-0.9), whereas fish intake was protective and inversely associated with advanced disease (OR, 0.41; CI, 0.2-0.9).

Consistent use versus nonuse of vitamin D from supplements was inversely associated with early disease only among those who did not drink milk every day (early AMD: OR, 0.67; 95% CI, 0.5-0.9).

Fish can be a rich source of vitamin D and may be protective, Dr. Mares said. In this study, fish did not correlate with serum vitamin D, possibly because of a low frequency of fish consumption, and the difficulty of distinguishing between fatty fish and other types. This she said, may help explain why no benefit was found for early disease and high intake of fish.

These results, the researchers said, support the idea that lower serum vitamin D levels may lead to progression of chronic diseases, specifically those associated with inflammation. This may be important to the health of older Americans who have particularly high rates of insufficient vitamin D intake, the researchers said.

Among the study's limitations, the researchers mentioned that the eye disease was determined in only one eye, leading to a possible underestimation of cases. Other sources of possible bias included the use of an unvalidated food frequency questionnaire, and that serum vitamin D exposure did not reflect sun exposure and food intake over recent weeks.

Summing up, the researchers cautioned that at this time there is insufficient epidemiologic evidence of the relationship between vitamin D and age-related macular degeneration to make recommendations regarding optimum vitamin D levels or milk and fish intake to protect against the eye disease or its progression.

This results, they said, warrant further investigation to confirm the role of vitamin D in other population studies.

No financial conflicts were reported for the NHANES III study. This research was supported by grants from the National Institutes of Health, Research to Prevent Blindness, and the Retina Research Foundation.