Omega-3 and fish intake may prevent AMD
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fish was associated with a significantly decreased risk of developing
age-related macular degeneration AMD.
There is no recognized means of AMD prevention other than avoiding
cigarette smoking. Thus, the identification of means to prevent or
delay the development of AMD would have marked public health
significance.
Cardiovascular disease and AMD have been hypothesized to share similar
mechanisms and risk factors. Dietary intake of fish, and specifically
omega-3 fatty acids concentrated in fish (docosahexaenoic acid [DHA]
and eicosapentaenoic acid [EPA]), has been linked with reduced rates
of cardiovascular events in epidemiologic studies and could have a
similar beneficial effect in AMD. Omega-3 fatty acids are known to
exert anti-inflammatory, anti-atherosclerotic, and antithrombotic
effects on the vasculature and may help to maintain or improve
choroidal blood flow in the eye.
Observational epidemiologic studies suggests an inverse relation
between regular dietary intake of fish and DHA and EPA and risks of
advanced AMD. However, available data for early AMD are limited and
inconsistent.
Methods & Results
A detailed food-frequency questionnaire was administered at baseline
among 39,876 female health professionals (mean age: 54.6 years). A
total of 38,022 women completed the questionnaire and were free of a
diagnosis of AMD. The main outcome measure was incident AMD
responsible for a reduction in best-corrected visual acuity to 20/30
or worse based on self-report confirmed by medical record review.
A total of 235 cases of AMD, most characterized by some combination of
drusen and retinal pigment epithelial changes, were confirmed during
an average of 10 years of follow-up. Women in the highest tertile of
intake for docosahexaenoic acid, compared with those in the lowest,
had a multivariate-adjusted relative risk of AMD of 0.62. For
eicosapentaenoic acid, women in the highest tertile of intake had a
relative risk of 0.66. Consistent with the findings for
docosahexaenoic acid and eicosapentaenoic acid, women who consumed 1
or more servings of fish per week, compared with those who consumed
less than 1 serving per month, had a relative risk of AMD of 0.58.
Discussion & Conclusions
In this large prospective cohort study of women, regular consumption
of DHA and EPA and fish was associated with a 35% to 45% lower risk of
visually significant AMD during 10 years of follow-up. This inverse
association was independent of other AMD risk factors and was not
materially altered after adjustment for saturated, monounsaturated,
and trans unsaturated fat intake. The study population comprised women
without a prior diagnosis of AMD, and the large majority of cases
documented during follow-up were characterized by some combination of
drusen and RPE changes signifying an early stage of disease
development. Thus, these findings suggest that dietary intake of DHA
and EPA and fish may be beneficial in the primary prevention of AMD.
Previous observational studies, including 5 prospective studies, are
suggestive of an inverse association between fish and omega-3
long-chain fatty acid intake and risks of advanced AMD (ie,
neovascular AMD or central geographic atrophy). For example, recent
prospective data from the Age-Related Eye Disease Study indicated that
those with the highest consumption of DHA and EPA, compared with the
lowest, had an approximate 30% lower risk of progression to advanced
AMD that was apparent even after 12 years of follow-up. However, the
data for early AMD are more limited and inconsistent. Of 5
cross-sectional studies that included cases of early AMD, 3 reported
an inverse relation with advanced AMD only, and 2 reported no
association with either early or advanced AMD.
Nurses Health Study & Health Professionals Follow-up Study
A report based on 567 cases of visually significant AMD identified
during 10 to 12 years of follow-up of 42,000 women in the Nurses’
Health Study and 30 000 men 50 years and older in the Health
Professionals Follow-up Study found that higher intake of DHA was
associated with a 30% lower risk of AMD. However, the RR was
attenuated and no longer significant after further adjustment for
other fats. A similar nonsignificant inverse relation was observed for
EPA in that study, while intake of alpha-linolenic acid was directly
related to risks of AMD in a fully adjusted model (RR, 1.41). That
study also found that men and women who reported eating fish 4 or more
times per week, compared with those who ate fish less than 4 times a
month, had a 35% lower risk of AMD (RR, 0.65). This lower risk
appeared to be due largely to intake of canned tuna fish (RR, 0.61);
no association was observed for intake of dark or white-meat fish in
that study.
Blue Mountains Eye Study
In the Blue Mountains Eye Study, a repeated eye examination at 5 years
for 2335 men and women 49 years and older documented 130 new cases of
early AMD and 22 cases of late AMD. Participants in the highest
quintile of intake for omega-3 long-chain fatty acids (DHA,
docosapentaenoic acid, and EPA), compared with the lowest quintile,
had a significantly lower risk of early AMD (odds ratio, 0.41).
Consumption of fish was also associated with significantly lower risks
of early AMD(and late AMD) at the 5-year follow-up. However, at 10
years, the inverse relation between early AMD and intake of omega-3
long chain fatty acids (DHA, docosapentaenoic acid, and EPA) and fish
was attenuated and no longer significant.
Reykjavik Study
In a third study, conducted among 846 men and women in Reykjavik,
Iceland, 50 years and older, a repeated eye examination at 5 years of
follow-up documented 126 new cases of early AMD. Those who reported
eating herring 2 times per week or more, vs less than once a month,
had a 39% lower risk of early AMD (RR, 0.61).
Our data, based on 10 years of follow-up of a large cohort of female
health professionals, are broadly consistent with these earlier
findings and appear to be the strongest observational evidence to date
in support of a possible role for intake of omega-3 long-chain fatty
acids and fish in the primary prevention of AMD. Moreover, because
early AMD is associated with an increased risk of developing advanced
AMD, our data further suggest that dietary intake of omega-3
long-chain fatty acids and fish by persons at usual risk may
ultimately reduce the number of persons who have advanced AMD.
There is strong biologic plausibility for an association of DHA and
EPA intake with AMD, and multiple mechanisms have been described.
Docosahexaenoic acid and EPA could affect AMD occurrence by modulating
inflammatory and immune processes thought to play a role in AMD
pathogenesis. Omega-3 and omega-6 fatty acids compete both for enzymes
that convert essential fatty acids alpha-linolenic acid and LA to
longer-chain DHA, EPA, and AA and for enzymes that initiate conversion
of these long-chain fatty acids to eicosanoids, locally acting lipids
more immediately involved in the control of inflammatory and immune
processes. Higher intake of omega-3 fatty acids reduces production of
AA-derived eicosanoids, which are generally proinflammatory, and
increases levels of EPA-derived eicosanoids, which are 10- to 100-fold
less active.
Our observation in the present study that the ratio of omega-6 to
omega-3 fatty acids (DHA plus EPA) was strongly predictive of early
AMD is consistent with similar findings for advanced AMD in prior
studies and supports the conclusion that both the level of omega-3
fatty acids and its ratio to omega-6 fatty acids are important in
determining risks of AMD. We also observed that the inverse relation
of DHA and EPA with AMD was more apparent in participants reporting
higher levels of omega-6 fatty acid intake, although tests of
interaction were not significant. This finding appears consistent with
subgroup findings for LA intake in the Age-Related Eye Disease Study
population but seems to conflict with 2 previous reports indicating a
benefit primarily among participants with the lowest levels of LA
intake. The reasons for these somewhat different findings are unclear
and require further investigation. Other mechanisms through which DHA
and EPA may contribute to a reduced risk of AMD include enhanced
production of resolvins and neuroprotectins, which are thought to
dampen and resolve inflammatory responses, and the modulation of
expression of signal transduction genes and genes for proinflammatory
cytokines.
In summary, these prospective data from a large population of women
with no prior diagnosis of AMD indicate that regular consumption of
DHA and EPA and fish significantly reduced the risk of incident AMD.
These data appear to be the strongest evidence to date to support a
role for omega-3 long-chain fatty acids in the primary prevention of
AMD.
Arch Ophthalmol. 2011 Jul;129(7):921-9
http://www.ncbi.nlm.nih.gov/pubmed/21402976
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