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Oily fish consumption, dietary docosahexaenoic acid and eicosapentaenoic acid intakes, and associations with neovascular age-related macular degeneration^1,2,3

¹ From the Department of Epidemiology & Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom (CA and AEF); the Department of Ophthalmology (UC) and the Centre for Clinical and Population Sciences (IY), Queen's University Belfast, Belfast, United Kingdom; the Centre for Environmental Risk, University of East Anglia, East Anglia, United Kingdom (GB); the Netherlands Institute for Neuroscience, KNAW, Department of Ophthalmology, Academic Medical Centre, Amsterdam, Netherlands (PTVMdJ); the Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, Netherlands (PTVMdJ and JRV); the Department of Epidemiology and Biostatistics, National Institute for Health Development, Tallinn, Estonia (MR); Øyeavdelingen, Haukeland Sykehus University of Bergen, Bergen, Norway (JS); Clinique Ophthalmologique, Universitaire De Creteil, Paris, France (GS); Clinica Oculistica, Università degli Studi di Verona, Verona, Italy (LT); the Department of Ophthalmology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece (FT); and the Department Salud Publica Universidad Miguel Hernandez, Alicante & CIBER Epidemiología y Salud Pública (CIBERESP), Altea, Spain (JRV)

² EUREYE was supported by the European Commission Vth Framework (QLK6-CT-1999-02094). Additional funding for the cameras was provided by the Macular Disease Society UK. MR was supported by the Estonian Ministry of Education and Science (target funding 01921112s02). Additional funding in Alicante was received from the Fondo de Investigacion Sanitaria. (grants FIS 01/1692E and RCESP C 03/09) and the Oficina de Ciencia y Tecnologia Generalitat Valenciana (grant CTGCA/2002/06). CA was supported by a grant from the Thomas Pocklington Trust.

³ Reprints not available. Address correspondence to AE Fletcher, Department of Epidemiology and Public Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom. E-mail: astrid.fletcher{at}lshtm.ac.uk.

	ABSTRACT

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Background: Fish intake, the major source of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may reduce the risk of age-related macular degeneration (AMD).

Objective: We investigated the association of oily fish and dietary DHA and EPA with neovascular AMD (NV-AMD).

Design: Participants aged 65 y in the cross-sectional population-based EUREYE study underwent fundus photography and were interviewed by using a food-frequency questionnaire. Fundus images were graded by the International Classification System for Age Related Maculopathy. Questionnaire data were converted to nutrient intakes with the use of food-composition tables. Survey logistic regression was used to calculate odds ratios (ORs) and 95% CIs of energy-adjusted quartiles of EPA or DHA with NV-AMD, taking into account potential confounders.

Results: Dietary intake data and fundus images were available for 105 cases with NV-AMD and for 2170 controls without any features of early or late AMD. Eating oily fish at least once per week compared with less than once per week was associated with a halving of the odds of NV-AMD (OR = 0.47; 95% CI: 0.33, 0.68; P = 0.002). Compared with the lowest quartile, there was a significant trend for decreased odds with increasing quartiles of either DHA or EPA. ORs in the highest quartiles were 0.32 (95% CI: 0.12, 0.87; P = 0.03) for DHA and 0.29 (95% CI: 0.11, 0.73; P = 0.02) for EPA.

Conclusions: Eating oily fish at least once per week compared with less than once per week was associated with a halving of the OR for NV-AMD.

	INTRODUCTION

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Age-related macular degeneration (AMD) is the major cause of adult blindness in developed countries and the third cause of global blindness (1, 2). There are 2 main types of AMD: neovascular AMD (NV-AMD) and geographic atrophy (GA). NV-AMD occurs within a background of degenerative change. Despite recent advances in the treatment of NV-AMD (3, 4), this condition remains a major cause of significant visual morbidity. Cigarette smoking is the most consistently identified modifiable lifestyle risk factor (5, 6). More recently, interest has focused on certain of the n–3 long-chain polyunsaturated (LCPUFAs), namely docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which have been postulated to influence the development of AMD. This hypothesis is largely based on animal and laboratory studies and has been extensively reviewed elsewhere (7). The main dietary source of DHA and EPA is oily fish (eg, mackerel, tuna, salmon, sardines, and herring) (8). Epidemiologic studies that have investigated the relation between fish intake and AMD, either in prospective (9-11), hospital based (12, 13), or population-based (14-17) studies, have generally found reduced effect estimates (risk ratios or odds ratios; ORs) with higher fish intake. However, in several studies, the results were not significant (probably because of the small number of cases of AMD) (10, 14, 15, 17), or were found only in those with low linoleic acid (11, 13). A few of these studies also investigated the associations with dietary measures of LCPUFAs (total, single, or combined EPA and DHA) (9, 10, 12, 13, 16), but only 2 studies found a significant association with both EPA and DHA (12, 16). The evidence to date, therefore, while suggestive of a beneficial effect of fish intake, is far from conclusive. Moreover, the largest study, which had a 12-y follow-up, found a significant inverse trend with total fish consumption, but no association with dark-meat fish intake (the richest source of DHA and EPA), no association with EPA, and only a weak trend for DHA, which was attenuated and disappeared in further adjustment (9). None of the studies reported above have been conducted in European populations. One study in Iceland reported a protective effect from increased herring consumption on the incidence of early AMD but had too few cases to investigate any association with late AMD (18).

The aim of our study was to investigate whether DHA and EPA in the diet of Europeans aged 65 y is associated with AMD. The primary outcome was NV-AMD. We could not test for the association with GA because the number of cases was too low. We also investigated an association with vitamin D because oily fish is rich in vitamin D, and vitamin D may protect against AMD because of its antiinflammatory properties (19).

	SUBJECTS AND METHODS

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Study population
The EUREYE study is a cross-sectional population-based study in persons aged 65 y in 7 centers located from north to south Europe (20). Ethics approval was obtained at each center from the relevant ethics committee. Study participants gave informed written consent. Participants were interviewed by fieldworkers, underwent an eye examination including fundus photography, and gave a blood sample. Interviews were carried out before the eye examination.

Fundus images were graded at a single reading center using the International Classification System for Age Related Maculopathy (ARM) (21) with 5 mutually exclusive grades: grade 0 (no early or late AMD), grade 1 [soft distinct drusen (63 µm and <125 µm) only or pigmentary irregularities only], grade 2 [soft indistinct (125 µm) or reticular drusen only or soft distinct drusen with pigmentary irregularities], grade 3 (soft indistinct or reticular drusen with pigmentary irregularities), and grade 4 [either NV-AMD (presence of any of the following: serous or hemorrhagic retinal or retinal pigment epithelial detachment, subretinal neovascular membrane, or periretinal fibrous scar) or GA (well-demarcated area of retinal pigment atrophy with visible choroidal vessels)]. This grading system had been validated in the Rotterdam Eye Study (22). Early AMD was defined as grades 1 to 3 and late AMD as grade 4. Subjects with NV-AMD and GA in the same eye were considered to have NV-AMD, because it was not possible to distinguish whether GA was already present before NV-AMD or resulted from longstanding leakage and hemorrhage because of NV-AMD. (Clinically, the latter is the most frequent cause of the combination of GA and NV-AMD). GA was graded only in the absence of NV-AMD.

Dietary assessment method
During the interview, dietary intake during the previous 12 mo was assessed by using a semiquantitative food-frequency questionnaire (FFQ). We used the UK European Prospective Investigation into Cancer and Nutrition (EPIC) Study FFQ (23), which was derived from the original FFQ devised by Willett (24). For each non-United Kingdom country in the study, we modified the FFQ for food items that were redundant or relevant using the EPIC country-specific questionnaires to identify additional food items or the local variety of a food item. In Estonia, where there was no equivalent EPIC questionnaire, we devised the FFQ after consultation with local nutrition researchers. Validation studies have been carried out on country-specific EPIC questionnaires, eg, for the United Kingdom (23), and we did not carry out any additional validation work on the questionnaires or on the Estonian questionnaire. Information on habitual consumption of foods during the previous year included portion size and was recorded in 9 different frequency categories, from never or less than once a month to 6 times/d. In the fish category, we asked separately about intake of oily fish, white fish, fried fish, and seafood. A medium serving of fish was considered to be 4 oz (113.4 g). Nutrient content was estimated by using the food-composition table of McCance and Widdowson (25) and EPA and DHA contents by using US Department of Agriculture tables (26), because EPA and DHA are not available in the table of McCance and Widdowson. For each study participant, the nutrient intake was calculated by multiplying the intake frequency for each food item by the nutrient content for the portion size. We asked about the use of vitamin supplements and recorded information on type and frequency, including fish oil and n–3 supplements.

Risk factor questionnaires and other measurements
We used structured questionnaires to collect demographic data (age, years of education, and occupation), current and past smoking habits, alcohol consumption, cardiovascular disease history (diabetes, stroke, and heart attack), and use of aspirin and other analgesics. We measured weight and the demi-span (the distance between the sternal notch and the finger roots with the arm outstretched laterally).

In the total sample size of 4753 participants with gradable fundus images, there were 158 cases of late AMD: 109 with NV-AMD and 49 with GA (27); 2262 had no signs of AMD. Of the 109 participants with NV-AMD, dietary food data were missing for 4, leaving 105 cases and 2173 controls without any signs of AMD. Of the 2173 controls, 2 were missing data on EPA and 1 on DHA.

Statistical analyses
Statistical analysis was carried out by using STATA 9 (Statcorp, College Station, TX). The primary outcome was NV-AMD. The primary exposures were energy-adjusted habitual dietary DHA and EPA and oily fish intake. Few people consumed fish at a high frequency (see below); therefore, fish intake was reclassified as less than once per week, once per week, and twice per week or more. For each study center the years of education were classified into low (for the lower third), middle (the middle third), and high (upper third) education groups. The Demiquet index, a measure of weight for body size, was calculated as weight (kg)/demi-span (m²) (20).

Dietary DHA and EPA were logarithmically transformed and adjusted for total energy intake by using the residual model of Willett et al (28). Energy-adjusted DHA and EPA were categorized into quartiles on the basis of the distribution among controls. Potential confounders were entered into models and removed if they did not change the ORs by 5%. Significant confounders for NV-AMD retained in the final models were age, sex, smoking status (current, ex, and never), diabetes, and aspirin use. Energy was forced into all models. Variables excluded were the Demiquet index, education level, history of myocardial infarction or stroke, supplementation with fish oil or n–3 fatty acids, alcohol use, and dietary intakes of vitamin C, vitamin E, retinol, β-carotene, and protein. Additionally, we examined the effect of combined DHA and EPA. We analyzed vitamin D separately and in models with EPA or DHA. We accounted for the study design (7 centers) by using the STATA survey commands in the estimation of SEs and corresponding P values and 95% CIs. We used survey logistic regression to examine the association of NV-AMD with different levels of fish consumption and energy-adjusted DHA and EPA intakes, adjusted for confounders. ORs and 95% CIs are reported.

	RESULTS

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Oily fish consumption
Oily fish was consumed less than once per week by 64% of the study population, once per week by 25%, and twice per week or more by 12% (Table 1). The age and sex distribution was similar in all 3 categories of oily fish intake. Dietary EPA and DHA were strongly associated with fish intake; other factors significantly associated with fish intake were self reported cardiovascular disease (heart attack or stroke) and mean dietary intake of vitamin D, zinc, vitamin E, and protein.

Table 2

Table 3

Table 4

There was a high correlation between mean dietary energy-adjusted vitamin D and servings of oily fish (0.73) and with energy-adjusted DHA and EPA intakes (0.87 and 0.86, respectively). Mean DHA and EPA intakes increased significantly with vitamin D intake, whereas lutein and zeaxanthin decreased significantly with vitamin D intake (data not shown).

Logistic regression analysis for energy-adjusted vitamin D and NV-AMD found a weak inverse trend (P = 0.06) with increasing quartiles of vitamin D intake; the OR for the top compared with the bottom quartile was 0.46 (95% CI: 0.17, 1.27; P = 0.1) when adjusted for age, sex, smoking, diabetes, aspirin, lutein and zeaxanthin, and energy. Including EPA or DHA in the models removed any association with vitamin D (data not shown).

	DISCUSSION

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In this European study of elderly people, we found that intakes of oily fish and higher dietary intakes of EPA or DHA were associated with a lower OR of NV-AMD. Previous studies that examined the association with fish intake and late AMD are shown in Table 5 and between dietary measures of DHA or EPA in Table 6. Some studies found that fish consumption was not associated with AMD (10, 11, 13-15, 17), but most of these studies had a small number of cases (50 or less in 4 studies, of which one was prospective; 10) and 3 were cross sectional (14, 15, 17) (Table 5). Moreover, these studies examined only total fish consumption and did not distinguish between types of fish, although DHA and EPA concentrations are considerably lower in nonoily fish than in oily fish (29). In our study we found a significant association for oily fish but not for white fish, ie, nonoily fish. In the Nurses’ and Health Professionals studies, significant associations were found with total fish consumption and with canned tuna but not with white or dark-meat fish (9). The negative results for dark-meat fish (principally oily fish) were therefore surprising but may reflect a much lower consumption of these types of fish than of canned tuna. The Age-Related Eye Disease Study (AREDS) also found a significant inverse association with higher total fish intake and baked fish and a nonsignificant trend (P = 0.06) for tuna or tuna casserole (12). In 2 studies that found no association with fish intake, a significant association was found in a subgroup of those with low levels of linoleic acid (an n–6 fatty acid) (11, 13). We found a near halving of the OR for fish consumption [a 4-oz (113.4-g) serving] of once per week, compared with less consumption, but we lacked the power to investigate fish consumption twice or more per week. The Nurses’ and Health Professionals Study observed a protective effect against AMD when total fish consumption was >1–4 servings/wk (portion size not given) [relative risk (RR) = 0.77] and a further reduction when total fish consumption was 4 servings/wk (RR = 0.65). In AREDS, the lowest OR was observed in those who consumed more than two 4-oz servings/wk.

Table 6

We adjusted for possible confounders, as was done in previous studies. Because a high consumption of fish may be a marker of general healthy behavior, we looked at lifestyle factors such as alcohol intake, smoking, and education. However, these behaviors were not associated with EPA and DHA in our study. We did not collect data on other lifestyle factors, such as physical activity, but we think that it was unlikely that this information would have altered our results substantially because physical activity is not an established risk factor for AMD and the Nurses’ Health Study, which did adjust for physical activity, reported significant effects for fish intake (9). We had no information on cardiovascular disease factors other than the self report of a history of heart attack or stroke. We did not collect information on statin use, but few elderly Europeans used statins at the time our study started. We also think that it was unlikely that our results would be materially altered by this information because studies such as AREDS, which collected detailed information on cardiovascular disease and medication use, reported results similar to ours.

Fish contain vitamin D and retinol, which may represent alternative or additional potentially protective agents for AMD. It has been postulated that vitamin D per se may reduce the risk of AMD because of its antiinflammatory properties, and several putative mechanisms support an antiinflammatory role for vitamin D (11). However, we found no independent association between dietary vitamin D and NV-AMD when either EPA or DHA were included in the model. Interestingly, one study (19) found an association of serum vitamin D with early AMD, but not for pigmentary abnormalities or advanced AMD. In that study from the United States, the main factor contributing to serum vitamin D was fortified milk; fish consumption was not associated with serum vitamin D.

Approximately one-third of the EUREYE study population had taken one or more supplements during the previous year, a figure similar to that found in a national dietary survey of Britons aged 65 y (30). Participants in the highest intake of oily fish in our study were more likely to be users of n–3 supplements. Only 8% of the study participants in EUREYE used these supplements, much less than the 63% of the British study population who took cod liver oil–based supplements (30).

Our study had several strengths. We assessed diet in the previous year, which avoided issues of changes in diet due to seasonality or to ill health. We measured a wide range of potentially confounding variables; the number of NV-AMD cases was large, and case identification was based on a rigorous analysis of digital fundus images. People with NV-AMD and controls were drawn from the same population to avoid possible biases observed in other studies in which controls were recruited from those receiving medical care. Our study was cross-sectional; therefore, caution is required when determining whether a causal association exists between EPA and DHA intakes and NV-AMD. We think that it was unlikely that people with AMD would have changed their diets because of knowledge of a possible benefit of fish consumption on AMD. In 2000, when our study started, there was only one publication showing a protective role of fish intake against AMD (15) (Table 5).

Various national, international, and professional organizations have made recommendations for fish or EPA and DHA consumption. The range of intake suggested for n–3 fatty acids is 0.2–1% of energy intake, and for EPA and DHA combined the most recent recommendations range from 400 to 1000 mg/d (29). The n–3 fatty acid content of fish, specifically DHA and EPA, varies by species and by how the fish are raised (ie, wild or farm-raised). EPA and DHA intakes range from as low as 0.134 g/85 g serving (3-oz serving equivalent) for Atlantic cod to as much as 1.83 g/85 g serving for farm salmon (29). Therefore, to meet the current recommendations of 500 mg EPA + DHA/d it has been estimated that this could be met either by consuming 2 servings (3 oz, or 85.05 g) of salmon per week or 26 servings of cod (29). n–3 Fatty acid supplements and n–3–enriched foods are therefore becoming increasingly important dietary options. Whether these intakes could be achieved by oral supplementation with DHA and EPA is currently being evaluated in a large randomized trial—AREDS2 (Internet: http://www.areds2.org/).

	ACKNOWLEDGMENTS

 
The authors’ responsibilities were as follows—AEF: had full access to all of the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis; CA(study coordinator): responsible for fieldworker training and micronutrient conversion; UC, JS, MR, GS, LT, FT, and JV: responsible for the acquisition of data in each of the local study centers; GB: responsible for the estimation of light exposure; IY: responsible for the antioxidant analyses; and PTVMdJ and JRV: responsible for the fundus grading. All authors commented on the drafts, were responsible for the decision to submit for publication, and contributed to the study design. The sponsors had no role in the data collection, data analysis, data interpretation, writing of the paper, or decision to submit the paper for publication.

GS is an investigator in a randomized trial using n–3 supplements sponsored by Bausch and Lomb. None of the authors had a conflict of interest.

	REFERENCES

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1. Congdon N, O'Colmain B, Klaver CC, et al. Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol 2004;122:477-85.[Abstract/Free Full Text]
2. Resnikoff S, Pascolini D, Etya'ale D, et al. Global data on visual impairment in the year 2002. Bull World Health Organ 2004;82:844-51.[Medline]
3. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 2006;355:1432-44.[Abstract/Free Full Text]
4. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006;355:1419-31.[Abstract/Free Full Text]
5. Chakravarthy U, Augood C, Bentham GC, et al. Cigarette smoking and age-related macular degeneration in the EUREYE Study. Ophthalmology 2007;114:1157-63.[CrossRef][Medline]
6. Thornton J, Edwards R, Mitchell P, Harrison RA, Buchan I, Kelly SP. Smoking and age-related macular degeneration: a review of association. Eye 2005;19:935-44.[CrossRef][Medline]
7. SanGiovanni JP, Chew EY. The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. Prog Retin Eye Res 2005;24:87-138.[CrossRef][Medline]
8. Nettleton JA. Omega-3 fatty acids: comparison of plant and seafood sources in human nutrition. J Am Diet Assoc 1991;91:331-7.[Medline]
9. Cho E, Hung S, Willett WC, et al. Prospective study of dietary fat and the risk of age-related macular degeneration. Am J Clin Nutr 2001;73:209-18.[Abstract/Free Full Text]
10. Chua B, Flood V, Rochtchina E, Wang JJ, Smith W, Mitchell P. Dietary fatty acids and the 5-year incidence of age-related maculopathy. Arch Ophthalmol 2006;124:981-6.[Abstract/Free Full Text]
11. Seddon JM, Cote J, Rosner B. Progression of age-related macular degeneration: association with dietary fat, transunsaturated fat, nuts, and fish intake. Arch Ophthalmol 2003;121:1728-37.[Abstract/Free Full Text]
12. SanGiovanni JP, Chew EY, Clemons TE, et al. The relationship of dietary lipid intake and age-related macular degeneration in a case-control study: AREDS report no. 20. Arch Ophthalmol 2007;125:671-9.[Abstract/Free Full Text]
13. Seddon JM, Rosner B, Sperduto RD, et al. Dietary fat and risk for advanced age-related macular degeneration. Arch Ophthalmol 2001;119:1191-9.[Abstract/Free Full Text]
14. Heuberger RA, Mares-Perlman JA, Klein R, Klein BE, Millen AE, Palta M. Relationship of dietary fat to age-related maculopathy in the Third National Health and Nutrition Examination Survey. Arch Ophthalmol 2001;119:1833-8.[Abstract/Free Full Text]
15. Mares-Perlman JA, Brady WE, Klein R, VandenLangenberg GM, Klein BE, Palta M. Dietary fat and age-related maculopathy. Arch Ophthalmol 1995;113:743-8.[Abstract/Free Full Text]
16. Seddon JM, George S, Rosner B. Cigarette smoking, fish consumption, omega-3 fatty acid intake, and associations with age-related macular degeneration: the US Twin Study of Age-Related Macular Degeneration. Arch Ophthalmol 2006;124:995-1001.[Abstract/Free Full Text]
17. Smith W, Mitchell P, Leeder SR. Dietary fat and fish intake and age-related maculopathy. Arch Ophthalmol 2000;118:401-4.[Abstract/Free Full Text]
18. Arnarsson A, Sverrisson T, Stefansson E, et al. Risk factors for five-year incident age-related macular degeneration: the Reykjavik Eye Study. Am J Ophthalmol 2006;142:419-28.[CrossRef][Medline]
19. Parekh N, Chappell RJ, Millen AE, Albert DM, Mares JA. Association between vitamin D and age-related macular degeneration in the Third National Health and Nutrition Examination Survey, 1988 through 1994. Arch Ophthalmol 2007;125:661-9.[Abstract/Free Full Text]
20. Augood C, Fletcher A, Bentham G, et al. Methods for a population-based study of the prevalence of and risk factors for age-related maculopathy and macular degeneration in elderly European populations: the EUREYE study. Ophthalmic Epidemiol 2004;11:117-29.[CrossRef][Medline]
21. The International ARM Epidemiological Study Group. An international classification and grading system for age-related maculopathy and age-related macular degeneration. Surv Ophthalmol 1995;39:367-74.[Medline]
22. Van Leeuwen R, Klaver CC, Vingerling JR, Hofman A, De Jong PTVM. The risk and natural course of age-related maculopathy: follow-up at 6 1/2 years in the Rotterdam study. Arch Ophthalmol 2003;121:519-26.[Abstract/Free Full Text]
23. Bingham SA, Welch AA, McTaggart A, et al. Nutritional methods in the European Prospective Investigation of Cancer in Norfolk. Public Health Nutr 2001;4:847-58.[Medline]
24. Willett W. Nutritional epidemiology. Oxford, United Kingdom: Oxford University Press, 1990;
25. Holland B, Welch A, Unwin I, Buss D, Paul A, Southgate D. McCance and Widdowson's composition of foods. London, United Kingdom: Her Majesty's Stationery Office, 1991;
26. US Department of Agriculture, Agricultural Research Service. USDA National Nutrient Database for Standard Reference, release 18. Washington, DC: USDA, 2005.
27. Augood CA, Vingerling JR, de Jong PT, et al. Prevalence of age-related maculopathy in older Europeans: the European Eye Study (EUREYE). Arch Ophthalmol 2006;124:529-35.[Abstract/Free Full Text]
28. Willett WC, Howe GR, Kushi LH. Adjustment for total energy intake in epidemiologic studies. Am J Clin Nutr 1997;65(suppl):1220S-8.[Medline]
29. Gebauer SK, Psota TL, Harris WS, Kris-Etherton PM. n–3 Fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits. Am J Clin Nutr 2006;83(suppl):1526S-35S.[Medline]
30. Finch S, Doyle W, Lowe C, et al. National Diet and Nutrition Survey—people aged 65 years and over. London, United Kingdom: The Stationery Office, 1998;

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