Dietary fat intake and early age-related lens opacities

¹ From the Nutritional Epidemiology Program (ML, GR, and PFJ) and the Laboratory for Nutrition and Vision Research (AT), Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA; the Departments of Epidemiology (SEH and WCW) and Nutrition (WCW), Harvard School of Public Health, Boston, MA; and the Channing Laboratory, Department of Medicine (SEH and WCW) and the Center for Ophthalmic Research, Department of Ophthalmology (LTC), Harvard Medical School and Brigham and Women’s Hospital, Boston, MA.

² Supported by the US Department of Agriculture under agreement No. 58-1950-4-401 and by grants no. 98-01023 and 92-37200-7704 from the National Research Initiative Competitive Grant Program; the Brigham Surgical Group; research grants EY-09611, EY-13250, EY-014183, and CA-879694 from the National Institutes of Health; grants from the Vitamins and Fine Chemicals Division, Roche; Kemin Foods; and the Florida Department of Citrus; and by a Johnson & Johnson Focused Giving Award (to AT).

³ Address reprint requests to PF Jacques, Nutritional Epidemiology Program, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111. E-mail: paul.jacques{at}tufts.edu.

ABSTRACT  
Background: Dietary fat may affect lens cell membrane composition and function, which are related to age-related cataract.

Objective: The objective of the study was to examine the association between long-term dietary fat intake and the prevalence of age-related nuclear, cortical, and posterior subcapsular lens opacities.

Design: Women (n = 440) aged 53–73 y from the Boston area without previously diagnosed cancer, diabetes, or cataract were selected from the Nurses’ Health Study cohort. Intakes of total fat and selected fatty acids were calculated as the average of intake data from 5 food-frequency questionnaires collected between 1980 and the study eye examination (1993–1995). Nuclear opacity was defined as grade 2.5, cortical opacity as grade 1.0, and posterior subcapsular opacity as grade 0.5 according to the Lens Opacities Classification System III.

Results: There were significant positive associations between linoleic and linolenic acid intakes and the prevalence of nuclear opacity. The odds ratios for nuclear opacity in women with intakes in the highest quartile and women with intakes in the lowest quartile were 2.2 (95% CI: 1.1, 4.6; P for trend = 0.02) for linoleic acid and 2.2 (95% CI: 1.1, 4.5; P for trend = 0.05) for linolenic acid. There were no significant associations between intakes of any type of fat and either cortical or posterior subscapular opacity.

Conclusions: High intake of the 18-carbon polyunsaturated fatty acids linoleic acid and linolenic acid may increase the risk of age-related nuclear opacity. Further study is needed to clarify the relation between dietary fat and cataract risk.

Key Words: Lens opacity • age-related cataract • diet • fatty acids • women • cross-sectional studies • polyunsaturated fatty acid • linoleic acid • linolenic acid

INTRODUCTION  
Age-related opacification of the eye lens results in increased light scattering and decreased transparency of the crystalline lens. Age-related cataract, the clinical manifestation of the opacification process, is a very common disorder that has substantial health and economic effects. Age-related cataract is the leading cause of blindness in the world today (1, 2). In the Beaver Dam Eye Study, the 10-y incidence proportions for persons aged 43–86 y were 0.24 for nuclear cataract, 0.22 for cortical cataract, and 0.08 for posterior subcapsular (PSC) cataract (3). The visual impairment associated with cataract can be corrected surgically but at a sizeable societal cost. For example, cataract extraction currently is the most frequently performed surgical procedure among Medicare beneficiaries in the United States, and the annual cost is approximately $3.5 billion (4, 5). Finding ways to delay age-related cataract formation would enhance the quality of life for older people and substantially reduce the economic burden associated with its treatment.

Cataractogenesis is associated with a perturbation of lens membrane composition, structure, and function (6–9), and a high concentration of polyunsaturated fatty acids (PUFAs) in the diet has been reported to delay the onset of mature cataracts in animal studies (10, 11). However, there is limited epidemiologic research on dietary fat intake and risk of cataract. Therefore, we examined the association between specific types of fat in the diet measured over a period of 10 to 15 y and the prevalence of nuclear, cortical, and PSC cataract, the 3 major types of lens opacities.

SUBJECTS AND METHODS  
Study population
In 1976, 121 700 US female registered nurses aged 30–55 y residing in 11 states completed questionnaires on known and suspected risk factors for cancer and heart disease. These women formed the Nurses’ Health Study (NHS) cohort (12). Every 2 y since 1976, follow-up questionnaires were sent to these women to obtain updated information on lifestyle factors, including diet and disease status.

We identified 1717 participants of the NHS, aged 54–73 y, who resided in the Boston area, were free of diagnosed cancer other than nonmelanoma skin cancer, had complete dietary data, and had both lenses intact. We received positive responses from 845 (49%) of the women. Between April 1993 and August 1995, 603 of these volunteers were examined as part of the Nutrition and Vision Project (NVP).

Written informed consent was obtained from all study participants. All procedures were approved by the Human Investigations Review Committee at the New England Medical Center and the Human Research Committee at the Brigham and Women’s Hospital.

Details regarding recruitment and participation were described previously (13). Briefly, participants and nonparticipants were similar in many relevant characteristics, including age, alcohol consumption, body mass index (BMI; in kg/m²), reported summer sunlight exposure, prevalence of hypertension, and use of vitamin C and multivitamin supplements between 1980 and 1994. In addition, the percentage of women seeing an eye doctor (the term the NHS questionnaire used) in 1990 was 83% for nonparticipants and 85% for the participants. Participants reported significantly fewer pack-years of smoking than did nonparticipants (17 and 21 pack-years, respectively), and participants also were slightly but significantly more likely than were nonparticipants to have used vitamin E supplements between 1980 and 1994 (35% and 29%, respectively).

Assessment of nutrient intake
In 1980, a 61-item semiquantitative food-frequency questionnaire (FFQ) was sent to the NHS participants for assessment of dietary intakes of specific fats and other nutrients (12). An expanded FFQ with 130 items was sent to these same women in 1984, 1986, and 1990 to assess usual food intakes in the previous year. A common unit or portion size for each food was specified, and participants were asked how often, on average, they had consumed that amount of the food or beverage during the previous year. There were 9 possible responses for each food item, ranging from "almost never" to "6 times/d." The average daily intake of fat and other nutrients was calculated by multiplying the frequency of consumption of each item by its nutrient content per serving and totaling the nutrient intake for all food items on the basis of US Department of Agriculture food-composition data. More than 90% of the total absolute intake of 70 nutrients was accounted for by this instrument (14). The reproducibility and validity of the FFQ were assessed previously by using long-term diet records (14, 15) and biochemical markers of nutrient status (16–18). In addition to the FFQ collected routinely as part of the NHS, we administered, as part of the NVP, an FFQ that included questions on vitamin supplement use (1993–1995).

We calculated the intake of all nutrients, except n–3 fatty acid, as the average of data from 5 FFQs collected between 1980 and 1993–1995. The intake of n–3 fatty acid was calculated as the average of data from the 4 most recent FFQs because the shorter FFQ collected in 1980 did not include the detailed questions needed for this calculation. We also calculated the percentage of energy contributed by each type of fat.

Assessment of lens status
All NVP participants underwent a detailed eye examination according to standardized techniques. The examination included an ocular history and medical history, the Bailey Lovie test of visual acuity and manifest refraction, external ocular examination, applanation tonometry, contrast sensitivity function and glare testing, and a slit-lamp examination of the anterior segment to determine the risk of angle-closure glaucoma. Intraocular pressure was measured to ascertain whether it was safe to perform a complete eye examination, which would include dilation. Before a slit-lamp examination of the lens, the pupils were dilated to a minimum of 6 mm with the use of phenylephrine and tropicamide. The posterior segment was examined by direct and indirect ophthalmoscopy. The examiner had no knowledge of the nutrient status of any subject.

Color film images were taken with the use of a photographic slit-lamp (Carl Zeiss, Oberkochen, West Germany) and film (Ektachrome 200; Kodak, Rochester, NY) to assess the degree of nuclear color and opalescence. Two digital black-and-white images were taken with a Nidek EAS 1000 retroillumination camera (Nidek, Hiroishi, Japan); one image was taken with an anterior image focus (ie, focused on the pupillary plane) to assess the degree of cortical opacification, and the other was taken with a posterior focus (ie, focused on the posterior lens capsule) to assess the degree of PSC opacification. The Lens Opacities Classification System III (LOCS III) was used to measure the degree of opalescence on a scale of 0.1 to 6.9 for nuclear opacity and on a scale of 0.1 to 5.9 for cortical and PSC opacity (19). All photographs were graded in several sessions within 2 mo after all photographs and images were obtained. Because of the difficulty in assessing certain features of the PSC region of the lens by using images, grading of PSC opacity was also done by the examiner at the slit-lamp by using LOCS III, and this latter measurement was used in our analyses. We considered an eye to have nuclear, cortical, or PSC opacity if the corresponding LOCS III grade was 2.5, 1.0, or 0.5, respectively. These thresholds represented early stages of opacification and were not associated with symptoms such as reduced vision.

Nondietary risk factors
Data on known or suspected nondietary determinants of cataract risk were obtained from the biennial NHS questionnaires administered 1980–1990. In our analyses, we considered a confirmed history of cancer, diabetes, and hypertension as reported on the NHS questionnaires from 1990 or earlier, cigarette pack-years smoked through 1990, summer sunlight exposure (8 h/wk) as reported on the 1980 questionnaire, alcohol intake based on the average of data from 5 FFQs collected between 1980 and 1993–5, physical activity [metabolic equivalents (METs)/wk] through 1990, and BMI (2), which was calculated as reported on the 1980 questionnaire.

Statistical analysis
The primary independent variables used in the analysis were the average percentage of energy contributed by each type of fat and the average intakes of the major fat-contributing foods. These variables were classified into quartile categories, and women with values in the lowest quartile were considered the reference category.

The odds ratios (ORs) relating the prevalence of lens opacities graded with LOCS III to the fat intake were calculated by using logistic regression with the GENMOD procedure on SAS software (version 8.2; SAS Institute Inc, Cary, NC). This procedure allowed the individual eyes to be the unit of observation. The generalized estimating equation approach to the estimation of logistic regression models adjusts the SEs of the model variables for the correlated data resulting from 2 outcome measurements in the same subject. ORs for the prevalence of lens opacities in fat intake quartile categories were calculated as the antilogarithm of the logistic regression coefficient for each of these categories. To assess trends across quartile categories, we assigned the median intake in each quartile to everyone with intakes in that quartile and then included this quartile median variable as a continuous factor in the logistic regression models. The P for trend was the resulting P value for the associated logistic regression coefficient. All ORs were adjusted for age at examination and for other potential confounders, including total energy intake, BMI, alcohol intake, physical activity level (METs/wk), hypertension, cigarette smoking, summer sunlight exposure, and duration of vitamin C and vitamin E supplement use.

Comparison of potentially confounding variables between study participants who did and did not have a lens opacity was performed by using the chi-square test for dichotomous variables. We used Wilcoxon’s rank-sum nonparametric test for continuous variables because the distributions of most of those variables were highly skewed.

RESULTS  
Participant characteristics
Of the 603 women examined as part of the NVP, we excluded 20 women who had implausible caloric intakes (<600 or > 3500 kcal/d) on any of the 4 NHS FFQs; 1 woman with a confirmed diagnosis of cancer; 31 women with a confirmed diagnosis of diabetes in or before 1990; 13 women with blood glucose concentrations >126 mg/dL; 20 women who had incomplete, questionable, or missing lens data; and 13 women whose information on the covariates that were used in these analyses was missing. To avoid the possibility that prior knowledge of lens opacification might influence nutrient intake, we also excluded 65 women who reported a history of cataracts at their study eye examination. The 440 remaining women were included in the analyses. Among these 440 women, 196 (44.5%) had clear lenses, 244 (55.5%) had 1 type of cataract, 145 (33.0%) had nuclear opacity (LOCS III grade 2.5), 153 (34.8%) had cortical opacity (LOCS III grade 1.0), and 49 (11.1%) had PSC opacity (LOCS III grade 0.5). The different types of cataract frequently occurred together. Forty-eight women (10.9%) had both nuclear and cortical opacities, 11 (2.5%) had both nuclear and PSC opacities, 10 (2.3%) had both cortical and PSC opacities, and 17 (3.9%) had all 3 forms of opacities.

As shown in Table 1, women with either nuclear or PSC opacity had a significantly lower energy intake than did those without lens opacities. Women with nuclear, cortical, or PSC opacities were significantly older than were those without lens opacities. Smoking history, BMI, summertime sunlight exposure, prevalence of hypertension, physical activity, duration of vitamin C and vitamin E supplement use, and plasma glucose concentrations were indistinguishable among the 4 groups.

View this table:
TABLE 1. Characteristics of participants by presence of nuclear, cortical, or (PSC) opacity¹

 
Dietary fat and major fat-containing foods and the prevalence of opacities
The association between the prevalence of nuclear lens opacity and the usual intake of dietary fats measured over a 10–15-y period is shown in Table 2, which also shows the median and range for each quartile category of dietary fat intake. There was a significant positive trend between PUFA intake and the prevalence of nuclear opacity (P = 0.02). The OR in the highest intake quartile category compared with the lowest intake quartile category was 2.3 (95% CI: 1.1, 4.8). Other fats were not significantly associated with nuclear opacity. There were no significant associations between any of the fats and either cortical or PSC opacity (data not shown).

View this table:
TABLE 2. Multivariate adjusted odds ratio (OR) of lens opacities according to quartile category of fat intake¹

 
The relations between the prevalence of nuclear lens opacity and usual intake of different PUFAs fatty acids are shown in Table 3. There was a significant positive trend between linoleic acid intake and the prevalence of nuclear opacity (P for trend = 0.02). The OR for the highest intake quartile category compared with the lowest quartile category was 2.2 (95% CI: 1.1, 4.6). There was also a significant positive trend between linolenic acid intake and the prevalence of nuclear opacity (P for trend = 0.05). The OR for the highest intake quartile category compared with the lowest quartile category was 2.2 (95% CI: 1.2, 4.5). There were no significant associations between any of the specific polyunsaturated fats and either cortical or PSC opacity (data not shown).

View this table:
TABLE 3. Multivariate adjusted odds ratio (OR) of lens opacities according to quartile category of polyunsaturated fatty acid intake¹

 
The associations between major fat-containing foods and the risk of nuclear lens opacity are presented in Table 4, as are the median and range for each quartile category for major fat-containing foods. The only significant finding for major fat-containing foods was a positive association between the intake of mayonnaise or another creamy salad dressing and nuclear opacity (P for trend = 0.03). The OR for the highest intake quartile category compared with the lowest intake quartile category was 2.6 (95% CI: 1.3, 5.1).

View this table:
TABLE 4. Multivariate adjusted odds ratio (OR) of lens opacities according to quartile category of major fat-containing food intake¹

 

DISCUSSION  
To our knowledge, no previous longitudinal study and only 3 cross-sectional studies have examined the relation between dietary fat intake and the risk of cataract. In one case-control study, Tavani et al (20) observed that high total dietary fat was related to higher risk of cataract extraction (OR: 1.8; 95% CI: 1.2, 2.8). This association appeared to be largely a consequence of the consumption of oils, particularly those other than olive oil (OR: 1.6; 95% CI: 1.1, 2.2). Total fat intake was unrelated to the prevalence of nuclear opacity in the Beaver Dam Study cohort (21), and, in the cross-sectional phase of the Blue Mountains Eye Study, the intake of PUFA was found to be associated with a lower prevalence of cortical cataract (OR: 0.7; 95% CI: 0.5, 0.9) (22). In our cross-sectional study of fat intake and lens opacities, we observed that women with higher overall polyunsaturated fat intakes and higher intakes of the 18-carbon PUFAs linoleic and linolenic acid had an increased risk of nuclear opacity. There is little consistency among the previous studies of fat intake and cataract, and our results were not consistent with the earlier findings from either the Beaver Dam or Blue Mountains Eye studies. Although we did not observe any association with total fat intake, our findings are consistent with the observation of Tavani et al relating edible oil consumption to cataract risk.

Linoleic acid (18:2n–6), an n–6 PUFA, is abundant in the Western diet (23, 24). It is the major fatty acid in safflower, sunflower, corn, soybean, and cottonseed oils, and it accounts for >50% of the total fatty acid content in these oils (25). Although linoleic acid is an essential fatty acid, the consumption of modest amounts, equivalent to 1% of total calories, is adequate to protect against essential fatty acid deficiency (26). In our study population, the intake of linoleic acid is 5% of total energy intake/d and > 85% of total PUFA intake/d. Thus, the positive association between nuclear opacity and PUFA intake may largely reflect the relation between nuclear opacity and linoleic acid intake.

Linoleic acid constitutes 0.2–0.5% of total fatty acids in the lens membrane (27, 28). Although there are no data on the relation of dietary linoleic acid with the lipid composition of the lens membrane, it is reasonable to assume that high intakes of linoleic acid may increase its concentration in lens membrane. Because linoleic acid is prone to lipid peroxidation (29), higher concentrations in the lens membrane may cause the same pathologic changes in the lens as are seen in other tissues (30). The oxidative damage to lens constituents is thought to be causally related to cataractogenesis (31, 32). A high intake of linoleic acid is associated with in vitro tumor promotion (33–35) and tumor incidence (36, 37) in experimental studies but with reduced incidence of coronary heart disease (38) and no evidence of increased cancer incidence (39) in humans.

Linolenic acid (18:3n–3) is a plant-derived n–3 PUFA found in soybean, canola, and flaxseed oils, in walnuts, and in green leafy vegetables. After its ingestion, a small and undetermined portion of linolenic acid (<10% and possibly < 1%) is converted into eicosapentaenoic acid and docosahexaenoic acid (40, 41). In 2 previous studies, the content of linolenic acid in the lens was basically undetectable (27, 28). Although there are no previous reports of an association between lens opacities and linolenic acid, linolenic acid was reported to be positively related to age-related macular degeneration (42). Because the linoleic and linolenic acids in the current study came from similar food sources, it is not possible to ascertain whether 1 or both of these 2 PUFAs contributed to the increased prevalence of nuclear opacification. In our study, linoleic and linolenic acid intakes were strongly correlated (correlation coefficient = 0.55; P < 0.001). Although it is possible that each of these 2 PUFAs contributed to the increased prevalence of nuclear opacification, it is possible that 1 of the 2 was largely responsible for the relation and the other was associated with the prevalence of nuclear lens opacification through confounding. When the 2 fatty acids were included simultaneously in the same model, neither was significantly associated with nuclear opacification.

Our failure to observe significant relations between linoleic or linolenic acid and lens opacities in the cortical and PSC regions may be due to the different amounts of antioxidants available to prevent lipid peroxidation in these locations. Concentrations of lutein or zeaxanthin and tocopherol in epithelia and cortical tissue are, respectively, 3- and 1.8-fold those in the nuclear part of the lens tissue. Specifically, the epithelial or cortical lens layer, composing approximately half of the tissue, contains 74% of the lutein or zeaxanthin (44 ng/g wet wt) and 65% of the -tocopherol (2227 ng/g wet wt) (43).

Whereas we controlled for the most likely known or suspected determinants of cataract risk, it is also possible that we have not adequately controlled for some unmeasured confounders. Another potential limitation is the retrospective nature of the study. However, in our study, dietary data were collected before the assessment of lens status, and we excluded women who reported a previous cataract diagnosis. Furthermore, most of the women had only early opacities and thus should not have experienced any visual symptoms. Any misclassification of fat intake should have been nondifferential and should have biased our association toward the null. Moreover, misclassification of exposure was reduced by averaging intakes over many years. Finally, given the number of associations that we examined, we must also consider the possibility that those associations were the result of chance and thus require confirmation.

In summary, the data from our study suggest that a high intake of linoleic and linolenic acids may contribute to an increased risk of nuclear opacity. We observed no significant association between fat intake and either cortical or PSC opacity. More studies are needed to help clarify the relation between dietary fat intake and cataract.

ACKNOWLEDGMENTS  
ML, AT, LTC, SEH, WCW, and PFJ contributed to study design; ML and GR contributed to data collection; ML, GR, and PFJ contributed to data analysis; ML drafted the manuscript; and AT, LTC, SEH, WCW, and PFJ contributed to manuscript editing. None of the authors had a financial or personal interest in the organization sponsoring this research.

REFERENCES  

1. Kupfer C. Bowman lecture. The conquest of cataract: a global challenge. Trans Ophthalmol Soc U K 1985;104:1–10.
2. Steinberg EP, Javitt JC, Sharkey PD, et al. The content and cost of cataract surgery. Arch Ophthalmol 1993;111:1041–9.
3. Klein BE, Klein R, Lee KE. Incidence of age-related cataract over a 10-year interval: the Beaver Dam Eye Study. Ophthalmology 2002;109:2052–7.
4. Javitt JC. Who does cataract surgery in the United States? Arch Ophthalmol 1993;111:1329.
5. Prevent Blindness America and the National Eye Institute. Vision problems in the U.S. Internet: http://www.preventblindness.org/vpus/VPUS_report_web.pdf (accessed 1 February 2004).
6. Simonelli F, Libondi T, Romano N, Nunziata G, D’Aloia A, Rinaldi E. Fatty acid composition of membrane phospholipids of cataractous human lenses. Ophthalmic Res 1996;28:101–4.
7. Borchman D, Cenedella RJ, Lamba OP. Role of cholesterol in the structural order of lens membrane lipids. Exp Eye Res 1996;62:191–7.
8. Kistler J, Bullivant S. Structural and molecular biology of the eye lens membranes. Crit Rev Biochem Molec Biol 1989;24:151–81.
9. Sato H, Borchman D, Ozaki Y, et al. Lipid-protein interactions in human and bovine lens membranes by Fourier transform Raman and infrared spectroscopies. Exp Eye Res 1996;62:47–53.
10. Hutton JC, Schofield PH, Williams JF, Regtop HL, Hollows FC. The effect of an unsaturated-fat diet on cataract formation in streptozotocin-induced diabetic rats. Br J Nutr 1976;36:161–77.
11. Hatcher H, Andrews JS. Changes in lens fatty acid composition during galactose cataract formation. Invest Ophthalmol 1970;9:801–6.
12. Willett WC, Stampfer MJ, Colditz GA, Rosner BA, Hennekens CH, Speizer FE. Dietary fat and the risk of breast cancer. N Engl J Med 1987;316:22–8.
13. Jacques PF, Chylack LT Jr, Hankinson SE, et al. Long-term nutrient intake and early age-related nuclear lens opacities. Arch Ophthalmol 2001;119:1009–19.
14. Willett WC, Sampson L, Stampfer MJ, et al. Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol 1985;122:51–65.
15. Rimm EB, Giovannucci EL, Stampfer MJ, Colditz GA, Litin LB, Willett WC. Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals. Am J Epidemiol 1992;135:1114–26; discussion 1127–36.
16. Ascherio A, Stampfer MJ, Colditz GA, Rimm EB, Litin L, Willett WC. Correlations of vitamin A and E intakes with the plasma concentrations of carotenoids and tocopherols among American men and women. J Nutr 1992;122:1792–801.
17. Willett WC, Stampfer MJ, Underwood BA, Speizer FE, Rosner B, Hennekens CH. Validation of a dietary questionnaire with plasma carotenoid and alpha-tocopherol levels. Am J Clin Nutr 1983;38:631–9.
18. Jacques PF, Sulsky SI, Sadowski JA, Phillips JC, Rush D, Willett WC. Comparison of micronutrient intake measured by a dietary questionnaire and biochemical indicators of micronutrient status. Am J Clin Nutr 1993;57:182–9.
19. Chylack LT Jr, Wolfe JK, Singer DM, et al. The Lens Opacities Classification System III. The Longitudinal Study of Cataract Study Group. Arch Ophthalmol 1993;111:831–6.
20. Tavani A, Negri E, La Vecchia C. Food and nutrient intake and risk of cataract. Ann Epidemiol 1996;6:41–6.
21. Mares-Perlman JA, Brady WE, Klein BE, et al. Diet and nuclear lens opacities. Am J Epidemiol 1995;141:322–34.
22. Cumming RG, Mitchell P, Smith W. Diet and cataract: the Blue Mountains Eye Study. Ophthalmology 2000;107:450–6.
23. Baghurst KI, Crawford DA, Worsley A, Record SJ. The Victorian Nutrition Survey—intakes and sources of dietary fats and cholesterol in the Victorian population. Med J Aust 1988;149:12–5, 18–20.
24. Mann NJ, Johnson LG, Warrick GE, Sinclair AJ. The arachidonic acid content of the Australian diet is lower than previously estimated. J Nutr 1995;125:2528–35.
25. Simopoulos A, Robinson J. The omega plan. New York: HarperCollins, 1998.
26. Holman RT. Control of polyunsaturated acids in tissue lipids. J Am Coll Nutr 1986;5:183–211.
27. Cotlier E, Obara Y, Toftness B. Cholesterol and phospholipids in protein fractions of human lens and senile cataract. Biochim Biophys Acta 1978;530:267–78.
28. Rosenfeld L, Spector A. Changes in lipid distribution in the human lens with the development of cataract. Exp Eye Res 1981;33:641–50.
29. Esterbauer H, Striegl G, Puhl H, Rotheneder M. Continuous monitoring of in vitro oxidation of human low density lipoprotein. Free Radic Res Commun 1989;6:67–75.
30. Spiteller G. Lipid peroxidation in aging and age-dependent diseases. Exp Gerontol 2001;36:1425–57.
31. Taylor A. Nutritional and environmental influences on risk for cataract. In: Taylor A, ed. Nutritional and environmental influences on the eye. Boca Raton, FL: CRC Press, 1999:53–93.
32. Taylor A, Jacques PF, Dorey CK. Oxidation and aging: impact on vision. Toxicol Ind Health 1993;9:349–71.
33. Gonzalez MJ, Schemmel RA, Gray JI, Dugan L Jr, Sheffield LG, Welsch CW. Effect of dietary fat on growth of MCF-7 and MDA-MB231 human breast carcinomas in athymic nude mice: relationship between carcinoma growth and lipid peroxidation product levels. Carcinogenesis 1991;12:1231–5.
34. Rose DP, Hatala MA, Connolly JM, Rayburn J. Effect of diets containing different levels of linoleic acid on human breast cancer growth and lung metastasis in nude mice. Cancer Res 1993;53:4686–90.
35. Wang JJ, Mitchell P, Simpson JM, Cumming RG, Smith W. Visual impairment, age-related cataract, and mortality. Arch Ophthalmol 2001;119:1186–90.
36. Roebuck BD, Longnecker DS, Baumgartner KJ, Thron CD. Carcinogen-induced lesions in the rat pancreas: effects of varying levels of essential fatty acid. Cancer Res 1985;45:5252–6.
37. Ip C, Carter CA, Ip MM. Requirement of essential fatty acid for mammary tumorigenesis in the rat. Cancer Res 1985;45:1997–2001.
38. Hu FB, Willett WC. Optimal diets for prevention of coronary heart disease. JAMA 2002;288:2569–78.
39. Hunter DJ, Spiegelman D, Adami HO, et al. Cohort studies of fat intake and the risk of breast cancer—a pooled analysis. N Engl J Med 1996;334:356–61.
40. Salem N Jr, Wegher B, Mena P, Uauy R. Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants. Proc Natl Acad Sci U S A 1996;93:49–54.
41. Marangoni F, Angeli MT, Colli S, et al. Changes of n–3 and n–6 fatty acids in plasma and circulating cells of normal subjects, after prolonged administration of 20:5 (EPA) and 22:6 (DHA) ethyl esters and prolonged washout. Biochim Biophys Acta 1993;1210:55–62.
42. 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.
43. Yeum KJ, Shang FM, Schalch WM, Russell RM, Taylor A. Fat-soluble nutrient concentrations in different layers of human cataractous lens. Curr Eye Res 1999;19:502–5.