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Nutritional Epidemiology Program, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University
Laboratory for Nutrition and Vision Research, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University
Department of Ophthalmology, Center for Ophthalmic Research, Harvard Medical School, Brigham and Women's Hospital
Channing Laboratory, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Department of Epidemiology, Harvard School of Public Health
Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
Address reprint requests to: Paul Jacques, Nutritional Epidemiology Program, USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111. E-mail: paul.jacques{at}tufts.edu
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSACKNOWLEDGMENTSREFERENCES |
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Methods: Women aged 52 to 73 years without previously diagnosed cancer, diabetes and cataracts from the Boston, Massachusetts area were selected from the Nurses’ Health Study cohort. Four hundred forty women participated in a baseline (1993–95) and a follow-up (1998–2000) eye examination. Intakes of total fat and selected fatty acids were calculated as the average intake from five food frequency questionnaires that were collected between 1980 and baseline. Change in the degree of nuclear density (opacification) was characterized by the difference between baseline and follow-up in pixel density at the central clear zone in the Scheimpflug slit image of the lens.
Results: Intake of alpha-linolenic acid (ALA) was positively associated with change in nuclear density. The geometric mean nuclear density change was 16% greater in the highest quartile category of ALA intake than in the lowest quartile category (P for trend = 0.05). For women in the high tertile category of baseline nuclear lens opacification, the geometric mean change in the highest quartile category of ALA acid intake was 70% higher than the change in the lowest quartile category (P for trend = 0.01). There were no significant associations between other dietary fats and change in nuclear density.
Conclusion: Higher ALA intake was associated with a greater age-related change in lens nuclear density.
Key words: lens opacities, cataract, diet, fatty acids, women, linolenic acid
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSACKNOWLEDGMENTSREFERENCES |
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The composition, structure and function of cell membranes are affected by dietary fat, while the development of cataract is associated with changes in the composition of the lens fiber cell membranes [3–6]. Animal experiments have shown that dietary fat intake can alter lens fiber cell membrane composition and function and affect risk of cataract formation. Specifically, a high level of polyunsaturated fatty acids in the diet has been reported to delay the development of advanced cataracts in two animal studies [7,8]. In spite of the potential importance of dietary fat in maintaining the integrity of the aging lens, there has been little epidemiological research on dietary fat intake and risk of cataract. We recently reported that the prevalence of newly diagnosed, age-related nuclear opacities was positively associated with alpha-linolenic and linoleic acid intake in a subset of women from the Nurses’ Health Study cohort [9]. In the present study conducted in this same group of women, we examine relationship between dietary fat intake and the change in nuclear lens opacification over a five-year follow-up period.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSACKNOWLEDGMENTSREFERENCES |
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We identified 1717 participants of the NHS, aged 52 to 73 years, who resided in the Boston area, were free of diagnosed cancer other than non-melanoma skin cancer, had complete dietary data, and had both lenses intact at the time of the 1990 NHS questionnaire. Details regarding recruitment and participation were described previously [11]. We received positive responses from 845 (49%) of the women and 603 of these volunteers were ultimately scheduled and examined as part of the Nutrition and Vision Project (NVP) between April 1993 and August 1995. After approximately five years of follow-up (November 1998 through November 2000), 451 women had their eyes examined. Participants with bilateral cataract extraction or missing baseline images (n = 26) were deemed ineligible and not invited to the follow-up examination. One hundred twenty-six of the eligible participants did not complete a follow-up exam for the following reasons: lack of interest (n = 79), illness or death (n = 27), relocation outside the Boston area (n = 13), and inability to contact and scheduling conflicts (n = 7). Informed consent was obtained from all study participants, and all procedures were approved by the Institutional Review Boards at the New England Medical Center and the Brigham and Women's Hospital.
Assessment of Nutrient Intake
In 1980, a 61-item semi-quantitative food frequency questionnaire (FFQ) was sent to the NHS participants to assess dietary intake of specific fats and other nutrients [10]. An expanded FFQ with approximately 130 items was sent to women in 1984, 1986, and 1990 to assess usual food intakes in the previous year. In addition to the FFQ collected routinely as part of the NHS, we administered an additional FFQ as part of the NVP (1993–1995).
The FFQ specified a common unit or portion size for each food, and asked participants how often, on average, they had consumed that amount of food or beverage during the previous year. There were nine possible responses for each food item, ranging from "almost never" to "6 or more times per day". 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 based on US Department of Agriculture food-composition data. Over 90% of the total absolute intake of 70 nutrients was accounted for by this instrument [12]. The reproducibility and validity of the food frequency questionnaire were assessed previously using long-term diet records [12] and biochemical markers of nutrient status [13–16]. The Pearson correlation coefficients for energy-adjusted total and specific types of fat assessed by two 1-week dietary records and the FFQ ranges from 0.48 to 0.79, with correction for attenuation due to random error in diet records [17]. Spearman correlation coefficients between fat intakes calculated from FFQ and the fatty acid composition of subcutaneous fat aspirates also indicated that the FFQ provided a reasonable measure of fatty acids from exogenous sources (r = 0.48 for long chain omega-3 fatty acids, r = 0.51 for trans fatty acid) [18].
We used data from women who completed five FFQs collected between 1980 and 1993–1995 to calculate the average total nutrient intake (except for omega-3 fatty acid) for each participant. The average intake of omega-3 fatty acid was calculated from four FFQs collected from 1984 because the shorter food frequency questionnaire collected in 1980 did not have the detailed questions needed for calculation of omega-3 fatty acids. The percentage of energy contributed by specific fatty acids was derived by dividing energy intake from each fatty acid by total energy intake.
Assessment of Lens Status
All NVP participants received a detailed eye examination using standardized techniques [11]. The examination included ocular and medical histories, 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 risk of angle-closure glaucoma. Intraocular pressure was measured to determine if it was safe to complete the eye exam, including dilation. Prior to a slit-lamp examination of the lens, the pupils were dilated to a minimum of 6 mm with phenylephrine and tropicamide. The posterior segment was examined by direct and indirect ophthalmoscopy. The examiner had no knowledge of the nutrient status of any of the subjects.
Scheimpflug black and white images of the lens nucleus were taken with a Nidek EAS 1000 camera. Baseline and follow-up images were graded in non-sequential portions of the same grading sessions. A single grader determined nuclear opalescence using the Nidek EAS 1000 digital image analysis software (version 1.23E). The amount of nuclear opacification was measured as a function of a standard gray scale ranging from 0 (clear) to 255 (opaque) and reported as pixel density units (pdu). Progression of nuclear cataract was characterized by the difference between baseline and follow-up in pixel density at the central clear zone in the Scheimpflug image of the lens. This method is highly reproducible and provides a sensitive procedure for measuring progression of nuclear density [19,20]. In a control set of 70 eyes that were graded twice, 80% of the scores were identical and 100% of scores were within ±3 pdu upon regrading.
Non-Dietary Risk Factors
Data on known or suspected non-dietary determinants of cataract risk were obtained from the 1980 through 1994 biennial NHS questionnaires. In our analyses, we considered confirmed history of diabetes, hypertension (yes or no), cigarette pack-years smoked, and physical activity [metabolic equivalents (METs) per week] as reported on the NHS questionnaires collected before the baseline examination (1992 questionnaire for women examined before June 1, 1994 and 1994 questionnaire for those examined after this date). We also included summertime sunlight exposure (
8 h/wk) as reported on the 1980 questionnaire, alcohol use based on the average from five food frequency questionnaires collected between 1980 and 1993–5, height reported in 1976 and weight reported on the NHS questionnaire collected before the baseline examination (1992 questionnaire for women examined before June 1, 1994 and 1994 questionnaire for those examined after this date). The latter two measures were used to calculate body mass index (weight in kg/height2 in meters).
Statistical Methods
We excluded those women who had implausible caloric intakes (<600 or >3,500 kcal/day) or who left more than 70 items blank on any food frequency questionnaire (n = 13). We also excluded 20 women with confirmed diagnosis of diabetes in 1990 or earlier and six women whose blood glucose concentration was 126 mg/dL because of our concern that diabetes might alter the association between nutrition and lens opacification. To avoid the possibility that prior knowledge of lens opacification might influence nutrient intake, we excluded 41 women because they reported a history of cataracts at their baseline eye examination. In addition, we excluded 34 women who had incomplete, questionable, or missing lens data.
The primary independent variables used in the analysis were the average percentage of energy contributed by each type of fat and average intake of major fat-contributing foods. These variables were classified into quartile categories with women in the lowest quartile category as the reference category. The median fat intake values and servings per day for major fat-containing foods within each intake quartile category are presented in Table 1 and Table 2, respectively. To assess trends across quartile categories, we assigned the median intake of each quartile category to everyone with intakes in the category and then included this quartile median variable as a continuous factor in the statistical models. The P-value for trend was the resulting P-value for the associated model coefficient. We also used the intake quartile category median variables to test for possible effect modification between fat and baseline nuclear density, age, cigarettes smoked at baseline, plasma vitamin C and vitamin E level. We used a Bonferroni corrected cutoff P-value of 0.001 to determine significant interactions based on the number of interaction models that we tested.
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All P values were 2-sided. Unless otherwise noted, statistical significance refers to a P-value <0.05.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSACKNOWLEDGMENTSREFERENCES |
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50 pdu).
Fat and Major Fat-Containing Food Intakes and Increased Nuclear Density
Associations between the five-year increase in nuclear density and usual intake of fat measured over a 10–15 y period are shown in Table 4. There was a significant positive trend between alpha-linolenic acid (ALA) intake and nuclear density change (P for trend = 0.05). The geometric mean change in the highest quartile category of ALA intake (19.2 pdu) was 2.7 pdu (16%) higher than the change in the lowest quartile category (16.5 pdu). Although the trend is not statistically significant for vegetable fat, the geometric mean change for the highest quartile category of vegetable fat intake was significantly higher than that for lowest intake category (P = 0.04). Intake of other fats was not significantly associated with nuclear density change. There were no significant relations between five-year increase in nuclear density and usual intake of major fat-containing foods (data not shown).
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49 pdu). For women with the highest baseline nuclear density, the difference represents a 70% greater nuclear density change among those with the highest ALA intake category compared with women in the lowest intake category. In spite of the significant interactions between baseline nuclear density and intakes of animal fat and monounsaturated fat, there were no significant associations between these measures of fat intake and nuclear density change within any of the baseline nuclear density tertile categories.
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DISCUSSION |
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ALA is a plant-derived 18-carbon, omega-3 fatty acid found in soybean, canola, and, especially, flaxseed oil, in nuts (primarily walnuts), and in green leafy vegetables. Of the commonly consumed oils in the United States, soybean and canola oil are the primary sources of ALA. The contents of ALA in soybean and canola oil are approximately 8% and 9%, respectively [21]. After ingestion, a small and as yet ill-defined portion of ALA (<10%; possibly <1%) is converted into eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) [22,23]. ALA is easily oxidized because it contains many unsaturated bonds. Oxidative stress is a major contributor to cataract formation [24].
Since we have considered the relations between change in nuclear density and many measures of fat intake, we must consider the possibility that the ALA association is spurious. However, the consistency of the relationship between nuclear opacification and ALA seen at baseline in this study population [9] lends added credibility to this association. In cross-sectional analyses from the NVP, we found a significant positive association between intake of ALA and the prevalence of nuclear opacities [9]. The OR for the highest compared with the lowest quartile category of ALA intake was 2.2 (95% CI: 1.1, 4.5, P for trend = 0.05).
Our current findings also show discrepancies with our earlier cross-sectional observations from the NVP and the prospective observations from the full NHS. We had previously observed a significant inverse association between long-chain omega-3 fatty acid intake and cataract extraction in the full NHS cohort [25] that we did not observe in the cross-sectional analyses of the NVP [9] or in the present study. It is also possible that long-chain omega-3 fatty acid may have a greater influence on the later stages of nuclear cataract development as captured in cataract extraction than on the early stages of cataract development that were examined in the NVP cohort. Differences in sample size and follow-up time also might contribute to the discrepancy. In addition, we failed to see an association between linoleic acid and nuclear opacities in the present study, an association that we had observed in our cross-sectional NVP analysis [9], but not in the entire NHS cohort [25]. Since vegetable oils and margarines are the best source for both linoleic and ALA, our ability to distinguish between linoleic acid and ALA intake is strongly dependent on the types of vegetable oil and margarine that the women reported that they usually use. There could be misclassification of linoleic acid and ALA for women who don’t always use the same type of oil or margarine, limiting the ability to identify specific associations with these two fatty acids. In our study sample, linoleic acid and linolenic acid intakes were strongly correlated (correlation coefficient = 0.55, P < 0.001).
Apart from the present study and the NHS study of fat intake and cataract described above [25], we are not aware of any other longitudinal studies that have systematically examined the relationship between dietary fat intake and cataract. In the cross-sectional phase of the Blue Mountains Eye Study [26] and the Beaver Dam Eye Study [27], fat intake was not found to be associated with prevalence of nuclear cataract. In a case-control study, Tavani et al. observed that high total dietary fat intake, particularly from oils other than olive oil, was related to greater risk of cataract extraction [28]. No other studies, except for our previously described studies, examined the associations between ALA intake and risk of cataract.
The clinical meaning of our results may not be readily apparent because the use of digitalized image analysis to assess nuclear density is fairly recent and limited. Therefore, the best means of quantifying the possible influence of nutrition on change in nuclear density scores based on this methodology is to consider the differences in rate of change over time among those with higher and lower nutrient intakes. For example, if we assume that the rate of change in nuclear density remains constant over time, then, using the data from Table 4, the annual increase in nuclear density among a woman who was in the highest quartile category of ALA intake would be 3.8 pdu/yr and the increase among those who were in the lowest intake quartile category would be 3.3 pdu/yr. Therefore, it would take a woman who was in the lowest quartile category of ALA intake about 14 months to achieve the same increase in nuclear density (i.e., 3.8 pdu) as a woman who was in the highest quartile intake category would experience in one year. In other words, assuming a linear change over time, women in lowest intake category of ALA would delay progression of nuclear density by approximately 2 months for each year of follow-up. This difference would become quite substantial over a longer time period. Moreover, these estimates are conservative since we know that the rate of change in nuclear density increases as the degree of nuclear density increases. Thus, the initial slowing of the increase of nuclear density with lower ALA intake would result in even greater differences between those with lower and higher nutrient intakes over time.
Although these findings suggest that ALA intake might contribute to the development or progression of nuclear lens opacities, the mechanism by which ALA might adversely affect the lens is uncertain since ALA is undetectable in cataractous as well as normal lenses with current instrumentation [3,29].
In summary, the data from our study provide support for a relation between a higher intake of ALA and increased nuclear lens opacification. However, more studies are needed to verify this association and clarify the relationship between intake of other fatty acids and age-related cataract.
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ACKNOWLEDGMENTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSACKNOWLEDGMENTSREFERENCES |
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Received June 21, 2005. Accepted November 11, 2005.
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