Abstract

Introduction

Presently, the only treatment shown to prevent progression of glaucoma is lowering of intraocular pressure (IOP), although it does not prevent progression and/or onset in all patients.[1,2] A primary prevention strategy for glaucoma is highly desirable. Epidemiologic studies on antioxidants, ingested through diet and supplements, have suggested benefit on the risk of multiple diseases, including late age-related macular degeneration, [3] cataract [4], cardiovascular disease, [5,6,7,8] cancers, [9,10,11] although data is still needed from randomized controlled trials for cataracts, cardiovascular disease and cancer. In vitro evidence suggests that oxidative stress may contribute to the etiology and progression of glaucoma via apoptosis and extracellular matrix remodeling of the trabecular meshwork and lamina cribosa. [12,13,14,15] It is biologically feasible that antioxidants found in the diet through fruits and vegetables may modify the risk of glaucoma development and/or progression.

We previously investigated associations between diet and glaucoma in a random sample of women from the Study of Osteoporotic Fractures. [16] Some associations, such as that between green leafy vegetables and glaucoma appeared stronger in the African American subgroup, however, the number of African American women in the sample was very small (n=144, 12.5% of study population). In this study, we further investigated a possible association between glaucoma and the consumption of fruits and vegetables in the entire cohort of African American women aged 65 and older (n=662) participating in the Study of Osteoporotic Fractures. The association between the antioxidant constituents of fruits and vegetables and glaucoma was also examined.

Methods

Results

Discussion

Our results suggest that higher daily consumption of fruit and dark green leafy vegetables may decrease the likelihood of having glaucoma in older African American women. Fruits and vegetables are rich with antioxidants, and in epidemiologic studies diets high in fruits/vegetables have been associated with decreased risk of coronary heart disease,[5,6,7,8] ischemic stroke, [23] cancer, [9,10,11] late AMD,[3] and cataract [4]. However, randomized controlled trials using high-dose supplements have not demonstrated a beneficial effect on the incidence of certain cancers and cardiovascular disease, and some have even shown harmful effects. [24,25] Antioxidants found in fruits and vegetables include vitamins A, C, E, provitamin A carotenoids that the body converts to vitamin A (α- and β-carotene, β-cryptoxanthin), and other carotenoids without vitamin A activity (lycopene, lutein, zeaxanthin). In our study population, higher dietary intakes of vitamins C and A and the provitamin carotenoids through the entire diet were significantly associated with reduced odds of glaucoma diagnosis, while higher intake of lutein/zeaxanthin and folate showed a near significant trend toward reduced odds of glaucoma diagnosis. Foods rich in vitamin A include eggs, meat, liver, dairy, and certain fish. Those rich in carotenoids include collards, kale, spinach, carrots, pumpkin, tomatoes, and oranges, among many others. Vitamin C rich food sources are citrus fruits/juices, strawberries, tomato, red pepper, broccoli, and potatoes.

There are multiple mechanisms by which the antioxidant constituents of fruits and vegetables may have a beneficial effect on glaucoma. Effects may be mediated directly on the trabecular meshwork, [26,27,28] on individual retinal ganglion cells,[13,29,30] on the vascular system nourishing the optic nerve, [31] by a combined mechanism, or by mechanisms not yet understood. While vitamin A and carotenoids were identified as having a statistically significant association with reduced glaucoma risk in our population, it is premature to recommend supplements of these nutrients. For example, observational studies have linked higher dietary intakes of beta-carotene to reduced risk of lung cancer,[9,10] but subsequent large, prospective randomized controlled trials of beta-carotene supplementation showed an increased risk of lung cancer.[32,33] Also, it is not yet clear whether the beneficial health effects of diets high in antioxidants are a direct result of the antioxidants or due to other factors associated with diets high in antioxidant-rich foods (for example, other life-style choices, such as regular exercise or choosing not to smoke). [34] However, in our study these and other potential confounders were controlled for and they did not negate the associations we observed.

There are only two previous studies examining the association between dietary intake and glaucoma. Both study populations are predominantly Caucasian. In analyses of over 110,000 men and women from the prospective Health Professionals Follow-up and Nurses' Health studies that identified 474 cases of self-reported glaucoma, no association was found between risk of glaucoma and six food groups, including green leafy vegetables, all fruits combined, and all vegetables combined. [15] Kang et al. concluded that there were no strong associations with higher intakes of the various antioxidants, although there were some reductions in risk that were close to reaching statistical significance. In their paper on dietary fat, they found a higher ratio of omega-3 to omega-6 was associated with higher risk of primary open angle glaucoma, a finding that was not duplicated in our study. [35] Of note, these studies used the Willet food frequency questionnaire, which is known to estimate nutrient intake differently than the Block questionnaire.[36] Besides lacking African American subjects (<10%), Kang's study population also significantly differed from ours in that it was mixed gender and younger by 2–3 decades, so that the prevalence of glaucoma would be expected to be lower. The Kang subjects also had healthier eating habits (median consumption of antioxidants among women in the Study of Osteoporotic Fractures falls within the first two quintiles of the Nurses' Health Study and Health Professional Follow-up Study populations). Finally, cases of glaucoma were identified by case report and then confirmed by chart review, and there was no random sample of the controls to confirm lack of glaucoma. Knowing that population-based studies found 50% of patients with glaucoma are unaware of having the disease, there may be many missed cases of glaucoma in their 100,000 plus controls.[37,38]

In a previous study by us in a predominantly Caucasian sample of the Study of Osteoporotic Fractures cohort with identical methods of glaucoma identification and nutrient assessment, [16] the odds of glaucoma risk were decreased by higher consumption of green collards/kale, carrots, and canned/dried peaches (foods found to be associated with decreased odds of glaucoma in this African American cohort), and of vitamin B2 (riboflavin). Vitamin A and α-carotene showed decreased risk coming close to reaching statistical significance. Higher intake of orange juice, spinach, and cryptoxanthin increased the odds of glaucoma. Possible reasons why different nutrients showed statistical significance in the predominantly Caucasian population compared to the African American population include: differences in eating habits, food preparation methods, and absorption and metabolism, which may be related to hormonal and genetic differences [39]. For example, high vitamin A intake doesn't necessarily equate to high blood levels of retinol--age, gender, hormones, and genetics can influence this relationship. [40] Also, carotenoid absorption depends on the presence of fat in a meal. Chopping, pureeing, and cooking carotenoid-containing vegetables in oil generally increases bioavailability because these preparation methods help release the carotenoids from their associated proteins within the plant matrix. [41,42] Perhaps the African American subjects tended to eat carrots raw, limiting the beneficial nutrients derived from this vegetable, while they chopped and prepared collard greens with oil, making the nutrients more bioavailable. Why spinach, orange juice, and cryptoxanthin, a nutrient found in high quantities within orange juice, were associated with increased odds of glaucoma in the Caucasian but not in the African American group may also be related to differences in diet preparation, genetics and metabolism. Of course, there is also the possibility that some of our findings in either study are due to chance and do not represent a true association.

Specific limitations of our study include residual confounding by unmeasured variables, such as intraocular pressure, family history of glaucoma, and certain lifestyle factors. In terms of family history, it is unlikely that diet would vary with family history since there is little to no information in the public suggesting that diet affects glaucoma. Secondly, gonioscopy was not performed, so the exact type of glaucomatous optic nerve damage diagnosed is unknown (this may be an issue because diet would not be expected to have an etiologic effect on acute angle closure glaucoma). Thirdly, we did not measure plasma nutrient levels. However, plasma and diet levels are not expected to highly correlate due to many factors other than diet that influence the plasma levels. [40] Nonetheless, studies are published that validate the Block Food Frequency Questionnaire against dietary records and plasma nutrient values.[19,20] Another limitation may be that our Food Frequency Questionnaires were conducted at the same time as the eye exam, and thus they may have missed the etiologically relevant diet exposure, if one assumes that diets change with age and time and that it is past diet that affects glaucoma development. At the present time, the relevant diet exposure (in childhood, young or middle adulthood) is unknown. There is also the issue of multiple comparisons of fruits/vegetables and antioxidants, which is a general limitation of all such studies and may lead to statistically significant findings by chance. Lastly, the cross-sectional design does not allow causality to be established.

Strengths of our study are that the African American women we studied appear to be representative of other African American populations studied. The prevalence of glaucoma reported here, 13.2%, falls within the prevalence confidence interval of a recent meta-analysis of the literature on open-angle glaucoma that specifically included black populations. [43] The prevalence of self-reported diabetes and hypertension in our older African American population is also consistent with the prevalence rates reported by the National Health and Nutrition Examination Surveys. [44,45]

In summary, using data from the African American participants of the Study of Osteoporotic Fractures, we found evidence that higher intake of vitamin A, vitamin C, dietary carotenoids, fruits and dark green leafy vegetables were associated with a lower likelihood of having glaucoma. It remains to be asked whether a randomized controlled trial is warranted if these findings can be confirmed by prospective studies. Any single constituent of fruits and vegetables may not fully explain the apparent beneficial association observed in this study, as such, it may be better to recommend increased overall intake of fruits and vegetables at this time, rather than supplements.

Acknowledgments

Footnotes

References