expert opinion

Micronutrients for the aging eye

October 1, 2013

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Elizabeth J. Johnson, US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA

“The number of Americans age 55 years and older will almost double between now and 2030, from 60 million to 108 million. This age-group suffers an increased incidence of age-related diseases, including such eye diseases as cataract, diabetic retinopathy, glaucoma, and age-related macular degeneration (AMD). Attention has focused on efforts to stop the progression of eye diseases or to prevent the damage leading to these conditions. Nutritional intervention is becoming recognized as a part of these efforts. Compared to most other organs, the eye is particularly susceptible to oxidative damage due to its exposure to light and high metabolism. Recent research indicates that nutri-ents important in vision health include vitamins and minerals with antioxidant functions (e.g., vitamins C and E, carotenoids, such as beta-carotene, lutein and zeaxanthin, and zinc) and compounds with anti-inflamma-tory properties (the omega-3 fatty acids eicosapentaenoic acid, EPA, and docosahexaenoic acid, DHA) may ameliorate the risk for age-related eye disease (1, 2).

The Age-Related Eye Disease Study (AREDS) found that daily supplementation with vitamins C (452 mg)

and E (400 IU of alpha-tocopherol), beta-carotene (17 mg resp. 28,640 IU of vitamin A), zinc (69.6 mg), and copper (1.6 mg) at levels well above the recommended daily allowances reduced the risk of developing advanced AMD by about 25% (3). Copper was added to prevent copper-deficiency anemia, a condition associated with high levels of zinc intake. Based on these results, the AREDS formulation is considered the standard of care for those at high risk for advanced AMD. The dietary information from AREDS pointed to the carotenoids lutein and zeaxanthin and the omega-3 fatty acids EPA and DHA as being protective against developing AMD (4, 5). AREDS2, a multicenter phase III randomized clinical trial, accessed the effects of oral supplementation of macular xanthophylls, lutein plus zeaxanthin, and/or EPA plus DHA as a treatment for cataract, AMD, and moderate vision loss. In secondary analysis, lutein and zeaxanthin supplements on top of the AREDS supplement lowered the progression to advanced AMD in persons with low dietary lutein and zeaxanthin (6).

While a recent survey finds that among the baby boomers (45–65 years old), vision is the most important of the five senses, well over half of those surveyed were not aware of the important nutrients that play a key role in eye health (7). This is evident from a national survey that finds that intake of these key nutrients from dietary sources is below the recommendations or guidelines. Therefore, it is important to educate this popu-lation and to create an awareness of the nutrients and foods of particular interest in the prevention of age-related eye disease.

Vitamin C (ascorbic acid) is required for the synthesis of collagen, an important structural component of blood vessels, tendons, ligaments, and bone. Natural and synthetic ascorbic acid are chemically identical, and there are no known differences in their biological activities or bioavailabilities (8). Vitamin C is also a highly effective antioxidant, protecting essential molecules in the body, such as proteins, lipids, carbohy-drates, DNA, and RNA, from damage by free radicals and reactive oxygen species that can be generated during normal metabolism as well as through exposure to toxins and pollutants like cigarette smoke. The eye has a particularly high metabolic rate, and thus has an added need for antioxidant protection. Plasma con-centrations of vitamin C, an indicator of intake, are related to levels in the eye tissue. In the eye, vitamin C may also be able to regenerate other antioxidants, such as vitamin E. Based on the intake data from the National Health and Nutrition Examination Survey (NHANES), a significant portion of men and women over
50 years of age in the US have vitamin C intakes below the recommended dietary allowance (RDA), which is 75 mg/day for women and 90 mg/day for men (9).

The main function of vitamin E (alpha-tocopherol – the form of vitamin E that is actively maintained in the human body and also the major form in blood and tissues) in humans appears to be that of an antioxidant. Fats, which are an integral part of all cell membranes, are vulnerable to destruction through oxidation by free radicals. Alpha-Tocopherol attacks free radicals to prevent a chain reaction of lipid oxidation. This is impor-tant, given that the retina is highly concentrated in fatty acids. Other functions of alpha-tocopherol that may be of benefit to ocular health include effects on the expression and activities of molecules and enzymes in immune and inflammatory cells. Furthermore, alpha-tocopherol has been shown to inhibit platelet aggrega-tion and to improve vasodilation (10). While the RDA for vitamin E is 15 mg/day alpha-tocopherol for both women and men, the average intake of vitamin E from foods in the US for men and women over 50 years of age is only 8.6 and 7.3 mg/day, respectively (9).

Beta-carotene is the primary dietary source of pro-vitamin A (11) and has shown in the AREDS trial – along with vitamins C and E, zinc, and copper – to reduce the risk of developing advanced AMD (3). There is no RDA for beta-carotene. Data from various populations suggest that 3–6 mg/day of beta-carotene from food sources is prudent to maintain plasma beta-carotene concentrations in the range associated with a lower risk of various chronic diseases (10) The average intake of beta-carotene from foods in the US for men and women over 50 years of age is 2.6 and 2.7 mg/day, respectively (9). In studies, the long-term intake of very high doses of beta-carotene (20 and 30 mg/day) has been associated with an increase in lung cancer risk for people already at risk of developing lung cancer (heavy smokers and people with occupatio-nal asbestos exposure). The reasons for the increase in lung cancer risk are thought to be due to the pro-oxidant effects of high doses of beta-carotene in an oxidative stressed environment, such as a smoker’s lung (12).

Lutein and zeaxanthin are concentrated in the macula or central region of the eye’s retina. In addition to their role as antioxidants, lutein and zeaxanthin are believed to limit retinal oxidative damage by absorbing incoming blue light and/or quenching reactive oxygen species (13). While there is no RDA for lutein and zeaxanthin, intakes of approximately 6 mg/day have been associated with a decreased risk of AMD (14). The current intakes of lutein and zeaxanthin among adults over 50 years of age falls well below this level, with average intake of below 2 mg/day for both men and women (9).

Zinc is important in maintaining the health of the retina, given that zinc is an essential constituent of many enzymes needed for optimal metabolism of the eye, such as superoxide dismutase, which plays an important role in scavenging superoxide radicals (15). In addition to its antioxidant function, zinc plays an important role in the structure of proteins and cell membranes, in cell signaling and nerve-impulse transmission. A significant portion of men and women over 50 years of age in the US have zinc intakes below the RDA, which is 8 mg/day for women and 11 mg/day for men (9).

The omega-3 fatty acids have a number of actions that provide neuroprotective effects in the retina. They include modulation of metabolic processes affecting oxidative stress, inflammation, and vascularization (2). DHA is a key fatty acid found in the retina, and is present in large amounts in this tissue. The fatty acid may affect photoreceptor- membrane function by altering permeability, fluidity, thickness, lipid-phase properties, and the activation of membrane-bound proteins. There is no RDA for EPA/DHA. However, the protective effects of omega-3 fatty acids in ocular health are thought to be similar to those for heart health, for which dietary recommendations have been set up by the American Heart Association: individuals with no history of coronary heart disease or myocardial infarction are recommended to consume oily fish or fish oils two times per week (16). Those having been diagnosed with coronary heart disease after infarction should consume
1 g EPA + DHA per day from oily fish or supplements. The current actual intakes for EPA/DHA among men and women over 50 years of age are 12 and 13 mg/day, respectively (9).”

Based on: Rasmussen H. M and Johnson E. J. Nutrients for the aging eye. Clinical Interventions in Aging. 2013; 8:741–748.

References

1. Chiu C. J. and Taylor A. Nutritional antioxidants and age-related cataract and maculopathy. Exp Eye Res. 2007; 84:229–245.

2. SanGiovanni J. P. and Chew E. Y. 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.

3. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no 8. Arch Ophthalmol. 2001; 119:1417–1436.

4. Age-Related Eye Disease Study Research Group, SanGiovanni J. P. et al. The relationship of dietary carotenoid and vitamin A, E and C intake with age-related macular degeneration in a case-control study: AREDS report no 22. Arch Ophthalmol. 2007; 125: 1225–1232.

5. Sangiovanni J. P. et al. omega-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study. Am J Clin Nutr. 2009; 90:1601–1607.

6. The Age-Related Eye Disease Study 2 (AREDS2) Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration. The Age-Related Eye Disease Study 2 (AREDS2) Randomized Clinical Trial. JAMA. 2013; 309(19):2005–2015.

7. Ocular Nutrition Society. Baby boomers value vision more than any other sense but lack focus on eye health. 2011. Available from: http://www.ocularnutritionsociety.org/boomers.

8. Gregory J. F. 3rd. Ascorbic acid bioavailability in foods and supplements. Nutr Rev. 1993; 51:301–303.

9. Centers for Disease Control and Prevention. National Health and Nutrition Examination Survey. Available from: http://www.cdc.gov/nchs/nhanes.htm. 2013.

10. Panel on Dietary Antioxidants and Related Compounds, Subcommittee on Upper Reference Levels of Nutrients, Subcommittee on Interpretation and Uses of DRIs, Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington: National Academies Press; 2000.

11. Krinsky N. I. and Johnson E. J. Carotenoid actions and their relation to health and disease. Mol Aspects Med. 2005; 26:459–516.

12. Wang X. D. and Russell R. M. Procarcinogenic and anticarcinogenic effects of beta-carotene. Nutr Rev. 1999; 57:263–272.

13. Krinsky N. I. Possible biologic mechanisms for a protective role of xanthophylls. J Nutr. 2002; 132:540–542.

14. Seddon J. M. et al. Dietary carotenoids, vitamins A, C and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA. 1994; 272:1413–1420.

15. O’Dell B. L. Role of zinc in plasma membrane function. J Nutr. 2000; 130:1432–1436.

16. Kris-Etherton P. M. et al. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002; 106:2747–2757.