An eye on nutrition: The role of vitamins, essential fatty acids, and antioxidants in age-related macular degeneration, dry eye syndrome, and cataract
Introduction
At a recent nutrition symposium, the speaker held up a common, square, orange cheese cracker and asked the audience, “Can anyone explain to me how we can make an eyeball out of this?” This question is a profound one. Vision is regarded to be the most valuable of the five senses; yet, how much do we really understand about eye health, nutrition, and disease prevention? Does nutrition play a role in the management of eye disease? Literature from the past two decades suggests yes.
A staggering percentage of the population suffers from eye disease, and these rates increase with advancing age. Cataracts are the main cause of vision impairment and blindness in developing countries; age-related macular degeneration (AMD) is the leading cause in industrialized societies. Although dry eye syndrome (DES) is less of a threat to vision, it stands as the most common complaint in ophthalmologic practice, with 68% of persons aged 60 and over reporting symptoms and discomfort associated with DES.1
Despite a greater understanding of nutrition, information may not be making it to those at greatest risk—the elderly and those in developing countries. A recent survey on health literacy in hospitalized patients found that patients with insufficient vision had lower health literacy scores than patients with sufficient vision (59% versus 38%, P < .001).2 The World Health Organization has initiated VISION 2020: “The Right to Sight” in an effort to eradicate global blindness, which is mainly due to deficiency of vitamin A.3
Global blindness is an epidemic—the World Health Organization reports that 285 million people are visually impaired worldwide.4 Unfortunately, previously there have been no known preventive therapies. Surgical, laser, and injectable treatments, although effective, are both costly and invasive. Consequently, patients and physicians have turned to nutritional therapies in an attempt to alleviate symptoms. In a study of patients with inflammatory eye disease, 42% (37/89) reported using complementary and alternative medical treatments to improve their condition.5
A few early studies addressed the concept of nutrition in the treatment of eye disease, including the promising results of a randomized controlled trial of oral zinc supplementation in macular degeneration.6 Given these encouraging results and the population’s draw toward complementary and alternative medical treatments, the National Eye Institute of the National Institutes of Health began recruiting people aged 55 to 80 to the Age-Related Eye Disease Study (AREDS),7 a long-term, prospective study designed to evaluate risk factors, clinical course, and prognosis of cataracts and AMD. The treatment arm, now regarded as the “AREDS formulation” (Table 1), consists of pharmacologic doses of vitamins and minerals chosen based on the recommendations of expert biochemists, ophthalmologists, and nutritionists. It has spurred several successive trials, including AREDS2, and efforts from industry to create a well-researched supplement based on these recommendations. The AREDS trials introduce the concept of pharmacologic doses of nutrients, a concept that many practitioners have, until now, been uncomfortable recommending. The focus of this paper is to take a more in-depth look at the nutrients of the AREDS and AREDS2 trials, present any further evidence in the treatment of AMD, cataract, and DES, and introduce potential mechanisms of prevention.
Section snippets
Experimental design
The primary objective of the retinal component of the Age-Related Eye Disease Study (AREDS) was to determine the effect of high-dose antioxidant supplementation in decreasing the rate of progression of AMD and associated vision loss. AREDS was a multicenter, double-blind placebo-controlled trial including 3640 individuals from 11 retinal subspecialty clinics, which was completed in 2001.8 Participants included patients between 55 and 80 years of age, and all were required to have a baseline
AREDS2
The goal of the Age-Related Eye Disease Study 2 (AREDS2) was to determine the effect of the addition of the carotenoids lutein and zeaxanthin, as well as the omega-3 long-chain polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on the risk of developing advanced AMD.[12], [13] An additional goal was to assess the effect of the removal of beta-carotene, and lowering the dosage of zinc, in the original AREDS formulation (Table 2).
Lutein and zeaxanthin
Lutein and zeaxanthin are found in high levels in egg yolk, corn, orange pepper, kiwi, grapes, spinach, zucchini, and squash.16 There has been no recommended daily intake established for lutein and zeaxanthin. The benefits seen in AREDS2 were from consuming 10 mg of lutein and 2 mg of zeaxanthin daily. Consuming 6 mg/day of lutein and zeaxanthin has also been found to reduce the risk of advanced AMD.17 Only 1 to 3 mg/day are obtained from the typical American diet.17
Of the 600 + carotenoids
Lutein, zeaxanthin, and HMG co-A reductase inhibitors
Egg yolk has been deemed the best source of lutein due to its higher fat content and, thus, better bioavailablility.20 Unfortunately, concern over cholesterol levels has led to a reduced intake of eggs. A randomized, crossover study of 33 men and women found that consuming 1 egg a day for 5 weeks raised lutein and zeaxanthin levels without a change in low-density lipoprotein, high-density lipoprotein, or triglycerides.21 Low-density lipoprotein is the main transporter for both lutein and
Vitamin C
Vitamin C–rich foods include berries, citrus fruits, broccoli, Brussel sprouts, and bell peppers. The National Institute of Medicine recommends a daily intake of 75 to 90 mg of vitamin C daily for an adult woman and man, respectively.24 This is approximately equivalent to a cup of orange or grapefruit juice. Larger doses are needed for smokers and during pregnancy (85 mg) and lactation (125 mg). The dose of vitamin C used in AREDS2 was 500 mg—or five to six times the RDI.24
Vitamin C is an
Vitamin E
Vitamin E exists naturally as eight distinct fat-soluble compounds of tocopherols and tocotrienols, each subgroup having α, β, γ, and δ subtypes. Nuts and seeds such as sunflower seeds, almonds, and hazelnuts are rich sources of vitamin E, in addition to dark leafy vegetables like spinach and collard greens. The recommended intake of vitamin E is 22.4 IU,25 whereas the dose used in AREDS2 was 400 IU daily. One ounce of sunflower seeds satisfies the daily RDI, yet 18 times that is needed to
Zinc
Oysters (and other seafood) contain more zinc per serving than any other food, with 3 oz containing 74 mg of zinc.27 Beef, poultry, and pork provide the necessary intake for the majority of Americans. Beans, cereals, and nuts are another source, but plant-based phytates can inhibit their absorption. In regions of the world where meat and seafood are scarce, zinc consumption may not be adequate.
Twenty-five mg of zinc were incorporated into the AREDS2 formula; the RDI for an adult man and woman
Essential fatty acids
Deep-sea fish, such as salmon (1.5 g/4 oz) and sardines (1.3 g/3.2 oz), contain high concentrations of DHA and EPA. Other excellent sources of omega-3 fatty acids include flaxseeds (3.2 g/2 tbsp) and walnuts (2.25 g/¼ cup).29 The ideal intake of omega-6 to omega-3 fats is modeled by the Mediterranean diet at 4:1. Intakes of the omega fats in the typical American diet reach 10 to 20:1. This ratio affects the balance of biologically active eicosanoids. A greater consumption of omega-3 fatty acids
Dry eye syndrome
Omega-3 fatty acids have been found to produce a benefit in DES. DES is the most common complaint in ophthalmologic practice and significantly affects quality of life.1 In general, DES is divided into aqueous-deficient, mucous-deficient, and evaporative subtypes. The exact pathophysiologic mechanisms involved in DES are not known but appear to be multifactorial. On the surface, DES appears mostly to be an inflammatory condition treated with topical lubricants. Other defects are observed in this
Cataract
Age-related cataract stands as the major cause of blindness in the world. It is estimated that more than 68% of people aged 79 and older have some degree of lens opacification or cataract.4 With age, the highly organized crystalline fibers of the transparent lens are thought to dehydrate and become photo-oxidized, leading to crosslinking and aggregation. Because oxidative damage is thought to be a mainstay in cataract development, many studies have sought to prove a protective effect of oral
AREDS cataract trial
The cataract analysis of the AREDS trial showed no difference between the intervention groups and placebo on the development or progression of age-related cataract or loss of visual acuity.37 In contrast to the Linxian study, the participants in AREDS were predominantly white (96%) and well nourished. The primary outcomes of the study were (1) progression of lens opacity or cataract surgery and (2) loss of visual acuity measured by loss of 15 or more letters in one eye over time. The odds of a
AREDS2 cataract trial
The primary outcome measure for AREDS-2 was progression to cataract surgery.38 This was measured at annual study intervals and at a 6-month phone call in between study visits. Cataract surgery documentation with the presence of pseudophakia or aphakia was the outcome measure. A secondary outcome measure was to evaluate the effects of lutein/zeaxanthin on the necessity for cataract surgery. Other secondary outcomes included progression to cataract surgery or an absolute increase in opacity size
Additional cataract randomized controlled trials
A multivitamin-multimineral regimen was evaluated in the Italian-American Clinical Trial of Nutritional Supplements and Age-Related Cataract (CTNS).39 CTNS was a 13-year, single-center clinical trial designed to evaluate the effects of a multivitamin-multimineral supplement containing RDI dosages (Centrum) on the prevention of age-related cataract. Visual acuity was a secondary end point. Participants had to be without nutritional supplementation for 1 year and have early or no cataract
Conclusions
Eye disease is at epidemic proportion in both developing and industrialized countries. With nearly 285 million people worldwide afflicted with visual disturbances, preventive therapies are needed globally. Vitamins, minerals, and omega-3 fatty acids are involved in many biochemical processes in the eye. Information obtained from recent clinical trials has helped clinicians sculpt nutritional recommendations to help age-related eye disease.
AREDS found a statistically significant reduction in the
References (40)
- et al.
Carotenoid composition of serum and egg yolks of hens fed diets varying in carotenoid composition
Poult Sci
(1988) - et al.
Consumption of 2 and 4 egg yolks/d for 5 wk increases macular pigment concentrations in older adults with low macular pigment taking cholesterol-lowering statins
Am J Clin Nutr
(2009) - et al.
α-Tocopherol is an effective Phase II enzyme inducer: protective effects on acrolein-induced oxidative stress and mitochondrial dysfunction in human retinal pigment epithelial cells
J Nutr Biochem
(2010) - et al.
The role of the omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina
Prog Retin Eye Res
(2005) - et al.
Oily fish consumption, dietary docosahexaenoic acid and eicosapentaenoic acid intakes, and associations with neovascular age-related macular degeneration
Am J Clin Nutr
(2008) - et al.
A multivitamin supplement and cataract and age-related macular degeneration in a randomized trial of male physicians
Ophthalmology
(2014) - et al.
Influence of aging on the polar and neutral lipid profiles in human meibomian gland secretions
Arch Ophthalmol
(2006) - et al.
More than meets the eye: relationship between low health literacy and poor vision in hospitalized patients
J Health Commun
(2013) What is "VISION 2020: The right to sight"?
Prevention of blindness and visual impairment
Prevalent use of complementary and alternative medicine by patients with inflammatory eye disease
Ocul Immunol Inflamm
Oral zinc in macular degeneration
Arch Ophthalmol
The age-related eye disease study (AREDS): design implications. AREDS report no. 1
Control Clin Trials
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
The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers
N Engl J Med
Risk factors for lung cancer and for intervention effects in CARET, the Beta Carotene and Retinol Efficacy Trial
J Natl Cancer Inst
Preferred Practice Pattern Guidelines. Age-related Macular Degeneration
Lutein+Zeaxanthin and omega-3 fatty acids for age-related macular degeneration. The Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial
JAMA
Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression. AREDS2 report no. 3
JAMA Ophthalmol
Dietary antioxidants and primary prevention of age related macular degeneration: systematic review and metanalysis
BMJ
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