ascorbic-acid and Macular-Degeneration

The aim of this paper is to summarize all available evidence from systematic reviews, randomized controlled trials (RCTs) and comparative nonrandomized studies (NRS) on the association between nutrition and antioxidant, vitamin, and mineral supplements and the development or progression of age-related macular degeneration (AMD). The Cochrane Database of Systematic Reviews, Cochrane register CENTRAL, MEDLINE and Embase were searched and studies published between January 2015 and May 2021 were included. The certainty of evidence was assessed according to the GRADE methodology. The main outcome measures were development of AMD, progression of AMD, and side effects. We included 7 systematic reviews, 7 RCTs, and 13 NRS. A high consumption of specific nutrients, i.e. β-carotene, lutein and zeaxanthin, copper, folate, magnesium, vitamin A, niacin, vitamin B6, vitamin C, docosahexaenoic acid, and eicosapentaenoic acid, was associated with a lower risk of progression of early to late AMD (high certainty of evidence). Use of antioxidant supplements and adherence to a Mediterranean diet, characterized by a high consumption of vegetables, whole grains, and nuts and a low consumption of red meat, were associated with a decreased risk of progression of early to late AMD (moderate certainty of evidence). A high consumption of alcohol was associated with a higher risk of developing AMD (moderate certainty of evidence). Supplementary vitamin C, vitamin E, or β-carotene were not associated with the development of AMD, and supplementary omega-3 fatty acids were not associated with progression to late AMD (high certainty of evidence). Research in the last 35 years included in our overview supports that a high intake of specific nutrients, the use of antioxidant supplements and adherence to a Mediterranean diet decrease the risk of progression of early to late AMD.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Humans; Macular Degeneration; Vitamins

Since the retina continuously receives light to enable vision, reactive oxygen species (ROS) are easily generated in neural retina. The oxidative stress induced by ROS may be involved in the onset and progression of blinding aging diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Although supply of antioxidants to the retina is important to maintain the redox homeostasis in neural retina, the blood-retinal barrier (BRB) is created by complex tight-junctions of retinal capillary endothelial cells and retinal pigment epithelial cells to prevent the free diffusion of substances. The BRB is equipped with several membrane transporters to supply nutrients and essential molecules including antioxidants and drugs which exhibit antiaging effect to the retina from the circulating blood. In this review, the transporter-mediated retinal distribution of key endogenous compounds and drugs, such as vitamin C, l-cystine and gabapentin, is introduced for antiaging of the retina.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood-Retinal Barrier; Cystine; Diabetic Retinopathy; Endothelial Cells; Gabapentin; Glaucoma; Homeostasis; Humans; Macular Degeneration; Oxidation-Reduction; Oxidative Stress; Rats; Reactive Oxygen Species; Retina; Tight Junctions

Editor's note: This is a summary of a nursing care-related systematic review from the Cochrane Library. For more information, see http://nursingcare.cochrane.org.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Female; Humans; Macular Degeneration; Male; Middle Aged; Vitamin E

There is inconclusive evidence from observational studies to suggest that people who eat a diet rich in antioxidant vitamins (carotenoids, vitamins C, and E) or minerals (selenium and zinc) may be less likely to develop age-related macular degeneration (AMD).. To determine whether or not taking antioxidant vitamin or mineral supplements, or both, prevent the development of AMD.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 2), MEDLINE Ovid (1946 to 29 March 2017), Embase Ovid (1947 to 29 March 2017), AMED (Allied and Complementary Medicine Database) (1985 to 29 March 2017), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/); searched 29 March 2017, the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 29 March 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 29 March 2017 and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 29 March 2017. We did not use any date or language restrictions in the electronic searches for trials.. We included all randomised controlled trials (RCTs) comparing an antioxidant vitamin or mineral supplement (alone or in combination) to control.. Both review authors independently assessed risk of bias in the included studies and extracted data. One author entered data into RevMan 5; the other author checked the data entry. We pooled data using a fixed-effect model. We graded the certainty of the evidence using GRADE.. We included a total of five RCTs in this review with data available for 76,756 people. The trials were conducted in Australia, Finland, and the USA, and investigated vitamin C, vitamin E, beta-carotene, and multivitamin supplements. All trials were judged to be at low risk of bias.Four studies reported the comparison of vitamin E with placebo. Average treatment and follow-up duration ranged from 4 to 10 years. Data were available for a total of 55,614 participants. There was evidence that vitamin E supplements do not prevent the development of any AMD (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.90 to 1.06; high-certainty evidence), and may slightly increase the risk of late AMD (RR 1.22, 95% CI 0.89 to 1.67; moderate-certainty evidence) compared with placebo. Only one study (941 participants) reported data separately for neovascular AMD and geographic atrophy. There were 10 cases of neovascular AMD (RR 3.62, 95% CI 0.77 to 16.95; very low-certainty evidence), and four cases of geographic atrophy (RR 2.71, 95% CI 0.28 to 26.0; very low-certainty evidence). Two trials reported similar numbers of adverse events in the vitamin E and placebo groups. Another trial reported excess of haemorrhagic strokes in the vitamin E group (39 versus 23 events, hazard ratio 1.74, 95% CI 1.04 to 2.91, low-certainty evidence).Two studies reported the comparison of beta-carotene with placebo. These studies took place in Finland and the USA. Both trials enrolled men only. Average treatment and follow-up duration was 6 years and 12 years. Data were available for a total of 22,083 participants. There was evidence that beta-carotene supplements did not prevent any AMD (RR 1.00, 95% CI 0.88 to 1.14; high-certainty evidence) nor have an important effect on late AMD (RR 0.90, 95% CI 0.65 to 1.24; moderate-certainty evidence). Only one study (941 participants) reported data separately for neovascular AMD and geographic atrophy. There were 10 cases of neovascular AMD (RR 0.61, 95% CI 0.17 to 2.15; very low-certainty evidence) and 4 cases of geographic atrophy (RR 0.31 95% CI 0.03 to 2.93; very low-certainty evidence). Beta-carotene was associated with increased risk of lung cancer in people who smoked.One study reported the comparison of vitamin C with placebo, and multivitamin (Centrum Silver) versus placebo. This was a study in men in the USA with average treatment duration and follow-up of 8 years for vitamin C and 11 years for multivitamin. Data were available for a total. Taking vitamin E or beta-carotene supplements will not prevent or delay the onset of AMD. The same probably applies to vitamin C and the multivitamin (Centrum Silver) investigated in the one trial reported to date. There is no evidence with respect to other antioxidant supplements, such as lutein and zeaxanthin. Although generally regarded as safe, vitamin supplements may have harmful effects, and clear evidence of benefit is needed before they can be recommended. People with AMD should see the related Cochrane Review on antioxidant vitamin and mineral supplements for slowing the progression of AMD, written by the same review team.

Topics: alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Drug Combinations; Humans; Macular Degeneration; Minerals; Randomized Controlled Trials as Topic; Vitamin E; Vitamins

Vision loss affects 37 million Americans older than 50 years and one in four who are older than 80 years. The U.S. Preventive Services Task Force concludes that current evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in adults older than 65 years. However, family physicians play a critical role in identifying persons who are at risk of vision loss, counseling patients, and referring patients for disease-specific treatment. The conditions that cause most cases of vision loss in older patients are age-related macular degeneration, glaucoma, ocular complications of diabetes mellitus, and age-related cataracts. Vitamin supplements can delay the progression of age-related macular degeneration. Intravitreal injection of a vascular endothelial growth factor inhibitor can preserve vision in the neovascular form of macular degeneration. Medicated eye drops reduce intraocular pressure and can delay the progression of vision loss in patients with glaucoma, but adherence to treatment is poor. Laser trabeculoplasty also lowers intraocular pressure and preserves vision in patients with primary open-angle glaucoma, but long-term studies are needed to identify who is most likely to benefit from surgery. Tight glycemic control in adults with diabetes slows the progression of diabetic retinopathy, but must be balanced against the risks of hypoglycemia and death in older adults. Fenofibrate also slows progression of diabetic retinopathy. Panretinal photocoagulation is the mainstay of treatment for diabetic retinopathy, whereas vascular endothelial growth factor inhibitors slow vision loss resulting from diabetic macular edema. Preoperative testing before cataract surgery does not improve outcomes and is not recommended.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antihypertensive Agents; Ascorbic Acid; Bevacizumab; Blindness; Cataract; Cataract Extraction; Diabetic Retinopathy; Fenofibrate; Glaucoma; Humans; Hypolipidemic Agents; Intravitreal Injections; Light Coagulation; Macular Degeneration; Mass Screening; Practice Guidelines as Topic; Ranibizumab; Vision Disorders; Vision, Low; Vitamin E; Vitamins

Age-related macular degeneration (AMD) is the most frequent cause of blindness in the Western World. While with new therapies that are directed towards vascular endothelial growth factor (VEGF), a potentially efficient treatment option for the wet form of the disease has been introduced, a therapeutic regimen for dry AMD is still lacking. There is evidence from several studies that oral intake of supplements is beneficial in preventing progression of the disease. Several formulations of micronutrients are currently available. The present review focuses on the role of supplements in the treatment and prevention of AMD and sums up the current knowledge about the most frequently used micronutrients. In addition, regulatory issues are discussed, and future directions for the role of supplementation in AMD are highlighted.

Topics: Administration, Oral; Antioxidants; Ascorbic Acid; beta Carotene; Copper; Dietary Supplements; Disease Progression; Drug Combinations; Humans; Lutein; Macular Degeneration; Vision Disorders; Vitamin E; Vitamins; Zeaxanthins; Zinc

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Clinical hallmarks of AMD are observed in one third of the elderly in industrialized countries. Preventative interventions through dietary modification are attractive strategies, because they are more affordable than clinical therapies, do not require specialists for administration and many studies suggest a benefit of micro- and macro-nutrients with respect to AMD with few, if any, adverse effects. The goal of this review is to provide information from recent literature on the value of various nutrients, particularly omega-3 fatty acids, lower glycemic index diets and, perhaps, some carotenoids, with regard to diminishing risk for onset or progression of AMD. Results from the upcoming Age-Related Eye Disease Study (AREDS) II intervention trial should be particularly informative.

Topics: Animals; Antioxidants; Ascorbic Acid; Carotenoids; Dietary Carbohydrates; Dietary Fats; Dietary Supplements; Fatty Acids, Omega-3; Feeding Behavior; Fishes; Glycemic Index; Guidelines as Topic; Humans; Macular Degeneration; Nutritional Status; Nuts; Randomized Controlled Trials as Topic; Risk Factors; Vitamin A; Vitamin D; Vitamin E; Vitamins; Zinc

Age-related macular degeneration (AMD) is one of the most important causes of blindness among the elderly. Although the disease presents a serious social problem, its pathogenesis is still unclear. AMD involves the posterior pole of the retina, the place responsible for acute vision. Retinal factors (intensive oxygen metabolism, continual exposure to light, a high concentration of polyunsaturated fatty acids, the presence of photosensitizers) increase the production of reactive oxygen species. Oxidative stress is aggravated by the presence of lipofuscin. The pigment accumulates with age, especially in the eyes of those with AMD. The most important risk factors for AMD, beside genetic predisposition, are factors leading to oxidative stress in the retina, e.g. age above 65 years, cigarettes smoking, obesity, exposition to blue light, and bright irises. Macular pigment is a natural barrier protecting the central retina against oxidative damage. It is formed by two dihydroxycarotenoids, lutein and zeaxanthin. The prereceptoral location of the macular pigment permits it to act as an optical filter that absorbs short-wavelength visible light. Carotenoids also demonstrate antioxidant activity. Eyes with a predisposition to develop AMD or which already have developed the disease have considerably less macular pigment and a greater risk of oxidative damage compared with healthy eyes. Investigations have shown that diet poor in antioxidant micronutrients (vitamin C, E, carotenoids, zinc) and low plasma levels of antioxidants may favor the development of the age-related macular degeneration. The findings demonstrated that micronutrient supplementation enhances antioxidant defense and might prevent or retard AMD or modify the course of the disease.

Topics: Aging; Antioxidants; Ascorbic Acid; Humans; Macular Degeneration; Oxidative Stress; Reactive Oxygen Species; Retina; Vitamin A; Vitamin E

Currently, age-related macular degeneration is one of the most common eye diseases causing severe and permanent loss of vision. This disease is estimated to affect approximately 300-500 thousand Hungarians. While earlier no treatment was available, in the recent decade an antioxidant therapy became very popular using combinations of high dosage antioxidant vitamins C, E, beta carotene and zinc. Based on theoretical concepts and mostly in vitro experiences, this combination was thought to be effective through neutralizing reactive oxygen species. According to a large clinical trial (AREDS) it reduced progression of intermediate state disease to advanced state, but did not influence early disease. This original combination, due to potential severe side effects, is not on the market anymore. However, the efficacy of modified formulas has not been proved yet. Recently, the metabolic therapy, a combination of omega-3 fatty acids, coenzyme Q10 and acetyl-L-carnitine has been introduced for treating early age-related macular degeneration through improving mitochondrial dysfunction, specifically improving lipid metabolism and ATP production in the retinal pigment epithelium, improving photoreceptor turnover and reducing generation of reactive oxygen species. According to a pilot study and a randomized, placebo-controlled, double blind clinical trial, both central visual field and visual acuity slightly improved after 3-6 months of treatment and they remained unchanged by the end of the study. The difference was statistically significant as compared to the base line or to controls. These functional changes were accompanied by an improvement in fundus alterations: drusen covered area decreased significantly as compared to the base line or to control. Characteristically, all these changes were more marked in less affected eyes. A prospective case study on long-term treatment confirmed these observations. With an exception that after slight improvement, visual functions remained stable, drusen regression continued for years. Sometimes significant regression of drusen was found even in intermediate and advanced cases. All these findings strongly suggested that the metabolic therapy may be the first choice for treating age-related macular degeneration. Currently, this is the only combination of ingredients corresponding to the recommended daily allowance, and at the same time, which showed clinically proved efficacy.

Topics: Acetylcarnitine; Adenosine Triphosphate; Antioxidants; Ascorbic Acid; beta Carotene; Coenzymes; Disease Progression; Drug Therapy, Combination; Fatty Acids, Omega-3; Humans; Hungary; Lipid Peroxidation; Macular Degeneration; Mitochondria; Photoreceptor Cells; Pigment Epithelium of Eye; Randomized Controlled Trials as Topic; Reactive Oxygen Species; Severity of Illness Index; Treatment Outcome; Ubiquinone; Visual Acuity; Visual Fields; Vitamin E; Vitamins; Zinc Compounds

The role of nutritional supplementation in prevention of onset or progression of ocular disease is of interest to health care professionals and patients. The aim of this review is to identify those antioxidants most appropriate for inclusion in an ideal ocular nutritional supplement, suitable for those with a family history of glaucoma, cataract, or age-related macular disease, or lifestyle factors predisposing onset of these conditions, such as smoking, poor nutritional status, or high levels of sunlight exposure. It would also be suitable for those with early stages of age-related ocular disease. Literature searches were carried out on Web of Science and PubMed for articles relating to the use of nutrients in ocular disease. Those highlighted for possible inclusion were vitamins A, B, C and E, carotenoids beta-carotene, lutein, and zeaxanthin, minerals selenium and zinc, and the herb, Ginkgo biloba. Conflicting evidence is presented for vitamins A and E in prevention of ocular disease; these vitamins have roles in the production of rhodopsin and prevention of lipid peroxidation respectively. B vitamins have been linked with a reduced risk of cataract and studies have provided evidence supporting a protective role of vitamin C in cataract prevention. Beta-carotene is active in the prevention of free radical formation, but has been linked with an increased risk of lung cancer in smokers. Improvements in visual function in patients with age-related macular disease have been noted with lutein and zeaxanthin supplementation. Selenium has been linked with a reduced risk of cataract and activates the antioxidant enzyme glutathione peroxidase, protecting cell membranes from oxidative damage while zinc, although an essential component of antioxidant enzymes, has been highlighted for risk of adverse effects. As well as reducing platelet aggregation and increasing vasodilation, Gingko biloba has been linked with improvements in pre-existing field damage in some patients with normal tension glaucoma. We advocate that vitamins C and E, and lutein/zeaxanthin should be included in our theoretically ideal ocular nutritional supplement.

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Ginkgo biloba; Humans; Lutein; Macular Degeneration; Nutritional Physiological Phenomena; Riboflavin; Vitamin A; Vitamin B 12; Vitamin E; Xanthophylls; Zeaxanthins

Age-related macular degeneration (AMD) is the leading cause of severe vision loss in the developed world. The lack of effective treatment modalities, coupled with evidence supporting an oxidative pathogenesis, has increased interest in the potential preventative role of nutritional supplementation. This article reviews seven randomised controlled trials (RCTs) that have investigated the role of nutritional supplementation in AMD. Three of these trials reported a positive effect of nutritional supplementation on AMD; the Age-related eye study (AREDS), the Lutein Antioxidant Supplementation Trial (LAST), and the oral zinc trial by Newsome et al. (1988). However, the oral zinc trial by Newsome et al. (1988) was unlikely to detect any difference between treatments smaller than 72%, and the AREDS results were based on a subgroup of their study population. Lutein was considered for the AREDS formulation, but was not commercially available at that time. The findings of the LAST support a possible therapeutic role of lutein in AMD.

Topics: alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Dietary Supplements; Drug Combinations; Humans; Lutein; Macular Degeneration; Nylidrin; Randomized Controlled Trials as Topic; Vitamin E; Vitamins; Zinc

FREE RADICALS AND THE THEORY OF AGING: Severe oxidative stress progressively leads to cell dysfunction and ultimately cell death. Oxidative stress is defined as an imbalance between pro-oxidants and/or free radicals on the one hand, and anti-oxidizing systems on the other. The oxygen required for living may indirectly be responsible for negative effects; these deleterious effects are due to the production of free radicals, which are toxic for the cells (superoxide anions, hydroxyl radicals, peroxyl radicals, hydrogen peroxide, hydroperoxides and peroxinitrite anions). Free radical attacks are responsible for cell damage and the targeted cells are represented by the cell membranes, which are particularly rich in unsaturated fatty acids, sensitive to oxidation reactions; DNA is also the target of severe attacks by these reactive oxygen species (ROS).. These are represented by the enzymes and free radical captors. The latter are readily oxidizable composites. The free radical captor or neutralization systems of these ROS use a collection of mechanisms, vitamins (E and C), enzymes [superoxide dismutase (SOD), glutathion peroxidase (GPx) and others], and glutathion reductase (GSH), capable of neutralizing peroxinitrite. The efficacy of this system is dependent on the genome for the enzymatic defence systems, and on nutrition for the vitamins. Some strategies aimed at reducing oxidative stress-related alterations have been performed in animals. However, only a few can be used and are efficient in humans, such as avoidance of unfavourable environmental conditions (radiation, dietary carcinogens, smoking...) and antioxidant dietary supplementation.. Epidemiological data suggest that antioxidants may have a beneficial effect on many age-related diseases: atherosclerosis, cancer, some neurodegenerative and ocular diseases. However, the widespread use of supplements is hampered by several factors: the lack of prospective and controlled studies; insufficient knowledge on the pro-oxidant, oxidant and ant-oxidant properties of the various supplements; growing evidence that free radicals are not only by-products, but also play an important role in cell signal transduction, apoptosis and infection control.. Although current data indicate that antioxidants cannot prolong maximal life span, the beneficial impact of antioxidants on various age-related degenerative diseases may forecast an improvement in life span and enhance quality of life. The current lack of sufficient data does not permit the systematic recommendation of anti-oxidants. Nevertheless, antioxidant-rich diets with fruit and vegetables should be recommended.

Topics: Aging; Alzheimer Disease; Animals; Antioxidants; Arteriosclerosis; Ascorbic Acid; Carotenoids; Cataract; Chronic Disease; Disease Models, Animal; Evidence-Based Medicine; Free Radicals; Humans; Lutein; Macular Degeneration; Neoplasms; Oxidative Stress; Parkinson Disease; Reactive Oxygen Species; Vitamin E

To assess the balance of benefits and risks of supplementation with beta-carotene, vitamin E, vitamin C, and multivitamins on cancer, cardiovascular (CVD), and eye diseases.. Physicians' Health Study II (PHS II) is a randomized, double-blind, placebo-controlled trial enrolling 15,000 willing and eligible physicians aged 55 years and older. PHS II will utilize a 2 x 2 x 2 x 2 factorial design to test alternate day beta-carotene, alternate day vitamin E, daily vitamin C, and a daily multivitamin, in the prevention of total and prostate cancer, CVD, and the age-related eye diseases, cataract and macular degeneration. PRIOR RESULTS: The final results of the recently completed Physicians' Health Study I (PHS I), a randomized, double-blind, placebo-controlled trial in 22,071 healthy US male physicians, indicated that beta-carotene supplementation (50 mg on alternate days) had no significant benefit or harm on cancer or CVD during more than 12 years of treatment and follow-up. In regards to cancer, there were possible benefits on total and prostate cancer in those with low baseline levels assigned to beta-carotene, a finding compatible with the Chinese Cancer Prevention Study for combined treatment with beta-carotene, vitamin E, and selenium in a poorly nourished population. Further, with respect to CVD, there were apparent benefits of beta-carotene supplementation on subsequent vascular events among a small subgroup of 333 men with prior angina or revascularization. The currently available data from randomized trials of primary prevention are sparse and inconsistent for vitamin E and non-existent for vitamin C and multivitamins. For eye diseases, namely cataract and age-related macular degeneration, there are no completed large-scale randomized trials of antioxidant vitamins.. PHS II is unique in several respects. PHS II is the only primary prevention trial in apparently healthy men testing the balance of benefits and risks of vitamin E on cancer and CVD. In addition, PHS II is the only primary prevention trial in apparently healthy men to test the balance of benefits and risks of vitamin C, multivitamins, as well as any single antioxidant vitamin, alone and in combination, on cancer, CVD, and eye diseases. Finally, PHS II is the only trial testing a priori the hypotheses that beta-carotene and vitamin E may reduce the risks of prostate cancer. Thus, PHS II will add unique as well as importantly relevant and complementary information to the totality of evidence from other completed and ongoing large-scale randomized trials on the balance of benefits and risks of beta-carotene, vitamin E, vitamin C, and multivitamins alone and in combination on prevention of cancer, CVD and eye diseases.

Topics: Aged; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Cataract; Double-Blind Method; Female; Follow-Up Studies; Humans; Macular Degeneration; Male; Middle Aged; Neoplasms; Sample Size; Vitamin E

Age-related cataract and age-related macular degeneration (AMD) are important public health problems. Approximately 50% of the 30 to 50 million cases of blindness worldwide result from unoperated cataract. In the US and other developed countries AMD is the leading cause of blindness, but age-related cataract remains the leading cause of visual disability. Age-related cataract and AMD represent an enormous economic burden. In the United States more than 1.3 million cataract extractions are performed annually at a cost of approximately $3.5 billion. Much of the experimental research on the etiology of cataract and AMD has focused on the role of nutritional antioxidants (vitamin C, vitamin E, and carotenoids). Evidence from epidemiologic studies support a role for nutritional antioxidants in delaying the onset of these age-related vision disorders. Although it is not yet possible to conclude that antioxidant nutrients have a role in prevention of cataract or AMD, a summary of the epidemiologic evidence suggests that it is prudent to consume diets high in vitamins C and E and carotenoids, particularly the xanthophylls, as insurance against the development of cataract and AMD.

Topics: Antioxidants; Ascorbic Acid; Carotenoids; Cataract; Dietary Supplements; Humans; Macular Degeneration; Riboflavin; Vitamin E; Vitamins

The purpose of this study was to evaluate the impact of supplemental macular carotenoids (including versus not including meso-zeaxanthin) in combination with coantioxidants on visual function in patients with nonadvanced age-related macular degeneration.. In this study, 121 participants were randomly assigned to group 1 (Age-Related Eye Disease Study 2 formulation with a low dose [25 mg] of zinc and an addition of 10 mg meso-zeaxanthin; n = 60) or group 2 (Age-Related Eye Disease Study 2 formulation with a low dose [25 mg] of zinc; n = 61). Visual function was assessed using best-corrected visual acuity, contrast sensitivity (CS), glare disability, retinal straylight, photostress recovery time, reading performance, and the National Eye Institute Visual Function Questionnaire-25. Macular pigment was measured using customized heterochromatic flicker photometry.. There was a statistically significant improvement in the primary outcome measure (letter CS at 6 cycles per degree [6 cpd]) over time (P = 0.013), and this observed improvement was statistically comparable between interventions (P = 0.881). Statistically significant improvements in several secondary outcome visual function measures (letter CS at 1.2 and 2.4 cpd; mesopic and photopic CS at all spatial frequencies; mesopic glare disability at 1.5, 3, and 6 cpd; photopic glare disability at 1.5, 3, 6, and 12 cpd; photostress recovery time; retinal straylight; mean and maximum reading speed) were also observed over time (P < 0.05, for all), and were statistically comparable between interventions (P > 0.05, for all). Statistically significant increases in macular pigment at all eccentricities were observed over time (P < 0.0005, for all), and the degree of augmentation was statistically comparable between interventions (P > 0.05).. Antioxidant supplementation in patients with nonadvanced age-related macular degeneration results in significant increases in macular pigment and improvements in CS and other measures of visual function. (Clinical trial, http://www.isrctn.com/ISRCTN13894787).

Topics: Aged; Antioxidants; Ascorbic Acid; Contrast Sensitivity; Double-Blind Method; Drug Therapy, Combination; Female; Glare; Humans; Lutein; Macular Degeneration; Macular Pigment; Male; Middle Aged; Photometry; Reading; Trace Elements; Visual Acuity; Vitamin E; Zeaxanthins; Zinc

To evaluate the impact of complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) risk alleles on the observed response to components of the Age-Related Eye Disease Study (AREDS) formulation.. Genetic and statistical subgroup analysis of a randomized, prospective clinical trial.. White patients from the AREDS with category 3 or 4 age-related macular degeneration (AMD) with available DNA (n = 989).. Four genotype groups based on CFH and ARMS2 risk allele number were defined. Progression to advanced AMD was analyzed by genotype and treatment using Cox proportionate hazards estimates and 7-year events.. The effect of predefined genotype group on treatment-specific progression to advanced AMD.. Patients with 2 CFH risk alleles and no ARMS2 risk alleles progressed more with zinc-containing treatment compared with placebo, with a hazard ratio (HR) of 3.07 (P = 0.0196) for zinc and 2.73 (P = 0.0418) for AREDS formulation (AF). Seven-year treatment-specific progression rates were: placebo, 17.0%; zinc, 43.2% (P = 0.023); and AF, 40.2% (P = 0.039). Patients with 0 or 1 CFH risk alleles and 1 or 2 ARMS2 risk alleles benefited from zinc-containing treatment compared with placebo, with an HR of 0.514 for zinc (P = 0.012) and 0.569 for AF (P = 0.0254). Seven-year treatment-specific AMD progression rates were as follows: placebo, 43.3%; zinc, 25.2% (P = 0.020); and AF, 27.3% (P = 0.011). Zinc and AF treatment each interacted statistically with these 2 genotype groups under a Cox model, with P values of 0.000999 and 0.00366, respectively. For patients with 0 or 1 CFH risk alleles and no ARMS2 risk alleles, neither zinc-containing treatment altered progression compared with placebo, but treatment with antioxidants decreased progression (HR, 0.380; P = 0.034). Seven-year progression with placebo was 22.6% and with antioxidants was 9.17% (P = 0.033). For patients with 2 CFH risk alleles and 1 or 2 ARMS2 risk alleles, no treatment was better than placebo (48.4%).. The benefit of the AREDS formulation seems the result of a favorable response by patients in only 1 genotype group, balanced by neutral or unfavorable responses in 3 genotype groups.

Topics: Adult; Aged; Alleles; Antioxidants; Ascorbic Acid; beta Carotene; Complement Factor H; Drug Therapy, Combination; Female; Genetic Predisposition to Disease; Genotype; Genotyping Techniques; Humans; Macular Degeneration; Male; Middle Aged; Polymorphism, Single Nucleotide; Proportional Hazards Models; Prospective Studies; Proteins; Risk Factors; Vitamin E; Zinc Compounds

The Age-Related Eye Disease Study (AREDS) showed that supplementation with their formula led to a significant decrease in progression of age-related macular degeneration (AMD). This study aims to assess the effect of different education protocols on concordance with the trial recommendations in two retinal clinics.. A prospective controlled survey of concordance with the AREDS recommendations in two retinal clinics was administered to 330 patients with AREDS category 3 or 4 AMD. The results were evaluated to assess the effect of differing levels of patient education. In clinic 1, there was a formal policy of giving the patient both verbal and written instructions and verbal repetition of these instructions from each staff member on each patient visit; in clinic 2, there was no specific education policy.. Clinic 1 had a concordance rate of 81.6% and clinic 2 of 44.1%. There were no significant differences in the patient demographics between the two clinics.. A high concordance rate can be achieved in clinical practice with rigorous patient education that includes a policy of having continual repetition of instructions.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; beta Carotene; Dietary Supplements; Disease Progression; Female; Guidelines as Topic; Humans; Macular Degeneration; Male; Middle Aged; Patient Compliance; Patient Education as Topic; Prospective Studies; Surveys and Questionnaires; Tertiary Care Centers; Vitamin E; Vitamins; Zinc

Observational data have suggested that high dietary intake of saturated fat and low intake of vegetables may be associated with increased risk of Alzheimer disease.. To test the effects of oral supplementation with nutrients on cognitive function.. In a double-masked randomized clinical trial (the Age-Related Eye Disease Study 2 [AREDS2]), retinal specialists in 82 US academic and community medical centers enrolled and observed participants who were at risk for developing late age-related macular degeneration (AMD) from October 2006 to December 2012. In addition to annual eye examinations, several validated cognitive function tests were administered via telephone by trained personnel at baseline and every 2 years during the 5-year study.. Long-chain polyunsaturated fatty acids (LCPUFAs) (1 g) and/or lutein (10 mg)/zeaxanthin (2 mg) vs placebo were tested in a factorial design. All participants were also given varying combinations of vitamins C, E, beta carotene, and zinc.. The main outcome was the yearly change in composite scores determined from a battery of cognitive function tests from baseline. The analyses, which were adjusted for baseline age, sex, race, history of hypertension, education, cognitive score, and depression score, evaluated the differences in the composite score between the treated vs untreated groups. The composite score provided an overall score for the battery, ranging from -22 to 17, with higher scores representing better function.. A total of 89% (3741/4203) of AREDS2 participants consented to the ancillary cognitive function study and 93.6% (3501/3741) underwent cognitive function testing. The mean (SD) age of the participants was 72.7 (7.7) years and 57.5% were women. There were no statistically significant differences in change of scores for participants randomized to receive supplements vs those who were not. The yearly change in the composite cognitive function score was -0.19 (99% CI, -0.25 to -0.13) for participants randomized to receive LCPUFAs vs -0.18 (99% CI, -0.24 to -0.12) for those randomized to no LCPUFAs (difference in yearly change, -0.03 [99% CI, -0.20 to 0.13]; P = .63). Similarly, the yearly change in the composite cognitive function score was -0.18 (99% CI, -0.24 to -0.11) for participants randomized to receive lutein/zeaxanthin vs -0.19 (99% CI, -0.25 to -0.13) for those randomized to not receive lutein/zeaxanthin (difference in yearly change, 0.03 [99% CI, -0.14 to 0.19]; P = .66). Analyses were also conducted to assess for potential interactions between LCPUFAs and lutein/zeaxanthin and none were found to be significant.. Among older persons with AMD, oral supplementation with LCPUFAs or lutein/zeaxanthin had no statistically significant effect on cognitive function.. clinicaltrials.gov Identifier: NCT00345176.

Topics: Aged; Aged, 80 and over; Algorithms; Ascorbic Acid; beta Carotene; Cognition; Copper; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Hispanic or Latino; Humans; Lost to Follow-Up; Lutein; Macular Degeneration; Male; Medication Adherence; Middle Aged; Neuropsychological Tests; Outcome Assessment, Health Care; Racial Groups; Time Factors; Vitamins; Zeaxanthins; Zinc Oxide

To describe the long-term effects (10 years) of the Age-Related Eye Disease Study (AREDS) formulation of high-dose antioxidants and zinc supplement on progression of age-related macular degeneration (AMD).. Multicenter, randomized, controlled, clinical trial followed by an epidemiologic follow-up study.. We enrolled 4757 participants with varying severity of AMD in the clinical trial; 3549 surviving participants consented to the follow-up study.. Participants were randomly assigned to antioxidants C, E, and β-carotene and/or zinc versus placebo during the clinical trial. For participants with intermediate or advanced AMD in 1 eye, the AREDS formulation delayed the progression to advanced AMD. Participants were then enrolled in a follow-up study. Eye examinations were conducted with annual fundus photographs and best-corrected visual acuity assessments. Medical histories and mortality were obtained for safety monitoring. Repeated measures logistic regression was used in the primary analyses.. Photographic assessment of progression to, or history of treatment for, advanced AMD (neovascular [NV] or central geographic atrophy [CGA]), and moderate visual acuity loss from baseline (≥15 letters).. Comparison of the participants originally assigned to placebo in AREDS categories 3 and 4 at baseline with those originally assigned to AREDS formulation at 10 years demonstrated a significant (P<0.001) odds reduction in the risk of developing advanced AMD or the development of NV AMD (odds ratio [OR], 0.66, 95% confidence interval [CI], 0.53-0.83 and OR, 0.60; 95% CI, 0.47-0. 78, respectively). No significant reduction (P = 0.93) was seen for the CGA (OR, 1.02; 95% CI, 0.71-1.45). A significant reduction (P = 0.002) for the development of moderate vision loss was seen (OR 0.71; 95% CI, 0.57-0.88). No adverse effects were associated with the AREDS formulation. Mortality was reduced in participants assigned to zinc, especially death from circulatory diseases.. Five years after the clinical trial ended, the beneficial effects of the AREDS formulation persisted for development of NV AMD but not for CGA. These results are consistent with the original recommendations that persons with intermediate or advanced AMD in 1 eye should consider taking the AREDS formulation.. The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Drug Therapy, Combination; Epidemiologic Studies; Female; Follow-Up Studies; Humans; Macular Degeneration; Male; Middle Aged; Odds Ratio; Photography; Survival Rate; Visual Acuity; Vitamin E; Vitamins; Zinc Oxide

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Double-Blind Method; Female; Humans; Macular Degeneration; Male; Treatment Outcome; Vitamin E; Vitamins; Zinc

The Age-Related Eye Disease Study (AREDS) demonstrated that antioxidant and zinc supplementation decreases progression to advanced age-related macular degeneration (AMD) in patients with moderate to severe disease. We evaluated the interaction of genetics and type of nutritional supplement on progression from moderate to advanced AMD.. Genetic analysis of a randomized, prospective clinical trial.. White patients with AREDS category 3 AMD in 1 eye and AREDS categories 1 through 4 AMD in the fellow eye enrolled in the AREDS with available peripheral blood-derived DNA (995).. Subjects were evaluated for known AMD genetic risk markers and treatment category. The progression rate to advanced AMD was analyzed by genotypes and AREDS treatment group using Cox regression.. The effect of inherited gene polymorphisms on treatment group-specific rate of progression to advanced AMD.. Over an average of 10.1 years, individuals with 1 or 2 complement factor H (CFH) risk alleles derived maximum benefit from antioxidants alone. In these patients, the addition of zinc negated the benefits of antioxidants. Treatment with zinc and antioxidants was associated with a risk ratio (RR) of 1.83 with 2 CFH risk alleles (P = 1.03E-02), compared with outcomes for patients without CFH risk alleles. Patients with age-related maculopathy sensitivity 2 (ARMS2) risk alleles derived maximum benefit from zinc-containing regimens, with a deleterious response to antioxidants in the presence of ARMS2 risk alleles. Treatment with antioxidants was associated with an RR of 2.58 for those with 1 ARMS2 risk allele and 3.96 for those with 2 ARMS2 risk alleles (P = 1.04E-6), compared with patients with no ARMS2 risk alleles. Individuals homozygous for CFH and ARMS2 risk alleles derived no benefit from any category of AREDS treatment.. Individuals with moderate AMD could benefit from pharmacogenomic selection of nutritional supplements. In this analysis, patients with no CFH risk alleles and with 1 or 2 ARMS2 risk alleles derived maximum benefit from zinc-only supplementation. Patients with one or two CFH risk alleles and no ARMS2 risk alleles derived maximum benefit from antioxidant-only supplementation; treatment with zinc was associated with increased progression to advanced AMD. These recommendations could lead to improved outcomes through genotype-directed therapy.

Topics: Aged; Alleles; Antioxidants; Ascorbic Acid; beta Carotene; Complement Factor H; Dietary Supplements; Disease Progression; Female; Humans; Macular Degeneration; Male; Pharmacogenetics; Polymorphism, Single Nucleotide; Prospective Studies; Proteins; Risk Factors; Vitamin E; Vitamins; Zinc Compounds

To report the secondary outcomes in the Carotenoids with Coantioxidants in Age-Related Maculopathy trial.. Randomized double-masked placebo-controlled clinical trial (registered as ISRCTN 94557601).. Participants included 433 adults 55 years of age or older with early age-related macular degeneration (AMD) in 1 eye and late-stage disease in the fellow eye (group 1) or early AMD in both eyes (group 2).. An oral preparation containing lutein (L), zeaxanthin (Z), vitamin C, vitamin E, copper, and zinc or placebo. Best-corrected visual acuity (BCVA), contrast sensitivity (CS), Raman spectroscopy, stereoscopic colour fundus photography, and serum sampling were performed every 6 months with a minimum follow-up time of 12 months.. Secondary outcomes included differences in BCVA (at 24 and 36 months), CS, Raman counts, serum antioxidant levels, and progression along the AMD severity scale (at 12, 24, and 36 months).. The differential between active and placebo groups increased steadily, with average BCVA in the former being approximately 4.8 letters better than the latter for those who had 36 months of follow-up, and this difference was statistically significant (P = 0.04). In the longitudinal analysis, for a 1-log-unit increase in serum L, visual acuity was better by 1.4 letters (95% confidence interval, 0.3-2.5; P = 0.01), and a slower progression along a morphologic severity scale (P = 0.014) was observed.. Functional and morphologic benefits were observed in key secondary outcomes after supplementation with L, Z, and coantioxidants in persons with early AMD.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Contrast Sensitivity; Double-Blind Method; Drug Therapy, Combination; Female; Fluorometry; Humans; Lutein; Macular Degeneration; Male; Mass Spectrometry; Middle Aged; Spectrum Analysis, Raman; Tablets; Trace Elements; Treatment Outcome; Visual Acuity; Vitamin E; Xanthophylls; Zeaxanthins

To test whether supplementation with alternate-day vitamin E or daily vitamin C affects the incidence of the diagnosis of age-related macular degeneration (AMD) in a large-scale randomized trial of male physicians.. Randomized, double-masked, placebo-controlled trial.. We included 14 236 apparently healthy United States male physicians aged ≥50 years who did not report a diagnosis of AMD at baseline.. Participants were randomly assigned to receive 400 international units (IU) of vitamin E or placebo on alternate days, and 500 mg of vitamin C or placebo daily. Participants reported new diagnoses of AMD on annual questionnaires and medical record data were collected to confirm the reports.. Incident diagnosis of AMD responsible for a reduction in best-corrected visual acuity to ≤20/30.. After 8 years of treatment and follow-up, a total of 193 incident cases of visually significant AMD were documented. There were 96 cases in the vitamin E group and 97 in the placebo group (hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.78-1.37). For vitamin C, there were 97 cases in the active group and 96 in the placebo group (HR, 0.99; 95% CI, 0.75-1.31).. In a large-scale, randomized trial of United States male physicians, alternate-day use of 400 IU of vitamin E and/or daily use of 500 mg of vitamin C for 8 years had no appreciable beneficial or harmful effect on risk of incident diagnosis of AMD.

Topics: Aged; Ascorbic Acid; Dietary Supplements; Double-Blind Method; Drug Combinations; Humans; Incidence; Macular Degeneration; Male; Middle Aged; Physicians; Risk Factors; Surveys and Questionnaires; United States; Visual Acuity; Vitamin E; Vitamins

To evaluate the influence of short-term carotenoid and antioxidant supplementation on retinal function in nonadvanced age-related macular degeneration (AMD).. Randomized controlled trial.. Twenty-seven patients with nonadvanced AMD and visual acuity > or =0.2 logarithm of the minimum angle of resolution were enrolled and randomly divided into 2 age-similar groups: 15 patients had oral supplementation of vitamin C (180 mg), vitamin E (30 mg), zinc (22.5 mg), copper (1 mg), lutein (10 mg), zeaxanthin (1 mg), and astaxanthin (4 mg) (AZYR SIFI, Catania, Italy) daily for 12 months (treated AMD [T-AMD] group; mean age, 69.4+/-4.31 years; 15 eyes); 12 patients had no dietary supplementation during the same period (nontreated AMD [NT-AMD] group; mean age, 69.7+/-6.23 years; 12 eyes). At baseline, they were compared with 15 age-similar healthy controls.. Multifocal electroretinograms in response to 61 M-stimuli presented to the central 20 degrees of the visual field were assessed in pretreatment (baseline) conditions and, in nonadvanced AMD patients, after 6 and 12 months.. Multifocal electroretinogram response amplitude densities (RAD, nanovolt/deg(2)) of the N1-P1 component of first-order binary kernels measured from 5 retinal eccentricity areas between the fovea and midperiphery: 0 degrees to 2.5 degrees (R1), 2.5 degrees to 5 degrees (R2), 5 degrees to 10 degrees (R3), 10 degrees to 15 degrees (R4), and 15 degrees to 20 degrees (R5).. At baseline, we observed highly significant reductions of N1-P1 RADs of R1 and R2 in T-AMD and NT-AMD patients when compared with healthy controls (1-way analysis of variance P<0.01). N1-P1 RADs of R3-R5 observed in T-AMD and NT-AMD were not significantly different (P>0.05) from controls. No significant differences (P>0.05) were observed in N1-P1 RADs of R1-R5 between T-AMD and NT-AMD at baseline. After 6 and 12 months of treatment, T-AMD eyes showed highly significant increases in N1-P1 RADs of R1 and R2 (P<0.01), whereas no significant (P>0.05) change was observed in N1-P1 RADs of R3-R5. No significant (P>0.05) changes were found in N1-P1 RADs of R1-R5 in NT-AMD eyes.. In nonadvanced AMD eyes, a selective dysfunction in the central retina (0 degrees -5 degrees ) can be improved by the supplementation with carotenoids and antioxidants. No functional changes are present in the more peripheral (5 degrees -20 degrees ) retinal areas.

Topics: Administration, Oral; Aged; Antioxidants; Ascorbic Acid; Carotenoids; Copper; Electroretinography; Female; Follow-Up Studies; Humans; Lutein; Macular Degeneration; Male; Middle Aged; Retina; Visual Acuity; Visual Fields; Vitamin E; Xanthophylls; Zeaxanthins; Zinc

To assess the association of ocular disorders and high doses of antioxidants or zinc with mortality in the Age-Related Eye Disease Study (AREDS).. Baseline fundus and lens photographs were used to grade the macular and lens status of AREDS participants. Participants were randomly assigned to receive oral supplements of high-dose antioxidants, zinc, antioxidants plus zinc, or placebo. Risk of all-cause and cause-specific mortality was assessed using adjusted Cox proportional hazards models.. During median follow-up of 6.5 years, 534 (11%) of 4753 AREDS participants died. In fully adjusted models, participants with advanced age-related macular degeneration (AMD) compared with participants with few, if any, drusen had increased mortality (relative risk [RR], 1.41; 95% confidence interval [CI], 1.08-1.86). Advanced AMD was associated with cardiovascular deaths. Compared with participants having good acuity in both eyes, those with visual acuity worse than 20/40 in 1 eye had increased mortality (RR, 1.36; 95% CI, 1.12-1.65). Nuclear opacity (RR, 1.40; 95% CI, 1.12-1.75) and cataract surgery (RR, 1.55; 95% CI, 1.18-2.05) were associated with increased all-cause mortality and with cancer deaths. Participants randomly assigned to receive zinc had lower mortality than those not taking zinc (RR, 0.73; 95% CI, 0.61-0.89).. The decreased survival of AREDS participants with AMD and cataract suggests that these conditions may reflect systemic rather than only local processes. The improved survival in individuals randomly assigned to receive zinc requires further study.

Topics: Aged; Aged, 80 and over; Aging; Antioxidants; Ascorbic Acid; beta Carotene; Cataract; Cataract Extraction; Cause of Death; Drug Therapy, Combination; Female; Humans; Macular Degeneration; Male; Middle Aged; Proportional Hazards Models; Survival Rate; United States; Vision Disorders; Visually Impaired Persons; Vitamin E; Zinc Oxide

Topics: Age of Onset; Aged; Aging; Antioxidants; Ascorbic Acid; beta Carotene; Disease Progression; Humans; Macular Degeneration; Middle Aged; National Institutes of Health (U.S.); Orthomolecular Therapy; United States; Vitamin E; Zinc

Observational and experimental data suggest that antioxidant and/or zinc supplements may delay progression of age-related macular degeneration (AMD) and vision loss.. To evaluate the effect of high-dose vitamins C and E, beta carotene, and zinc supplements on AMD progression and visual acuity.. The Age-Related Eye Disease Study, an 11-center double-masked clinical trial, enrolled participants in an AMD trial if they had extensive small drusen, intermediate drusen, large drusen, noncentral geographic atrophy, or pigment abnormalities in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye. At least 1 eye had best-corrected visual acuity of 20/32 or better. Participants were randomly assigned to receive daily oral tablets containing: (1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg); (2) zinc, 80 mg, as zinc oxide and copper, 2 mg, as cupric oxide; (3) antioxidants plus zinc; or (4) placebo.. (1) Photographic assessment of progression to or treatment for advanced AMD and (2) at least moderate visual acuity loss from baseline (> or =15 letters). Primary analyses used repeated-measures logistic regression with a significance level of.01, unadjusted for covariates. Serum level measurements, medical histories, and mortality rates were used for safety monitoring.. Average follow-up of the 3640 enrolled study participants, aged 55-80 years, was 6.3 years, with 2.4% lost to follow-up. Comparison with placebo demonstrated a statistically significant odds reduction for the development of advanced AMD with antioxidants plus zinc (odds ratio [OR], 0.72; 99% confidence interval [CI], 0.52-0.98). The ORs for zinc alone and antioxidants alone are 0.75 (99% CI, 0.55-1.03) and 0.80 (99% CI, 0.59-1.09), respectively. Participants with extensive small drusen, nonextensive intermediate size drusen, or pigment abnormalities had only a 1.3% 5-year probability of progression to advanced AMD. Odds reduction estimates increased when these 1063 participants were excluded (antioxidants plus zinc: OR, 0.66; 99% CI, 0.47-0.91; zinc: OR, 0.71; 99% CI, 0.52-0.99; antioxidants: OR, 0.76; 99% CI, 0.55-1.05). Both zinc and antioxidants plus zinc significantly reduced the odds of developing advanced AMD in this higher-risk group. The only statistically significant reduction in rates of at least moderate visual acuity loss occurred in persons assigned to receive antioxidants plus zinc (OR, 0.73; 99% CI, 0.54-0.99). No statistically significant serious adverse effect was associated with any of the formulations.. Persons older than 55 years should have dilated eye examinations to determine their risk of developing advanced AMD. Those with extensive intermediate size drusen, at least 1 large druse, noncentral geographic atrophy in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye, and without contraindications such as smoking, should consider taking a supplement of antioxidants plus zinc such as that used in this study.

Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Disease Progression; Double-Blind Method; Drug Evaluation; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Macular Degeneration; Male; Middle Aged; Prospective Studies; Risk Factors; Vision Disorders; Visual Acuity; Vitamin E; Zinc

To assess the balance of benefits and risks of supplementation with beta-carotene, vitamin E, vitamin C, and multivitamins on cancer, cardiovascular (CVD), and eye diseases.. Physicians' Health Study II (PHS II) is a randomized, double-blind, placebo-controlled trial enrolling 15,000 willing and eligible physicians aged 55 years and older. PHS II will utilize a 2 x 2 x 2 x 2 factorial design to test alternate day beta-carotene, alternate day vitamin E, daily vitamin C, and a daily multivitamin, in the prevention of total and prostate cancer, CVD, and the age-related eye diseases, cataract and macular degeneration. PRIOR RESULTS: The final results of the recently completed Physicians' Health Study I (PHS I), a randomized, double-blind, placebo-controlled trial in 22,071 healthy US male physicians, indicated that beta-carotene supplementation (50 mg on alternate days) had no significant benefit or harm on cancer or CVD during more than 12 years of treatment and follow-up. In regards to cancer, there were possible benefits on total and prostate cancer in those with low baseline levels assigned to beta-carotene, a finding compatible with the Chinese Cancer Prevention Study for combined treatment with beta-carotene, vitamin E, and selenium in a poorly nourished population. Further, with respect to CVD, there were apparent benefits of beta-carotene supplementation on subsequent vascular events among a small subgroup of 333 men with prior angina or revascularization. The currently available data from randomized trials of primary prevention are sparse and inconsistent for vitamin E and non-existent for vitamin C and multivitamins. For eye diseases, namely cataract and age-related macular degeneration, there are no completed large-scale randomized trials of antioxidant vitamins.. PHS II is unique in several respects. PHS II is the only primary prevention trial in apparently healthy men testing the balance of benefits and risks of vitamin E on cancer and CVD. In addition, PHS II is the only primary prevention trial in apparently healthy men to test the balance of benefits and risks of vitamin C, multivitamins, as well as any single antioxidant vitamin, alone and in combination, on cancer, CVD, and eye diseases. Finally, PHS II is the only trial testing a priori the hypotheses that beta-carotene and vitamin E may reduce the risks of prostate cancer. Thus, PHS II will add unique as well as importantly relevant and complementary information to the totality of evidence from other completed and ongoing large-scale randomized trials on the balance of benefits and risks of beta-carotene, vitamin E, vitamin C, and multivitamins alone and in combination on prevention of cancer, CVD and eye diseases.

Topics: Aged; Ascorbic Acid; beta Carotene; Cardiovascular Diseases; Cataract; Double-Blind Method; Female; Follow-Up Studies; Humans; Macular Degeneration; Male; Middle Aged; Neoplasms; Sample Size; Vitamin E

In a prospective cohort study, the authors examined whether self-selection for antioxidant vitamin supplement use affects the incidence of age-related maculopathy. The study population consisted of 21,120 US male physician participants in the Physicians' Health Study I who did not have a diagnosis of age-related maculopathy at baseline (1982). During an average of 12.5 person-years of follow-up, a total of 279 incident cases of age-related maculopathy with vision loss to 20/30 or worse were confirmed by medical record review. In multivariate analysis, as compared with nonusers of supplements, persons who used vitamin E supplements had a possible but nonsignificant 13% reduced risk of age-related maculopathy (relative risk = 0.87, 95 percent confidence interval (CI) 0.53-1.43), while users of multivitamins had a possible but nonsignificant 10% reduced risk (relative risk = 0.90, 95% CI 0.68-1.19). Users of vitamin C supplements had a relative risk of 1.03 (95% CI 0.71-1.50). These observational data suggest that among persons who self-select for supplemental use of antioxidant vitamin C or E or multivitamins, large reductions in the risk of age-related maculopathy are unlikely. Randomized trial data are accumulating to enable reliable detection of the existence of more plausible small-to-moderate benefits of these agents alone and in combination on age-related maculopathy.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Double-Blind Method; Humans; Macular Degeneration; Male; Middle Aged; Physicians; Prospective Studies; Risk; Smoking; United States; Vitamin E

The Age-Related Eye Disease Study (AREDS) was initially conceived as a long-term multicenter, prospective study of the clinical course of age-related macular degeneration (AMD) and age-related cataract. Data on progression rates and risk factors from the study will increase understanding of the clinical course of both conditions, generate hypotheses about etiology, and aid in the design of clinical trials of potential interventions. In addition to collecting natural history data, AREDS includes a clinical trial of high-dose vitamin and mineral supplements for AMD and a clinical trial of high-dose vitamin supplements for cataract. The clinical trials were initiated largely because of the widespread public use in the United States of commercially available pharmacologic doses of vitamins and minerals to treat these two eye conditions and the absence of definitive studies on the safety and efficacy of their use. Important design issues for the clinical trials include: defining cataract and AMD, estimating event rates, determining the type and dosage of vitamins and minerals to be tested for each condition, and identifying the parameters necessary for monitoring safety and efficacy. This paper describes the AREDS design, including the study rationale and operational structure, and the approach adopted to combine, for two diseases, clinical trials with a natural history study.

Topics: Aged; Aged, 80 and over; Aging; Antioxidants; Ascorbic Acid; Cataract; Disease Progression; Drug Monitoring; Follow-Up Studies; Humans; Longitudinal Studies; Macular Degeneration; Middle Aged; Placebos; Prospective Studies; Research Design; Risk Factors; Safety; Vitamin E; Zinc

Age-related macular degeneration (AMD) is the main cause of a reduction in visual acuity in patients over the age of 65 years. A positive influence of medical treatment (i.e. with vitamins and trace minerals) has been suggested but remains unproven. In this randomized, double-blind study, 20 patients in an early stage of AMD were included. Over a period of 6 months, 9 patients were treated with Visaline and 11 with a placebo. The effect of the treatment was not statistically different between the two groups, admittedly small in number, in terms of visual and retinal acuity, color vision, and contrast sensitivity. Despite the lack of such measureable differences, the patients' own subjective assessments, however, were much better in the Visaline-treated group. Due to the short duration of the observation time, we can not comment on a possible long-term effect.

Topics: Adrenergic beta-Agonists; Aged; alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Double-Blind Method; Drug Combinations; Female; Humans; Intraocular Pressure; Macular Degeneration; Male; Nylidrin; Pilot Projects; Tablets; Tocopherols; Vision, Ocular; Visual Acuity; Vitamin E

We compared and analyzed the concentrations of vitamin C, vitamin E, zinc, and copper in both national and regional brands of dietary supplements recommended for patients who are at risk for macular degeneration.. Prospective cross-sectional study.. National brand name and generic multivitamin formulations for age-related macular degeneration were obtained. Comparative analysis of the vitamin C and vitamin E content was performed by gas chromatography-mass spectrometry and the zinc and copper content was analyzed by atomic absorption spectroscopy in an institutional chemistry laboratory.. All national brand name vitamins, both tablet and gel capsule formulations, and generic brands in tablet form were relatively accurate in their product labeling. For most of the samples tested, the measured quantities of vitamin C, vitamin E, zinc, and copper were slightly higher than labeled but not to an amount that would cause any systemic toxicity if taken at the recommended dosages.. Physicians may recommend national brand name vitamins and generic brands in tablet form to their patients with some confidence; however, the content may have some inaccuracies regarding labeling.

Topics: Ascorbic Acid; Biomarkers; Cross-Sectional Studies; Gas Chromatography-Mass Spectrometry; Humans; Macular Degeneration; Prospective Studies; Reproducibility of Results; Spectrophotometry, Atomic; Vitamin E; Vitamins; Zinc

Topics: Aged; Antioxidants; Ascorbic Acid; Carotenoids; Case-Control Studies; Diet; Diet Surveys; Fatty Acids, Omega-3; Female; Humans; Macular Degeneration; Male; Middle Aged; Risk Factors; Turkey; Vitamin E; Zinc

To investigate the impact of ascorbate, via DNA hydroxymethylation, on VEGF expression in retinal pigment epithelial (RPE) cells.. Dot-blot and hydroxymethylated DNA immunoprecipitation sequencing were applied to evaluate the impact of ascorbate on DNA hydroxymethylation in ARPE-19 cells. RNA sequencing (RNA-seq) was carried out to analyze the transcriptome. Quantitative RT-PCR and ELISA were conducted to examine the transcription and secretion of VEGF from cultured cells. Primary human fetal RPE cells and RPE-J cells were used to verify the effect of ascorbate on VEGF expression. ELISA was used to measure VEGF in the vitreous humor of Gulo-/- mice, which, like humans, cannot synthesize ascorbate de novo.. Treatment with ascorbate (50 μM) promoted 5-hydroxymethycytosine (5hmC) generation and changed the genome-wide profiles of 5hmC in ARPE-19 cells. Ascorbate also caused a dramatic shift in the transcriptome-3186 differential transcripts, of which 69.3% are correlated with altered 5hmC in promoters or gene bodies. One of the most downregulated genes was VEGFA, which encodes the VEGF protein. The suppression of VEGF by ascorbate is independent of hypoxia-inducible factor 1-alpha (HIF-1α) but correlates with increased 5hmC in the gene body. The decreased transcription and secretion of VEGF by ascorbate were verified in primary human fetal RPE cells. Furthermore, adding ascorbate in the diet for Gulo-/- mice resulted in decreased levels of VEGF in the RPE/choroid and vitreous humor.. Ascorbate inhibits VEGF expression in RPE cells likely via DNA hydroxymethylation. Thus, ascorbate could be implicated in the prevention or treatment of diseases such as age-related macular degeneration (AMD).

Topics: Animals; Ascorbic Acid; Cell Survival; Cells, Cultured; DNA; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; Humans; Immunoblotting; Macular Degeneration; Mice; Real-Time Polymerase Chain Reaction; Retinal Pigment Epithelium; Vascular Endothelial Growth Factor A

Age-related macular degeneration (AMD) is one of the major causes of irreversible blindness. The objective of this study was to determine whether there is any relationship between dietary intake of fruits and vegetables (F&V) and antioxidant nutrients including carotenoids and AMD according to smoking status in elderly men.. We performed a cross-sectional analysis using nationally representative samples of elderly aged ≥ 65 years (n = 1414) from the Korea National Health and Nutrition Examination Survey (KNHANES, 2010-2012).. The current smokers consumed less food in total, and, in particular, less cereals/potatoes/sugar products, fruits and vegetables than the nonsmokers and former smokers (p < 0.05). Intake of energy, thiamin, vitamin C, vitamin A, and β-carotene were significantly lower in the current smokers than in the nonsmokers and the former smokers. For current smokers, the ORs of the highest tertile compared with the lowest tertile were 0.36 (95% CI: 0.14-0.96, p for trend = 0.0576) for F&V, 0.32 (95% CI: 0.12-0.85, p for trend = 0.0561) for vitamin C, 0.23 (95% CI: 0.08-0.67, p for trend = 0.0038) for α-carotene, 0.13 (95% CI: 0.04-0.46, p for trend = 0.0003) for β-carotene after adjusting for confounding factors. In contrast, there was no association between antioxidant nutrient intake and AMD among the nonsmokers and former smokers.. These results suggest that increased consumption of fruits and vegetables containing antioxidant components such as vitamin C, α-carotene, and β-carotene may have a protective effect on AMD. These effects may be more evident among current smokers.

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Cross-Sectional Studies; Diet; Fruit; Humans; Macular Degeneration; Male; Nutrition Surveys; Republic of Korea; Smoking; Vegetables; Vitamins

Knowledge of the risk factor profile of patients presenting with late-stage age-related macular degeneration (AMD) could help identify the most frequent modifiable AMD precursors among people who are referred for treatment. We aimed to assess dietary behaviours by comparing adjusted mean intakes of micronutrients and major food groups (fruits, vegetables, fish) among patients with AMD and a sample of age-sex-matched controls.. Cross-sectional analysis of 480 late AMD cases and 518 population-based age-sex-matched controls with no AMD signs. AMD cases (aged 60+ years) were those presenting for treatment to a hospital eye clinic in Sydney, Australia, during 2012-2015. The comparator group were obtained from a cohort study (Blue Mountains Eye Study; Sydney, Australia) during 2002-2009. Dietary intake was assessed using a semiquantitative food-frequency questionnaire. AMD lesions were assessed from retinal photographs.. After multivariable adjustment, patients with late-stage AMD compared with controls had significantly lower intakes of vitamin E (7.4 vs 9.8 mg/day; p<0.0001), beta-carotene (6232 vs 7738 μg/day; p<0.0001), vitamin C (161 vs 184 mg/day; p=0.0002) and folate (498.3 vs 602 μg/day; p<0.0001); but had higher intakes of zinc (13.0 vs 11.9 mg/day; p<0.0001). A significantly lower proportion of patients with late AMD met the recommended intake of vegetables than controls: 52.9% versus 64.5%; p=0.0002.. This study showed significant differences in intakes of vitamins C and E, beta-carotene, folate and vegetables between patients with late-stage AMD and healthy controls, and thus has provided a better understanding of the nutritional intake of patients presenting with advanced AMD.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; beta Carotene; Case-Control Studies; Cross-Sectional Studies; Diet; Fish Products; Food; Fruit; Humans; Macular Degeneration; Male; Micronutrients; Middle Aged; Vegetables; Vitamin E

To evaluate the rate of adherence to prescribed nutritional supplementation in patients affected by age-related macular degeneration, in an Italian tertiary referral tertiary center.. Patients with age-related macular degeneration, age-related eye disease study Categories 3 and 4, were recruited and underwent an 11-item questionnaire.. The study included a total of 193 patients meeting the age-related eye disease study nutritional supplementation criteria (174 patients with age-related eye disease study Category 4 and 19 with Category 3). Seventy-seven (40%) were taking oral supplementation, 70 of whom (90%) 1 tablet/day. Oral supplementation was recommended by the personal ophthalmologist in 85 patients (44%), including all those currently receiving it. Eight patients of 85 (9.4%) rejected supplementation despite it being recommended, mostly because they were already taking other medicines. Ninety-four patients (48%) claimed they had not received any information from their ophthalmologist.. Our data reveal that Italian patients with age-related eye disease study Categories 3 and 4 have a low adherence to nutritional supplementation. In 65% of cases, patients were not adequately informed by their ophthalmologist of the potential benefits of oral supplementation for age-related macular degeneration; indeed, 108 patients (56%) were not even aware such nutritional treatments are available. Ophthalmologists should be aware of the importance of giving advice to persons with age-related macular degeneration regarding the benefits of oral supplements.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Cross-Sectional Studies; Dietary Supplements; Disease Progression; Fatty Acids, Omega-3; Female; Humans; Italy; Macular Degeneration; Male; Middle Aged; Nutritional Physiological Phenomena; Patient Compliance; Practice Patterns, Physicians'; Surveys and Questionnaires; Vitamins; Zinc

This case-control study reports the association between nutrient intake and neovascular age-related macular degeneration (AMD) in Japan. The nutrient intake of 161 neovascular AMD cases from two university hospitals and 369 population-based control subjects from a cohort study was assessed using a brief-type self-administered questionnaire on diet history, which required respondent recall of the usual intake of 58 foods during the preceding month. Energy-adjusted nutrient intake values were compared between the groups. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% CIs adjusted for smoking history, age, sex, chronic disease history, supplement use, and alcohol consumption. Logistic regression analysis demonstrated that low intakes of n-3 fatty acid, α-tocopherol, zinc, vitamin D, vitamin C, and β-carotene were associated with neovascular AMD (Trend P < 0.0001 for n-3 fatty acid, Trend P < 0.0001 for α-tocopherol, Trend P < 0.0001 for zinc, Trend P = 0.002 for vitamin D, Trend P = 0.04 for vitamin C, Trend P = 0.0004 for β-carotene). There was no association with retinol or cryptoxanthin intake and neovascular AMD (P = 0.67, 0.06).

Topics: Aged; Aged, 80 and over; alpha-Tocopherol; Ascorbic Acid; beta Carotene; Case-Control Studies; Dietary Supplements; Energy Intake; Fatty Acids, Omega-3; Female; Humans; Japan; Logistic Models; Macular Degeneration; Male; Risk Factors; Surveys and Questionnaires; Vitamin D; Zinc

To compare ingredients contained in top-selling brands of ocular nutritional supplements with the Age-Related Eye Disease Study (AREDS) and AREDS2 formulae and investigate the validity of claims made by manufacturers of leading brands of ocular nutritional supplements.. Descriptive.. None.. We examined the 5 top-selling brands of ocular nutritional supplements in the United States according to dollar sales tracked by SymphonyIRI (Waltham, MA) from June 2011 to June 2012. We reviewed the ingredients and manufacturer claims of 11 ocular nutritional supplements on the companies' consumer information websites; the ingredients were compared with those contained in the AREDS and AREDS2 formulae.. Proportion of ocular nutritional supplements that contained the same ingredients, in the same doses, as the AREDS or AREDS2 formula; proportion of nutritional supplements with unsubstantiated claims made by the manufacturer.. All of the ocular nutritional supplements contained the ingredients from the AREDS or AREDS2 formula; 36% (4/11) of the supplements contained equivalent doses of AREDS or AREDS2 ingredients; 55% (6/11) included some information about the AREDS on their consumer information websites. Product descriptions from 4 of the 11 supplements (36%) stated that the supplements were important to maintain general eye health; none of these supplements duplicated the AREDS or AREDS2 formula. All the individual supplements claimed to "support," "protect," "help," or "promote" vision and eye health, but none specified that there is no proven benefit in using nutritional supplements for primary prevention of eye disease.. The majority of top-selling ocular nutritional supplements did not contain the identical ingredient dosages of the AREDS or AREDS2 formula and had product description claims that lacked level 1 evidence, underscoring the importance of ophthalmologists educating their patients on the evidence-based role of nutritional supplements in the management of eye health.

Topics: Ascorbic Acid; beta Carotene; Chemistry, Pharmaceutical; Dietary Supplements; Drug Compounding; Drug Industry; Evidence-Based Practice; Humans; Lutein; Macular Degeneration; Niacin; Riboflavin; Vitamin E

To examine effect modification between genetic susceptibility to age-related macular degeneration (AMD) and dietary antioxidant or fish consumption on AMD risk.. Pooled data analysis of population-based cohorts.. Participants from the Blue Mountains Eye Study (BMES) and Rotterdam Study (RS).. Dietary intakes of antioxidants (lutein/zeaxanthin [LZ], β-carotene, and vitamin C), long-chain omega-3 polyunsaturated fatty acids, and zinc were estimated from food frequency questionnaires. The AMD genetic risk was classified according to the number of risk alleles of CFH (rs1061170) or ARMS2 (rs10490924) as low (no or 1 risk allele) or high (≥ 2 risk alleles). Interactions between dietary intake and genetic risk levels were assessed. Associations between dietary intake and AMD risk were assessed comparing the highest with the 2 lower intake tertiles by genetic risk subgroups using discrete logistic regression, conducted in each study separately and then using pooled data. Participants without AMD lesions at any visit were controls. We adjusted for age and sex in analyses of each cohort sample and for smoking status and study site in pooled-data analyses.. All 15-year incident late AMD cases were confirmed by chief investigators of the Beaver Dam Eye Study, BMES, and RS. Intergrader reproducibility was assessed in an early AMD subsample, with 86.4% agreement between BMES and RS graders, allowing for a 1-step difference on a 5-step AMD severity scale.. In pooled data analyses, we found significant interaction between AMD genetic risk status and LZ intake (P=0.0009) but nonsignificant interactions between genetic risk status and weekly fish consumption (P=0.05) for risk of any AMD. Among participants with high genetic risk, the highest intake tertile of LZ was associated with a >20% reduced risk of early AMD, and weekly consumption of fish was associated with a 40% reduced risk of late AMD. No similar association was evident among participants with low genetic risk. No interaction was detected between β-carotene or vitamin C and genetic risk status.. Protection against AMD from greater LZ and fish consumption in persons with high genetic risk based on 2 major AMD genes raises the possibility of personalized preventive interventions.

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Complement Factor H; Diet; Fatty Acids, Omega-3; Feeding Behavior; Female; Fish Products; Fruit; Genetic Predisposition to Disease; Genotyping Techniques; Humans; Incidence; Lutein; Macular Degeneration; Male; Middle Aged; Molecular Epidemiology; Netherlands; New South Wales; Proteins; Surveys and Questionnaires; Vegetables; Xanthophylls; Zeaxanthins; Zinc Compounds

To evaluate the patient's understanding of the importance and adherence to the various lifestyle and Age-Related Eye Disease Study (AREDS) supplement recommendations for age-related macular degeneration (AMD).. Cross-sectional study.. Patients with AMD treated at the vitreoretinal service clinic.. Telephone questionnaire survey was administered to assess knowledge and adherence to various recommendations made to patients with AMD about lifestyle and AREDS supplements in this single-institution study.. Among 92 patients with AMD contacted, dietary modification, exercise and weight reduction, smoking cessation, and AREDS supplementation recommendations were recalled by 47 (51%), 21 (23%), 5 (5%), and 90 (98%) patients, respectively. The necessity of making these interventions was believed by 29 (62%), 16 (76%), 4 (80%), and 67 (74%) patients, respectively. Patient adherence to dietary modification was 81%, to exercise and weight reduction was 76%, to smoking cessation was 0%, and to AREDS supplementation was 88% (71% on correct dose). Financially, 29% of the patients noted a mean increase of $88 per month in expenditure because of making dietary modifications, but most reported such as justified; 61% noted a mean increase of $25 per month in expenditure from consumption of AREDS supplements, and most (96%) believed this was justified.. Patients with AMD recalled recommendations for AREDS supplementation more often than other lifestyle changes but generally felt recommendations were necessary and affordable. Adherence to smoking cessation recommendation was poor (0%), but to other recommendations was good.

Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; California; Cross-Sectional Studies; Dietary Supplements; Feeding Behavior; Female; Guideline Adherence; Health Knowledge, Attitudes, Practice; Health Surveys; Humans; Life Style; Macular Degeneration; Male; Middle Aged; Patient Compliance; Quality of Life; Surveys and Questionnaires; Vitamin E; Vitamins; Zinc Compounds

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Drug Combinations; Humans; Macular Degeneration; Male; Middle Aged; Visual Acuity; Vitamin E; Vitamins; Zinc

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Attitude of Health Personnel; beta Carotene; Dietary Supplements; Female; Health Surveys; Humans; Japan; Lutein; Macular Degeneration; Male; Micronutrients; Middle Aged; Nutritional Support; Ophthalmology; Surveys and Questionnaires; Vitamin E; Zinc

To determine if short-term Age-Related Eye Disease Study (AREDS) antioxidant and zinc supplementation affects biomarkers of oxidative stress, possibly serving as a predictor of their efficacy.. Prospective interventional case series.. Nineteen subjects, 12 with intermediate or advanced age-related macular degeneration (AMD) (AREDS categories 3 or 4) and 7 non-AMD controls, were admitted to the Vanderbilt General Clinical Research Center and placed on a controlled diet for 7 days. Antioxidant and zinc supplements were stopped 2 weeks prior to study enrollment. Dietary supplementation with 500 mg vitamin C, 400 IU vitamin E, 15 mg β-carotene, 80 mg zinc oxide, and 2 mg cupric oxide per day was instituted on study day 2. Blood was drawn on study days 2 and 7, and plasma concentrations of cysteine (Cys), cystine (CySS), glutathione (GSH), isoprostane (IsoP), and isofuran (IsoF) were determined.. Short-term AREDS supplementation significantly lowered mean plasma levels of CySS in participants on a regulated diet (P = .034). No significant differences were observed for Cys, GSH, IsoP, or IsoF. There were no significant differences between AMD patients and controls.. This pilot interventional study shows that a 5-day course of antioxidant and zinc supplements can modify plasma levels of CySS, suggesting that this oxidative stress biomarker could help predict how likely an individual is to benefit from AREDS supplementation. Further, CySS may be useful for the evaluation of new AMD therapies, particularly those hypothesized to affect redox status.

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Copper; Cysteine; Cystine; Dietary Supplements; Female; Furans; Glutathione; Humans; Isoprostanes; Macular Degeneration; Male; Oxidative Stress; Pilot Projects; Prospective Studies; Vitamin E; Zinc Oxide

To measure the oxidative and antioxidant biochemical parameters in the serum of Chinese patients with age-related macular degeneration (AMD) and in a similar age control group from the same area.. A case-control study.. 56 AMD patients ( 21 early dry, 13 geographic atrophy and 22 wet form) and 34 normal subjects, similar for age and sex were studied.. Both groups completed a questionnaire about demographic characters and dieatry habit, and the levels of serum lipid peroxidation (malondialdehyde, MDA) and antioxidants parameters (vitamin C and E, the activities of superoxide dismutase--SOD, total antioxidant capacity--TAC ) were determined.. There was a significantly higher frequency of daily intake of fruit and legumes in controls than in AMD patients. There was a significantly increased serum MDA levels and SOD activities, and significantly decreased serum vitamin C and total antioxidant capacity in AMD patients as compared to controls. The intensity of lipid peroxidation was higher with the progression of AMD. There was not difference in serum vitamin E levels between AMD patients and controls.. Oxido-reduction disturbance may be involved in the pathogenesis of AMD. There is a significantly decreased antioxidant capacity in AMD patients.

Topics: Antioxidants; Ascorbic Acid; Asian People; Biomarkers; Blood Chemical Analysis; Case-Control Studies; Feeding Behavior; Female; Humans; Lipid Peroxidation; Macular Degeneration; Male; Malondialdehyde; Middle Aged; Oxidation-Reduction; Superoxide Dismutase; Vitamin E

Genetic variation in complement factor H (CFH) has been implicated as a major risk factor for age-related macular degeneration (AMD). The reduction in CFH amount or its complement-modulating activity may lead to inadequate control of complement-driven inflammation at the outer retina. We explored the effect of photo-oxidative stress and inflammatory cytokine on the expression of CFH in retinal pigment epithelial (RPE) cells.. Cultured human RPE cells were exposed to blue light in the presence of interferon-γ (IFN-γ). CFH expression in cell lysate was examined by Western blot and the secretory CFH in culture medium was analyzed by ELISA. RPE cells were treated with vitamin C and exogenous superoxide dismutase mimetic (Tempol) before photo-oxidative treatments. The intracellular reactive oxygen species were examined by flow cytometry.. IFN-γ increased CFH expression in RPE and the expression was suppressed significantly under concomitant blue light illumination. The secretory CFH level also decreased significantly under blue light illumination, which was related to the decreased intracellular mRNA and protein expressions of CFH. The suppression was mediated through an oxidative mechanism, and was particularly related to superoxide anion generation. The suppression of CFH expression in RPE under blue light illumination was abrogated by vitamin C and Tempol.. Photo-oxidative stress reduces the ability of IFN-γ to increase CFH expression in RPE. Apart from reducing the oxidative damage, vitamin C reduces the suppression of CFH under photo-oxidative stress. These results suggest a new perspective of the interaction between oxidative stress and inflammation, and provide a potential novel treatment strategy for age-related macular degeneration.

Topics: Antioxidants; Ascorbic Acid; Blotting, Western; Cell Survival; Cells, Cultured; Complement Factor H; Cyclic N-Oxides; Cytokines; Follow-Up Studies; Gene Expression Regulation; Genetic Variation; Humans; Inflammation; Intracellular Fluid; Macular Degeneration; Oxidative Stress; Reactive Oxygen Species; Retinal Pigment Epithelium; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Spin Labels

The purposes of this study were to determine the rate of adherence to the recommendations of the Age-Related Eye Disease Study (AREDS) regarding vitamin supplement use among patients with age-related macular degeneration (AMD) at a tertiary retina center and to identify factors associated with adherence.. Consecutive patients with a history of AMD were administered an in-person survey designed to assess use of vitamin supplementation as well as to investigate factors that may influence supplementation use patterns. A retina specialist performed dilated funduscopic examinations and categorized patients' AMD severity according to the AREDS classification system. The main outcome measure was rate of adherence to AREDS recommendations.. Sixty-four patients with AMD completed the survey. Sixty-three percent of patients met AREDS criteria for vitamin supplementation. Of those patients who met the criteria, only 43% reported taking AREDS vitamins in the recommended dosages. Among patients using AREDS vitamins as recommended, 100% were return patients to the tertiary retina center and reported a retina specialist as the primary recommendation source for supplement use. Of patients who met AREDS criteria for vitamin supplementation but were not taking vitamins as per AREDS recommendations, 87% were new patients to the retina service and 75% reported that vitamin supplementation had never been recommended to them.. Patients with intermediate or advanced AMD in at least one eye show a low adherence rate to the AREDS recommendations for vitamin supplementation.

Topics: Ascorbic Acid; beta Carotene; Dietary Supplements; Female; Guidelines as Topic; Health Surveys; Humans; Macular Degeneration; Male; Nutrition Policy; Patient Compliance; Surveys and Questionnaires; Vitamin E; Vitamins; Zinc

Because foods provide many nutrients that may interact to modify risk for multifactorial diseases such as age-related macular degeneration (AMD), we sought to develop a composite scoring system to summarize the combined effect of multiple dietary nutrients on AMD risk. This has not been done previously.. Cross-sectional study.. From the 4003 participants in the Age-Related Eye Disease Study (AREDS), there were 7,934 eyes included in this study.. Considering dietary intakes of vitamins C and E, zinc, lutein/zeaxanthin, docosahexaenoic acid, eicosapentaenoic acid, and low-dietary glycemic index (dGI) from AREDS baseline information, we assigned each nutrient a percentile rank score then summed them into a compound score for each participant. Using eye as the unit of analysis, we evaluated the association between the compound score and risk of prevalent AMD. Validation, fitness, and performance of the model were evaluated using bootstrapping techniques, adjusted quasi-likelihood under the independence model criterion, and the c-index, respectively.. Stereoscopic fundus photographs of the macula were taken and graded at baseline using the AREDS protocol and AMD Classification System.. Our results showed that higher compound scores were associated with lower risk for early AMD, indicated by drusen, and advanced AMD. Validation analyses indicated that these relationships are robust (the average 50-time bootstrapping per quartile odds ratios = 0.727, 0.827, and 0.753, respectively, for drusen, and 0.616, 0.536, and 0.572, respectively, for advanced AMD). Model selection analyses suggested that the compound score should be included, but that measures of dietary beta-carotene should not be included.. We found that consuming diets that provide low dGI and higher intakes of these nutrients were associated with the greatest reduction in risk for prevalent drusen and advanced AMD, whereas dietary beta-carotene did not affect these relationships. These findings warrant further prospective studies.. Proprietary or commercial disclosure may be found after the references.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Cross-Sectional Studies; Diet; Diet Surveys; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Energy Intake; Fatty Acids, Unsaturated; Feeding Behavior; Female; Glycemic Index; Humans; Lutein; Macular Degeneration; Male; Middle Aged; Retinal Drusen; Risk Assessment; Vitamin E; Xanthophylls; Zeaxanthins; Zinc

To examine the association of sunlight exposure and antioxidant level with age-related macular degeneration (AMD).. Four thousand seven hundred fifty-three participants aged 65 years or older in the European Eye Study underwent fundus photography, were interviewed for adult lifetime sunlight exposure, and gave blood for antioxidant analysis. Blue light exposure was estimated by combining meteorologic and questionnaire data.. Data on sunlight exposure and antioxidants were available in 101 individuals with neovascular AMD, 2182 with early AMD, and 2117 controls. No association was found between blue light exposure and neovascular or early AMD. Significant associations were found between blue light exposure and neovascular AMD in individuals in the quartile of lowest antioxidant level-vitamin C, zeaxanthin, vitamin E, and dietary zinc-with an odds ratio of about 1.4 for 1 standard deviation unit increase in blue light exposure. Higher odds ratios for blue light were observed with combined low antioxidant levels, especially vitamin C, zeaxanthin, and vitamin E (odds ratio, 3.7; 95% confidence interval, 1.6-8.9), which were also associated with early stages of AMD.. Although it is not possible to establish causality between sunlight exposure and neovascular AMD, our results suggest that people in the general population should use ocular protection and follow dietary recommendations for the key antioxidant nutrients.

Topics: Age Distribution; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Case-Control Studies; Cohort Studies; Dietary Supplements; Environmental Exposure; Europe; Female; Humans; Incidence; Logistic Models; Macular Degeneration; Male; Multivariate Analysis; Reference Values; Risk Assessment; Severity of Illness Index; Sex Distribution; Sunlight; Surveys and Questionnaires; Vitamin E; Xanthophylls; Zeaxanthins; Zinc

To assess the relationship between baseline dietary and supplement intakes of antioxidants and the long-term risk of incident age-related macular degeneration (AMD).. Australian population-based cohort study.. Of 3654 baseline (1992-1994) participants initially 49 years of older, 2454 were reexamined after 5 years, 10 years, or both.. Stereoscopic retinal photographs were graded using the Wisconsin Grading System. Data on potential risk factors were collected. Energy-adjusted intakes of alpha-carotene; beta-carotene; beta-cryptoxanthin; lutein and zeaxanthin; lycopene; vitamins A, C, and E; and iron and zinc were the study factors. Discrete logistic models assessed AMD risk. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated after adjusting for age, gender, smoking, and other risk factors.. Incident early, late, and any AMD.. For dietary lutein and zeaxanthin, participants in the top tertile of intake had a reduced risk of incident neovascular AMD (RR, 0.35; 95% CI, 0.13-0.92), and those with above median intakes had a reduced risk of indistinct soft or reticular drusen (RR, 0.66; 95% CI, 0.48-0.92). For total zinc intake the RR comparing the top decile intake with the remaining population was 0.56 (95% CI, 0.32-0.97) for any AMD and 0.54 (95% CI, 0.30-0.97) for early AMD. The highest compared with the lowest tertile of total beta-carotene intake predicted incident neovascular AMD (RR, 2.68; 95% CI, 1.03-6.96; P = 0.029, for trend). Similarly, beta-carotene intake from diet alone predicted neovascular AMD (RR comparing tertile 3 with tertile 1, 2.40; 95% CI, 0.98-5.91; P = 0.027, for trend). This association was evident in both ever and never smokers. Higher intakes of total vitamin E predicted late AMD (RR compared with the lowest tertile, 2.83; 95% CI, 1.28-6.23; and RR, 2.55; 95% CI, 1.14-5.70 for the middle and highest tertiles, respectively; P = 0.22, for trend).. In this population-based cohort study, higher dietary lutein and zeaxanthin intake reduced the risk of long-term incident AMD. This study confirmed the Age-Related Eye Disease Study finding of protective influences from zinc against AMD. Higher beta-carotene intake was associated with an increased risk of AMD.

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Choroidal Neovascularization; Cohort Studies; Dietary Supplements; Feeding Behavior; Female; Follow-Up Studies; Humans; Incidence; Macular Degeneration; Male; Middle Aged; New South Wales; Risk Factors; Vitamin E; Zinc

Evidence continues to accumulate that oxidative stress is etiologically important in the pathogenesis of age-related maculopathy (ARM) and that appropriate antioxidants of dietary origin may protect against this condition.. Risk factors for ARM may be classed as established or putative. We report a study designed to investigate whether such risk factors are associated with a dietary lack of antioxidants relevant to retinal health.. Dietary, anthropometric, and sociodemographic details relating to 828 healthy Irish subjects aged 20-60 y were recorded in a cross-sectional fashion and analyzed for associations between risk factors for ARM and dietary intake of relevant nutrients.. Of the established risk factors for ARM, increasing age was associated with a relative lack of dietary zeaxanthin (P < 0.05) and tobacco use with a relative lack of dietary vitamin C (P < 0.05). Of the putative risk factors for ARM, alcohol consumption was associated with a relative lack of dietary alpha-linoleic acid (P < 0.05), and female sex was associated with a relative lack of dietary zinc (P < 0.05).. We showed that several variables related to risk for ARM are associated with a relative dietary lack of key nutrients. Our finding that age, the most important and universal risk factor for ARM, is associated with a relative lack of dietary zeaxanthin, is an important finding that warrants further investigation.

Topics: Adult; Age Factors; Alcohol Drinking; Antioxidants; Ascorbic Acid; Cross-Sectional Studies; Diet; Female; Humans; Ireland; Linoleic Acid; Macular Degeneration; Male; Middle Aged; Oxidative Stress; Risk Factors; Sex Factors; Smoking; Surveys and Questionnaires; Xanthophylls; Zeaxanthins; Zinc

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antioxidants; Ascorbic Acid; beta Carotene; Drug Therapy, Combination; Humans; Macular Degeneration; Middle Aged; Ranibizumab; Vitamin E

Topics: Ascorbic Acid; beta Carotene; Dietary Supplements; Humans; Macular Degeneration; Vitamin E; Vitamins; Zinc Oxide

To evaluate the relationship of dietary carotenoids, vitamin A, alpha-tocopherol, and vitamin C with prevalent age-related macular degeneration (AMD) in the Age-Related Eye Disease Study (AREDS).. Demographic, lifestyle, and medical characteristics were ascertained on 4519 AREDS participants aged 60 to 80 years at enrollment. Stereoscopic color fundus photographs were used to categorize participants into 4 AMD severity groups and a control group (participants with < 15 small drusen). Nutrient intake was estimated from a self-administered semiquantitative food frequency questionnaire at enrollment. Intake values were energy adjusted and classified by quintiles. The relationship between diet and AMD status was assessed using logistic regression analyses.. Dietary lutein/zeaxanthin intake was inversely associated with neovascular AMD (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.45-0.93), geographic atrophy (OR, 0.45; 95% CI, 0.24-0.86), and large or extensive intermediate drusen (OR, 0.73; 95% CI, 0.56-0.96), comparing the highest vs lowest quintiles of intake, after adjustment for total energy intake and nonnutrient-based covariates. Other nutrients were not independently related to AMD.. Higher dietary intake of lutein/zeaxanthin was independently associated with decreased likelihood of having neovascular AMD, geographic atrophy, and large or extensive intermediate drusen.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Carotenoids; Case-Control Studies; Choroidal Neovascularization; Diet; Eating; Energy Intake; Feeding Behavior; Female; Humans; Lutein; Macular Degeneration; Male; Middle Aged; Nutrition Surveys; Regression Analysis; Surveys and Questionnaires; Vitamin A; Vitamin E; Xanthophylls; Zeaxanthins

Topics: Antioxidants; Ascorbic Acid; Cataract; Clinical Trials as Topic; Dietary Supplements; Eye Diseases; Glaucoma; Humans; Macular Degeneration; Risk Factors; Smoking; Vitamin E; Vitamins

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Humans; Macular Degeneration; Middle Aged; Vitamin E; Zinc

To assess longitudinal associations between dietary fat and incident age-related maculopathy (ARM) in an older, population-based, historical cohort.. A total of 3654 persons, 49 years or older, participated in the Blue Mountains Eye Study (1992-1994); 2335 (75.1% of survivors) were reexamined after 5 years (1997-1999). Dietary data were collected from 2895 people (79%) at baseline by means of a semiquantitative food frequency questionnaire to calculate dietary fat intakes. Presence of ARM was graded from retinal photographs (Wisconsin ARM Grading System). Logistic regression adjusted for age, sex, vitamin C intake, and smoking.. Participants with the highest vs lowest quintiles of n-3 polyunsaturated fat intake had lower risk of incident early ARM (odds ratio [95% confidence interval], 0.41 [0.22-0.75). A 40% reduction of incident early ARM was associated with fish consumption at least once a week (odds ratio [95% confidence interval], 0.58 [0.37-0.90]), whereas fish consumption at least 3 times per week could reduce the incidence of late ARM (odds ratio [95% confidence interval], 0.25 [0.06-1.00]). We found no association between incident ARM and butter, margarine, or nut consumption.. A regular diet high in n-3 polyunsaturated fat, especially from fish, suggests protection against early and late ARM in this older Australian cohort. Our study could not confirm deleterious effects of higher polyunsaturated fat intakes reported by other clinic-based studies.

Topics: Aged; Ascorbic Acid; Diet Records; Dietary Fats, Unsaturated; Eating; Fatty Acids, Omega-3; Feeding Behavior; Female; Follow-Up Studies; Humans; Incidence; Macular Degeneration; Male; Middle Aged; New South Wales; Odds Ratio; Risk Factors; Smoking; Surveys and Questionnaires; Urban Population

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Diet; Diet Surveys; Humans; Macular Degeneration; Risk; Vitamin E; Zinc

Report # 8 of the Age Related Eye Disease Study (AREDS) showed the interest of a cocktail of antioxidant micronutrients for the uni- or bilateral intermediate forms and the unilateral evolved forms of Age related Macular Degeneration. This use of supranutritional amounts aiming at obtaining a therapeutic effect corresponds to the concept of "neutraceuticals" which can be opposed to the concept of nutritional amounts. Although the AREDS was carried out under strict conditions, the evolution of knowledge in micronutrition since its design has led to some criticism of both the amounts of the micronutrients and the composition of the formulation. For example several authors pointed out that beta-carotene used at 3 fold the daily recommendations could have harmful effects, especially among smokers or former smokers. Other authors pointed out that vitamin E, at amounts corresponding to 40 to 60 fold the amounts recommended could be correlated with a lethal risk. We develop here some notions about safety and/or harmlessness of the antioxidant micronutrients.

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Comorbidity; Humans; Macular Degeneration; Micronutrients; Middle Aged; Smoking; Vitamin E; Zinc

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Disease Progression; Humans; Macular Degeneration; Vitamin E; Zinc

Determine whether antioxidant supplements alter the plasma glutathione and/or cysteine redox potential in age-related macular degeneration (AMD) patients.. This was an ancillary study to the Age-Related Eye Disease Study (AREDS), where subset of AREDS subjects at two sites were studied at two time points, an average of 1.7 and 6.7 years after enrollment.. Plasma glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), and cystine (CySS) were measured by high-performance liquid chromatography, and redox potentials of GSH/GSSG (E(h) GSH) and Cys/CySS (E(h) Cys) were calculated. The means of the metabolites and redox potentials were compared by repeated-measures analysis of variance for subjects receiving antioxidants and those not receiving antioxidants.. At the first blood draw, the means for the antioxidant group (n = 153) and no antioxidant group (n = 159) were not significantly different for any of the metabolites or redox potentials. At the second draw, the GSH parameters were not significantly different between the antioxidant (n = 37) and no antioxidant (n = 45) groups; however, mean Cys was significantly higher in the antioxidant group (9.5 vs 7.2 micromol/l, P = .008). Also, mean E(h) Cys was significantly more reduced in the antioxidant group (-74 vs -67.3 mV, P = .03).. The AREDS antioxidant supplements reduced oxidation of E(h) Cys but had no effect on GSH. Because Cys is important for cell growth, apoptosis, and immune function, the beneficial effect of antioxidant supplementation on progression to advanced AMD may be partially explained by its effect on E(h) Cys and/or its effect on Cys availability.

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Chromatography, High Pressure Liquid; Copper; Cysteine; Cystine; Dietary Supplements; Female; Glutathione; Glutathione Disulfide; Humans; Macular Degeneration; Male; Oxidation-Reduction; Randomized Controlled Trials as Topic; Vitamin E; Zinc Oxide

Age-related macular degeneration (AMD) is the most prevalent cause of irreversible blindness in developed countries. Recently, high-dose supplementation with beta carotene, vitamins C and E, and zinc was shown to slow the progression of AMD.. To investigate whether regular dietary intake of antioxidants is associated with a lower risk of incident AMD.. Dietary intake was assessed at baseline in the Rotterdam Study (1990-1993) using a semiquantitative food frequency questionnaire. Incident AMD until final follow-up in 2004 was determined by grading fundus color transparencies in a masked way according to the International Classification and Grading System.. Population-based cohort of all inhabitants aged 55 years or older in a middle-class suburb of Rotterdam, the Netherlands.. Of 5836 persons at risk of AMD at baseline, 4765 had reliable dietary data and 4170 participated in the follow-up.. Incident AMD, defined as soft distinct drusen with pigment alterations, indistinct or reticular drusen, geographic atrophy, or choroidal neovascularization.. Incident AMD occurred in 560 participants after a mean follow-up of 8.0 years (range, 0.3-13.9 years). Dietary intake of both vitamin E and zinc was inversely associated with incident AMD. The hazard ratio (HR) per standard deviation increase of intake for vitamin E was 0.92 (95% confidence interval [CI], 0.84-1.00) and for zinc was 0.91 (95% CI, 0.83-0.98). An above-median intake of all 4 nutrients, beta carotene, vitamin C, vitamin E, and zinc, was associated with a 35% reduced risk (HR, 0.65; 95% CI, 0.46-0.92) of AMD. Exclusion of supplement users did not affect the results.. In this study, a high dietary intake of beta carotene, vitamins C and E, and zinc was associated with a substantially reduced risk of AMD in elderly persons.

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Cohort Studies; Diet; Diet Surveys; Female; Humans; Macular Degeneration; Male; Middle Aged; Netherlands; Risk; Vitamin E; Zinc

Patients are increasingly well informed about the availability of antioxidant products and the claims made for their benefits in age-related macular degeneration (AMD). Consequently, their use is becoming widespread. The purpose of this study is to conduct a survey of the commonly encountered products, and to compare their ingredients with the current Age-Related Eye Disease Study (AREDS) recommendations.. A search was undertaken for products sold as 'eye nutrients' at local pharmacies and health food shops, and for products advertised via the Internet. Information about these products was collated and analysed.. We identified 22 eye nutrient products. Analysis of their constituents showed that, although over 75% contained all the constituents used in AREDS, only two matched the dosage profiles recommended in the study.. The authors draw no conclusion on the efficacy of nutritional supplements in the prevention of AMD. In order to advise their patients, ophthalmologists should be familiar with these products. The compiled list in this paper should provide a useful reference for them.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Copper; Dietary Supplements; Humans; Macular Degeneration; Vitamin E; Zinc

The Age-Related Eye Disease Study (AREDS) Research Group recently reported significant reduction in the progression of certain categories of age-related macular degeneration (AMD) with the use of high-dose antioxidant and zinc supplementation. We studied the current use of dietary supplementation in our patients with AMD to determine whether dosages recommended in the AREDS were being achieved. We also evaluated the easiest and most cost-effective method to reach recommended dosages using supplements currently available in Canada.. Cross-sectional descriptive study conducted by patient survey from Feb. 1 to Mar. 31, 2002. All patients with the diagnosis of AMD were surveyed during an office visit at a retinal specialty clinic in Edmonton. The following information was collected: demographic information, duration of AMD, smoking status and current use of dietary supplements. For patients using supplements, we also noted duration of use, reason for use, who recommended use, and type and dosage of supplements (including vitamin, mineral and herbal supplements). The exact dosages were confirmed by follow-up telephone interview. Cost estimates were determined by averaging retail prices from several local pharmacies. We compared methods of reaching the recommended dosages using various combinations of commercially available multivitamin formulations and individual beta-carotene, vitamin C and E, and zinc supplements. The goal was to match the dosage recommended in the AREDS (without exceeding it if possible) at maximum convenience and minimum cost and without increasing the risk of toxic effects.. Of 108 patients with AMD surveyed, 85 (79%) were taking dietary supplements, and 73 (68%) were taking at least one AREDS ingredient. The mean dosages of beta-carotene, vitamins C and E, and zinc were all below those recommended in the AREDS. None of our patients met the recommended dosages for all four ingredients. We identified four methods of reaching recommended dosages using various combinations of ICAPS TR, Ocuvite and Vitalux as well as Centrum multivitamin and individual supplements.. Patients with AMD may not be receiving the dosages of beta-carotene, vitamins C and E, and zinc recommended in the AREDS. Until new formulations of high-dose antioxidant and zinc supplements are available in Canada, patients should be counselled to attempt to meet recommended dosages by using combinations of currently available supplements.

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Cross-Sectional Studies; Dietary Supplements; Female; Humans; Macular Degeneration; Male; Nutrition Policy; Vitamin E; Zinc

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Clinical Trials as Topic; Dietary Supplements; Humans; Macular Degeneration; Safety; Vitamin E; Zinc

The aim of this study was to evaluate the ferric reducing ability of plasma (FRAP), selected enzymatic and non-enzymatic components of the antioxidative system, and the intensity of peroxidative processes in the blood of patients with age-related macular degeneration (AMD).. In the peripheral blood, we evaluated FRAP; concentrations of vitamins C, A, and E; and of thiols. We assayed the activity of enzymatic components of the antioxidative system-superoxide dismutase, catalase, ceruloplasmin and the concentration of reduced glutathione as an indicator of glutathione peroxidase activity. In order to determine the intensity of lipid peroxidation, we measured the concentrations of malondialdehyde and hydroxyalkenales (MDA-HNA) and conjugated diens (CD).. We found a significant increase in FRAP in patients with AMD compared with the control group. The average concentrations of vitamins A and C were low and vitamins E and GSH were significantly higher in AMD than in the control group. The activity of almost all the antioxidative enzymes was high. We found a significant increase in MDA-HNA but no difference in CD.. The significantly higher concentration of lipid peroxidation products in patients with AMD indicates an important pathogenic role of oxido-reduction disturbance. The high FRAP concentration may be one of the protective mechanisms in oxidation stress. The adaptive increase of the antioxidant barrier mostly involves the enzymatic components.

Topics: Aged; Antioxidants; Ascorbic Acid; Catalase; Ceruloplasmin; Female; Glutathione; Humans; Lipid Peroxidation; Lipid Peroxides; Macular Degeneration; Malondialdehyde; Middle Aged; Sulfhydryl Compounds; Superoxide Dismutase; Vitamin A; Vitamin E

Topics: Aged; Aged, 80 and over; Aging; Antioxidants; Ascorbic Acid; beta Carotene; Humans; Jaundice; Lung Neoplasms; Macular Degeneration; Middle Aged; Randomized Controlled Trials as Topic; Smoke Inhalation Injury; Vitamin E; Zinc

To estimate the potential public health impact of the findings of the Age-Related Eye Disease Study (AREDS) on reducing the number of persons developing advanced age-related macular degeneration (AMD) during the next 5 years in the United States.. The AREDS clinical trial provides estimates of AMD progression rates and of reduction in risk of developing advanced AMD when a high-dose nutritional supplement of antioxidants and zinc is used. These results are applied to estimates of the US population at risk, to estimate the number of people who would potentially avoid advanced AMD during 5 years if those at risk were to take a supplement such as that used in AREDS.. An estimated 8 million persons at least 55 years old in the United States have monocular or binocular intermediate AMD or monocular advanced AMD. They are considered to be at high risk for advanced AMD and are those for whom the AREDS formulation should be considered. Of these people, 1.3 million would develop advanced AMD if no treatment were given to reduce their risk. If all of these people at risk received supplements such as those used in AREDS, more than 300,000 (95% confidence interval, 158,000-487,000) of them would avoid advanced AMD and any associated vision loss during the next 5 years.. If people at high risk for advanced AMD received supplements such as those suggested by AREDS results, the potential impact on public health in the United States would be considerable during the next 5 years.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Clinical Trials as Topic; Dietary Supplements; Disease Progression; Humans; Macular Degeneration; Middle Aged; Public Health; Risk Reduction Behavior; United States; Vision Disorders; Vitamin E; Zinc

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Disease Progression; Humans; Macular Degeneration; Public Health; Risk Reduction Behavior; United States; Vision Disorders; Vitamin E; Zinc

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Clinical Trials as Topic; Dietary Supplements; Disease Progression; Humans; Macular Degeneration; Zinc

Topics: Aged; Antioxidants; Ascorbic Acid; Dietary Supplements; Humans; Macular Degeneration; Middle Aged; Vitamin E; Zinc

Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Copper; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fluorescein Angiography; Follow-Up Studies; Humans; Macular Degeneration; Middle Aged; Optic Disk Drusen; Randomized Controlled Trials as Topic; Vitamin E; Zinc Oxide

Topics: Ascorbic Acid; beta Carotene; Clinical Trials as Topic; Dietary Supplements; Humans; Macular Degeneration; Vitamin E; Zinc

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Disease Progression; Humans; Macular Degeneration; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Treatment Outcome; Vitamin E; Zinc

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Copper; Drug Combinations; Humans; Macular Degeneration; Middle Aged; Risk; Treatment Outcome; Vitamin E; Zinc

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Clinical Trials as Topic; Dietary Supplements; Drug Therapy, Combination; Humans; Macular Degeneration; Vision Disorders; Vitamin E; Zinc

To assess associations between the stages of age-related maculopathy (ARM) and dietary intake of carotene, vitamin C, retinol, and zinc.. Cross-sectional, population-based study.. A total of 3654 subjects 49 years of age and older from a defined area, west of Sydney, Australia, participated. A total of 2900 participants (79.4%) completed accurate food records.. Masked grading of stereoscopic macular photographs, detailed interviewer-administered questionnaire, and 145-item self-administered food frequency questionnaire.. Late ARM and early ARM were diagnosed from photographic grading.. The authors found no statistically significant associations between ARM and dietary intake of either carotene, zinc, or vitamins A or C, either from diet or supplements or from the combined intake from diet and supplements. Multivariate-adjusted odds ratios (95% confidence interval) were calculated comparing highest to lowest dietary intake quintiles. For late ARM, the odds ratios were carotene, 0.7 (range, 0.3-2.0); vitamin A, 1.2 (range, 0.5-3.3); vitamin C, 1.3 (range, 0.5-3.4); and zinc, 1.0 (range, 0.4-2.8). For early ARM, the odds ratios were carotene, 0.7 (range, 0.4-1.1); vitamin A, 1.2 (range, 0.7-2.0); vitamin C, 0.9 (range, 0.5-1.4); and zinc, 0.8 (range, 0.5-1.3). No significant trends were apparent. Adjustment for energy intake also showed no associations between these antioxidants and ARM. Further, no associations were found between increasing intake of foods high in antioxidant vitamins and decreasing prevalence of either late or early ARM.. The authors found no associations between ARM and dietary antioxidants, either from diet alone or including supplements, or from selected foods, in the Blue Mountains Eye Study population.

Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Carotenoids; Cross-Sectional Studies; Diet; Dietary Supplements; Energy Intake; Feeding Behavior; Female; Humans; Macular Degeneration; Male; Middle Aged; New South Wales; Odds Ratio; Surveys and Questionnaires; Vitamin A; Zinc

To give the levels of antioxidant nutrients in relation to age-related macular degeneration (AMD).. Pathologies Oculaires Liees a l'Age is a population-based study on cataract and AMD and their risk factors, carried out on 2584 inhabitants of Sete, France. Age-related macular degeneration was defined by findings from fundus photographs according to an international classification. Biological measurements were taken from fasting blood samples.. After multivariate adjustment, plasma alpha-to-copherol levels showed a weak negative association with late AMD (P = .07). Lipid-standardized plasma alpha-tocopherol levels showed a significant negative association with late AMD (P= .003): the risk of late AMD was reduced by 82% in the highest quintile compared with the lowest. Similarly, lipid-standardized plasma alpha-tocopherol levels were inversely associated with early signs of AMD (odds ratio, 0.72 [95% confidence interval, 0.53-0.98]; P=.04). No associations were found with plasma retinol and ascorbic acid levels or with red blood cell glutathione values.. These results suggest that vitamin E may provide protection against AMD. Only randomized interventional studies could prove the protective effect of vitamin E on AMD.

Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Cataract; Female; France; Humans; Macular Degeneration; Male; Middle Aged; Nutritional Status; Prevalence; Vitamin A; Vitamin E

To confirm the hypothesis that antioxidants and angiogenetic factors may be associated with the development of age-related macular degeneration (exudative type), we compared serum levels of vitamins A, C, and E and carotinoid, zinc, selenium and b-FGF (basic-fibroblast growth factor) in 35 patients with age-related macular degeneration (exudative type) with the levels in 66 controls. The average serum zinc level was significantly lower in the patient group than in the control group. Serum vitamin E-alpha levels also tended to be lower. Most serum b-FGF levels were below the standard value in each group. Based on the above results, we conclude that subnormal levels of zinc and vitamin E may be associated with the development of age-related macular degeneration.

Topics: Aged; Ascorbic Acid; Carotenoids; Fibroblast Growth Factor 2; Humans; Macular Degeneration; Middle Aged; Selenium; Vitamin A; Vitamin E; Zinc

OBJECTIVE--To evaluate the relationships between dietary intake of carotenoids and vitamins A, C, and E and the risk of neovascular age-related macular degeneration (AMD), the leading cause of irreversible blindness among adults. DESIGN--The multicenter Eye Disease Case-Control Study. SETTING--Five ophthalmology centers in the United States. PATIENTS--A total of 356 case subjects who were diagnosed with the advanced stage of AMD within 1 year prior to their enrollment, aged 55 to 80 years, and residing near a participating clinical center. The 520 control subjects were from the same geographic areas as case subjects, had other ocular diseases, and were frequency-matched to cases according to age and sex. MAIN OUTCOME MEASURES--The relative risk for AMD was estimated according to dietary indicators of antioxidant status, controlling for smoking and other risk factors, by using multiple logistic-regression analyses. RESULTS--A higher dietary intake of carotenoids was associated with a lower risk for AMD. Adjusting for other risk factors for AMD, we found that those in the highest quintile of carotenoid intake had a 43% lower risk for AMD compared with those in the lowest quintile (odds ratio, 0.57; 95% confidence interval, 0.35 to 0.92; P for trend = .02). Among the specific carotenoids, lutein and zeaxanthin, which are primarily obtained from dark green, leafy vegetables, were most strongly associated with a reduced risk for AMD (P for trend = .001). Several food items rich in carotenoids were inversely associated with AMD. In particular, a higher frequency of intake of spinach or collard greens was associated with a substantially lower risk for AMD (P for trend < .001). The intake of preformed vitamin A (retinol) was not appreciably related to AMD. Neither vitamin E nor total vitamin C consumption was associated with a statistically significant reduced risk for AMD, although a possibly lower risk for AMD was suggested among those with higher intake of vitamin C, particularly from foods. CONCLUSION--Increasing the consumption of foods rich in certain carotenoids, in particular dark green, leafy vegetables, may decrease the risk of developing advanced or exudative AMD, the most visually disabling form of macular degeneration among older people. These findings support the need for further studies of this relationship.

Topics: Aged; Aged, 80 and over; Aging; Antioxidants; Ascorbic Acid; Blindness; Carotenoids; Case-Control Studies; Data Collection; Diet; Eating; Female; Humans; Logistic Models; Macular Degeneration; Male; Middle Aged; Nutritional Physiological Phenomena; Risk Factors; Smoking; Vitamin A; Vitamin E

We evaluated the hypothesis that higher serum levels of micronutrients with antioxidant capabilities may be associated with a decreased risk of neovascular age-related macular degeneration by comparing serum levels of carotenoids, vitamins C and E, and selenium in 421 patients with neovascular age-related macular degeneration and 615 controls. Subjects were classified by blood level of the micronutrient (low, medium, and high). Persons with carotenoid levels in the medium and high groups, compared with those in the low group, had markedly reduced risks of neovascular age-related macular degeneration, with levels of risk reduced to one half and one third, respectively. Although no statistically significant protective effect was found for vitamin C or E or selenium individually, an antioxidant index that combined all four micronutrient measurements showed statistically significant reductions of risk with increasing levels of the index. Although these results suggest that higher blood levels of micronutrients with antioxidant potential, in particular, carotenoids, may be associated with a decreased risk of the most visually disabling form of age-related macular degeneration, it would be premature to translate these findings into nutritional recommendations.

Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Carotenoids; Case-Control Studies; Female; Humans; Macula Lutea; Macular Degeneration; Male; Middle Aged; Neovascularization, Pathologic; Odds Ratio; Risk Factors; Selenium; Vitamin E

To provide optimum care for patients who have age-related macular degeneration, primary care physicians need to be aware of symptoms such as acute loss of vision and distorted vision. Immediate referral to an ophthalmologist is necessary so that diagnosis can be confirmed and laser treatment can begin if indicated. Patients are at risk for recurrence and should use an Amsler grid daily to detect further visual changes. Current studies are investigating the role of dietary supplements in preventing macular degeneration.

Topics: Ascorbic Acid; Fluorescein Angiography; Humans; Laser Therapy; Macular Degeneration; Risk Factors; Zinc

Data from the first National Health and Nutrition Examination Survey collected between 1971 and 1972 were used to determine what factors are associated with the prevalence of age-related macular degeneration. The study was limited to those who were at least 45 years old at the time of the ophthalmology examination. Stratified analysis, adjusting for age, showed that education, systolic blood pressure, past history of hypertension, cerebrovascular disease, and refractive error were all associated with macular degeneration. With the exception of education, these factors remained statistically significant when simultaneously entered into a logistic regression model. The frequency of consumption of fruits and vegetables rich in vitamins A and C suggested a negative association with the prevalence of macular degeneration after stratified adjustment for age. In a logistic regression analysis, adjusting for demographic and medical factors, the inverse association of vitamin C with age-related macular degeneration was no longer present. The frequency of consumption of fruits and vegetables rich in vitamin A remained negatively correlated with age-related macular degeneration even after adjustment for demographic and medical factors.

Topics: Age Factors; Aged; Ascorbic Acid; Female; Fruit; Health Surveys; Humans; Hypertension; Macular Degeneration; Male; Middle Aged; United States; Vegetables; Vitamin A