Age-Related Eye Disease Study Supplements Research Articles

Nutritional Supplements for Healthy Aging: A Critical Analysis Review

Background: Healthy aging is defined as survival to advanced age while retaining autonomy in activities of daily living, high societal participation, and good quality of life. Sarcopenia, insomnia, cognitive impairment, and changes in sensation can be key hinderances to healthy aging, but nutritional supplements may abate their impact. As research advances, an updated review on their efficacy on age-related conditions is warranted. Results: Sarcopenia can be mitigated through proper protein intake, supplements like creatine, and in certain situations Branched-Chain Amino Acids and Vitamin D, in adults over 65. Melatonin supplementation has moderate evidence for improving sleep, while valerian root lacks evidence. Magnesium, tart cherry, and kiwifruits have shown promising impacts on sleep in limited articles. Magnesium, Vitamin D, and B vitamin supplementation have been shown to improve cognition in those with mild cognitive impairment and Alzheimer’s disease but require further study prior to recommendation. The Age-Related Eye Disease Study supplement combination is routinely recommended to reduce risk of progression to advance stages of age-related macular degeneration. Alpha-Lipoic Acid and Folate have been investigated for their roles in mitigating age-related hearing losses. Conclusions: Nutritional supplements and lifestyle changes may mitigate disabilities across multiple domains of age-related illnesses and promote healthy aging.

HEALTH CONDITIONS LINKED TO AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH DARK ADAPTATION.

To determine the association between dark adaption (DA) and different health conditions linked with age-related macular degeneration (AMD). Cross-sectional study, including patients with AMD and a control group. Age-related macular degeneration was graded according to the Age-Related Eye Disease Study (AREDS) classification. We obtained data on medical history, medications, and lifestyle. Dark adaption was assessed with the extended protocol (20 minutes) of AdaptDx (MacuLogix). For analyses, the right eye or the eye with more advanced AMD was selected. Multivariate linear and logistic regressions were performed, accounting for age and AMD stage. Seventy-eight subjects (75.6% AMD; 24.4% controls) were included. Multivariate assessments revealed that body mass index (BMI; β = 0.30, P = 0.045), taking AREDS vitamins (β = 5.51, P < 0.001), and family history of AMD (β = 2.68, P = 0.039) were significantly associated with worse rod intercept times. Abnormal DA (rod intercept time ≥ 6.5 minutes) was significantly associated with family history of AMD (β = 1.84, P = 0.006), taking AREDS supplements (β = 1.67, P = 0.021) and alcohol intake (β = 0.07, P = 0.017). Besides age and AMD stage, a higher body mass index, higher alcohol intake, and a family history of AMD seem to impair DA. In this cohort, the use of AREDS vitamins was also statistically linked with impaired DA, most likely because of an increased severity of disease in subjects taking them.

Cost-effectiveness of age-related macular degeneration study supplements in the UK: combined trial and real-world outcomes data

AimsTo evaluate the cost-effectiveness of Age-Related Eye Disease Study (AREDS) 1 & 2 supplements in patients with either bilateral intermediate age-related macular degeneration, AREDS category 3, or unilateral neovascular age-related...

Benefits, Potential Harms, and Optimal Use of Nutritional Supplementation for Preventing Progression of Age-Related Macular Degeneration.

To briefly review age-related macular degeneration (AMD), the main findings from the Age Related Eye Disease Study (AREDS) report number 8 on the use of nutritional supplements for AMD, and to focus on data suggesting that supplement use should be guided using genetic testing of AMD risk genes. A literature search (January 2001 through October 26, 2016) was conducted using MEDLINE and the following MeSH terms: Antioxidants/therapeutic use, Genotype, Macular Degeneration/drug therapy, Macular degeneration/genetics, Dietary Supplements, Proteins/genetics, and Zinc Compounds/therapeutic use. Bibliographies of publications identified were also reviewed. English-language studies assessing AREDS supplement response in patients with AMD in relation to complement factor H gene ( CFH) and age-related maculopathy susceptibility 2 gene ( ARMS2) risk alleles were evaluated. Three of the 4 studies demonstrated a treatment interaction between ARMS2 and CFH genotypes and a differential response to supplements. The fourth study documented an interaction for the CFH genotype only. Reported response interactions included attenuated response, no response, and good response, whereas a subset showed increased progression of AMD. Conversely, one study reported no interactions between CFH and ARMS2 risk alleles and response to supplements. The weight of the evidence supports using genetic testing to guide selection of ocular vitamin use. This approach will avoid using supplements that could speed the progression of AMD in vulnerable patients, avoid using supplements that will have little to no effect in others, and result in appropriately using supplements in those that are likely to derive meaningful benefits.

Response to AREDS supplements according to genetic factors: survival analysis approach using the eye as the unit of analysis

Background/aimsThe Age-Related Eye Disease Study (AREDS) reported the beneficial impact of antioxidant and zinc supplements on the risk of progression to advanced stages of age-related macular degeneration (AMD). We evaluated...

Reprint of: Survey of patients with age-related macular degeneration: knowledge and adherence to recommendations

ObjectiveTo 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). DesignCross-sectional study. ParticipantsPatients with AMD treated at the vitreoretinal service clinic. MethodsTelephone 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. ResultsAmong 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. ConclusionsPatients 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.

Nutritional Supplements for Age-Related Macular Degeneration.

The Age-Related Eye Disease Study (AREDS) and The Age-Related Eye Disease Study 2 (AREDS2), are the only large-scale, long-term, randomized controlled trials to demonstrate a role of nutritional supplements in reducing risk of progression to advanced forms of age-related macular degeneration (AMD). This review summarizes the study design, main results, and implications of these trials in the clinical care of nonexudative AMD patients. In addition, it discusses other recent prospective studies focusing on efficacy of nutritional supplementation for prevention or slowing progression of AMD as well as briefly discusses possible effect of genotypes on response to AREDS supplementation.

Genetic Testing in Persons with Age-Related Macular Degeneration and the Use of the AREDS Supplements: To Test or Not to Test?

The controversy surrounding the use of genetic testing to guide the treatment of persons with age-related macular degeneration (AMD) continues. In 2001, the results of the Age-Related Eye Disease Study (AREDS), a placebo-controlled trial, demonstrated that oral supplementation with a combination of antioxidant vitamins and zinc reduced the risk of progression to late AMD by 25% in persons with intermediate AMD in at least one eye.1 Klein et al evaluated the influence of the genotypes complement factor H (CFH) (Y402H, rs1061170) and LOC387715/age-related maculopathy susceptibility 2 (ARMS2) (A69S, rs10490924) on the response to treatment with AREDS supplements (combination of antioxidants and zinc), zinc alone, or antioxidants alone in 876 AREDS participants who had available DNA and who were at high risk of developing advanced AMD.2 Although there was a possible interaction between CFH genotype and treatment, Klein et al concluded that the AREDS supplements were associated with a general reduction in the risk of developing late AMD in all genotype groups compared with placebo, and neither antioxidant alone nor zinc alone was superior to the antioxidant and zinc combination in any of the genetic groups examined. Awh and his colleagues created a genetic test to evaluate CFH and ARMS2 genes, and performed retrospective analyses of AREDS subgroups (n=989).3 They claimed that treatment with the AREDS supplements should be tailored according to the patient’s genotype, suggesting the need to genotype all patients taking the AREDS supplements. The AREDS investigators compared response to treatment in individuals with different genotype configurations in a larger group of AREDS participants (n=1,237) and failed to find statistically significant differences in response to treatment with AREDS supplement.4 In this current issue, Awh et al have further refined their genetic subgroups based on outcome, and furthered their claim that AREDS supplements can be harmful to individuals with certain genotypes.5 Are these findings by Awh et al true associations or are they the result of chance, selection bias, or some other confounder? Our request for the identification codes of the AREDS participants in their analyses was turned down. Since the DNA and data used by Awh et al. originated from our AREDS dataset, we have reconstructed their sample – which represents only a subset of AREDS participants for whom genetic information is available. Based on when and how the DNA were requested, we are confident of the identification codes for 893 (90%) of the 989 participants used in their analyses, which we verified by finding similar progression rates to late AMD and similar risk ratios for each of the supplements in each of their genetic risk groups. We agree with Awh et al, that the ultimate test of the validity of their study is a replication sample.5 Thus, it is fortuitous that Awh and colleagues had access to only a portion of the AREDS patients with available DNA. We were able to assemble a validation cohort from the remaining patients (n=526) and this cohort is referred here as the “residual cohort”. If the findings from Awh’s recent report are correct, the results of the analysis from this residual cohort will likely be in the same direction (either beneficial or harmful), and on average, of the same magnitude as those published by Awh et al, validating their analysis. However, if Awh’s results were generated by selection bias and not true associations, the results would be different, likely regressing to the overall mean differences observed in the AREDS primary study results.

No Clinically Significant Association between CFH and ARMS2 Genotypes and Response to Nutritional Supplements: AREDS Report Number 38

To determine whether genotypes at 2 major loci associated with late age-related macular degeneration (AMD), complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2), influence the relative benefits of Age-Related Eye Disease Study (AREDS) supplements. Unplanned retrospective evaluation of a prospective, randomized, placebo-controlled clinical trial of vitamins and minerals for the treatment of AMD. AREDS participants (mean age, 69 years) who were at risk of developing late AMD and who were randomized to the 4 arms of AREDS supplement treatment. Analyses were performed using the Cox proportional hazards model to predict progression to late AMD (neovascular or central geographic atrophy). Statistical models, adjusted for age, gender, smoking status, and baseline AMD severity, were used to examine the influence of genotypes on the response to therapy with 4 randomly assigned arms of AREDS supplement components: placebo, antioxidants (vitamin C, vitamin E, β-carotene), zinc, or a combination. The influence of the genotype on the relative treatment response to the randomized components of the AREDS supplement, measured as progression to late AMD. Of the 1237 genotyped AREDS participants of white ethnicity, late AMD developed in 385 (31.1%) during the mean follow-up of 6.6 years. As previously demonstrated, CFH genotype (P = 0.005), ARMS2 (P< 0.0001), and supplement were associated individually with progression to late AMD. An interaction analysis found no evidence that the relative benefits of AREDS supplementation varied by genotype. Analysis of (1) CFH rs1061170 and rs1410996 combined with ARMS2 rs10490924 with the 4 randomly assigned arms of AREDS supplement and (2) analysis of the combination of CFH rs412852 and rs3766405 with ARMS2 c.372_815del443ins54 with the AREDS components resulted in no interaction (P = 0.06 and P = 0.45, respectively, before multiplicity adjustment). The AREDS supplements reduced the rate of AMD progression across all genotype groups. Furthermore, the genotypes at the CFH and ARMS2 loci did not statistically significantly alter the benefits of AREDS supplements. Genetic testing remains a valuable research tool, but these analyses suggest it provides no benefits in managing nutritional supplementation for patients at risk of late AMD.

Survey of patients with age-related macular degeneration: knowledge and adherence to recommendations

ObjectiveTo 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). DesignCross-sectional study. ParticipantsPatients with AMD treated at the vitreoretinal service clinic. MethodsTelephone 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. ResultsAmong 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. ConclusionsPatients 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.

The Short-term Effects of Antioxidant and Zinc Supplements on Oxidative Stress Biomarker Levels in Plasma: A Pilot Investigation

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.

Does eating particular diets alter the risk of age-related macular degeneration in users of the Age-Related Eye Disease Study supplements?

Background:Recent information suggests that the Age-Related Eye Disease Study (AREDS) supplement, enhanced intake of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and reducing dietary glycaemic index (dGI) are protective against...

CFH and LOC387715/ARMS2 Genotypes and Treatment with Antioxidants and Zinc for Age-Related Macular Degeneration

To determine if CFH and LOC387715/ARMS2 genotypes influence treatment response to AREDS-type nutritional supplementation with antioxidants and zinc. Retrospective analysis of participants in a randomized, controlled clinical trial, the Age-Related Eye Disease Study (AREDS). Eight hundred seventy-six AREDS study participants who were considered at high risk for developing advanced age-related macular degeneration (AMD). Using DNA extracted from venous blood of 876 white participants in AREDS categories 3 and 4, that is, those considered to be at high risk for progression to advanced AMD, the authors genotyped for the single nucleotide polymorphisms in the CFH (Y402H, rs1061170) and LOC387715/ARMS2 (A69S, rs10490924) genes. The authors performed adjusted unconditional logistic regression analysis and assessed interactions of these genotypes to determine the relationship between CFH and LOC387715/ARMS2 genotype and treatment with antioxidants plus zinc. Interaction between genetic variants and treatment response as determined by progression from high-risk to advanced AMD. Progression occurred in 264 of 876 patients from AREDS category 3 (intermediate AMD) to category 4 or 5 (unilateral or bilateral advanced AMD, respectively), or from category 4 to category 5. A treatment interaction was observed between the CFH Y402H genotype and supplementation with antioxidants plus zinc (CC; P = 0.03). An interaction (P = 0.004) was observed in the AREDS treatment groups taking zinc when compared with the groups taking no zinc, but not in groups taking antioxidants compared with those taking no antioxidants (P = 0.59). There were no significant treatment interactions observed with LOC387715/ARMS2. The findings of this study indicate that an individual's response to AREDS supplements may be related to CFH genotype. This could have clinical relevance by predicting treatment outcome and potentially preventing unwanted side effects in those who may not benefit. Corroboration of these analyses is needed before considering modification of current management. This is among the first pharmacogenetic studies to suggest interaction between genotype and treatment.

Vitamin Usage Patterns in the Prevention of Advanced Age-Related Macular Degeneration

To describe micronutrient usage patterns among patients at a tertiary ophthalmic center. Cross-sectional clinical case series. Three hundred thirty-two adult patients with a diagnosis of age-related macular degeneration (AMD). Participants were surveyed about micronutrient usage patterns. The treating ophthalmologist recorded AMD severity using the Age-Related Eye Disease Study (AREDS) classification system. Responses to study questionnaire and level of AMD severity. Among 332 participants, 309 (93%) were using supplements, among which 174 (52%) supplemented with an AREDS-like formulation. Of these 174, 140 (80%) were considered AREDS supplement candidates based on study guidelines. Applying AREDS supplementation guidelines to the full cohort, 228 (69%) were candidates for supplementation. Only 140 (61%) of these individuals were confirmed to be using the correct formulation and dosage; an additional 13 (6%) used the AREDS formulation but were not using the recommended dosage. Among patients receiving care for AMD at a tertiary retinal center, more than one third of those deemed candidates for AREDS-type supplements were not using them or were using an incorrect dose. Furthermore, nearly one fifth of participants who were using high-dose supplements did not have a level of AMD anticipated to benefit from usage. Increased patient education is needed regarding the recommendations of AREDS.

Vitamin E and the Age-Related Eye Disease Study Supplementation for Age-Related Macular Degeneration

Vitamin E and the Age-Related Eye Disease Study Supplementation for Age-Related Macular Degeneration