A Randomized Study of Nutritional Supplementation in Patients with Unilateral Wet Age-Related Macular Degeneration.

The purpose of this study is evaluate the efficacy and safety of medicinal products containing the original Age-Related Eye Disease group (AREDS) formulation at doses approved in Europe (EU, control group; n = 59) with a product that adds DHA, lutein, zeaxanthin, resveratrol and hydroxytyrosol to the formula (intervention group; n = 50). This was a multicenter, randomized, observer-blinded trial conducted in patients aged 50 years or older diagnosed with unilateral exudative Age related Macular Degeneration AMD. At month 12, the intervention did not have a significant differential effect on visual acuity compared with the control group, with an estimated treatment difference in Early Treatment Diabetic Retinopathy Study (ETDRS) of -1.63 (95% CI -0.83 to 4.09; p = 0.192). The intervention exhibited a significant and, in most cases, relevant effect in terms of a reduction in some inflammatory cytokines and a greater improvement in the fatty acid profile and serum lutein and zeaxantin concentration. In patients with unilateral wet AMD, the addition of lutein, zeaxanthin, resveratrol, hydroxytyrosol and DHA to the AREDS EU recommended doses in the short-term did not have a differential effect on visual acuity compared to a standard AREDS EU formula but, in addition to improving the fatty acid profile and increasing carotenoid serum levels, may provide a beneficial effect in improving the proinflammatory and proangiogenic profile of patients with AMD.

Effects of Lutein Supplementation in Japanese Patients with Unilateral Age-Related Macular Degeneration: The Sakai Lutein Study.

This prospective randomized double-masked study investigated the effects of 20 mg lutein supplementation with two different capsules (beeswax or glycerol fatty acid esters) for 6 months on the fellow eyes of 39 Japanese patients with unilateral age-related macular degeneration, and assessed the factors associated with baseline plasma lutein concentration via lifestyle interviews. Macular pigment optical density (MPOD), determined with the two-wavelength autofluorescence method, increased over time in the beeswax group (ANOVA, p = 0.0451), although the increase from 3 months to 6 months was only marginally significant. No significant increase was observed in the glycerol fatty acid esters group (ANOVA, p = 0.7396). Plasma lutein concentrations significantly increased at 3 and 6 months from baseline in both groups (both p < 0.01). In a multiple regression model, age was negatively associated with higher plasma lutein concentration (p = 0.0305), while consumption of green vegetables was positively associated with baseline plasma lutein concentration (p = 0.0322). In conclusion, a significant increase in MPOD was not fully confirmed with 6 months intake duration despite a significant increase in plasma lutein concentrations. Consumption of green vegetable was confirmed to be associated with plasma lutein concentration after adjusting for other potential factors including age.

The Relationship Between Plasma Concentrations of Lutein and Zeaxanthin with Self-Reported and Actual Prevalence of AMD in an Irish Population-Based Sample.

PURPOSE: To investigate plasma lutein (L) and zeaxanthin (Z) concentrations with grading-confirmed and self-reported prevalence of age-related macular degeneration (AMD). MATERIAL AND METHODS: Data collected from a nationally representative prospective cohort study of community-dwelling adults aged 50 years and over in the Republic of Ireland. Participants underwent a computer-assisted personal interview and a center-based health assessment. Plasma concentrations of L and total Z (Z and meso-zeaxanthin [MZ]) were measured by high performance liquid chromatography, and retinal photographs were graded using a version of the AMD International Classification and Grading System. Consumption of supplements containing L and/or Z and/or MZ was recorded as supplement use. Four groups were identified: Group 1 (n = 24): AMD-afflicted and correctly aware; Group 2 (n = 264): AMD-afflicted but unaware; Group 3 (n = 41): AMD-free and incorrectly believed that they were afflicted with the condition; Group 4 (n = 4094): AMD-free and correctly self-reported absence of AMD. RESULTS: Of 4,423 participants with plasma concentrations of L and Z and gradable retinal photographs, 288 (6.5%) were afflicted with AMD, and 65 (1.5%) self-reported AMD. Controlling for family history and age, the relationship between grading-confirmed AMD and plasma L was positive and significant (p < 0.001). Mean plasma concentrations of L in Group 2 (mean = 0.2162 ± 0.132 µmol) and Group 4 (mean = 0.2040 ± 0.121 µmol/L) were significantly lower than Group 1 (mean = 0.4691 ± 0.0.372 µmol/L) and Group 3 (mean = 0.3176 ± 0.0.235 µmol/L). Supplement use was reported by 41.7% and 17.1% of participants in Groups 1 and 3, respectively, but only 2.7% and 1.9% of participants in Groups 2 and 4, respectively. CONCLUSION: A belief that one suffers from AMD, whether justified or not, is associated with supplement use and with higher plasma concentrations of L.

Prospective study of plasma homocysteine, its dietary determinants, and risk of age-related macular degeneration in men.

PURPOSE: Cross-sectional and case-control studies generally support a direct association between elevated plasma homocysteine and age-related macular degeneration (AMD), but data from prospective studies are limited. We examined the prospective relation of plasma homocysteine level, its dietary determinants, and risk of AMD in a large cohort of apparently healthy male physicians. METHODS: During a mean follow-up of 11.2 years, we identified 146 incident cases of visually significant AMD (responsible for a reduction of visual acuity to 20/30 or worse), and 146 controls matched for age, smoking status, and time of blood draw. We measured concentration of homocysteine in blood samples collected at baseline using an enzymatic assay. and we assessed dietary intake of B vitamins and related compounds betaine and choline with a food frequency questionnaire administered at baseline. RESULTS: AMD was not associated with plasma level of homocysteine; the multivariable-adjusted odds ratio (OR) of AMD comparing the highest and lowest quartile of homocysteine was 1.09 (95% confidence interval [95% CI]: 0.52-2.31; p for trend = 0.99). However, AMD was inversely associated with quartile of intake of total folate (OR: 0.55; 95% CI: 0.24-1.23; p for trend = 0.08), vitamin B6 from food (OR: 0.39; 95% CI: 0.17-0.88; p for trend = 0.01), and betaine (OR: 0.53; 95% CI: 0.22-1.27; p for trend = 0.048). CONCLUSIONS: These prospective data from a cohort of apparently healthy men do not support a major role for homocysteine in AMD occurrence, but do suggest a possible beneficial role for higher intake of several nutrients involved in homocysteine metabolism.

Dietary guidance for lutein: consideration for intake recommendations is scientifically supported.

Lutein, a yellow xanthophyll carotenoid found in egg yolks and many colorful fruits and vegetables, has gained public health interest for its putative role in visual performance and reducing the risk of age-related macular degeneration. The National Academies of Sciences, Engineering and Medicine's recommended Dietary Reference Intakes (DRIs) focus on preventing deficiency and toxicity, but there is a budding interest in establishing DRI-like guidelines for non-essential bioactives, like lutein, that promote optimal health and/or prevent chronic diseases. Lupton et al. developed a set of nine criteria to determine whether a bioactive is ready to be considered for DRI-like recommendations. These criteria include: (1) an accepted definition; (2) a reliable analysis method; (3) a food database with known amounts of the bioactive; (4) cohort studies; (5) clinical trials on metabolic processes; (6) clinical trials for dose-response and efficacy; (7) safety data; (8) systematic reviews and/or meta-analyses; (9) a plausible biological rationale. Based on a review of the literature supporting these criteria, lutein is ready to be considered for intake recommendations. Establishing dietary guidance for lutein would encourage the consumption of lutein-containing foods and raise public awareness about its potential health benefits.

Dietary intake of α-linolenic acid and risk of age-related macular degeneration.

Background: The relation between α-linolenic acid (ALA), a plant-derived omega-3 (n-3) fatty acid, and age-related macular degeneration (AMD) is unclear. European researchers reported that ≤40% of ALA can be present as trans forms.Objective: We aimed to evaluate the associations between intake of ALA and intermediate and advanced AMD.Design: Seventy-five thousand eight hundred eighty-nine women from the Nurses' Health Study and 38,961 men from Health Professionals Follow-Up Study were followed up from 1984 to 2012 and from 1986 to 2010, respectively. We assessed dietary intake by a validated food-frequency questionnaire at baseline and every 4 y thereafter. One thousand five hundred eighty-nine incident intermediate and 1356 advanced AMD cases (primarily neovascular AMD) were confirmed by medical record review.Results: The multivariable-adjusted HR for intermediate AMD comparing ALA intake at the top quintile to the bottom quintile was 1.28 (95% CI: 1.05, 1.56; P-trend = 0.01) in the analyses combining 2 cohorts. The HR in each cohort was in the positive direction but reached statistical significance only in the women. However, the positive association was apparent only in the pre-2002 era in each cohort and not afterward (P-time interaction = 0.003). ALA intake was not associated with advanced AMD in either time period. Using gas-liquid chromatography, we identified both cis ALA (mean ± SD: 0.13% ± 0.04%) and trans ALA isomers (0.05% ± 0.01%) in 395 erythrocyte samples collected in 1989-1990. In stepwise regression models, mayonnaise was the leading predictor of erythrocyte concentrations of cis ALA and one isomer of trans ALA. We also found trans ALA in mayonnaise samples.Conclusions: A high intake of ALA was associated with an increased risk of intermediate AMD before 2002 but not afterward. The period before 2002 coincides with the same time period when trans ALA was found in food and participants' blood; this finding deserves further study.

Nutritional Supplementation Inhibits the Increase in Serum Malondialdehyde in Patients with Wet Age-Related Macular Degeneration.

Purpose. To compare serum levels of malondialdehyde (MDA) in patients with wet age-related macular degeneration (wAMD), patients with dry AMD (dAMD), and patients without AMD and to evaluate the efficacy of nutritional supplementation for treating elevated serum MDA in patients with wAMD. Methods. MDA levels were measured in sera from 20 patients with wAMD, 20 with dAMD, and 24 without AMD. Patients with wAMD were randomized to receive or not receive nutritional supplementation (10 patients in each group), and MDA levels were measured after 3 months of treatment. Results. MDA levels in patients with wAMD were significantly greater compared with patients without AMD. In eyes with wAMD, there was a significant correlation between MDA levels and choroidal neovascularization lesion area. Serum MDA levels decreased in most patients that received supplementation and significantly increased in those who did not. Conclusion. Baseline serum MDA levels were elevated in patients with wAMD, and MDA levels were directly correlated with choroidal neovascularization lesion area. In addition, nutritional supplementation appeared to exert a protective effect against oxidative stress in patients with wAMD.

Systemic confounders affecting serum measurements of omega-3 and -6 polyunsaturated fatty acids in patients with retinal disease.

BACKGROUND: Omega-3 polyunsaturated fatty acids (PUFAs) have a highly anti-angiogenic effect in animal models. However, the clinical relevance of omega-3PUFAs in human retinal pathologies remains unclear. The ARED 2 study found no effect of omega-3 PUFA supplementation on progression of age related macular degeneration (AMD). The aim of this study was to compare serum levels of omega-3- and omega-6 PUFAs between patients with diabetic retinopathy (DR), AMD and retinal vein occlusion (RVO), and to identify potential confounders of serum level measurements. METHODS: Venous blood samples were collected from 44 patients with DR, 25 with AMD, 12 with RVO and 27 controls. The lipid phase was extracted and analyzed using mass spectrometry. Retinal disease staging was done by indirect funduscopy and FAG where appropriate. Patient demographics and medical history including current medication and fasting state were acquired. Tukey contrasts for multiple comparisons of the mean and linear regression analysis were used for statistical analysis. RESULTS: Our data revealed no significant differences in omega-6 PUFA serum levels between patients with AMD, DR, RVO and controls (p > 0.858). Uncorrected omega-3 PUFA levels were significantly higher in patients with AMD compared to DR but not compared to controls (p = 0.004). However, after correcting for possible confounders such as body mass index (BMI), age, sex, fasting and use of statins, no statistically significant difference remained for serum omega-3 PUFA levels. Fasting was identified as an independent confounder of total omega-6 PUFAs, three individual omega-6 PUFAs and one omega-3 PUFA(p < 0.0427). Statin use was identified as an independent confounder of α-linolenic acid (an omega-3PUFA; p = 0.0210). CONCLUSION: In this pilot study with relatively low patient numbers, we report significant differences in serum levels of omega-3PUFAs among patients with different types of retinal diseases. However, these differences were not robust for disease specificity after correction for possible confounders in our cohort. Our results demonstrate that serum lipid profiles need to be interpreted with caution since they are significantly altered by variables like fasting and medication use independent from the underlying disease. Correcting for respective confounders is thus necessary to compare serum lipid profiles in clinical studies.

Serum and retinal responses to three different doses of macular carotenoids over 12 weeks of supplementation.

The macular carotenoids lutein (L), zeaxanthin (Z), and mesozeaxanthin (MZ) have been shown to have neuroprotective and visual performance benefits once deposited in retinal tissues. The purpose of this 12-week trial was to determine biweekly the absorption kinetics, efficiency of retinal deposition, and effects on the spatial profile of macular pigment for three levels of L + Z + MZ supplement. This study was a double-blind, placebo-controlled 12-week trial. Twenty-eight healthy subjects, aged 18-25 yrs participated. Subjects were randomly assigned to one of four daily supplementation groups: placebo (safflower oil; n = 5), 7.44 mg total macular carotenoid (n = 7), 13.13 mg total macular carotenoid (n = 8), and 27.03 (n = 8) mg total macular carotenoid. Ratios of the three carotenoids were virtually identical for the three levels of supplement (83% L, 10% Z, 7% MZ). At baseline and every two weeks thereafter over the 12-week study period, a fasting blood draw was conducted and, via heterochromatic flicker photometry, spatial profiles of macular pigment optical density (MPOD) were determined. Compared to placebo, serum concentrations of both L and total Z, for each of the supplement levels, were found to increase significantly from baseline after two weeks of daily ingestion (p < 0.001). Likewise, MPOD increased significantly in all treatment groups (p < 0.001) compared to placebo. Serum responses (L, Z, and L + Z) were linearly related to dose (p < 0.001 for all), but not to retinal response. L: Z serum response ratios decreased exponentially with increases in dose (p = 0.008). The ratio of MPOD change: total serum response was found to be highest for the 13.13 mg level of supplement (p = 0.021), followed by 27.03- and 7.44-mg doses. The very center of the spatial profile of MPOD increased in a fashion commensurate with dose level. Although L serum responses increased with dose, the slope of increase was shallower than for Z. Given the higher levels of L in the supplements, this is suggestive of a compressed response with relatively high doses of L. Although all three doses significantly augmented MPOD, the 13.13 mg/day L + Z supplement level was the most efficient in doing so. The data regarding efficiency may inform recommendations regarding macular carotenoid supplementation for age-related macular degeneration. Lastly (although not statistically significant), the shift toward a more pronounced central peak in the spatial profile of MPOD in all treatment groups suggests that central retinal deposition of Z and MZ was efficient and can be seen after a short period of supplementation, especially with higher (e.g. 27.03 mg) daily doses of macular carotenoids. ISRCTN trial registration number: ISRCTN54990825.

Regression of Some High-risk Features of Age-related Macular Degeneration (AMD) in Patients Receiving Intensive Statin Treatment.

IMPORTANCE: Age-related macular degeneration (AMD) remains the leading cause of blindness in developed countries, and affects more than 150 million worldwide. Despite effective anti-angiogenic therapies for the less prevalent neovascular form of AMD, treatments are lacking for the more prevalent dry form. Similarities in risk factors and pathogenesis between AMD and atherosclerosis have led investigators to study the effects of statins on AMD incidence and progression with mixed results. A limitation of these studies has been the heterogeneity of AMD disease and the lack of standardization in statin dosage. OBJECTIVE: We were interested in studying the effects of high-dose statins, similar to those showing regression of atherosclerotic plaques, in AMD. DESIGN: Pilot multicenter open-label prospective clinical study of 26 patients with diagnosis of AMD and the presence of many large, soft drusenoid deposits. Patients received 80 mg of atorvastatin daily and were monitored at baseline and every 3 months with complete ophthalmologic exam, best corrected visual acuity (VA), fundus photographs, optical coherence tomography (OCT), and blood work (AST, ALT, CPK, total cholesterol, TSH, creatinine, as well as a pregnancy test for premenopausal women). RESULTS: Twenty-three subjects completed a minimum follow-up of 12 months. High-dose atorvastatin resulted in regression of drusen deposits associated with vision gain (+ 3.3 letters, p = 0.06) in 10 patients. No subjects progressed to advanced neovascular AMD. CONCLUSIONS: High-dose statins may result in resolution of drusenoid pigment epithelial detachments (PEDs) and improvement in VA, without atrophy or neovascularization in a high-risk subgroup of AMD patients. Confirmation from larger studies is warranted.

Dietary Components Affect the Plasma and Tissue Levels of Lutein in Aged Rats with Lutein Deficiency--A Repeated Gavage and Dietary Study.

UNLABELLED: The aim of this study was to find out the influence of selected dietary components on plasma and tissue response of repeated micellar and dietary lutein in aged rats with lutein deficiency. In repeated (16 d) gavage study, micellar lutein was co-ingested with either phosphatidylcholine (PC), lyso-phosphatidylcholine (lysoPC), ß-carotene, dietary fiber or vegetable fat (3% soybean oil). In dietary study, rats were fed (4 wk) semi-synthetic diet either with lutein + PC, lutein + dietary fiber or B. alba (lutein source) + PC. The post-prandial plasma and tissue response of lutein was measured by HPLC. Results showed that micellar fat, PC and lysoPC significantly (P ≤ 0.05) increased the lutein levels in plasma (31.1%, 26.8%, and 34.9%), liver (27.4%, 29.5%, and 8.6%), and eyes (63.5%, 90.2%, and 86%) compared to the control group (group gavaged micelles with no dietary components studied). Similarly, dietary study showed an enhanced plasma, liver, and eye lutein levels by 44.8%, 24.1%, and 42.0% (lutein + PC group) and 51.7%, 39.8%, and 31.7% (B.alba + PC group), respectively compared to control. The activity of antioxidant enzymes in plasma and liver of both the studies were also affected compared to control. Result reveals, that PC enhance the intestinal absorption of both micellar and dietary lutein which is either in free or bound form with food matrices in aged rats with lutein deficiency. Hence, PC at a concentration used in this study can be considered to improve the lutein bioavailability in lutein deficiency. PRACTICAL APPLICATION: Lutein and zeaxanthin are macular pigments acquired mostly from greens, that play an significant role in protecting vision from Age related macular degeneration (AMD). However, their biological availability is poor and affected by dietary components. This study demonstrates the positive influence of dietary PC and lyso PC in improving intestinal uptake of lutein. Our previous and present finding shows there is a possibility of developing functional/supplemental foods with PC and lyso PC targeted to elderly populace thus minimizing or delaying the vision complication associated like AMD.

Effect of supplemental lutein and zeaxanthin on serum, macular pigmentation, and visual performance in patients with early age-related macular degeneration.

PURPOSE: To compare the 2-year effect of multiple doses of lutein/zeaxanthin on serum, macular pigmentation, and visual performance on patients with early age-related macular degeneration (AMD). METHODS: In this randomized, double-blinded, and placebo-controlled trial, 112 early AMD patients randomly received either 10 mg lutein, 20 mg lutein, a combination of lutein (10 mg) and zeaxanthin (10 mg), or placebo daily for 2 years. Serum concentration of lutein/zeaxanthin, macular pigment optical density (MPOD), visual functions including best-spectacle corrected visual acuity (BCVA), contrast sensitivity (CS), flash recovery time (FRT), and vision-related quality of life (VFQ25) was quantified. RESULTS: Serum lutein concentration and MPOD significantly increased in all the active treatment groups. Supplementation with 20 mg lutein was the most effective in increasing MPOD and CS at 3 cycles/degree for the first 48 weeks. However, they both significantly increased to the same peak value following supplementation with either 10 mg or 20 mg lutein during the intervention. No statistical changes of BCVA or FRT were observed during the trial. CONCLUSIONS: Long-term lutein supplementation could increase serum lutein concentration, MPOD, and visual sensitivities of early AMD patients. 10 mg lutein daily might be an advisable long-term dosage for early AMD treatment.

The New Era of Omega-3 Fatty Acids Supplementation: Therapeutic Effects on Dry Age-Related Macular Degeneration.

One of the major causes of reduced vision over the age of 50 is age-related macular degeneration (AMD). Although such a common pathology, there are no current guidelines for the first-line treatment of dry AMD. The aim of this study is to evaluate the therapeutic effects of high omega-3 fatty acids as anti-inflammatory agents in two sub-groups of dry AMD patients with 1) mild to moderate visual impairment and 2) with severe visual impairment (blindness). The key feature of this investigation is the frequent monitoring of the levels of specific fatty acids in patient's blood in order to adjust the treatment dose within the ideal therapeutic window. Following the positive outcome from our initial observational studies in patients with dry AMD, who demonstrated significant improvement in visual acuity (gain of ≥ 1 line of vision in 4.5 months) when taking a total of 5 g/day eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), additional studies were encouraged. The latest data which is presented in this chapter suggests that the eyes which had the greatest gain in vision (≥ 15 letters gain at 6 months) were from patients with mild to moderate visual impairment, who were taking between 5-7.5 g/day EPA and DHA and had a ratio of arachidonic acid (AA)/EPA < 2. In addition, a sub-group of dry AMD patients with severe visual impairment (< 6/60), showed significant increase in their visual acuity only 3 months following treatment with omega-3 fatty acids. The preliminary results indicate a promising therapeutic regime for dry AMD and perhaps for other types of retinopathies as well. Although initial results are encouraging, further investigations are necessary to establish a better understanding of the mode of action of these supplements and to observe their long-term effects.

Lutein supplementation leads to decreased soluble complement membrane attack complex sC5b-9 plasma levels.

PURPOSE: The purpose of this study was to investigate the effect of lutein on systemic complement activation in elderly individuals. METHODS: Seventy patients with signs of early age-related macular degeneration (AMD) were included in this study. All subjects were randomly assigned to receive a 10 mg daily dose of lutein or a placebo for a time period of 1 year. EDTA blood was collected before and at various time-points during the study (0, 4, 8 and 12 months). The plasma level of the soluble complement membrane attack complex sC5b-9 was measured by ELISA. RESULTS: We found a significant 1.1 ng/ml monthly decrease in the plasma sC5b-9 concentration in the lutein group (p<0.001), resulting in a decrease from 60.3 ng/ml at baseline to 46.3 ng/ml at 12 months. For the placebo group, we found a significant 0.6 ng/ml monthly increase in plasma sC5b-9 concentration (p=0.001), resulting in an increase from 51.6 ng/ml at baseline to 58.4 ng/ml at 12 months. CONCLUSIONS: Lutein supplementation inhibits the systemic activation of the complement system, which provides further functional evidence for the reported beneficial effects of this carotenoid in the management of AMD.

Macular response to supplementation with differing xanthophyll formulations in subjects with and without age-related macular degeneration.

PURPOSE: Our aim was to investigate the macular response to three different supplements containing lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) in normal subjects and those with age-related macular degeneration (AMD). MATERIALS AND METHODS: Macular pigment optical density (MPOD) and serum xanthophyll concentrations were measured in normal (n = 31) and AMD subjects (n = 32), randomly assigned to: group 1 (20 mg L, 2 mg Z, 0.3 mg MZ), group 2 (10 mg L, 2 mg Z, 10 mg MZ) or group 3 (3 mg L, 2 mg Z, 17 mg MZ). MPOD was measured at baseline, 2, 4, 6 and 8 weeks and at 0.25°, 0.5°, 1.0° and 1.75° of eccentricity using customised heterochromatic flicker photometry and serum xanthophylls by HPLC. RESULTS: MPOD increased significantly at all eccentricities in each group (p < 0.05), except at 1.75° in group 3 (p = 0.242). There was no difference in MPOD measurements between AMD and normal subjects, except for group 2, where AMD subjects exhibited a greater response at 1.75° (p = 0.012). Final serum concentrations of MZ were positively and significantly related to final MPOD values at each eccentricity in all subjects. Targeted analysis of those subjects receiving the MZ-containing supplements exhibited stronger relationships between serum MZ concentrations and MPOD at 0.25° in group 3 than group 2; in group 2 all associations were positive, but only significant at 1.75°. CONCLUSIONS: Serum concentrations of MZ were strongly correlated with MPOD after 8 weeks of supplementation with the group 3 formulation, but the inclusion of L in the group 2 formulation may result in greater MPOD augmentation across the spatial profile.

Zinc supplementation inhibits complement activation in age-related macular degeneration.

UNLABELLED: Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. AMD is a multifactorial disorder but complement-mediated inflammation at the level of the retina plays a pivotal role. Oral zinc supplementation can reduce the progression of AMD but the precise mechanism of this protective effect is as yet unclear. We investigated whether zinc supplementation directly affects the degree of complement activation in AMD and whether there is a relation between serum complement catabolism during zinc administration and the complement factor H (CFH) gene or the Age-Related Maculopathy susceptibility 2 (ARMS2) genotype. In this open-label clinical study, 72 randomly selected AMD patients in various stages of AMD received a daily supplement of 50 mg zinc sulphate and 1 mg cupric sulphate for three months. Serum complement catabolism-defined as the C3d/C3 ratio-was measured at baseline, throughout the three months of supplementation and after discontinuation of zinc administration. Additionally, downstream inhibition of complement catabolism was evaluated by measurement of anaphylatoxin C5a. Furthermore, we investigated the effect of zinc on complement activation in vitro. AMD patients with high levels of complement catabolism at baseline exhibited a steeper decline in serum complement activation (p<0.001) during the three month zinc supplementation period compared to patients with low complement levels. There was no significant association of change in complement catabolism and CFH and ARMS2 genotype. In vitro zinc sulphate directly inhibits complement catabolism in hemolytic assays and membrane attack complex (MAC) deposition on RPE cells. This study provides evidence that daily administration of 50 mg zinc sulphate can inhibit complement catabolism in AMD patients with increased complement activation. This could explain part of the mechanism by which zinc slows AMD progression. TRIAL REGISTRATION: The Netherlands National Trial Register NTR2605.

Consuming a buttermilk drink containing lutein-enriched egg yolk daily for 1 year increased plasma lutein but did not affect serum lipid or lipoprotein concentrations in adults with early signs of age-related macular degeneration.

Dietary lutein intake is postulated to interfere with the development of age-related macular degeneration (AMD). Because egg yolk-derived lutein has a high bioavailability, long-term consumption of lutein-enriched eggs might be effective in preventing AMD development, but alternatively might increase cardiovascular disease risk. Here, we report the effect of 1-y daily consumption of a buttermilk drink containing 1.5 lutein-rich egg yolks on serum lipid and lipoprotein and plasma lutein concentrations. Additionally, subgroups that could potentially benefit the most from the intervention were identified. Men and women who had early signs of AMD in at least 1 eye, but were otherwise healthy, participated in a 1-y randomized, placebo-controlled parallel intervention trial. At the start of the study, 101 participants were included: 52 in the experimental (Egg) group and 49 in the control (Con) group. Final analyses were performed with 45 participants in the Egg group and 43 participants in the Con group. As expected, the increase in plasma lutein concentrations in the Egg group was 83% higher than that in the Con group (P < 0.001). Changes in serum total, HDL, and LDL cholesterol, as well as the ratio of total cholesterol to HDL cholesterol, were not different between the 2 groups. Interestingly, participants classified as cholesterol absorbers had higher serum HDL cholesterol concentrations than participants classified as cholesterol synthesizers or participants with average campesterol-to-lathosterol ratios (P < 0.05) at baseline. In addition, cholesterol absorbers had a 229% higher increase in plasma lutein concentrations than participants who were classified as having an average campesterol-to-lathosterol ratio upon consumption of the lutein-enriched egg yolk drink (P < 0.05). Moreover, the change in serum HDL cholesterol upon consumption was significantly different between these 3 groups (P < 0.05). We suggest that cholesterol absorbers particularly might benefit from the lutein-enriched buttermilk drink. This study was registered at clinicaltrials.gov as NCT00902408.

The effect of modified eggs and an egg-yolk based beverage on serum lutein and zeaxanthin concentrations and macular pigment optical density: results from a randomized trial.

UNLABELLED: Increasing evidence suggests a beneficial effect of lutein and zeaxanthin on the progression of age-related macular degeneration. The aim of this study was to investigate the effect of lutein or zeaxanthin enriched eggs or a lutein enriched egg-yolk based buttermilk beverage on serum lutein and zeaxanthin concentrations and macular pigment levels. Naturally enriched eggs were made by increasing the levels of the xanthophylls lutein and zeaxanthin in the feed given to laying hens. One hundred healthy volunteers were recruited and randomized into 5 groups for 90 days. Group one added one normal egg to their daily diet and group two received a lutein enriched egg-yolk based beverage. Group three added one lutein enriched egg and group four one zeaxanthin enriched egg to their diet. Group five was the control group and individuals in this group did not modify their daily diet. Serum lutein and zeaxanthin concentrations and macular pigment densities were obtained at baseline, day 45 and day 90. Macular pigment density was measured by heterochromatic flicker photometry. Serum lutein concentration in the lutein enriched egg and egg yolk-based beverage groups increased significantly (p<0.001, 76% and 77%). A strong increase in the serum zeaxanthin concentration was observed in individuals receiving zeaxanthin enriched eggs (P< 0.001, 430%). No changes were observed in macular pigment density in the various groups tested. The results indicate that daily consumption of lutein or zeaxanthin enriched egg yolks as well as an egg yolk-based beverage show increases in serum lutein and zeaxanthin levels that are comparable with a daily use of 5 mg supplements. TRIAL REGISTRATION: ClinicalTrials.gov NCT00527553.

Circulating omega-3 Fatty acids and neovascular age-related macular degeneration.

PURPOSE: We assessed the associations of serum, red blood cell membranes (RBCM) and dietary long-chain n-3 polyunsaturated fatty acids (LC-PUFAs) with neovascular age-related macular degeneration (AMD). METHODS: We included 290 patients of the Nutritional AMD Treatment 2 Study (NAT2) with neovascular AMD in one eye and early AMD lesions in the other eye, and 144 normal vision controls without AMD. Dietary intake of seafood was estimated by food frequency questionnaire. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) composition in serum and RBCM were determined by gas chromatography from 12-hour fasting blood samples and was expressed as percentages of total fatty acids profile. Logistic regressions estimated associations of neovascular AMD with dietary intake of seafood and circulating n-3 LC-PUFAs. RESULTS: Dietary oily fish and seafood intake were significantly lower in AMD patients than in controls. After adjustment for all potential confounders (age, sex, CFH Y402H, ARMS2 A69S, and ApoE4 polymorphisms, plasma triglycerides, hypertension, hypercholesterolemia, and family history of AMD), serum EPA was associated significantly with a lower risk for neovascular AMD (odds ratio [OR] = 0.41; 95% confidence interval [CI], 0.22-0.77; P = 0.005). Analysis of RBCM revealed that EPA and EPA+DHA were associated significantly with a lower risk for neovascular AMD (OR = 0.25; 95% CI, 0.13-0.47; P < 0.0001 and OR = 0.52; 95% CI, 0.29-0.94; P = 0.03, respectively). CONCLUSIONS: The RBCM EPA and EPA+DHA, as long-term biomarkers of n-3 dietary PUFA status, were associated strongly with neovascular AMD and may represent an objective marker identifying subjects at high risk for neovascular AMD, who may most benefit from nutritional interventions. (http://www.controlled-trials.com/isrctn number, ISRCTN98246501).

Age-related macular degeneration: Effects of a short-term intervention with an oleaginous kale extract--a pilot study.

OBJECTIVE: Age-related macular degeneration (AMD) is a multifactorial degenerative disease of the retina, which accounts for slowly progressive visual impairment in the elderly. An increased dietary intake of xanthophylls is suggested to be inversely related to the risk of macular disease. METHODS: The present study was designed as a randomized, double-blind, placebo-controlled, parallel trial examining the influence of a short-term intervention with an oleaginous extract of Brassica oleracea var. sabellica L. (kale) on plasma xanthophyll concentrations and the optical density of the macular pigment xanthophylls (MPOD). Twenty patients with non-exudative AMD were recruited for a 10-wk study period (2-wk run-in, 4-wk intervention, 4-wk washout). All participants received 50 mL of a beverage containing either an oleaginous extract of kale (kale) or refined rapeseed oil (placebo). The verum product provides 10 mg lutein and 3 mg zeaxanthin per day. RESULTS: The concentrations of the xanthophylls in plasma and the MPOD increased significantly in the kale group after 4 wk of intervention. The successive washout period resulted in a significant decline of the values in plasma and macula. The values at the end of the study were still significantly higher than the initial values. Nevertheless, the improvements did not persist over 4 wk of washout. CONCLUSION: The distribution of the xanthophylls in the macula seems to be more dynamic than originally assumed.