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Abstracts

LE Magazine May 2006
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Macular Degeneration, Cataracts

Biomarkers of cardiovascular disease as risk factors for age-related macular degeneration.

PURPOSE: To measure and contrast 2 biomarkers of cardiovascular disease, C-reactive protein (CRP) and plasma homocysteine, in individuals with age-related macular degeneration (AMD) and control individuals without AMD. DESIGN: Case-control study. PARTICIPANTS: Seventy-nine affected individuals and 77 unaffected individuals from the AMD Genetic Study Group returned to obtain CRP and homocysteine levels. METHODS: Both affected and unaffected individuals underwent testing for CRP and homocysteine. A detailed cardiovascular history was taken. MAIN OUTCOME MEASURES: Mean CRP and homocysteine levels in affected and unaffected individuals. RESULTS: Mean CRP levels for affected and unaffected individuals were 3.42 and 2.30 mg/l, respectively (P = 0.03). Mean homocysteine levels for affected and unaffected individuals were 11.72 and 8.88 micromol/l, respectively (P<0.0001). In logistic regression models, older age, higher CRP, and higher homocysteine were risk factors for AMD. There were no significant differences between cases and controls in terms of gender, diabetes, hypertension, use of statin drugs, and smoking. The control group was significantly younger and had a lower rate of vitamin usage than the affected group. CONCLUSIONS: Elevated CRP and homocysteine levels are associated with AMD and implicate the role of chronic inflammation and atherosclerosis.

Ophthalmology. 2005 Dec;112(12):2076-80

Dietary intake of antioxidants and risk of age-related macular degeneration.

CONTEXT: 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. OBJECTIVE: To investigate whether regular dietary intake of antioxidants is associated with a lower risk of incident AMD. DESIGN: 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. SETTING: Population-based cohort of all inhabitants aged 55 years or older in a middle-class suburb of Rotterdam, the Netherlands. PARTICIPANTS: Of 5836 persons at risk of AMD at baseline, 4765 had reliable dietary data and 4170 participated in the follow-up. MAIN OUTCOME MEASURE: Incident AMD, defined as soft distinct drusen with pigment alterations, indistinct or reticular drusen, geographic atrophy, or choroidal neovascularization. RESULTS: 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. CONCLUSION: 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.

JAMA. 2005 Dec 28;294(24):3101-7

Evaluation of plasma homocysteine and risk of age-related macular degeneration.

PURPOSE: To assess the relationship between plasma levels of homocysteine and age-related macular degeneration (AMD). DESIGN: Cross-sectional, case-control study. METHODS: Fasting plasma homocysteine levels were measured at two centers in 934 individuals who were participating in an ancillary study of the Age-Related Eye Disease Study. There were 547 cases and 387 control subjects, who were determined by fundus photography. Conditional logistic regression analyses were conducted to assess the association of homocysteine with AMD. RESULTS: Median values of homocysteine were higher among advanced AMD cases (9.51 mmol/l) compared with persons with no AMD (8.81 mmol/l; P = .01). Values of >12 mmol/l vs < or =12 mmol/l were also associated with an increased risk of AMD (P = .023), when controlled for other covariates. CONCLUSION: Results are consistent with a possible small, independent association between higher homocysteine levels and AMD. Homocysteine may be a modifiable risk factor for AMD.

Am J Ophthalmol. 2006 Jan;141(1):201-3

Carnosine and carnosine-related antioxidants: a review.

First isolated and characterized in 1900 by Gulewitsch, carnosine (beta-alanyl-L-hystidine) is a dipeptide commonly present in mammalian tissue, and in particular in skeletal muscle cells; it is responsible for a variety of activities related to the detoxification of the body from free radical species and the by-products of membrane lipids peroxidation, but recent studies have shown that this small molecule also has membrane-protecting activity, proton buffering capacity, formation of complexes with transition metals, and regulation of macrophage function. It has been proposed that carnosine could act as a natural scavenger of dangerous reactive aldehydes from the degradative oxidative pathway of endogenous molecules such as sugars, polyunsaturated fatty acids (PUFAs) and proteins. In particular, it has been recently demonstrated that carnosine is a potent and selective scavenger of alpha,beta-unsaturated aldehydes, typical by-products of membrane lipids peroxidation and considered second messengers of the oxidative stress, and inhibits aldehyde-induced protein-protein and DNA-protein cross-linking in neurodegenerative disorders such as Alzheimer’s disease, in cardiovascular ischemic damage, in inflammatory diseases. The research for new and more potent scavengers for HNE and other alpha,beta-unsaturated aldehydes has produced a consistent variety of carnosine analogs, and the present review will resume, through the scientific literature and the international patents, the most recent developments in this field.

Curr Med Chem. 2005;12(20):2293-315

Association between C-reactive protein and age-related macular degeneration.

CONTEXT: C-reactive protein (CRP) is a systemic inflammatory marker associated with risk for cardiovascular disease (CVD). Some risk factors for CVD are associated with age-related macular degeneration (AMD), but the association between CRP and AMD is unknown. OBJECTIVE: To test the hypothesis that elevated CRP levels are associated with an increased risk for AMD. DESIGN, SETTING, AND PARTICIPANTS: A total of 930 (91%) of 1026 participants at 2 centers in the Age-Related Eye Disease Study (AREDS), a multicenter randomized trial of antioxidant vitamins and minerals, were enrolled in this case-control study. There were 183 individuals without any maculopathy, 200 with mild maculopathy, 325 with intermediate disease, and 222 with advanced AMD (geographic atrophy or neovascular AMD). The AMD status was assessed by standardized grading of fundus photographs, and stored fasting blood specimens drawn between January 1996 and April 1997 were analyzed for high-sensitivity CRP levels. MAIN OUTCOME MEASURE: Association between CRP and AMD. RESULTS: The CRP levels were significantly higher among participants with advanced AMD (case patients) than among those with no AMD (controls; median values, 3.4 vs 2.7 mg/L; P =.02). After adjustment for age, sex, and other variables, including smoking and body mass index, CRP levels were significantly associated with the presence of intermediate and advanced stages of AMD. The odds ratio (OR) for the highest vs the lowest quartile of CRP was 1.65 (95% confidence interval [CI], 1.07-2.55; P for trend =.02). The OR for CRP values at or above the 90th percentile (10.6 mg/L) was 1.92 (95% CI, 1.20-3.06), and the OR for CRP values at or above the mean plus 2 SDs (16.8 mg/L) was 2.03 (95% CI, 1.03-4.00). A trend for an increased risk for intermediate and advanced AMD with higher levels of CRP was seen for smokers (OR, 2.16; 95% CI, 1.33-3.49) and those who never smoked (OR, 2.03; 95% CI, 1.19-3.46) with the highest level of CRP. CONCLUSION: Our results suggest that elevated CRP level is an independent risk factor for AMD and may implicate the role of inflammation in the pathogenesis of AMD.

JAMA. 2004 Feb 11;291(6):704-10

C-reactive protein concentration and concentrations of blood vitamins, carotenoids, and selenium among United States adults.

OBJECTIVE: To examine the relationships between circulating concentrations of C-reactive protein and concentrations of retinol, retinyl esters, vitamin C, vitamin E, carotenoids, and selenium. DESIGN: Cross-sectional study using National Health and Nutrition Examination Survey III (1988-1994) data. SETTING: United States population. SUBJECTS: Up to 14 519 US noninstitutionalized civilian men and women aged > or=20 y. RESULTS: C-reactive protein concentration (dichotomized at the sex-specific 85th percentile) was inversely and significantly associated with concentrations of retinol, retinyl esters, vitamin C, alpha-carotene, beta-carotene, cryptoxanthin, lutein/zeaxanthin, lycopene, and selenium after adjustment for age, sex, race or ethnicity, education, cotinine concentration, body mass index, leisure-time physical activity, and aspirin use. CONCLUSIONS: These results suggest that the inflammatory process, through the production of reactive oxygen species, may deplete stores of antioxidants. Whether increased consumption of foods rich in antioxidants or supplementation with antioxidants can provide health benefits to people characterized by elevated C-reactive protein concentrations may be worthy of further study.

Eur J Clin Nutr. 2003 Sep;57(9):1157-63

Lutein, but not alpha-tocopherol, supplementation improves visual function in patients with age-related cataracts: a 2-y double-blind, placebo-controlled pilot study.

OBJECTIVE: We investigated the effect of long-term antioxidant supplementation (lutein and alpha-tocopherol) on serum levels and visual performance in patients with cataracts. METHODS: Seventeen patients clinically diagnosed with age-related cataracts were randomized in a double-blind study involving dietary supplementation with lutein (15 mg; n = 5), alpha-tocopherol (100 mg; n = 6), or placebo (n = 6), three times a week for up to 2 y. Serum carotenoid and tocopherol concentrations were determined with quality-controlled high-performance liquid chromatography, and visual performance (visual acuity and glare sensitivity) and biochemical and hematologic indexes were monitored every 3 mo throughout the study. Changes in these parameters were assessed by General Linear Model (GLM) repeated measures analysis. RESULTS: Serum concentrations of lutein and alpha-tocopherol increased with supplementation, although statistical significance was reached only in the lutein group. Visual performance (visual acuity and glare sensitivity) improved in the lutein group, whereas there was a trend toward the maintenance of and decrease in visual acuity with alpha-tocopherol and placebo supplementation, respectively. No significant side effects or changes in biochemical or hematologic profiles were observed in any of the subjects during the study. CONCLUSIONS: Visual function in patients with age-related cataracts who received the lutein supplements improved, suggesting that a higher intake of lutein, through lutein-rich fruit and vegetables or supplements, may have beneficial effects on the visual performance of people with age-related cataracts.

Nutrition. 2003 Jan;19(1):21-4

Efficacy of N-acetylcarnosine in the treatment of cataracts.

PURPOSE: To evaluate the effects of 1% N-acetylcarnosine (NAC) solution on lens clarity over 6 and 24 months in patients with cataracts. TRIAL DESIGN: Randomised, placebo-controlled study. PARTICIPANTS: 49 subjects (76 affected eyes) with an average age of 65.3 +/- 7.0 years with a diagnosis of senile cataract with minimum to advanced opacification in various lens layers. METHODS: 26 patients (41 eyes) were allocated to topical NAC 1% eyedrops twice daily. The control group consisted of 13 patients (21 eyes) who received placebo eyedrops and 10 patients (14 eyes) who did not receive eyedrops. MAIN OUTCOME MEASURES: All patients were evaluated at entry and followed up every 2 months for a 6-month period (trial 1), or at 6-month intervals for a 2-year period (trial 2), for best-corrected visual acuity and glare testing. In addition, cataract was measured using stereocinematographic slit-images and retro-illumination examination of the lens. Digital analysis of lens images displayed light scattering and absorbing centres in two- and three-dimensional scales. RESULTS: The overall intra-reader reproducibility of cataract measurements (image analysis) was 0.830, and glare testing 0.998. After 6 months, 90% of NAC-treated eyes showed improvement in best corrected visual acuity (7 to 100%) and 88.9% showed a 27 to 100% improvement in glare sensitivity. Topographic studies indicated fewer areas of posterior subcapsular lens opacity and 41.5% of treated eyes had improvement in image analysis characteristics. The overall ratios of image analysis characteristics at 6 months compared with baseline measures were 1.04 and 0.86 for the control and NAC-treated group, respectively (p < 0.001). The apparent benefits of treatment were sustained after 24 months’ treatment. No treated eyes demonstrated worsening of vision. The overall visual outcome in the control group showed significant worsening after 24 months in comparison with both baseline and the 6-month follow-up examination. The overall clinical results observed in the NAC-treated group by the 24-month period of examination differed significantly (p < 0.001) from the control group in the eyes with cortical, posterior subcapsular, nuclear or combined lens opacities. Tolerability of NAC eyedrops was good in almost all patients, with no reports of ocular or systemic adverse effects. CONCLUSION: Topical NAC shows potential for the treatment and prevention of cataracts.

Drugs R D. 2002;3(2):87-103

Alpha tocopherol supplementation decreases serum C-reactive protein and monocyte interleukin-6 levels in normal volunteers and type 2 diabetic patients.

Type 2 diabetic subjects have an increased propensity to premature atherosclerosis. Alpha tocopherol (AT), a potent antioxidant, has several anti-atherogenic effects. There is scanty data on AT supplementation on inflammation in Type 2 diabetic subjects. The aim of the study was to test the effect of RRR-AT supplementation (1200 IU/d) on plasma C-reactive protein (CRP) and interleukin-6 (IL-6) release from activated monocyte in Type 2 diabetic patients with and without macrovascular complications compared to matched controls. The volunteers comprised Type 2 diabetic subjects with macrovascular disease (DM2-MV, n = 23), Type 2 diabetic subjects without macrovascular complications (DM2, n = 24), and matched controls (C, n = 25). Plasma high sensitive CRP (Hs-CRP) and Monocyte IL-6 were assayed at baseline, following 3 months of supplementation and following a 2 month washout phase. DM2-MV subjects have elevated HsCRP and monocyte IL-6 compared to controls. AT supplementation significantly lowered levels of C-reactive protein and monocyte interleukin-6 in all three groups. In conclusion, AT therapy decreases inflammation in diabetic patients and controls and could be an adjunctive therapy in the prevention of atherosclerosis.

Free Radic Biol Med. 2000 Oct 15;29(8):790-2

The antioxidant activity of standardized extract of ginkgo biloba (EGb 761) in rats.

The standardized extract of ginkgo biloba (EGb 761) has been widely employed for its significant benefit in neurodegenerative disorders. Although antioxidative actions have been attributed to this extract, the mechanisms of the multiple principles involved in this pharmacological activity are not completely established. Parkinson’s and Alzheimer’s diseases are frequently associated with oxidative stress and defects in the cellular protective mechanisms. In this study, the lipid peroxidation (LPO) and the activity of the antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD) were evaluated in the hippocampus, striatum and substantia nigra (SN) of rats treated with EGb 761. An increase in the CAT and SOD activities in the hippocampus, striatum and SN, and a decrease of the LPO in the hippocampus were observed. These data are additional to the antioxidant properties of EGb 761 reported in the literature and indicate a possible role for the extract in the treatment of diseases involving free radicals and oxidative damage.

Phytother Res. 2001 Aug;15(5):449-51

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