Antioxidants and Age-Related Macular Degeneration

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Hi All,

Age-related macular degeneration is theoretically an inversely CR-related event.

See:

http://en.wikipedia.org/wiki/Age-Related_Macular_Degeneration

Note from the above web site, that the CRON-related factors for age related

macular

degeneration include aging, hypertension, blood cholesterol level, body mass

index,

oxidation and low saturated fat and maybe all fats.

The below is an editorial introduction and then a pdf-available paper. The

paper

seems to indicate that age-related macular degeneration is inversely related to

dietary antioxidants.

Where do things really stand? The wikipedia pages describe many factors that in

the

paper seemed not to be so relevant. For never-smokers, there seemed to be an

ironical albeit not significantly less age-related macular degeneration for

those

who ate low compared with moderate levels of antioxidants.

This Week in JAMA

JAMA. 2005;294:3057.

Antioxidants and Age-Related Macular Degeneration

High-dose supplementation of beta carotene, vitamins C and E, and zinc in

combination has been shown to reduce progression of age-related macular

degeneration

(AMD), but it is not known whether regular dietary intake of these antioxidants

reduces the risk of incident AMD. In a population-based cohort study with a mean

follow-up of 8 years, van Leeuwen and colleagues estimated the risk of incident

AMD

associated with dietary intake of antioxidant nutrients at baseline. They found

that

high dietary intake of beta carotene, vitamins C and E, and zinc was associated

with

a reduced risk of incident AMD.

Dietary Intake of Antioxidants and Risk of Age-Related Macular Degeneration

Redmer van Leeuwen; Sharmila Boekhoorn; Johannes R. Vingerling; C. M.

Witteman; Caroline C. W. Klaver; Albert Hofman; us T. V. M. de Jong

JAMA. 2005;294:3101-3107.

ABSTRACT

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.

Table 1. Baseline Characteristics of the Study Sample (N=4170)*

==============================

Characteristics---Incident Age-Related Macular Degeneration (n=560)---No

Age-Related

Macular Degeneration at Follow-up (n=3610)---P Value^†

==============================

Age, y 68.2 (7.1) 66.4 (7.2) <.001

Women, No. (%) 321 (57.3) 2151 (59.6) .31

Body mass index^‡ 26.3 (3.5) 26.35 (3.6) .66

Total cholesterol, mmol/L 6.6 (1.2) 6.7 (1.2) .93

High-density lipoprotein cholesterol, mmol/L 1.38 (0.36) 1.35 (0.36) .02

Atherosclerosis composite score^¶ 2.7 (1.1) 2.5 (1.1) .21

Alcohol intake, g/d 10.8 (15.3) 10.6 (15.3) .20

Antioxidant supplement users, No. (%) 60 (10.7) 499 (13.8) .09

Smoking status, No. (%)

Never 183 (32.8) 1207 (33.6)

Former 248 (44.4) 1561 (43.4) .86

Current 127 (22.8) 825 (23.0)

Pack-years of smoking 18.5 (23.8) 16.4 (21.8) .04

Blood pressure, mm Hg

Systolic 138.9 (20.3) 137.1 (21.5) .76

Diastolic 73.4 (10.7) 73.9 (11.0) .56

==============================

SI conversions: To convert total and high-density lipoprotein cholesterol to

mg/dL, divide by 0.0259.

*Data are expressed as mean (SD) unless otherwise indicated.

^†Adjusted for age and sex.

^‡Body mass index was calculated as weight in kilograms divided by the square

of

height in meters.

^¶Information on the atherosclerosis composite score is presented in the

“Methods” section of the text.

Table 2. Mean Dietary Intake of Nutrients by Quartile in the Total Study Sample

(N=4170)

==============================

Quartile of Dietary Intake, mg/d

1 2 3 4

4x [Mean (SD)]

==============================

Carotenoids

Alpha carotene 0.5 (0.2) </=0.7 0.9 (0.01) >0.7-</=1.0 1.2 (0.1) >1.0-</=1.4

2.0

(1.2) >1.4

Beta carotene 2.1 (0.6) </=2.7 3.2 (0.2) >2.7-</=3.6 4.0 (0.3) >3.6-</=4.6

6.2

(0.3) >4.6

Beta cryptoxanthin 0.05 (0.04) </=0.1 0.2 (0.04) >0.1-</=0.3 0.3 (0.04)

>0.3-</=0.4 0.6 (0.2) >0.4

Lutein/zeaxanthin 1.4 (0.3) </=1.8 2.0 (0.1) >1.8-</=2.2 2.5 (0.2)

>2.2-</=2.8

3.6 (1.3) >2.8

Lycopene 0.1 (0.07) </=0.3 0.5 (0.1) >0.3-</=0.7 0.8 (0.1) >0.7-</=1.1 1.8

(0.8)

>1.1

Vitamins

Vitamin A (retinol equivalents) 0.5 (0.1) </=0.6 0.7 (0.03) >0.6-</=0.8 0.8

(0.04) >0.8-</=0.9 1.2 (0.5) >0.9

Vitamin C 63.7 (15.5) </=84.5 99.4 (8.2) >84.5-</=113.6 128.4 (9.2)

>113.6-</=146.1 189.3 (46.6) >146.1

Vitamin E 7.6 (1.9) </=9.9 11.4 (0.8) >9.9-</=12.8 14.4 (1.0) >12.8-</=16.2

20.2

(4.1) >16.2

Trace elements

Iron 9.5 (1.0) </=10.7 11.3 (0.4) >10.7-</=11.9 12.6 (0.4) >11.9-</=13.3 14.8

(1.6) >13.3

Zinc 7.3 (0.9) </=8.3 9.0 (0.4) >8.3-</=9.6 10.2 (0.4) >9.6-</=10.9 12.3

(1.4)

>10.9

Table 3. Risk of Age-Related Macular Degeneration per Standard Deviation (SD)

Increase in Dietary Intake of Antioxidant Nutrients

==============================

Nutrients Mean intake (SD), mg/d Adjusted HR per 1-SD increase (95% Confidence

Interval)*

==============================

Carotenoids

Alpha carotene 1.12 (0.84) 0.99 (0.94-1.06)

Beta carotene 3.84 (2.23) 1.00 (0.94-1.06)

Beta cryptoxanthin 0.29 (0.22) 1.01 (0.92-1.10)

Lutein/zeaxanthin 2.37 (1.08) 1.01 (0.93-1.09)

Lycopene 0.80 (0.80) 1.01 (0.97-1.04)

Vitamins

Vitamin A (retinol equivalents) 0.82 (0.35) 0.95 (0.86-1.05)

Vitamin C 120.20 (52.49) 1.02 (0.94-1.10)

Vitamin E 13.42 (5.19) 0.92 (0.84-1.00)

Trace elements

Iron 12.04 (2.16) 0.95 (0.86-1.04)

Zinc 9.67 (2.01) 0.91 (0.83-0.98)

==============================

*Adjusted for age, sex, body-mass index, smoking status, pack-years of

smoking,

systolic blood pressure, athero-sclerosis composite score, serum total

cholesterol,

and alcohol intake.

HR=Hazard ratio

Table 4. Risk of Age-Related Macular Degeneration by Category of Combined Intake

of

4 Predefined Antioxidant Nutrients (Vitamins C and E, Beta Carotene, and Zinc)

==============================

Category of Dietary Intake*

Low (n=466) Middle (n=3270) High (n=434)

==============================

Cases of age-related macular degeneration, No. (%) 76 (16.3) 442 (13.5) 42 (9.7)

Hazard ratio (95% confidence interval)

Unadjusted 1.31 (1.03-1.67) 1.00 0.65 (0.48-0.89)

Age- and sex-adjusted 1.23 (0.97-1.58) 1.00 0.68 (0.49-0.93)

Fully adjusted^† 1.20 (0.92-1.56) 1.00 0.65 (0.46-0.92)

==============================

*Categories were defined by using the median energy-adjusted daily intake per

nutrient as a cutoff value and classi-fying above-median intake of all nutrients

as

high intake and below-median intake of all nutrients as low intake. Cut-off

values

were 114 mg for vitamin C, 13 mg for vitamin E, 3.6 mg for beta carotene, and

9.6 mg

for zinc.

^†Adjusted for age, sex, body mass index, smoking status, pack-years of

smoking,

systolic blood pressure, athero-sclerosis composite score, serum total

cholesterol,

and alcohol intake.

Table 5. Risk of Age-Related Macular Degeneration by Category of Combined Intake

of

4 Predefined Antioxidant Nutrients (Vitamins C and E, Beta Carotene, and Zinc),

Excluding Supplement Users and Stratified by Smoking Status

==============================

Category of Dietary Intake*

Low Middle High

==============================

Excluding supplement users n=419 n=2816 n=376

Cases, No. (%) 67 (16.0) 396 (14.1) 37 (9.8)

HR (95% CI)^† 1.11 (0.84-1.46) 1.00 0.62 (0.43-0.90)

Smoking status

Never n=128 n=1096 n=160

Cases, No. (%) 17 (13.3) 144 (13.3) 16 (10.0)

HR (95% CI)^‡ 0.85 (0.48-1.50) 1.00 0.74 (0.42-1.31)

Former n=182 n=1434 n=193

Cases, No. (%) 31 (17.0) 199 (13.9) 18 (9.3)

HR (95% CI)^‡ 1.26 (0.84-1.99) 1.00 0.58 (0.34-0.98)

Current n=154 n=727 n=77

Cases, No. (%) 28 (18.2) 97 (13.3) 8 (10.4)

HR (95% CI)^‡ 1.44 (0.93-2.22) 1.00 0.65 (0.30-1.40)

==============================

Abbreviations: CI indicates confidence interval; HR, hazard ratio.

*Categories were defined by using the median energy-adjusted daily intake per

nutrient as a cutoff value and classi-fying above-median intake of all nutrients

as

high intake and below-median intake of all nutrients as low intake. Cut-off

values

were 114 mg for vitamin C, 13 mg for vitamin E, 3.6 mg for beta carotene, and

9.6 mg

for zinc.

^†Adjusted for age, sex, body mass index, smoking status, pack-years of

smoking,

systolic blood pressure, athero-sclerosis composite score, serum total

cholesterol,

and alcohol intake.

^‡Adjusted for all of the above except smoking status and pack-years of

smoking.

.... This study suggests that the risk of AMD can be modified by diet; in

particular,

by dietary vitamin E and zinc. A higher intake of vitamin E can be achieved by

consumption of whole grains, vegetable oil, eggs, and nuts. High concentrations

of

zinc can be found in meat, poultry, fish, whole grains, and dairy products.

Carrots,

kale, and spinach are the main suppliers of beta carotene, while vitamin C is

found

in citrus fruits and juices, green peppers, broccoli, and potatoes. Based on

this

study, foods high in these nutrients appear to be more important than

nutritional

supplements. ... our observational data suggest that a high intake of specific

antioxidants from a regular diet may delay the development of AMD.

Al Pater, PhD; email: old542000@...

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