Macular degeneration/function
1. The role of oxidative stress in the pathogenesis of age-related macular
degeneration. Beatty S, KohH, Phil M, Henson D, Boulton M. Academic Department
of Ophthalmology, Manchester Royal Eye Hospital, Manchester, United Kingdom.
Surv Ophthalmol 2000 Sep-Oct;45(2):115-34
Age-related macular degeneration (AMD) is the leading cause of blind
registration in the developed world, and yet its pathogenesis remains
poorly understood. Oxidative stress, which refers to cellular damage caused
by reactive oxygen intermediates (ROI), has been implicated in many disease
processes, especially age-related disorders. ROIs include free radicals,
hydrogen peroxide, and singlet oxygen, and they are often the byproducts
of oxygen metabolism. The retina is particularly susceptible to oxidative
stress because of its high consumption of oxygen, its high proportion
of polyunsaturated fatty acids, and its exposure to visible light. In
vitro studies have consistently shown that photochemical retinal injury
is attributable to oxidative stress and that the antioxidant vitamins
A, C, and E protect against this type of injury. Furthermore, there is
strong evidence suggesting that lipofuscin is derived, at least in part,
from oxidatively damaged photoreceptor outer segments and that it is itself
a photoreactive substance. However, the relationships between dietary
and serum levels of the antioxidant vitamins and age-related macular disease
are less clear, although a protective effect of high plasma concentrations
of alpha-tocopherol has been convincingly demonstrated. Macular pigment
is also believed to limit retinal oxidative damage by absorbing incoming
blue light and/or quenching ROIs. Many putative risk-factors for AMD have
been linked to a lack of macular pigment, including female gender, lens
density, tobacco use, light iris color, and reduced visual sensitivity.
Moreover, the Eye Disease Case-Control Study found that high plasma levels
of lutein and zeaxanthin were associated with reduced risk of neovascular
AMD. The concept that AMD can be attributed to cumulative oxidative stress
is enticing, but remains unproven. With a view to reducing oxidative damage,
the effect of nutritional antioxidant supplements on the onset and natural
course of age-related macular disease is currently being evaluated.
2. Lutein and zeaxanthin in the eyes, serum and diet of human subjects.
Bone RA, Landrum JT, Dixon Z, Chen Y, Llerena CM. Department of Physics,
Florida International University, Miami, FL 33199, USA. Exp Eye Res 2000
Sep;71(3):239-45
Inverse associations have been reported between the incidence of advanced,
neovascular, age-related macular degeneration (AMD) and the combined lutein
(L) and zeaxanthin (Z) intake in the diet, and L and Z concentration in
the blood serum. We suggest that persons with high levels of L and Z in
either the diet or serum would probably have, in addition, relatively
high densities of these carotenoids in the macula, the so-called 'macular
pigment'. Several lines of evidence point to a potential protective effect
by the macular pigment against AMD. In this study we examined the relationship
between dietary intake of L and Z using a food frequency questionnaire;
concentration of L and Z in the serum, determined by high-performance
liquid chromatography, and macular pigment optical density, obtained by
flicker photometry. Nineteen subjects participated. We also analysed the
serum and retinas, as autopsy samples, from 23 tissue donors in order
to obtain the concentration of L and Z in these tissues. The results reveal
positive, though weak, associations between dietary intake of L and Z
and serum concentration of L and Z, and between serum concentration of
L and Z and macular pigment density. We estimate that approximately half
of the variability in the subjects' serum concentration of L and Z can
be explained by their dietary intake of L and Z, and about one third of
the variability in their macular pigment density can be attributed to
their serum concentration of L and Z. These results, together with the
reported associations between risk of AMD and dietary and serum L and
Z, support the hypothesis that low concentrations of macular pigment may
be associated with an increased risk of AMD.
3. Macular pigment in donor eyes with and without AMD: a case-control
study. Bone RA, Landrum JT, Mayne ST, Gomez CM, Tibor SE, Twaroska EE.
Department of Physics, Florida International University, Miami, Florida
33199, USA. bone@fiu.edu Invest Ophthalmol Vis Sci 2001 Jan;42(1):235-40
PURPOSE: To determine whether there is an association between the density
of macular pigment in the human retina and the risk of age-related macular
degeneration (AMD). METHODS: Retinas from 56 donors with AMD and 56 controls
were cut into three concentric regions centered on the fovea. The inner,
medial, and outer regions covered the visual angles 0 degrees to 5 degrees,
5 degrees to 19 degrees, and 19 degrees to 38 degrees, respectively. The
amounts of lutein (L) and zeaxanthin (Z) extracted from each tissue sample
were determined by high-performance liquid chromatography. RESULTS: L
and Z levels in all three concentric regions were less, on average, for
the AMD donors than for the controls. The differences decreased in magnitude
from the inner to medial to outer regions. The lower levels found in the
inner and medial regions for AMD donors may be attributable, in part,
to the disease. Comparisons between AMD donors and controls using the
outer (peripheral) region were considered more reliable. For this region,
logistic regression analysis indicated that those in the highest quartile
of L and Z level had an 82% lower risk for AMD compared with those in
the lowest quartile (age- and sex-adjusted odds ratio = 0.18, 95% confidence
interval = 0.05-0.64). CONCLUSIONS: The results are consistent with a
theoretical model that proposes an inverse association between risk of
AMD and the amounts of L and Z in the retina. The results are inconsistent
with a model that attributes a loss of L and Z in the retina to the destructive
effects of AMD.
4. Lutein, zeaxanthin, and the macular pigment. Landrum JT, Bone RA.
Department of Chemistry, Florida International University, Miami 33199,
USA. landrumj@fiu.edu Arch Biochem Biophys 2001 Jan 1;385(1):28-40
The predominant carotenoids of the macular pigment are lutein, zeaxanthin,
and meso-zeaxanthin. The regular distribution pattern of these carotenoids
within the human macula indicates that their deposition is actively controlled
in this tissue. The chemical, structural, and optical characteristics
of these carotenoids are described. Evidence for the presence of minor
carotenoids in the retina is cited. Studies of the dietary intake and
serum levels of the xanthophylls are discussed. Increased macular carotenoid
levels result from supplementation of humans with lutein and zeaxanthin.
A functional role for the macular pigment in protection against light-induced
retinal damage and age-related macular degeneration is discussed. Prospects
for future research in the study of macular pigment require new initiatives
that will probe more accurately into the localization of these carotenoids
in the retina, identify possible transport proteins and mechanisms, and
prove the veracity of the photoprotection hypothesis for the macular pigments.
5. Lutein and zeaxanthin concentrations in rod outer segment membranes
from perifoveal and peripheral human retina. Rapp LM, Maple SS, Choi JH.
Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine,
Houston, Texas 77030, USA. lrapp@bcm.tmc.edu Invest Ophthalmol Vis Sci
2000 Apr;41(5):1200-9
PURPOSE: In addition to acting as an optical filter, macular (carotenoid)
pigment has been hypothesized to function as an antioxidant in the human
retina by inhibiting the peroxidation of long-chain polyunsaturated fatty
acids. However, at its location of highest density in the inner (prereceptoral)
layers of the foveal retina, a specific requirement for antioxidant protection
would not be predicted. The purpose of this study was to determine whether
lutein and zeaxanthin, the major carotenoids comprising the macular pigment,
are present in rod outer segment (ROS) membranes where the concentration
of long-chain polyunsaturated fatty acids, and susceptibility to oxidation,
is highest. METHODS: Retinas from human donor eyes were dissected to obtain
two regions: an annular ring of 1.5- to 4-mm eccentricity representing
the area centralis excluding the fovea (perifoveal retina) and the remaining
retina outside this region (peripheral retina). ROS and residual (ROS-depleted)
retinal membranes were isolated from these regions by differential centrifugation
and their purity checked by polyacrylamide gel electrophoresis and fatty
acid analysis. Lutein and zeaxanthin were analyzed by high-performance
liquid chromatography and their concentrations expressed relative to membrane
protein. Preparation of membranes and analysis of carotenoids were performed
in parallel on bovine retinas for comparison to a nonprimate species.
Carotenoid concentrations were also determined for retinal pigment epithelium
harvested from human eyes. RESULTS: ROS membranes prepared from perifoveal
and peripheral regions of human retina were found to be of high purity
as indicated by the presence of a dense opsin band on protein gels. Fatty
acid analysis of human ROS membranes showed a characteristic enrichment
of docosahexaenoic acid relative to residual membranes. Membranes prepared
from bovine retinas had protein profiles and fatty acid composition similar
to those from human retinas. Carotenoid analysis showed that lutein and
zeaxanthin were present in ROS and residual human retinal membranes. The
combined concentration of lutein plus zeaxanthin was 70% higher in human
ROS than in residual membranes. Lutein plus zeaxanthin in human ROS membranes
was 2.7 times more concentrated in the perifoveal than the peripheral
retinal region. Lutein and zeaxanthin were consistently detected in human
retinal pigment epithelium at relatively low concentrations. CONCLUSIONS:
The presence of lutein and zeaxanthin in human ROS membranes raises the
possibility that they function as antioxidants in this cell compartment.
The finding of a higher concentration of these carotenoids in ROS of the
perifoveal retina lends support to their proposed protective role in age-related
macular degeneration. 6. Am J Clin Nutr. 2001 Dec;74(6):796-802.
6. Relation between dietary intake, serum concentrations, and retinal
concentrations of lutein and zeaxanthin in adults in a Midwest population.
Curran-Celentano J, Hammond BR Jr, Ciulla TA, Cooper DA, Pratt LM, Danis
RB. Department of Animal and Nutritional Sciences, University of New Hampshire,
Durham, NH 03824, USA. joannec@christa.unh.edu
BACKGROUND: Information on concentrations of retinal carotenoids (macular
pigment, or MP) is of particular interest because MP protects against
age-related macular degeneration, the leading cause of irreversible blindness
in
the United States. OBJECTIVE: This study was designed to evaluate the
relation
between dietary intake, blood concentrations, and retinal concentrations
of
carotenoids in a large group of volunteers. DESIGN: Two hundred eighty
volunteers in the Indianapolis area completed health and diet questionnaires,
donated a blood sample, and participated in MP density assessment to determine
retinal carotenoid status. Dietary intake was assessed by food-frequency
questionnaire. Serum concentrations of lutein, zeaxanthin, and beta-carotene
were measured by HPLC. MP optical density (MPOD) was determined psychophysically
with a 460-nm, 1 degrees test stimulus. RESULTS: Average MPOD was 0.21
+/- 0.13.
Average intakes of lutein + zeaxanthin and beta-carotene were 1101 +/-
838 and
2935 +/- 2698 microg/d, respectively. Although several key dietary intake
variables (eg, lutein + zeaxanthin and beta-carotene) differed by sex,
no
significant sex differences were found in either serum concentrations
of lutein
and zeaxanthin or MPOD. Serum beta-carotene concentrations were significantly
higher in women than in men. Serum lutein + zeaxanthin and dietary intake
of
lutein + zeaxanthin were significantly correlated and significantly related
to
variations in MPOD (r = 0.21, P < 0.001, and r = 0.25, P < 0.001,
respectively).
CONCLUSIONS: Retinal carotenoids can be measured in epidemiologic studies.
In
this study, MPOD was associated with lutein + zeaxanthin in the diet and
the
serum. Retinal concentrations, however, were influenced by other factors
as
well. To understand the effect of dietary lutein + zeaxanthin intake on
the
retina and risk of age-related eye disease, future studies should include
measures of macular concentrations of these pigments.
7. EXS. 1992;62:280-98.
Carotenoids in the retina--a review of their possible role in preventing
or
limiting damage caused by light and oxygen.
Schalch W.
Vitamins & Fine Chemical Division, F. Hoffmann - La Roche, Basel,
Switzerland.
Two of the circa 600 naturally occurring carotenoids, zeaxanthin and
lutein, the
major carotenoids of maize and melon respectively, are the constituents
of the
macula lutea, the yellow spot in the macula, the central part of the retina
in
primates and humans. Of the circa ten carotenoids found in the blood these
two
are specifically concentrated in this area, which is responsible for sharp
and
detailed vision. This paper reviews the ideas that this concentration
of dietary
carotenoids in the macula is not accidental, but that their presence may
prevent
or limit damage due to their physicochemical properties and their capability
to
quench oxygen free radicals and singlet oxygen, which are generated in
the
retina as a consequence of the simultaneous presence of light and oxygen.
Additionally, in vitro and in vivo animal experiments are reviewed as
well as
observational and epidemiological data in humans. These show that there
is
enough circumstantial evidence for a protective role of carotenoids in
the
retina to justify further research. Some emphasis will be put on age-related
macular degeneration (AMD), a multifactorial degenerative retinal disease
for
which the exposure to light and thus photochemical damage has been suggested
as
one of the etiological factors. Recent attempts at nutritional intervention
in
this condition will also be reviewed.
8. J Am Coll Nutr. 2000 Oct;19(5 Suppl):522S-527S.
The potential role of dietary xanthophylls in cataract and age-related
macular
degeneration.
Moeller SM, Jacques PF, Blumberg JB.
Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University,
Boston, Massachusetts 02111, USA.
The carotenoid xanthophylls, lutein and zeaxanthin, accumulate in the
eye lens
and macular region of the retina. Lutein and zeaxanthin concentrations
in the
macula are greater than those found in plasma and other tissues. A relationship
between macular pigment optical density, a marker of lutein and zeaxanthin
concentration in the macula, and lens optical density, an antecedent of
cataractous changes, has been suggested. The xanthophylls may act to protect
the
eye from ultraviolet phototoxicity via quenching reactive oxygen species
and/or
other mechanisms. Some observational studies have shown that generous
intakes of
lutein and zeaxanthin, particularly from certain xanthophyll-rich foods
like
spinach, broccoli and eggs, are associated with a significant reduction
in the
risk for cataract (up to 20%) and for age-related macular degeneration
(up to
40%). While the pathophysiology of cataract and age-related macular degeneration
is complex and contains both environmental and genetic components, research
studies suggest dietary factors including antioxidant vitamins and xanthophylls
may contribute to a reduction in the risk of these degenerative eye diseases.
Further research is necessary to confirm these observations.
9. Lutein and zeaxanthin status and risk of age-related macular degeneration.
Gale CR, Hall NF, Phillips DI, Martyn CN.
Medical Research Council Environmental Epidemiology Unit, University
of
Southampton, Southampton General Hospital, Southampton, United Kingdom.
crg@mrc.soton.ac.uk
PURPOSE: To investigate the relation between plasma concentrations of
lutein and
zeaxanthin and age-related macular degeneration in a group of elderly
men and
women. METHODS: The Wisconsin Age-Related Maculopathy Grading System was
used to grade features of early and late macular degeneration in 380 men
and women, aged 66 to 75 years, from Sheffield, United Kingdom. Fasting
blood samples were taken
to assess plasma concentrations of lutein and zeaxanthin. RESULTS: Risk
of
age-related macular degeneration (early or late) was significantly higher
in
people with lower plasma concentrations of zeaxanthin. Compared with those
whose
plasma concentrations of zeaxanthin were in the highest third of the
distribution, people whose plasma concentration was in the lowest third
had an
odds ratio for risk of age-related macular degeneration of 2.0 (95% confidence
interval [CI] 1.0-4.1), after adjustment for age and other risk factors.
Risk of
age-related macular degeneration was increased in people with the lowest
plasma
concentrations of lutein plus zeaxanthin (odds ratio [OR] 1.9, 95% CI
0.9-3.5)
and in those with the lowest concentrations of lutein (OR 1.7, 95% CI
0.9-3.3),
but neither of these relations was statistically significant. CONCLUSIONS:
These
findings provide support for the view that zeaxanthin may protect against
age-related macular degeneration.
10. Curr Eye Res. 1999 Dec;19(6):491-5.
Lutein and zeaxanthin are associated with photoreceptors in the human
retina.
Sommerburg OG, Siems WG, Hurst JS, Lewis JW, Kliger DS, van Kuijk FJ.
University of Texas Medical Branch, Department of Ophthalmology &
Visual
Sciences TX, Galveston 77555-1067, USA.
PURPOSE. Previous studies showed that lutein and zeaxanthin, the major
human
retinal carotenoids, are concentrated in the macula. In this study, the
carotenoids in human macular and peripheral retina and the retinal pigment
epithelium (RPE) were analyzed. They were also determined in the rod outer
segments (ROS) before and after removal of extrinsic membrane proteins.
METHODS.
Carotenoids were extracted from the macular and peripheral sections of
human
retina and RPE with hexane in dim light and analyzed by high performance
liquid
chromatography (HPLC). ROS samples equivalent to the amount in a single
retina
were also analyzed. RESULTS. Retinal carotenoid amounts were similar to
previous
reports, but only low levels were detected in the RPE. Regional ratios
of
lutein:zeaxanthin were similar in the retina and RPE. Approximately 25%
of the
total retinal carotenoids were found in the ROS, indicating that a substantial
portion of peripheral retinal carotenoids are present in the ROS. However,
after
removal of the extrinsic membrane proteins and subsequent analysis, carotenoids
were not detected. CONCLUSIONS: Most of the carotenoids in the human peripheral
retina are present in the ROS. These ROS carotenoids are associated with
soluble
or salt-dependently bound proteins.
11. Fruits and vegetables that are sources for lutein and zeaxanthin:
the macular
pigment in human eyes.
Sommerburg O, Keunen JE, Bird AC, van Kuijk FJ.
Department of Ophthalmology and Visual Sciences, University of Texas
Medical
Branch, Galveston 77555-1067, USA.
BACKGROUND: It has been suggested that eating green leafy vegetables,
which are
rich in lutein and zeaxanthin, may decrease the risk for age related macular
degeneration. The goal of this study was to analyse various fruits and
vegetables to establish which ones contain lutein and/or zeaxanthin and
can
serve as possible dietary supplements for these carotenoids. METHODS:
Homogenates of 33 fruits and vegetables, two fruit juices, and egg yolk
were
used for extraction of the carotenoids with hexane. Measurement of the
different
carotenoids and their isomers was carried out by high performance liquid
chromatography using a single column with an isocratic run, and a diode
array
detector. RESULTS: Egg yolk and maize (corn) contained the highest mole
percentage (% of total) of lutein and zeaxanthin (more than 85% of the
total
carotenoids). Maize was the vegetable with the highest quantity of lutein
(60%
of total) and orange pepper was the vegetable with the highest amount
of
zeaxanthin (37% of total). Substantial amounts of lutein and zeaxanthin
(30-50%)
were also present in kiwi fruit, grapes, spinach, orange juice, zucchini
(or
vegetable marrow), and different kinds of squash. The results show that
there
are fruits and vegetables of various colours with a relatively high content
of
lutein and zeaxanthin. CONCLUSIONS: Most of the dark green leafy vegetables,
previously recommended for a higher intake of lutein and zeaxanthin, have
15-47%
of lutein, but a very low content (0-3%) of zeaxanthin. Our study shows
that
fruits and vegetables of various colours can be consumed to increase dietary
intake of lutein and zeaxanthin.
12. Optom Vis Sci. 1997 Jul;74(7):499-504.
Density of the human crystalline lens is related to the macular pigment
carotenoids, lutein and zeaxanthin.
Hammond BR Jr, Wooten BR, Snodderly DM.
Vision Sciences Laboratory, College of Arts & Sciences, Arizona State
University, Phoenix, USA. BHammond@asuvm.inre.asu.edu
PURPOSE: Although oxidative stress may play an important role in the
development
of age-related cataract, the degree of protection reported for antioxidant
vitamins and carotenoids has been inconsistent across studies. These varied
results may be due in part to the lack of good biomarkers for measuring
the
long-term nutritional status of the eye. The present experiments investigated
the relationship between retinal carotenoids (i.e., macular pigment),
used as a
long-term measure of tissue carotenoids, and lens optical density, used
as an
indicator of lens health. METHODS: Macular pigment (460 nm) and lens (440,
500,
and 550 nm) optical density were measured psychophysically in the same
individuals. Groups of younger subjects--7 females (ages 24 to 36 years),
and 5
males (ages 24 to 31 years)--were compared with older subjects--23 older
females
(ages 55 to 78 years), and 16 older males (ages 48 to 82 years). RESULTS:
Lens
density (440 nm) increased as a function of age (r = 0.65, p < 0.001),
as
expected. For the oldest group, a significant inverse relationship (y
=
1.53-0.83x, r = -0.47, p < 0.001) was found between macular pigment
density (440
nm) and lens density (440 nm). No relationship was found for the youngest
group
(p < 0.42). CONCLUSIONS: The main finding of this study was an age-dependent,
inverse relationship between macular pigment density and lens density.
Macular
pigment is composed of lutein and zeaxanthin, the only two carotenoids
that have
been identified in the human lens. Thus, an inverse relationship between
these
two variables suggests that lutein and zeaxanthin, or other dietary factors
with
which they are correlated, may retard age-related increases in lens density.
13. Invest Ophthalmol Vis Sci. 2001 Feb;42(2):439-46.
Macular pigment and risk for age-related macular degeneration in subjects
from a
Northern European population.
Beatty S, Murray IJ, Henson DB, Carden D, Koh H, Boulton ME.
University Department of Ophthalmology, Manchester Royal Eye Hospital,
Manchester, UK. stephen@stiofanbetagh.demon.co.uk
PURPOSE: Age and advanced disease in the fellow eye are the two most
important
risk factors for age-related macular degeneration (AMD). In this study,
the
authors investigated the relationship between these variables and the
optical
density of macular pigment (MP) in a group of subjects from a northern
European
population. METHODS: The optical density of MP was measured psychophysically
in
46 subjects ranging in age from 21 to 81 years with healthy maculae and
in 9
healthy eyes known to be at high-risk of AMD because of advanced disease
in the
fellow eye. Each eye in the latter group was matched with a control eye
on the
basis of variables believed to be associated with the optical density
of MP
(iris color, gender, smoking habits, age, and lens density). RESULTS:
There was
an age-related decline in the optical density of macular pigment among
volunteers with no ocular disease (right eye: r(2) = 0.29, P = 0.0006;
left eye:
r(2) = 0.29, P < 0.0001). Healthy eyes predisposed to AMD had significantly
less
MP than healthy eyes at no such risk (Wilcoxon's signed rank test: P =
0.015).
CONCLUSIONS: The two most important risk factors for AMD are associated
with a
relative absence of MP. These findings are consistent with the hypothesis
that
supplemental lutein and zeaxanthin may delay, avert, or modify the course
of
this disease.
14. J Opt Soc Am A Opt Image Sci Vis. 2002 Jun;19(6):1172-86.
In vivo resonant Raman measurement of macular carotenoid pigments in
the young
and the aging human retina.
Gellermann W, Ermakov IV, Ermakova MR, McClane RW, Zhao DY, Bernstein
PS.
Department of Physics and Dixon Laser Institute, University of Utah,
Salt Lake
City 84112, USA. werner@physics.utah.edu
We have used resonant Raman scattering spectroscopy as a novel, noninvasive,
in
vivo optical technique to measure the concentration of the macular carotenoid
pigments lutein and zeaxanthin in the living human retina of young and
elderly
adults. Using a backscattering geometry and resonant molecular excitation
in the
visible wavelength range, we measure the Raman signals originating from
the
single- and double-bond stretch vibrations of the pi-conjugated molecule's
carbon backbone. The Raman signals scale linearly with carotenoid content,
and
the required laser excitation is well below safety limits for macular
exposure.
Furthermore, the signals decline significantly with increasing age in
normal
eyes. The Raman technique is objective and quantitative and may lead to
a new
method for rapid screening of carotenoid pigment levels in large populations
at
risk for vision loss from age-related macular degeneration, the leading
cause of
blindness in the elderly in the United States.
15. Surv Ophthalmol. 2000 Sep-Oct;45(2):115-34.
The role of oxidative stress in the pathogenesis of age-related macular
degeneration.
Beatty S, Koh H, Phil M, Henson D, Boulton M.
Academic Department of Ophthalmology, Manchester Royal Eye Hospital,
Manchester,
United Kingdom.
Age-related macular degeneration (AMD) is the leading cause of blind
registration in the developed world, and yet its pathogenesis remains
poorly
understood. Oxidative stress, which refers to cellular damage caused by
reactive
oxygen intermediates (ROI), has been implicated in many disease processes,
especially age-related disorders. ROIs include free radicals, hydrogen
peroxide,
and singlet oxygen, and they are often the byproducts of oxygen metabolism.
The
retina is particularly susceptible to oxidative stress because of its
high
consumption of oxygen, its high proportion of polyunsaturated fatty acids,
and
its exposure to visible light. In vitro studies have consistently shown
that
photochemical retinal injury is attributable to oxidative stress and that
the
antioxidant vitamins A, C, and E protect against this type of injury.
Furthermore, there is strong evidence suggesting that lipofuscin is derived,
at
least in part, from oxidatively damaged photoreceptor outer segments and
that it
is itself a photoreactive substance. However, the relationships between
dietary
and serum levels of the antioxidant vitamins and age-related macular disease
are
less clear, although a protective effect of high plasma concentrations
of
alpha-tocopherol has been convincingly demonstrated. Macular pigment is
also
believed to limit retinal oxidative damage by absorbing incoming blue
light
and/or quenching ROIs. Many putative risk-factors for AMD have been linked
to a
lack of macular pigment, including female gender, lens density, tobacco
use,
light iris color, and reduced visual sensitivity. Moreover, the Eye Disease
Case-Control Study found that high plasma levels of lutein and zeaxanthin
were
associated with reduced risk of neovascular AMD. The concept that AMD
can be
attributed to cumulative oxidative stress is enticing, but remains unproven.
With a view to reducing oxidative damage, the effect of nutritional antioxidant
supplements on the onset and natural course of age-related macular disease
is
currently being evaluated.
Cataracts
16. Curr Eye Res. 1999 Dec;19(6):502-5.
Fat-soluble nutrient concentrations in different layers of human cataractous
lens.
Yeum KJ, Shang FM, Schalch WM, Russell RM, Taylor A.
Tufts University, Jean Mayer United States Department ofAgriculture Human
Nutrition Research Center onAging at Tufts University, Boston, M A 0211,
USA.
PURPOSE. Recent epidemiologic studies suggest that differential risk
for
cataract in different areas of the lens may be related to intake of carotenoids,
retinol, and tocopherol. Nevertheless, there is little information about
differential localization of these nutrients in the lens. To determine
the
spatial distribution of fat-soluble nutrients within the lens, we determined
levels of these nutrients in the epithelium/ outer cortex vs. inner
cortex/nucleus. METHODS. Concentrations of carotenoids, retinol, and tocopherol
were determined in the epithelial/cortical (younger, more metabolically
active
tissue) and nuclear (older, less metabolically active) layers of human
cataractous lenses (n = 7, 64-75 yr) by reverse-phase high-performance
liquid
chromatography (HPLC). RESULTS. Lutein/zeaxanthin was the only carotenoid,
which
was detected, in human lens. Consistent with prior reports, no beta-carotene
or
lycopene were detected. Concentrations of lutein/zeaxanthin, tocopherol,
and
retinol in epithelium/cortex tissue were approximately 3-, 1.8-, and 1.3-fold
higher than in the older lens tissue. Specifically, the epithelial/cortical
lens
layer, comprising about half of the tissue, contains 74% of lutein/zeaxanthin
(44 ng/g wet wt), 65% of alpha-tocopherol (2227 ng/g wet wt), and 60%
of retinol
(30 ng/g wet wt). CONCLUSIONS. The data suggest that upon development
and aging,
there is differential localization of these nutrients. The data are also
consistent with a protective role of these nutrients against oxidative
damage in
the epithelium and cortex of the human lens.
17. Arch Ophthalmol. 2002 Dec;120(12):1732-7.
Lens aging in relation to nutritional determinants and possible risk
factors for
age-related cataract.
Berendschot TT, Broekmans WM, Klopping-Ketelaars IA, Kardinaal AF, Van
Poppel G,
Van Norren D.
Department of Ophthalmology, Universitair Medisch Centrum Utrecht, AZU
E03.136,
Heidelberglaan 100, PO Box 85500, NL-3508 GA Utrecht, the Netherlands.
tosb@isi.uu.nl
OBJECTIVE: To investigate whether nutritional factors and possible risk
factors
for cataract influence the lens optical density (LOD). DESIGN: Three hundred
seventy-six subjects, aged 18 to 75 years, were recruited. In a cross-sectional
design, serum was analyzed for lutein, zeaxanthin, vitamin C, alpha-tocopherol,
and cholesterol levels. Adipose tissue (n = 187) was analyzed for lutein
level.
The LOD and the macular pigment optical density (MPOD) were measured by
spectral
fundus reflectance. RESULTS: The mean +/- SD LOD at 420 nm was 0.52 +/-
0.17. It
showed a significant association with age (beta =.008, P<001) and MPOD
(beta =
-.096, P =.02). For subjects 50 years and younger (mean +/- SD LOD, 0.45
+/-
0.11), we found only a single significant beta coefficient, for age (beta
=.006,
P<.001). For subjects older than 50 years (mean +/- SD LOD, 0.68 +/-
0.16), we
found significant beta coefficients for age (beta =.011, P<.001) and
MPOD (beta
= -.240, P =.005). Controlling for age, we found no associations between
LOD and
other possible risk factors for age-related cataract or serum or adipose
tissue
concentrations of carotenoids, vitamin C, and alpha-tocopherol. CONCLUSIONS:
Macular pigment is composed of lutein and zeaxanthin, the only carotenoids
found
in human lenses. The inverse relationship between LOD and MPOD suggests
that
lutein and zeaxanthin may retard aging of the lens.
18. J Nutr. 2002 Mar;132(3):518S-524S.
The body of evidence to support a protective role for lutein and zeaxanthin
in
delaying chronic disease. Overview.
Mares-Perlman JA, Millen AE, Ficek TL, Hankinson SE.
Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison
Medical School, Madison, WI 53705-2397, USA. jmaresp@facstaff.wisc.edu
Recent evidence introduces the possibility that lutein and zeaxanthin
may
protect against the development of the two common eye diseases of aging,
cataract and macular degeneration. This potential and the lack of other
effective means to slow the progression of macular degeneration have fueled
high
public interest in the health benefits of lutein and zeaxanthin and the
proliferation of supplements containing them on pharmacy shelves. An
understanding of the biologic consequences of limiting or supplementing
with
these carotenoids is only beginning to emerge. Some epidemiologic evidence
supports a role in eye disease and, to a lesser extent, cancer and
cardiovascular disease. However, the overall body of evidence is insufficient
to
conclude that increasing levels of lutein and zeaxanthin, specifically,
will
confer an important health benefit. Future advances in scientific research
are
required to gain a better understanding of the biologic mechanisms of
their
possible role in preventing disease. Additional research is also required
to
understand the effect of their consumption, independent of other nutrients
in
fruits and vegetables, on human health. The newly advanced ability to
measure
levels of lutein and zeaxanthin in the retina in vivo creates a unique
opportunity to contribute some of this needed evidence.
Function
19. Exp Eye Res. 2001 Mar;72(3):215-23.
Identification and quantitation of carotenoids and their metabolites
in the
tissues of the human eye.
Bernstein PS, Khachik F, Carvalho LS, Muir GJ, Zhao DY, Katz NB.
Department of Ophthalmology and Visual Sciences, Moran Eye Center, University
of
Utah School of Medicine, Salt Lake City, UT 84132, USA.
paul.bernstein@hsc.utah.edu
There is increasing evidence that the macular pigment carotenoids, lutein
and
zeaxanthin, may play an important role in the prevention of age-related
macular
degeneration, cataract, and other blinding disorders. Although it is well
known
that the retina and lens are enriched in these carotenoids, relatively
little is
known about carotenoid levels in the uveal tract and in other ocular tissues.
Also, the oxidative metabolism and physiological functions of the ocular
carotenoids are not fully understood. Thus, we have set out to identify
and
quantify the complete spectrum of dietary carotenoids and their oxidative
metabolites in a systematic manner in all tissues of the human eye in
order to
gain better insight into their ocular physiology.Human donor eyes were
dissected, and carotenoid extracts from ocular tissues [retinal pigment
epithelium/choroid (RPE/choroid), macula, peripheral retina, ciliary body,
iris,
lens, vitreous, cornea, and sclera] were analysed by high-performance
liquid
chromatography (HPLC). Carotenoids were identified and quantified by comparing
their chromatographic and spectral profiles with those of authentic
standards.Nearly all ocular structures examined with the exception of
vitreous,
cornea, and sclera had quantifiable levels of dietary (3R,3'R,6'R)-lutein,
zeaxanthin, their geometrical (E / Z) isomers, as well as their metabolites,
(3R,3'S,6'R)-lutein (3'-epilutein) and 3-hydroxy-beta,epsilon-caroten-3'-one.
In
addition, human ciliary body revealed the presence of monohydroxycarotenoids
and
hydrocarbon carotenoids, while only the latter group was detected in human
RPE/choroid. Uveal structures (iris, ciliary body, and RPE/choroid) account
for
approximately 50% of the eye's total carotenoids and approximately 30%
of the
lutein and zeaxanthin. In the iris, these pigments are likely to play
a role in
filtering out phototoxic short-wavelength visible light, while they are
more
likely to act as antioxidants in the ciliary body. Both mechanisms, light
screening and antioxidant, may be operative in the RPE/choroid in addition
to a
possible function of this tissue in the transport of dihydroxycarotenoids
from
the circulating blood to the retina. This report lends further support
for the
critical role of lutein, zeaxanthin, and other ocular carotenoids in protecting
the eye from light-induced oxidative damage and aging. Copyright 2001
Academic
Press.
Lung cancer
20. Cancer Causes Control. 2003 Feb;14(1):85-96.
Dietary carotenoids, vegetables, and lung cancer risk in women: the Missouri
women's health study (United States).
Wright ME, Mayne ST, Swanson CA, Sinha R, Alavanja MC.
Department of Epidemiology, and Public Health, Yale University School
of
Medicine, New Haven, CT 05620-8034, USA
OBJECTIVE: To examine the effect of specific dietary carotenoids and
their
primary plant food sources on lung cancer risk in a population-based
case-control study of women. METHODS: Data were available for 587 incident
primary lung cancer cases and 624 controls frequency matched to cases
based on
age. A modified version of the 100-item NCI-Block food-frequency questionnaire
was used to obtain information concerning usual diet 2-3 years prior to
interview. RESULTS: In models adjusted for age, total calorie intake,
pack-years
of smoking, and education, beta-carotene, beta-cryptoxanthin, lutein +
zeaxanthin, and total carotenoid intake were each associated with a
significantly lower risk of lung cancer. Several vegetable groups were
predictive of lower lung cancer risk, particularly the frequency of total
vegetable intake. Individual and total carotenoids were no longer significantly
associated with lower lung cancer risk in models adjusted for total vegetable
intake. However, total vegetable intake remained significantly inversely
associated with risk in models adjusted for total carotenoids. CONCLUSIONS:
These results indicate that consumption of a wide variety of vegetables
has a
greater bearing on lung cancer risk in a population of smoking and nonsmoking
women than intake of any specific carotenoid or total carotenoids.
Chronic disease
21. Int J Epidemiol. 2001 Feb;30(1):136-43.
Comment in:
Int J Epidemiol. 2001 Feb;30(1):143-4.
Serum carotenoids, alpha-tocopherol and mortality risk in a prospective
study
among Dutch elderly.
De Waart FG, Schouten EG, Stalenhoef AF, Kok FJ.
The Division of Human Nutrition and Epidemiology, Wageningen University
and
Research Center, Wageningen, The Netherlands. frouwkje.hans@consunet.nl
BACKGROUND: Although beta-carotene has shown inverse associations with
chronic
diseases involving free radical damage in observational epidemiological
studies
less attention has been paid to five other major carotenoids also showing
antioxidant activity in vitro. METHODS: We studied the associations between
7.2-year mortality and serum levels of six carotenoids, and alpha-tocopherol,
measured in stored serum, sampled in 1991/1992 during a health survey
among 638
independently living elderly subjects aged 65-85 years. Proportional hazards
regression was used to estimate hazard ratios of all-cause mortality for
the
lowest tertiles of serum vitamins with the highest tertiles, adjusting
for
possible confounding effects. RESULTS: During a follow-up period of 7.2
years
171 elderly died. The adjusted hazard ratios for all-cause mortality for
the
lowest tertiles of vitamins compared with the highest tertiles were between
1.02
and 1.73. The strongest increase in mortality risk was seen for
beta-cryptoxanthin (1.52, 95% CI : 1.00, 2.32), lutein (1.56, 95% CI :
1.05,
2.31) and zeaxanthin (1.32, 95% CI : 0.89, 1.97) and their sum (oxygenated
carotenoids: 1.73, 95% CI : 1.12, 2.67). Tests for trend were significant
(P <
0.05) for all-cause mortality risk and serum levels of total carotenoids,
oxygenated carotenoids and beta-cryptoxanthin. CONCLUSIONS: Our findings
suggest
that serum levels of individual carotenoids, particularly the oxygenated
species
are inversely associated with all-cause mortality and should be considered
as
candidates for further investigations.
Anticarcinogenic
22. Int J Vitam Nutr Res. 1993;63(2):93-121.
Anticarcinogenic effect of common carotenoids.
Gerster H.
Vitamin Research Department, VFEH, F. Hoffmann-La Roche, Basel, Switzerland.
Of the common carotenoids present in food, beta carotene, alpha carotene,
lycopene, lutein, zeaxanthin as well as canthaxanthin can be considered
potential prophylactic agents against carcinogenesis. They are absorbed
by the
human organism in reasonable amounts, and they have antioxidant properties,
immunomodulating effects and may possibly influence gene expression enhancing
gap junction communication. Recent suggestions that beta carotene may
be
metabolized directly to retinoic acid in retinoic acid target tissue and
the
discovery of retinoic acid nuclear receptors open up new perspectives
for
research. The best established chain of evidence for a protective effect
of
carotenoids against cancer development is available for beta carotene.
Positive
effects were observed in cell culture and experimental animal studies
as well as
in dietary and blood level studies in humans. More conclusive evidence
will be
provided by double-blind intervention trials in humans that are in progress.
Beta carotene appears to be active in the promotion phase of carcinogenesis
stabilizing initiated cells. Canthaxanthin, which has often been included
in
animal experiments for comparative purposes having little or no provitamin
A
activity, also exhibits strong protective effects. Of the other carotenoids
only
limited data are available. Depending on the experimental model used,
lycopene,
lutein or alpha carotene was particularly active. In preliminary human
blood
level studies, lycopene was inversely associated with cancers of the pancreas
and cervix. Much work remains to be done. Of particular interest is the
question
of organ specificity of individual carotenoids.
HIV
23. J Acquir Immune Defic Syndr. 2000 Apr 1;23(4):321-6.
Improved antioxidant status among HIV-infected injecting drug users on
potent
antiretroviral therapy.
Tang AM, Smit E, Semba RD, Shah N, Lyles CM, Li D, Vlahov D.
Department of Epidemiology, School of Hygiene and Public Health, Johns
Hopkins
University', Baltimore, Maryland, USA.
Low serum antioxidant levels in HIV-infected people have been attributed
to
altered metabolism associated with excess oxidative stress. We conducted
a study
to examine serum antioxidant levels in 175 HIV-positive and 210 HIV-negative
injecting drug users (IDUs) in Baltimore, Maryland. At the time of data
collection, 30 of the HIV-positive IDUs were receiving antiretroviral
therapies
(ART) including a protease inhibitor (PI), 43 ART without a PI, 22
monotherapies, and 80 not on any ART. Serum antioxidants examined included
retinol, alpha-tocopherol and gamma-tocopherol, alpha-carotene and
beta-carotene, lycopene, lutein/zeaxanthin, and beta-cryptoxanthin. Mean
serum
levels of lycopene and lutein/zeaxanthin were significantly lower in
HIV-positive IDUs than HIV-negative IDUs. Contrary to the findings in
other
studies, however, levels of the remaining antioxidants in HIV-positive
study
subjects were not lower than in HIV-negative study subjects. In fact,
serum
alpha-tocopherol levels were significantly higher in HIV-positive IDUs
than
HIV-negative IDUs (medians = 744 microg/dl and 718 microg/dl, respectively;
p =
.04). Among HIV-positive study subjects, there were significant differences
in
antioxidant levels by ART regimen. In multivariate models adjusting for
injecting drug use, dietary intake, supplement intake, gender, and alcohol
intake, significant overall differences by ART regimen were observed for
alpha-tocopherol, beta-carotene, and beta-cryptoxanthin. Serum levels
of these
three antioxidants were significantly higher in the PI group than in the
other
three ART groups combined (p = .0008, 0.02, and 0.02, respectively). These
data
provide indirect evidence of the effectiveness of PIs in lowering oxidative
stress levels in HIV-positive IDUs.
24. Nutrition. 2001 Jul-Aug;17(7-8):567-72.
Relation of vitamin A and carotenoid status to growth failure and mortality
among Ugandan infants with human immunodeficiency virus.
Melikian G, Mmiro F, Ndugwa C, Perry R, Jackson JB, Garrett E, Tielsch
J, Semba
RD.
Department of Ophthalmology, Johns Hopkins University School of Medicine,
Baltimore, Maryland, USA.
Although growth failure is common during pediatric infection with human
immunodeficiency virus (HIV) and associated with increased mortality,
the
relation of specific nutrition factors with growth and mortality has not
been
well characterized. A longitudinal study was conducted with 194 HIV-infected
infants in Kampala, Uganda. Plasma vitamin A, carotenoids (alpha-carotene,
beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin), and
vitamin
E were measured at age 14 wk, and weight and height were followed up to
age 12
mo. Vitamin A and low plasma carotenoid concentrations were predictive
of
decreased weight and height velocity. Between ages 14 wk and 12 mo, 32%
of
infants died. Underweight, stunting, and low concentrations of plasma
carotenoids were associated with increased risk of death in univariate
analyses.
Plasma vitamin A concentrations were not associated with risk of death.
In a
final multivariate model adjusting for weight-for-age, plasma beta-carotene
was
significantly associated with increased mortality (odds ratio: 3.16, 95%
confidence interval: 1.38 to 7.21, P < 0.006). These data suggest that
low
concentrations of plasma carotenoids are associated with increased risk
of death
during HIV infection among infants in Uganda.
Cardiovascular
25. Free Radic Biol Med. 2002 Jan 15;32(2):148-52.
Plasma lipophilic antioxidants and malondialdehyde in congestive heart
failure
patients: relationship to disease severity.
Polidori MC, Savino K, Alunni G, Freddio M, Senin U, Sies H, Stahl W,
Mecocci P.
Institute of Physiological Chemistry I, Heinrich-Heine University, Dusseldorf,
Germany. polidori@uni-duesseldorf.de
Plasma levels of malondialdehyde (MDA), vitamin A, and of antioxidant
micronutrients including vitamin E, lutein, zeaxanthin, beta-cryptoxanthin,
lycopene, and alpha- and beta-carotene were measured in 30 patients with
class
II and III congestive heart failure (CHF) according to the New York Heart
Association (NYHA) classification and in 55 controls. Ejection fraction
was
evaluated by echocardiography in all patients as a measure of the emptying
capacity of the heart. Plasma levels of all measured compounds were
significantly lower and MDA significantly higher in patients compared
to
controls (p <.001). Class II NYHA patients showed significantly lower
MDA levels
and significantly higher levels of vitamin A, vitamin E, lutein, and lycopene
than class III patients. Ejection fraction was inversely correlated with
MDA
levels and directly correlated with vitamin A, vitamin E, lutein, and
lycopene
levels in patients. The present study supports the concept that an increased
consumption of vitamin-rich fruits and vegetables might help in achieving
cardiovascular health.
26. Nutrition. 2002 Jan;18(1):26-31.
Plasma status of retinol, alpha- and gamma-tocopherols, and main carotenoids
to
first myocardial infarction: case control and follow-up study.
Ruiz Rejon F, Martin-Pena G, Granado F, Ruiz-Galiana J, Blanco I, Olmedilla
B.
Servicio de Cardiologia, Servicio de Medicina Interna, Hospital de Mostoles,
Madrid, Spain. ferruiz@inicia.es
OBJECTIVE: Epidemiologic studies have suggested that dietary intake and
plasma
concentrations of antioxidants have an inverse relation with coronary
heart
disease. To test whether fat-soluble antioxidants can play a role against
the
occurrence of myocardial infarction (MI), we measured plasma levels of
retinol,
tocopherols, and individual carotenoids in MI patients. METHODS: A case-control
and follow-up study of patients in the Mostoles area (Madrid, Spain).
One
hundred six patients (62 after 1 y) and 104 control subjects participated
in the
study. Blood samples were collected after overnight fast or during the
first 24
h of MI onset for biochemical profiles of retinol, alpha- and gamma-tocopherols,
and carotenoid by means of a quality-controlled high-performance liquid
chromatography. RESULTS: During the acute phase after MI onset, plasma
levels of
retinol, gamma-tocopherol, and xanthophylls (lutein/zeaxanthin and
beta-cryptoxanthin) decreased, whereas alpha-tocopherol, alpha-carotene,
beta-carotene, and lycopene showed levels similar to those of control
subjects.
Logistic regression analysis showed low concentrations of gamma-tocopherol
(and
retinol) in plasma as the only statistically significant factor associated
with
MI, after adjusting for traditional risk factors. However, 1 y later,
the MI
patients showed a general improvement in plasma lipids and fat-soluble
antioxidant status, and none of the analytes was associated with MI.
CONCLUSIONS: The decreased plasma status of retinol, gamma-tocopherol,
and
xanthophylls during the acute phase of MI normalized the year after the
MI
event, suggesting that most subjects had followed an overall healthier
lifestyle
and dietary pattern. The results also raise concerns on the usefulness
of these
plasma compounds as specific, relevant, and predictive markers in relation
to
coronary heart disease.
27. Am J Clin Nutr. 2001 Oct;74(4):442-8.
Improvements in circulating cholesterol, antioxidants, and homocysteine
after
dietary intervention in an Australian Aboriginal community.
Rowley KG, Su Q, Cincotta M, Skinner M, Skinner K, Pindan B, White GA,
O'Dea K.
University of Melbourne, Department of Medicine, St Vincent's Hospital,
Fitzroy,
VIC, Australia. kevinr@medstv.unimelb.edu.au
BACKGROUND: Poor nutrition contributes to high rates of coronary heart
disease
among Australian Aboriginal populations. Since late 1993, the Aboriginal
community described here has operated a healthy lifestyle program aimed
at
reducing the risk of chronic disease. OBJECTIVE: We evaluated the effectiveness
of a community-directed intervention program to reduce coronary heart
disease
risk through dietary modification. DESIGN: Intervention processes included
store
management policy changes, health promotion activities, and nutrition
education
aimed at high-risk individuals. Dietary advice was focused on decreasing
saturated fat and sugar intake and increasing fruit and vegetable intake.
Evaluation of the program included conducting sequential, cross-sectional
risk
factor surveys at 2-y intervals; measuring fasting cholesterol, lipid-soluble
antioxidants, and homocysteine concentrations; and assessing smoking status.
Nutrient intakes were estimated from analysis of food turnover in the
single
community store. RESULTS: There was a significant reduction in the prevalence
of
hypercholesterolemia (age-adjusted prevalences were 31%, 21%, and 15%
at
baseline, 2 y, and 4 y, respectively; P < 0.001). There were significant
increases in plasma concentrations of alpha-tocopherol, lutein and zeaxanthin,
cryptoxanthin, and beta-carotene across the population. Retinol and lycopene
concentrations did not change significantly. Mean plasma homocysteine
concentrations decreased by 3 micromol/L. There was no significant change
in
smoking prevalence between the 2 follow-up surveys. There was an increase
in the
density of fresh fruit and vegetables and carotenoids in the food supply
at the
community store. CONCLUSION: This community-directed dietary intervention
program reduced the prevalence of coronary heart disease risk factors
related to
diet.
28. Am J Epidemiol. 2000 Dec 1;152(11):1065-71.
Serum carotenoids and markers of inflammation in nonsmokers.
Kritchevsky SB, Bush AJ, Pahor M, Gross MD.
Department of Preventive Medicine, University of Tennessee, Memphis 38105,
USA.
skritchevsky@utmem.edu
One explanation for discrepant results between epidemiologic studies
and
randomized trials of beta-carotene and cardiovascular disease may be a
failure
to consider inflammation as a confounder. To evaluate the potential for
such
confounding, the authors relate the serum concentrations of five carotenoids
(alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and
lutein/zeaxanthin) to levels of three inflammatory markers (C-reactive
protein,
fibrinogen, and white blood cell count) measured during the Third National
Health and Nutrition Survey, 1988-1994. The analysis included 4,557 nonsmoking
participants aged 25-55 years. Adjusted concentrations of all five carotenoids
were significantly lower in those with C-reactive protein levels above
0.88
mg/dl (p = 0.001). There was a trend toward lower adjusted beta-cryptoxanthin
concentrations with increasing level of fibrinogen (p value test for trend
=
0.01), but other carotenoids were not related. Many of the carotenoid
concentrations were lower among participants with high white blood cell
counts.
After log transformation, only adjusted mean beta-carotene levels were
significantly lower in those with white blood cell counts above 7.85 x
10(9)/liter (p < 0.01). These cross-sectional data do not clarify the
biologic
relation between carotenoids and C-reactive protein but, to the extent
that the
carotenoids are associated with C-reactive protein levels, a carotenoid-heart
disease association may be, in part, an inflammation-heart disease association.
Concentrations among people
29. Ethn Dis. 2000 Spring-Summer;10(2):208-17.
Variations in serum carotenoid concentrations among United States adults
by
ethnicity and sex.
Ford ES.
Division of Nutrition and Physical Activity, National Center for Chronic
Disease
Prevention and Health Promotion, Centers for Disease Control and Prevention,
Atlanta, GA 30341, USA. esf2@cdc.gov
Increased fruit and vegetable intake is associated with a lower risk
of heart
disease and cancer. Carotenoids, which occur primarily in fruits and vegetables,
have been associated with reduced risk of some chronic diseases. To examine
the
distribution of serum carotenoid concentrations among US adults by ethnicity
and
sex, the author used data from the Third National Health and Nutrition
Examination Survey, conducted from 1988 to 1994. After exclusions, 14,914
participants aged > or =20 years who attended the medical examination
clinic had
their serum carotenoid concentrations determined. Mexican-American men
had
higher total concentrations than European Americans and African Americans.
In
general, European-American participants were characterized by high lycopene
but
low beta-cryptoxanthin and lutein/zeaxanthin concentrations; African Americans
by high lutein/zeaxanthin and low alpha-carotene and beta-cryptoxanthin
concentrations; and Mexican Americans by high alpha-carotene,
beta-cryptoxanthin, and lutein/zeaxanthin concentrations. The implications
of
these different carotenoid concentration patterns for future risk of disease
within the ethnic and sex groups remain to be clarified.
30. Int J Vitam Nutr Res. 2001 Mar;71(2):97-102.
Plasma carotenoids in relation to food consumption in Granada (southern
Spain)
and Malmo (southern Sweden).
van Kappel AL, Martinez-Garcia C, Elmstahl S, Steghens JP, Chajes V,
Bianchini
F, Kaaks R, Riboli E.
Unit of Nutrition and Cancer, International Agency for Research on Cancer,
150
cours Albert-Thomas, 69372 Lyon, France.
We conducted a cross-sectional pilot study on healthy pre-menopausal
women (aged
45-50 years) living in Granada, in the south of Spain (n = 39) and Malmo,
in the
south of Sweden (n = 38) in order to compare their plasma carotenoid levels
and
to investigate the relationship between the differences in food consumption.
Plasma concentrations of six carotenoids were measured using high performance
liquid chromatography, habitual diet (at individual level) was estimated
by food
frequency questionnaires and 24-hour diet recalls were used for standardised
measurement of diet at group-level. We found that women in Granada consumed
more
fruit and vegetables than women in Malmo. Plasma concentrations of
beta-cryptoxanthin, lycopene, zeaxanthin, total carotenoids and alpha-tocopherol
were higher in Granada than in Malmo, although plasma concentrations of
alpha-carotene and retinol were higher in Malmo. Both within and between
study
centres, consumption of fruit and vegetables correlated positively with
plasma
concentrations of different carotenoids. The study showed that differences
in
consumption of fruit and vegetables between the two European centres were
reflected in plasma carotenoid concentrations.
Antioxidant
31. Arch Neurol. 2002 May;59(5):794-8.
Lymphocyte oxidative DNA damage and plasma antioxidants in Alzheimer
disease.
Mecocci P, Polidori MC, Cherubini A, Ingegni T, Mattioli P, Catani M,
Rinaldi P,
Cecchetti R, Stahl W, Senin U, Beal MF.
Institute of Gerontology and Geriatrics, University of Perugia, Via Eugubina
42,
06122 Perugia, Italy. mecocci@unipg.it
CONTEXT: A large body of experimental evidence suggests that in Alzheimer
disease (AD) pathogenesis an important role is played by oxidative stress,
but
there is still a lack of data on in vivo markers of free radical-induced
damage.
OBJECTIVES: To evaluate levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG),
a marker
of oxidative damage to DNA, in peripheral lymphocytes; to measure plasma
concentrations of several nonenzymatic antioxidants; and to assess the
relationships between any observed changes in lymphocyte DNA 8-OHdG content
and
plasma antioxidant levels in patients with AD and healthy aged control
subjects.
SUBJECTS: Forty elderly outpatients with AD and 39 healthy age- and sex-matched
controls were studied. MAIN OUTCOME MEASURES: The level of 8-OHdG was
determined
in DNA extracted from lymphocytes and plasma levels of vitamin C, vitamin
A,
vitamin E, and carotenoids (zeaxanthin, beta-cryptoxanthin, lycopene,
lutein,
and alpha- and beta-carotene) were measured by high-performance liquid
chromatography. RESULTS: Lymphocyte DNA 8-OHdG content was significantly
higher
and plasma levels of antioxidants (with the exception of lutein) were
significantly lower in patients with AD compared with controls. In patients
with
AD, a significant inverse relationship between lymphocyte DNA 8-OHdG content
and
plasma levels of lycopene, lutein, alpha-carotene, and beta-carotene,
respectively, was observed. CONCLUSIONS: Markers of oxidative damage are
increased in AD and correlate with decreased levels of plasma antioxidants.
These findings suggest that lymphocyte DNA 8-OHdG content in patients
with AD
reflects a condition of increased oxidative stress related to a poor antioxidant
status.
32. Surv Ophthalmol. 2000 Sep-Oct;45(2):115-34.
The role of oxidative stress in the pathogenesis of age-related macular
degeneration.
Beatty S, Koh H, Phil M, Henson D, Boulton M.
Academic Department of Ophthalmology, Manchester Royal Eye Hospital,
Manchester,
United Kingdom.
Age-related macular degeneration (AMD) is the leading cause of blind
registration in the developed world, and yet its pathogenesis remains
poorly
understood. Oxidative stress, which refers to cellular damage caused by
reactive
oxygen intermediates (ROI), has been implicated in many disease processes,
especially age-related disorders. ROIs include free radicals, hydrogen
peroxide,
and singlet oxygen, and they are often the byproducts of oxygen metabolism.
The
retina is particularly susceptible to oxidative stress because of its
high
consumption of oxygen, its high proportion of polyunsaturated fatty acids,
and
its exposure to visible light. In vitro studies have consistently shown
that
photochemical retinal injury is attributable to oxidative stress and that
the
antioxidant vitamins A, C, and E protect against this type of injury.
Furthermore, there is strong evidence suggesting that lipofuscin is derived,
at
least in part, from oxidatively damaged photoreceptor outer segments and
that it
is itself a photoreactive substance. However, the relationships between
dietary
and serum levels of the antioxidant vitamins and age-related macular disease
are
less clear, although a protective effect of high plasma concentrations
of
alpha-tocopherol has been convincingly demonstrated. Macular pigment is
also
believed to limit retinal oxidative damage by absorbing incoming blue
light
and/or quenching ROIs. Many putative risk-factors for AMD have been linked
to a
lack of macular pigment, including female gender, lens density, tobacco
use,
light iris color, and reduced visual sensitivity. Moreover, the Eye Disease
Case-Control Study found that high plasma levels of lutein and zeaxanthin
were
associated with reduced risk of neovascular AMD. The concept that AMD
can be
attributed to cumulative oxidative stress is enticing, but remains unproven.
With a view to reducing oxidative damage, the effect of nutritional antioxidant
supplements on the onset and natural course of age-related macular disease
is
currently being evaluated.
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