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Three Carotene intervention studies (the Beta Carotene and Retinol Efficacy
Trial (CARET), the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study
(ATBC), and the Physician's Health Study (PHS)) have all pointed to a lack of
effect of synthetic beta-carotene in decreasing cardiovascular disease or
cancer risk in well-nourished populations (PATRICK, 2000). Since the efficacy
of carotenoid containing food products is well supported attention has turned
to the other carotenoids Lutein, Zeaxanthin, and Lycopene. Lutein and
Zeaxanthin are the predominant carotenoid pigments in the maculalutea (the
yellow spot in the center of the retina encompassing the fovea,the area of
sharpest vision where only rods and no cones are found). Loss of Lutein
and Zeaxanthin are assumed to be causative for the age-related
maculardegeneration (AMD) leading to age blindness (SEDDON 1994, SNODDERLEY
1995, LANDRUM 1997).
Age-related macular degeneration (AMD) is the leading cause of
blindregistration in the developed world. Oxidative stress, which refers to
cellular damage caused by reactive oxygen intermediates (ROI), has been
implicated in many disease processes, especially age-related disorders. 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. A protective effect of high plasma concentrations of
alpha-tocopherol has been convincingly demonstrated. Moreover, an Eye Disease
Case-Control Study found that high plasma levels of lutein and zeaxanthin were
associated with reduced risk of neovascular AMD. (BEATTY, 2000)
RAPP (2000) investigated the concentration of these carotenoid pigments in
different compartments of the retina and found the highest concentration in the
outer segments of the rods which supports the assumption that they function as
antioxidants.
JUNGHANS (2000) used unilamellar liposomes as models for the antioxidant
interaction in cells. The vesicle membrane was loaded with lipophilic
antioxidants (Carotenoids, Tocopherol) whereas the aqueous core space with
hydrophilic Glutathione (GSH) ascorbate. Lipid peroxidation of GSH was
initiated with 2,2'-azobis-[2,4-dimethylvaleronitrile] (AMVN). The
antioxidateive effect of lutein, beta-carotene and lycopene was measured by
determination of Malondialdehyde (MDA) formation and the loss of GSH. Lutein
inhibited lipid peroxidation in a dose-dependent manner whereas Beta-Carotene
protected at lower concentrations but was prooxidative at higher ones.
BEATTY (2001) measured the optical density of macular pigment in 46 subjects.
He found lower optical densities in subjects with fellow eyes already suffering
from age-related macular degeneration (AMD). BONE (2001) determined the Lutein
and Zeaxanthin concentration in retina sections from donors who has suffered
from AMD (56, versus 56 controls). He
confirmed the correlation between AMD and lower carotenoid content. SUJAK
(2000) suggests a different role of Lutein and Zeaxanthin in the retina:
Zeaxanthin in the protection of the lipid phase against oxidative damage and
lutein in absorbing short wavelength radiation penetrating retina membranes.
BERENDSCHOTT (2000) describes two methods for the determination of the optical
density of the macula (as measure of its carotenoid content). The density
increased after a 12 week supplemtation period with 10 mg Lutein per
person and day. BONE (2000) investigated the dietary intake of Lutein and
Zeaxanthin by frequency questionaires. By the determination of the blood serum
concentration of these Carotenoids and of the optical density of the macula
he concluded that approx. half of the variation of the serum concentration and
about one third of the macular optical density is explained by the dietary
intake.
Sixteen participants suffering from Retinitis pigmentosa and other retinal
degeneration recruited via the internet completed a 26-week program of lutein
supplementation (40 mg/day for 9 weeks, 20 mg/day thereafter); participants
self-tested their visual acuity on their computer screen and their central
visual-field extent on a wall chart. Mean visual acuity improved by 0.7 dB
and mean visual-field area by 0.35 dB. Visual acuity gains were strongly
correlated with eye color, the benefit of the supplementation was greatest for
blue eyed participants (DAGNELIE 2000).
The AREDS studies no. 8 and 9 found that supplementation with Beta-Carotene
supplementation had little or no effect against AMD (AREDS, 2001(I);
ARED, 2001(II).
BERTON (2001) reports an inverse relationship between lutein/zeaxanthin intake
and cancer (40% decrease of ovarian cancer incidence for the group with the
highest intake (24000 microgram/week). Intake of alpha-carotene, beta-carotene,
retinol and total vitamin A was unrelated to risk. BOON (1996) reports that
dietary Lutein increased in rats the tumor latency,
suppressed mammary tumor growths and enhanced lymphocyte proliferation.
AREDS Report No. 8 (Age-Related Eye Disease
Study Research Group), 2001 (I): A Randomized, Placebo-Controlled, Clinical
Trial of High-Dose Supplementation With Vitamins C and E, Beta Carotene, and
Zinc for Age-Related Macular Degeneration and Vision Loss. Arch
Ophthalmol. 2001;119:1417-1436
AREDS Report No. 9, 2001 (II): A Randomized, Placebo-Controlled, Clinical Trial
of High-Dose Supplementation With Vitamins C and E and Beta Carotene for
Age-Related Cataract and Vision Loss. Achives of Ophthalmol. 2001;119:1439-1452
BEATTY, S. et al, 2000: The role of oxidative stress in the pathogenesis of
age-related macular degeneration. Surv Ophthalmol 2000 Sep-Oct;45(2):115-34.
BEATTY, S. et al. 2001: Macular pigment and risk for age-related macular
degeneration in subjects from a Northern European population. Invest Ophthalmol
Vis Sci 2001 Feb;42(2):439-46.
BERENDSCHOTT, T.T. et al., 2000: Influence of lutein supplementation on macular
pigment, assessed with two objective techniques. Invest Ophthalmol Vis Sci 2000
Oct;41(11):3322-6.
BERTON, E.R. et al., 2001: A population-based case-control study of carotenoid
and vitamin A intake and ovarian cancer (
BONE, R.A. et al., 2000: Lutein and zeaxanthin in the eyes, serum and diet of
human subjects. Exp Eye Res 2000 Sep;71(3):239-45.
BOON, P.C., etr al., 1996: Effects of Lutein from Marigold Extract on Immunity
and Growth of Mammary Tumors in Mice. Anticancer Research 16:3689-3694 (1996)
DAGNELIE, G. et al., 2000: Lutein improves visual function in some
patients with retinal degeneration: a pilot study via the Internet. Optometry
2000,Mar;71(3):147-64.
JUNGHANS, A. et al.: 2000): Carotenoid-containing unilamellar liposomes loaded
with glutathione: a model to study hydrophobic-hydrophilic antioxidant
interaction. Free Radic Res 2000 Dec;33(6):801-8.
LANDRUM, J.T. et al., 1997: The Macular Pigment. A possible Role in Protection
from Age-Related Macular Degeneration. Advances in Pharcology, vol 18, 1997, p.
537-556
PATRICK, L., 2000: Beta-carotene: the controversy continues. Altern Med Rev
2000 Dec;5(6):530-45.
RAPP, L.M. et al., 2000: Lutein and zeaxanthin concentrations in rod outer
segment membranes from perifoveal and peripheral human retina. Invest Ophthalmol Vis Sci 2000
Apr;41(5):1200-9.
SEDDON, M.J. et al.,
1994: Dietary Carotenoids, Vitamin A, C, and E, and Advanced Age-Related
Macular Degernation. JAMA, November 9, 1994, Vol 272, no. 18, p. 1413
SNODDERLEY, D.M., 1995: Evidence for protection against age-related macular
degeneration by carotenoids and antioxidant vitamins. Am.J.Clin.Nutr. 1995;62
(suppl):1448S-61S
SUJAK, A. et al., 2000: Organisation of xanthophyll pigments lutein and
zeaxanthin in lipid membranes formed with dipalmitoylphosphatidylcholine.
Biochim Biophys Acta 2000 Dec 20;1509(1-2):255-63.