156
prevalence were found between subjects with high and low
dietary intakes of L plus Z. However, analysis of a sub-group
of women under 75 with stable L plus Z intakes revealed a
reduced risk of this subtype of AMD in association with a
high dietary intake of those antioxidants. A diet rich in L
plus Z may protect against intermediate AMD
(27)
.
In 2007,
AREDS (Age-related Eye Disease Study report
22)
, a case-control study with 4519 participants, concluded
that a high dietary intake of L and Z was independently
associated with a decreased likelihood of neovascular AMD,
geographic atrophy, and large and extensive drusen
(28)
.
Up to the present date, seven important interventional
studies have investigated the role of L supplementation in
AMD patients
(29-35)
.
Of the aforementioned studies, two assume major
importance:
LAST (Lutein Antioxidant Supplementation Trial)
was
the first study to show that L supplementation improved
visual function in AMDpatients. Furthermore, it reinforced
the notion that AMD is a nutrition-responsive disease.
The results of this trial were confirmed in 2004. In this trial,
90 AMD patients received either a daily supplement con-
sisting of 10mg of L, a supplement consisting of 10 mg of
L and a mixed antioxidant formula (containing vitamin A,
beta-carotene, vitamin C, vitamin E, vitamin B complex,
copper, zinc, manganese, magnesium, selenium and other
minerals), or placebo, for 12 months. Results showed that
patients receiving the L supplement displayed significant
improvements in several objective visual function measures
(contrast sensitivity or visual acuity) when compared to the
placebo group. Slightly better results were observed in sub-
jects consuming the combined supplement
(34)
.
CARMA (Carotenoids in Age-related Maculopathy
Study)
was an important European intervention study,
published in 2008. This randomised, double-blind clinical
trial of antioxidant supplementation versus placebo enrolled
433 patients from two centres in Ireland, with signs of early
AMD of sufficient severity in at least one eye, or any level
of AMD in one eye and late AMD (neovascular AMD or
central geographic atrophy) in the fellow eye. The aim of the
CARMA Study was to investigate whether administration
of 12 mg of L and 2 mg of Z, in combination with antioxi-
dants (120 mg of vitamin C, 15mg of vitamin E, 20mg of
zinc and 0.4 mg of copper), had a beneficial effect on visual
function and/or was able to delay progression of early to late
disease stages.
The primary outcome was improved or distance visual acu-
ity was preserved at 12 months. Although no beneficial
effects were demonstrated in the primary outcome measure
at the stated end point (12 months), secondary outcomes
favoured the supplemented group
(35)
.
3.1.2 Key points:
The aforementioned findings are consistent with the
hypothesis that low L and Z levels in the human macula
may represent a pathogenic risk factor for AMD develop-
ment. They also suggest that supplementation may contrib-
ute to maintaining eye health.
3.2 Antioxidants
3.2.1 Vitamin and mineral supplements
Antioxidants are recommended for AMD due to oxida-
tive stress on photoreceptors in the retina and the fact that
cumulative damage caused by blue light enhances free radi-
cal production. It has been proposed that antioxidants may
prevent cellular damage in the retina by reacting with free
radicals
(36)
.
The substances that possess antioxidant activity are vitamins
C and E, beta-carotene and some minerals, such as zinc,
copper, selenium and manganese.
Some studies indicate that diets rich in antioxidants may
protect against the appearance of signs of early AMD; in
common perception, a diet rich in antioxidants is capable
of protecting against AMD.
Randomised control trials and observational studies have
been conducted in well-nourished Western populations;
however, the role of dietary antioxidants in the primary pre-
vention of AMD remains unclear.
In the 90’s, several studies reported a protective effect against
AMD development for high intakes of antioxidant vitamins
and minerals.
In 1993, the
EDCCS (Eye Disease Case-Control Study)
,
performed a comparison between 421 patients with neo-
vascular age-related macular degeneration and 615 con-
trol subjects, the results revealed that high plasma levels of
antioxidants (vitamins A, C, E, selenium and carotenoids)
are associated with a lower risk of developing neovascular
AMD. Additional carotenoid intakes, particularly of those
present in the retina, are associated with a lower risk of
developing AMD
(37)
.
In 1994, the authors of the
Baltimore Longitudinal Study
on Aging
, a study involving 976 patients, reported a pro-
tective effect against AMD for high plasma concentrations
of Vitamin E. The authors also found an antioxidant com-
bination of Vitamin C, Vitamin E and beta-carotene to be
protective
(38)
.
In 1998, the
Beaver Dam Eye Study
, in which a cohort
