155
Preventive AMD Treatments
assess whether forms of the AREDS nutritional supple-
ment with reduced zinc and/or no beta-carotene works
as well as the original supplement in reducing the risk of
progression to advanced AMD.
2.2.1 AREDS 2 formulation:
Antioxidant vitamins – 500 mg of vitamin C;
400 IU of vitamin E
15 mg of beta-carotene
80 mg of zinc oxide and 2 mg of cupric oxide
Macular pigments – xanthophylls
10 mg of lutein
2 mg of zeaxanthin
1 g of omega-3 fatty acids (DHA +EPA)
This study will also investigate whether the current
AREDS formulation might be modified by eliminating
beta-carotene.
As previously mentioned, beta-carotene, which is not pres-
ent within the eye, constitutes a problem for smokers, due
to the high incidence of lung cancer in this patient group.
A secondary randomisation in AREDS 2 will evalu-
ate the possibility of eliminating and/or lowering the
amount of zinc in the AREDS formulation, since zinc
levels in the current formulation are considered high and
available evidence suggests that the body is only able to
absorb 25 mg of zinc per day.
3. Ocular Micronutrition
3.1 Carotenoids
3.1.1 Macular pigments: lutein and zeaxanthin
Over 600 carotenoids have been identified to the pres-
ent date; however, only about 50 are found in normal
human diets. Vegetables are the only source of carot-
enoids. Macular pigments (MP) consist of two natural
xanthophylls from the carotenoid family: lutein (L) and
zeaxanthin (Z), as well as the products of their transfor-
mation in the body, notably meso-zeaxanthin
(16)
.
These pigments are not synthesised by the human body
and have been investigated for their ability to promote
visual health. Macular pigments are found in photore-
ceptor axons in the pigment epithelium and in the exter-
nal segment. The latter contains very high levels of poly-
unsaturated fatty acids, at a high risk of oxidation
(17,18,19)
.
Macular concentrations of L and Z decrease with age,
which exacerbates the harmful effects of blue light on
photoreceptors. Their protective mechanism is unknown;
however, two mechanisms have been proposed: macular
pigments may act as an optical filter, due to their ability
to absorb blue light, and they are strong antioxidants,
neutralising free radicals generated by light
(20,21)
.
Several observational studies have demonstrated a cor-
relation between plasma L and Z levels, macular pigment
density and a lower risk of AMD.
Increased intake of L and Z supplements resulted in
increased plasma levels, which were positively and sig-
nificantly associated with the optical density of macular
pigment
(22)
.
Furthermore, various well-conducted population-based
longitudinal studies have suggested that high dietary anti-
oxidant levels, specifically L and Z, may have protective
and beneficial effects, delaying progression to advanced
AMD. The following are some examples of observational
studies investigating the relationship between dietary
and/or serum antioxidant levels and the risk of AMD.
EDCCS (Eye Disease Case-Control Study)
: this study,
published in 1992, demonstrated a high significant
inverse relationship (p= 0.001) between the prevalence
of AMD and serum L and Z concentrations: the risk
of neovascular lesions was 70% lower in subjects with
the highest serum L and Z concentrations, compared to
those with the lowest levels (odds ratio: 0.4; 95% CI:
0.2-0.6; p= 0.0001)
(23)
.
In 1994, the same group concluded that the risk of devel-
oping the most severe form of macular degeneration was
43% lower in individuals who consume large amounts
of fruits and vegetables rich in L and Z (6mg/day) (odds
ratio: 0.57; 95% CI: 0.35-0.92; p= 0.02)
(24)
.
Another observational study conducted in 2002 showed
that average L and Z levels were 32% lower in AMD
eyes than in control eyes, in elderly subjects, provided
the latter were not consuming high doses of L supple-
ments. This study demonstrated that average levels of
macular pigments in patients who had begun to regularly
consume supplements containing high doses of L (> 4
mg/day) after the initial diagnosis of AMD were within
the normal range and significantly higher than in AMD
patients not consuming this supplementation
(25)
.
In 2006, the
POLA study (Pathologies Oculaires Liées
a l’Age)
found that high plasma L and total L and Z
concentrations are associated with a reduced risk of age-
related maculopathy (ARM)
(26)
.
CAREDS (Carotenoids in Age-related Eye Disease
Study)
: in this observational study, conducted in 2006, no
statistically significant differences in intermediate AMD
