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Carotenoids Actions on Age-related Macular Degeneration: A Review

Livija Wells
Russell Sage College
November 4, 2016



The eyes are the windows to the soul is the expression that is often used to express a
deep connection two people share when looking into each others eyes. Eyes are not only
important for developing a greater sense of ones soul, they are also essential to how humans
perceive the world. Sight and vision are significant because together they help maintain the
sharpness of the mind, which provides safety to the body (NIH 2016). Impairment of sight and
vision has the potential to diminish the value of a persons optimal health and quality of life.
There are numerous diseases of the eye associated with aging, such as cataracts, glaucoma, dry
eye and age related macular degeneration. Research has shown that the progression of these
diseases can be mitigated with the help of vitamins and minerals (Rodriguez-Amaya, 2016).
Age-Related Macular (AMD) degeneration is an eye condition that affects people above
the age of 60, resulting in the loss of a person's central field of vision. It is characterized by
thinning of the macula further leading to vision loss (Trumbo, & Ellwood 2006). AMD is the
leading cause of blindness in individuals above the age of 60 in the United States (Mozaffarieh,
Sacu, & Wedrich, 2003). Approximately 1.6% of individuals around 65 years of age are affected,
and this number leaps to 30% in the 75-year-old age group (Mozaffarieh et al., 2003). As the
population ages, the burden of AMD on the public healthcare system continues to grow with no
end in sight.
Age-related macular degeneration presents itself differently in many patients, but can be
classified generally as either wet or dry. The most common type of AMD is dry, which can
progress to wet if left untreated. In wet AMD, blood vessels generate to compensate for the lack
of blood supply to retinal tissue and resulting in retinal hemorrhage (Trumbo, & Ellwood 2006).
Dry AMD is identified by the presence of yellow deposits under the macula (retina), otherwise
known as drusen, which cause deterioration of the retina. It is considered dry because unlike wet


AMD, it does not result in leakage of blood (Zampatti, Ricci, Cusumano, Marsella, Novelli, &
Giardina, 2014). Dry AMD is considered atrophic and makes up about 85-90% of the cases of
AMD (Trumbo, & Ellwood 2006). The severity of each dry AMD case is defined using a
classification system consisting of three stages or levels. Thee three stages are early, intermediate
and advanced. At the early onset of AMD, small and a few medium-sized drusen can be observed
on the retina (Trumbo, & Ellwood 2006). Multiple medium size drusen or one or more large
drusen are characteristics of intermediate AMD, while the combination of drusen and a blurred
spot are products of advanced AMD. Currently, AMD is irreversible for intermediate and
advanced cases, resulting in a permanent loss of vision (Zampatti, et al., 2014).
Although there are several preventative measures, there is no cure for age-related macular
degeneration. A major movement in the nutrition field is the belief that increasing levels of lutein
and zeaxanthin in the body may prevent the early development of AMD (Trumbo, & Ellwood
2006). The use of specific foods for disease treatment and prevention is not a new idea, but the
validity of this treatment method as well as the proof behind it remains relatively unknown. In
this paper, the use of specific carotenoids (lutein and zeaxanthin) for the treatment of age-related
macular degeneration, their effects on the disease progression as well as the limitations of these
research studies will be explored.

Pigmentation and Food

Healthcare professionals around the world continuously recommend for their clients to
eat the rainbow not only because it makes each meal more visually appealing, but because a
variety of color provides a plethora of nutrients which have been shown to be beneficial for
optimal health. The colors exhibited in food are due to protein complexes known as pigments.


There are countless pigments in foods but a few examples include carotenoids, anthocyanin,
betanin and chlorophylls (Rodriguez-Amaya, 2016).
Carotenoids are colorful, liposoluble pigments that create the yellow, orange and red
color of fruits. (Milani, Basirnejad, Shahbazi, & Bolhassani, 2016). The over 600 types of
carotenoids can be divided into three major groups: carotenes, xanthophylls and lycopene.
Xanthophylls are responsible for green vegetables, red pigmentation of tomatoes is created by
lycopene, and the bright orange appearance of the carrot is caused by -carotene.
Though these carotenoids exhibit different functions and colorations, they are all similar
in structure. This common structure consists of a central carbon chain, single and double bonds,
and cyclic or acyclic end groups. In addition to having similar structure, groups of carotenoids
can also have similar effects on the human body. For example, carotenoids related to eye health
include lycopene, zeaxanthin, lutein, and -carotene (Mozaffarieh, et al., 2003). These
carotenoids are believed to defer the progression of eye diseases such as age-related macular
Carotenoids are recognized for their coloration properties as well as their effects on
health and preventing disease. Lutein and zeaxanthin are carotenoids majorly found in the human
macula and retina (Mozaffarieh et al., 2003). The macula appears on the retina as a yellow spot,
which is the pigmentation created by the presence of carotenoids lutein and zeaxanthin
(Zampatti, et al., 2014). Together, these carotenoids make up the macular pigment, which is
known to protect the eye against damage from photochemical reactions (Mozaffarieh et al.,


Figure 1. The carotenoid content (mg/100g wet wt) present in a wide variety of everyday vegetables (Johnson 2002)

Dietary sources of lutein and can be found in most fruits and vegetables whereas
zeaxanthin is less common, as shown in Figure 1. Zeaxanthin is limited to certain yellow/orange
fruits and vegetables such as corn, oranges, papaya and squash (Mozaffarieh et al., 2003). Lutein
and zeaxanthin together can be found primarily in egg yolk (McCusker, Durrani, Payette, &
Suchecki, 2016). With these nutrients being present both in the body as well as daily foods, there
needs to be research into the effects these nutrients have on the body and if these nutrients can be
harnessed to improve overall health.

Effects of Nutrient Actions on Age Related Macular Degeneration

Antioxidants are known for their role in protecting the body from harmful molecules by
delaying cell damage. Recently, specific carotenoids have been studied and shown to exhibit
these anti-oxidizing effects on the body, at the cellular level. One study showed that lutein and
zeaxanthin demonstrated antioxidant effects that protected the photoreceptor cell layer,
responsible for sight, from light damage in the macular pigment (Zampatti et al., 2014). Another
study showed that the antioxidant properties of lutein and zeaxanthin can also minimize the


effects of oxidative stress by reducing the amount of oxygen entering the cell membrane
(Perlman, Millen, Ficek, & Hankinson, 2002).

Figure 2. Correlation graph between lutein serum levels and overall vision quality (Olmedilla et al. 2001)

One groundbreaking study showed a direct correlation between lutein levels in blood
serum and improved vision. In this study it was shown that the supplementation of lutein and
zeaxanthin, was positively correlated to increased vision quality, as shown in figure 2 (Olmedilla,
Granado, Blanco, Vaquero, & Cajigal 2001). In this study, increased lutein serum levels were
linked to improved vision quality in a numerous patients, leading authors to believe that lutein
levels in the blood has a direct effect on eye disease progression and vision quality.
With age, an individuals antioxidant defenses decrease, increasing the productivity of
reactive oxygen species and ultimately resulting in the generation of free radicals (Zampatti et
al., 2014). More specifically, patients with AMD develop photochemical damage in the retina
mainly caused by oxidative stress, which is an overabundance of reactive oxygen species
(Zampatti et al., 2014). Some studies combining both antioxidants and other types of nutrients


have shown beneficial results on the progression of AMD (Zampatti et al., 2014). Harnessing the
protective properties of antioxidants and pairing them with other nutrients is a promising
approach to decreasing the risk factors associated with AMD.
Epidemiologic studies are conducted to analyze patterns, causes, and effects of health
related conditions in certain populations. These types of studies are required in obtaining
information regarding the importance of lutein and zeaxanthin in lowering risks of age-related
macular degeneration and their relevance to human disease (Mares-Perlman, et al., 2002). In
three cohort studies, high intakes of lutein and zeaxanthin lowered prevalence of macular
degeneration in men and women by 20-50% (Mares-Perlman, et al., 2002); however, due to a
small sample size, the results cannot be accepted as fact.
In western countries there is epidemiologic evidence that the consumption of carotenoids
such as lutein and zeaxanthin lowers an individuals risk for macular degeneration (MaresPerlman, et al., 2002); however, in other associated studies, discrepancies were present. These
inconsistencies are believed to be due to experimental design and the observations only being
considered for specific population subgroups (Mares-Perlman, Brady, Klein, Klein, Bowen,
Stacewicz-Sapuntzakis, Palta 1995 & Mares-Perlman, Klein, Klein, Greger, Brady, Palta, Ritter
1996). The conflicting results from these studies may be due to a number of factors including,
but not limited to the sample size, sample demographic and experimental design. To confirm or
disprove the effects of lutein and zeaxanthin on macular degeneration, additional studies must be

Research Gaps


The current knowledge surrounding the use of carotenoids, such as lutein and zeaxanthin,
for the protection of the eye (against disease) remains relatively limited. The limitation of this
knowledge lies in the fact that a majority of experimentation focused on this research topic has
been conducted in cell cultures and/or animal models (primarily rodents). The major issue with
these approaches is the translation of the results obtained from cell culture and animal models
into the human body. In other words, the results obtained from these models is not necessarily
applicable to humans due to the complexity of the human body.
One exception to this would be the use of a specific animal model, the non-human
primate. This animal model has been used for many different studies due to the similarities
between the non-human primate and human body. For example, monkeys have been used in
some experiments to study the effects of carotenoids on eyesight degeneration. This is significant
because monkeys have the anatomical features (macula) which are a part of the eye (retina) that
is in charge of vision and vision quality. In order for the results of experiments to have a higher
significance and effect on everyday human life, more studies using this advanced model should
be done prior to moving into human, clinical testing. Then and only then can the use of lutein
and zeaxanthin for AMD treatment be recommended for patients suffering from AMD effects.

Age-related macular degeneration is a big problem in the United States and with an aging
population the burden on the healthcare system is expected to grow. There is no cure for AMD
currently and therefore research efforts have shifted towards treatments that may slow or halt the
disease progression. One of these research areas focuses on the use of carotenoids, specifically
lutein and zeaxanthin. Using these carotenoids researchers have been able to show that eye


health, specifically in the retina, can be improved using supplemented diets rich in lutein and
zeaxanthin; however, these studies have primarily been based on results from cell culture and
rodent models. These findings must be tested in more advanced experimental models before
clinical testing can be conducted and these technique adopted into everyday life. With this said,
the supplementation of lutein and zeaxanthin is a promising approach to treating the symptoms
of patients with age-related macular degeneration.




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