This study will explore whether taking the vitamins lutein and zeaxanthin, with or without
Omega-3 fatty acid (fish oil or docosahexanoic acid, also known as DHA) will change the
amount of lutein and zeaxanthin in the blood among people with age-related macular
degeneration (AMD). AMD is one of the leading causes of legal blindness among people over
the age of 50 in developed countries. In the disease, the retina of the eye, the sensory
portion, worsens in condition. AMD causes progressive loss of central vision, with only
peripheral vision remaining, that is, the ability for someone to see from the edges of the
eye. To date, there is not any effective treatment to improve vision for most people whose
AMD is advanced. Yet some data from research studies suggest a possible role of
antioxidants, including lutein, in reducing the risk of AMD and cataracts. Lutein and
zeaxanthin belong to the carotenoid family of vitamins, of which there are more than 600.
There are 40 or 50 carotenoids in the typical diet of human beings, but only 14 major
dietary ones are identified in human plasma. Lutein, in particular, is a vitamin that is
found naturally in the retina, especially in the macula, the region of the eye that is
essential for fine, detailed vision. Previous studies have shown that higher levels of foods
rich in Omega-3 fatty acid were associated with a lower likelihood of AMD.
Patients ages 60 and older who may or may not have AMD, who do not have certain other
serious eye disorders, and who have not had potentially life-threatening illness in the last
year may be eligible for this study. About 40 people will participate.
Patients will undergo a medical history and physical examination. A blood collection of
about 4 tablespoons will be done to measure the amount of lutein and other vitamins in the
blood. Patients will have a complete eye examination consisting of procedures standard to
those given by ophthalmologists. Participants will have photographs taken of their eyes, and
they will undergo a visual field test. Flicker photometry also will be conducted. This
consists of the patients looking at a flashing bluish light with one eye at a time, and
turning a knob until the light stops flashing. Then during the test, patients will look away
from the light and turn the knob until the flashing stops.
During this study study, patients will be asked to not take more than two tablets each day
of multivitamins that contain lutein. The vitamin supplements will be provided as pills that
represent one of two vitamin regimens given on a random basis: either lutein and zeaxanthin
with DHA or lutein and zeaxanthin without DHA added. The amounts would be 10 mg/day of
lutein and 2 mg/day of zeaxanthin, with or without 1 g/day of DHA. Patients will return to
the study center for follow-up visits at 1 month, 3 months, 6 months, and 9 months. During
those visits, some of the examinations done earlier will be repeated so that the researchers
can evaluate the effects of supplements on patients' eyes. Patients will also be watched for
possible side effects from the vitamins supplements. Lutein and zeaxanthin supplements are
considered to be safe with possible minor side effects, such as headaches and difficulty in
swallowing the tablets. Fish oil or DHA supplements may also cause abdominal discomfort.
If information obtained from this study may be important for participants' health, they will
be informed when it is available. There are no plans to give participants the results of any
medical tests, evaluations, or other research data. Further research may be necessary before
such results become meaningful.
The current proposed study is a necessary pilot study to prepare for a large-scale phase III
randomized clinical trial planned to investigate whether oral supplementation with macular
xanthophylls (lutein and zeaxanthin) and omega-3 long-chain polyunsaturated fatty acids
(LCPUFAs) will decrease the progression of age-related macular degeneration (AMD) when
compared to placebo. The primary objective of this pilot study is to investigate whether
additional oral supplementation of omega-3 LCPUFAs (1 g/day) to daily supplementation of
lutein (10 mg/day) and zeaxanthin (2 mg/day) will change the plasma levels of lutein and
zeaxanthin in participants over age 60. The secondary objective is to study whether changes
in serum levels of xanthophylls, lutein and zeaxanthin following oral supplementation will
result in changes in the macular pigment density. In this study, forty participants (20
participants per arm) will take the study medications of lutein (10 mg/day) and zeaxanthin
(2 mg/day) with or without the omega-3 LCPUFAs (1 g/day) for 6 months and will be followed
for a total of 9 months (the initial 6 months with supplementation and the last 3 months
without supplementation). Participants will range from those with no AMD and little or no
drusen in either eye through advanced AMD (geographic atrophic, retinal pigment epithelial
detachment, or other signs of neovascular/exudative disease) in one eye. AMD severity will
be classified using Age-Related Eye Disease Study (AREDS) criteria for the definition of
advanced AMD. This is a preliminary study to be conducted prior to a large-scale phase III
randomized clinical trial of omega -3 LCPUFAs and lutein/zeaxanthin for patients with
moderate to high risk of AMD. The estimates of increases in serum lutein and zeaxanthin
levels and the corresponding changes of macular pigment densities will provide essential
information in conducting a large phase III randomized trial.
- INCLUSION CRITERIA:
Participants will range from those with no AMD and little or no drusen in either eye
through end stage AMD (geographic atrophic, retinal pigment epithelial detachment, or
other signs of neovascular/exudative disease) in one eye. AMD severity will be classified
using AREDS criteria for the definition of advanced AMD. Children are not included because
AMD is, by definition, an adult disease and the study is designed to assess the effect of
oral administration of lutein in persons in the age group affected by AMD.
- Men and women aged 60 years or older.
- Eligible participants may have no evidence of AMD with little or no drusen in either
eye, or may have any stage of AMD through end stage (geographic atrophic, retinal
pigment epithelial detachment, or other signs of neovascular/exudative disease) in
- The ability to understand and sign an informed consent form prior to enrollment.
- People who currently smoke are eligible to enroll in this study. However, if smokers
take an AREDS-like supplement, they must not take the AREDS-like supplement during
- Ocular disease (other than AMD) which confounds assessment of the retina including
diabetic retinopathy, central serous choroidopathy, optic atrophy, retinal vein
occlusion, active uveitis, significant explained or unexplained visual field loss, or
any other type of retinopathy or retinal degeneration.
- Chronic requirement for any systemic or ocular medication for other eye diseases such
- Regular use of lutein/zeaxanthin of 6 mg or more: during the last 3 months or
currently taking these supplements. The daily use of the new Centrum or Centrum
Silver or other similar multivitamins will be allowed but is limited to a maximum of
twice a day.
- Participant has regularly taken 1 gm of fish oil (DHA, EPA) during the last 3 months
or currently taking fish oil supplementation
- Inability or unwillingness to be followed for the nine-month study period.
- Acute, potentially life-threatening illness such as heart attack in the last year, or
malignancy or blood disease not in remission.
- Any history of lung cancer.