Lutein and zeaxanthin improve vision function in early AMD
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increased macular pigment optical density (MPOD) and improved visual
function in men with mild to moderate age-related macular degeneration
(AMD).
Macular pigment is composed principally of 2 isomeric carotenoids,
lutein (L), zeaxanthin (Zx), and the L metabolite meso-Zx (meso-Zx is
also found in minimal amounts in seafood). In the central 3 mm of the
macula, L, Zx, and MZ are present in approximately equal amounts. The
macula selectively concentrates L and Zx at levels up to 1,000 times
greater than found in any other body tissues. Furthermore, the macula
selectively places Zx in its foveal center where the greatest
protection is needed, which is last to degenerate. Zx has a chemical
structure with an extra conjugated double bond (11 conjugated double
bonds vs. 10 for L) and may make this a superior antioxidant. Zx is a
minor component of the diet of the population of the United States
(chiefly corn and yellow peppers), being no greater than one fourth as
prevalent as L. By contrast, a cup of Chinese goji (Wolfberry, Fructus
barbarum) berries is the highest known Zx food source, having some 200
times the amount in a cup of corn and 65 times the Zx dose found in a
cup of yellow peppers. Despite the fact that L is at least 4 times as
prevalent as Zx in human serum, there is a greater concentration of Zx
in the central portion of the macula by 2 times. This fact has been
shown in quail, monkeys, and humans. Also, relative intake of Zx to L
decreases with age.
It is known that dietary L and Zx increases human MPOD. The
possibility for AMD vision improvement by macular pigment enhancement
with carotenoids or nutritional cofactors has been confirmed by
multiple prospective interventional and observational clinical trials.
Methods & Results
This was a 1-year, n = 60 (57 men, 3 women), 4-visit,
intention-to-treat, prospective, randomized controlled clinical trial
of patients (74.9 years) with mild-to-moderate age-related macular
degeneration (AMD) randomly assigned to 1 of 2 dietary supplement
carotenoid pigment intervention groups: 8 mg Zx (n = 25) and 8 mg Zx
plus 9 mg lutein (L) (n = 25) or 9 mg L ("Faux Placebo," control
group, n = 10). Estimated foveal heterochromic flicker photometry, 1°
macular pigment optical density (MPOD QuantifEye), low- and
high-contrast visual acuity, foveal shape discrimination, 10° yellow
kinetic visual fields (KVF), glare recovery, contrast sensitivity
function (CSF), and 6° blue cone ChromaTest color thresholds were
obtained serially at 4, 8, and 12 months.
Ninety percent of subjects completed = 2 visits with an initial
Age-Related Eye Disease Study retinopathy score of 1.4/4.0 and pill
intake compliance of 96% with no adverse effects. There were no
intergroup differences in 3 major AMD risk factors: age, smoking, and
body mass index as well as disease duration and Visual Function
Questionnaire 25 composite score differences. Randomization resulted
in equal MPOD variance and MPOD increasing in each of the 3 groups
from 0.33 density units (du) baseline to 0.51 du at 12 m, (P = 0.03),
but no between-group differences. In the Zx group, detailed
high-contrast visual acuity improved by 1.5 lines, Retina Foundation
of the Southwest shape discrimination sharpened from 0.97 to 0.57 (P =
0.06, 1-tail), and a larger percentage of Zx patients experienced
clearing of their KVF central scotomas (P = 0.057). The "Faux Placebo"
L group was superior in terms of low-contrast visual acuity, CSF, and
glare recovery, whereas Zx showed a trend toward significance.
Discussion & Conclusions
In this study Zx or L significantly elevated low-normal MPOD to normal
ranges in older men with AMD at 1 year, and they benefited visually
from this intervention. These results may not be generalized to women,
who typically have a higher percentage of adipose fat and different
lipoprotein profiles.
This data suggest that Zx has unique visual cone-enhancing attributes
consistent with its foveal position. Zx improved high-contrast visual
acuity by 1.5 lines and sharpened 1° Foveal Shape Discrimination, a
test of foveal cone alignment. In some cases, the macula kinetic
visual field data and correlative 3-dimensional MPOD plots
demonstrated complete resolution of central scotomas. The
autofluorescence lipofuscin data suggested amelioration. In the
rod-dominant parafovea L, ostensibly owing to its more parafoveal
retinal distribution, proved superior, with statistically significant
improvement in contrast sensitivity, glare recovery, and enhanced
blue-yellow increment db thresholds from parafoveal blue cones. These
visual effects were not mutually exclusive, as there were weak trends
toward significance with Zx for rod-dominant visual parameters, while
the L group also manifested overlapping properties with respect to
cone function.
This study also investigated whether there was added benefit of Zx to
traditional L supplementation. In this case, higher dose 1:1 ratio of
Zx plus L barely increased MPOD and inconsistently enhanced visual
function, suggesting carotenoid duodenal, hepatic-lipoprotein, or
retinal competition when introduced at equal supplement doses. This is
not surprising, as dietary L predominates 5:1 and foveal Zx
predominates 2:1 over L, so equal doses of each carotenoid are unusual
from a dietary or tissue standpoint.
In the current study not everyone who was supplemented experienced
elevated MPOD, as reported by others.
Macular pigment is associated with all 3 primary AMD risk
factors—age, smoking, and obesity. Evidence from epidemiologic
studies consistently shows high dietary intake of fruits and
vegetables rich in L and Zx reduces the risk of AMD.
This study is consistent with other studies showing that Zx raises
MPOD. Raising macular pigment via Zx supplementation results in
salutary visual benefits to AMD patients with mild disease, through
enhancement of visual acuity, shape discrimination, scotoma
resolution, as well as weaker negative effects on CSF, glare recovery,
and blue-yellow color thresholds.
Patients with AMD might want to enhance their declining vision with
carotenoids apart from the question of whether carotenoid
supplementation can decrease the risk of progression to end-stage
disease. MPOD enhancement via dietary manipulation is possible.
MPOD measurement is rarely used in clinical practice. This results in
failure to capture the subtleties of disease progression that we can
correlate to patient complaints. The aging of the U.S. population and
attendant increase in AMD has implications for night driving and
public safety.
In summary, supplementation with high dose Zx (8 mg), L (9 mg), or
both resulted in increased MPOD and improvements in macular function.
All three supplements produced nearly equal improvement in MPOD by
heterochromic flicker photometry (no significant between-group
differences) and improvements in vision function.
Optometry. 2011 Nov;82(11):667-680
http://www.ncbi.nlm.nih.gov/pubmed/22027699
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