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responses. The question of whether nonresponders exist or whether these individuals merely respond
more slowly to supplementation than normal remains an unanswered question.
In contrast, supplementation with zeaxanthin or (meso)-zeaxanthin has received much less atten-
tion and there is a paucity of published data. Modest increases of plasma concentrations and MPOD
increases after supplementation with (meso)-zeaxanthin were reported by Bone et al. (2007). In
another study, the authors supplemented two subjects with 30 mg/day of pure (
R
,
R
)-zeaxanthin
extracted from
Flavobacteria
for 4 months and reported statistically signii cant MPOD increases of
about 10%. These MPOD increases were smaller than those observed with lutein in an earlier study
of the same authors (Landrum et al. 1997). However, this most probably was due to differences in
formulation of the zeaxanthin and lutein. In another slightly larger study, eight subjects were supple-
mented with pure zeaxanthin. MPOD increases could be identii ed by heterochromatic l icker pho-
tometry (HFP) in i ve of the subjects, whereas at the end of supplementation, MPOD values below
baseline and thus a decrease of MPOD, were reported in the other three (Garnett et al. 2002). Schalch
et al. (2007) have supplemented pure, chemically synthesized zeaxanthin and reported a corrected
MPOD increase of 15% as measured by HFP; the correction of MPOD was for the increase in
pigment concentration in the parafoveal region. Pigment increases such as these in the parafoveal
location that HFP uses as reference can cause MPOD to appear to decline, which was observed.
This may indicate a similar situation occurred in the study reported above (Garnett et al. 2002). This
observation of parafoveal pigment increases upon supplementation with xanthophylls is consistent
with results from several other supplementation studies. In one of them (Wenzel et al. 2007), three
subjects consumed 30 mg lutein and 2.7 mg zeaxanthin/day for 120 days. The authors recorded
MPOD by HFP at four discrete eccentricities from 20
. In all three subjects MPOD increased
signii cantly at the two most central measurement loci. However, a trend of increasing pigment at
the reference location at 7° eccentricity was observed as well, suggesting that parafoveal pigment
increases may not be specii c to zeaxanthin but can also be observed with lutein in special situations
in particular when supplementing at higher doses (Johnson et al. 2008b). This phenomenon was also
reported in an epidemiological study that investigated the age dependency of MPOD (Berendschot
and van Norren 2005).
′
to 120
′
13.7.4 M
ODULATORS
OF
MPOD
In addition to supplementation or dietary intake of the xanthophylls, several other modulators that
inl uence the MPOD response of subjects to supplementation with xanthophylls were reported
(Mares et al. 2006). Larger waist circumference and the presence of diabetes predicted a decrease of
MPOD. In contrast to earlier i ndings, iris color was not related to MPOD. No dependence of MPOD
on age was revealed in this study but this may be because of its lower age limit of 53 years.
Among the possible determinants of MPOD, age as the most evident risk factor for AMD is
probably the most important. The earliest report on an observation relevant to the presence or
absence of the yellow MP at birth is from Schwalbe (1874), who stated that the pigment is rarely
present at birth. This is consistent with the observation of Bone et al. (1988), based on HPLC deter-
mination of xanthophylls in the central retina of postmortem eye, that the xanthophylls are present
in prenatal eyes but that they do not form a visible yellow spot until about 6 months after birth. Bone
et al. (1988) also report that the youngest eyes have lutein as the predominating xanthophyll and that
it is only in older eyes that zeaxanthin becomes more dominant. Their data suggest that the retinal
content of xanthophylls is independent of age. In contrast to this conclusion, Nolan et al. (2007b)
have reported a decline of MPOD with age in an Irish population (
n
= 800). In the same article they
also have reviewed 23 studies published earlier and pointed out that in 14 of these studies a decline
of MPOD was found. Together with their own study and a more recent study from Japan (Obana
et al. 2008), it appears that the majority of studies do indeed suggest a decline of MPOD with age,
but a i nal conclusion on this topic has not yet been reached, mainly because the results may be
dependent on the method chosen for MPOD measurement.
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