Chemistry Reference
In-Depth Information
carotenoid-free diet (Malinow et al. 1980). In this experiment, the carotenoid-deprived macaques
did not have measurable plasma concentrations of carotenoids including lutein and zeaxanthin and
no yellow MP. Over the years, the xanthophyll deprivation of the macula led to distinct ophthalmic
consequences, so-called window defects, visible during l uorescein angiography, which signal a
malfunction in the cells of the RPE. The observed defects were similar to those seen in human
AMD. This experiment was probably the i rst controlled attempt to modulate MPOD in nonhu-
man primates by dietary means (Malinow et al. 1980) and the i rst indication that a long-lasting
xanthophyll dei ciency can have ophthalmic consequences. Under special conditions, deprivation
of carotenoids can also occur in humans. The human disease cystic i brosis, a consequence of
which is that the absorption of fat-soluble nutrients including carotenoids is severely impaired, pro-
vides a model for this. Schupp et al. (2004) have evaluated MPOD and plasma levels of lutein and
zeaxanthin in 10 cystic i brosis patients. Their results indicated that in comparison to age- and
gender-matched healthy subjects these patients had about 50% lower MPOD levels along with total
plasma xanthophyll concentrations that on average were as much as 57% lower than those in the
control group. This indicates that MP density decreases if the supply of lutein and zeaxanthin is not
maintained. The reverse situation, namely, the response of the human organism to supplementation
with lutein and zeaxanthin has also been studied, mostly in terms of lutein and zeaxanthin plasma
concentrations and MPOD.
13.7.2 R
ESPONSES
OF
P
LASMA
C
ONCENTRATION
If xanthophylls are ingested, they appear in the plasma within a few hours and dei nitive responses
of the plasma concentrations of lutein and zeaxanthin can normally be observed. These responses
have systematically been evaluated by many authors with Thürmann et al. (2005) being one of the
more recent evaluations for lutein and Hartmann et al. (2004) for zeaxanthin. To study the pharma-
cokinetic characteristics of the xanthophylls, the authors supplemented 16 subjects with daily lutein
doses of 4.1 or 20.5 mg/day of lutein for 42 days and concomitantly measured their plasma concentra-
tions. This supplementation led to about 3.5- and 10-fold increases of lutein plasma concentrations,
respectively. The study also provided evidence that the concentration of the other plasma carote-
noids measured remained unchanged, despite the drastic increase in lutein plasma concentrations.
Later, the same formulation of lutein and zeaxanthin was studied in the LUXEA Study by Schalch
et al. (2007), using doses of 10 and 20 mg/day. Combining the data of these two studies gave the
opportunity to evaluate the general pharmacokinetic characteristics of the xanthophylls and it could
be deduced that the response of plasma concentrations to supplementation with xanthophylls was
dose-dependent, following saturable kinetics, so that the highest plasma concentration that can be
attained by xanthophyll supplementation is limited at about 3
mol/L (
v
max
in Figure 13.5). Plasma
responses to supplementation with xanthophylls including (meso)-zeaxanthin were recently mea-
sured by Thurnham et al. (2008), who supplemented 19 subjects with a mixture of lutein, (meso)-
zeaxanthin, and zeaxanthin for 3 weeks. The authors concluded that (meso)-zeaxanthin was less
well absorbed than (3
R
,3
μ
R
)-zeaxanthin from the administered mixture but they did not measure
MPOD levels as Bone et al. (2007) did (see Section 13.7.3).
While the presence of lutein and zeaxanthin in plasma is obviously an important condition for
the accumulation of these substances in the retina, the question is whether higher plasma levels lead
also to higher macular levels. This relationship between plasma concentrations of xanthophylls and
MPOD has been studied by many investigators. Two recent publications (Mares et al. 2006, Nolan
et al. 2007a) have analyzed this relationship in two different cohorts (one from the United States
and one from Ireland, each with about 700 subjects), and have reported statistically signii cant
direct correlations between lutein and zeaxanthin plasma concentrations and MPOD, coni rming
independent earlier reports from other authors (i.e., Bone et al. [2003]), that higher plasma levels of
lutein and zeaxanthin are correlated with a denser MP. The next strongest predictor for MPOD was
dietary intake of xanthophylls.
′
Search WWH ::
Custom Search