Chemistry Reference
In-Depth Information
MPOD may, at least partly, be dependent on genetic factors, as suggested by a recent study
(Liew et al. 2005). A genetic linkage may not be the primary determining factor, however: MPOD
appeared to be different in monozygotic twins (Hammond et al. 1995), who apparently can have
different levels of MPOD depending on differences in their specii c environment, particularly with
regard to their diet.
From 2005 onward, several research groups have independently identii ed genes that appear to
be strongly linked with the risk for AMD (Marx 2006). Whether and how the presence or absence
of these genes is linked to an individual's MPOD remains to be established. A recent publication
suggests that plasma concentration of only lycopene and
-cryptoxanthin, but not lutein and zeax-
anthin, differ in subjects bearing different single nucleotide polymorphisms of genes involved in
lipid metabolism (Borel et al. 2007). Furthermore, ethnicity seems to inl uence plasma levels of car-
otenoids (Kant and Graubard 2007) as well as MPOD levels and distribution (Wolf-Schnurrbusch
et al. 2007). The question remains whether dietary or supplemental intake of the macular xan-
thophylls can inl uence the course of the disease in subjects who possess one or more genes that
have been identii ed as risk factors for AMD.
β
13.7.5 S
UPPLEMENTATION
E
XPERIMENTS
IN
M
ONKEYS
A series of publications has reported results of supplementation experiments with monkeys.
Motivated by an earlier investigation (Malinow et al. 1980), the authors supplemented groups of car-
otenoid-depleted rhesus monkeys with either pure lutein or pure zeaxanthin at doses of 2.2 mg/kg/
day (equivalent to 12-24 mg of carotenoid/day and animal) for 6-12 months (Neuringer et al. 2004).
Plasma concentrations of lutein rose faster, to higher initial levels, than those of zeaxanthin but by
approximately 16 weeks both had stabilized at comparable levels of about 0.8
mol/L. This was
equivalent to a 10-fold increase compared with plasma levels of normal chow-fed animals. MPOD
increased gradually and variably in both groups. However, by 16 months MPOD had approached
levels of only around 50% of that seen in monkeys that were fed normal monkey chow throughout
their lives. The lifelong carotenoid deprivation may have impaired the retina's natural ability to
accumulate xanthophylls to its full extent during the supplementation period.
μ
13.8 THE FUNCTIONAL ROLE OF XANTHOPHYLLS
The observation that lutein and zeaxanthin occur in the highest concentration in the macula soon
raised expectations that the macular xanthophylls may be essential in maintaining structure and
function of the retina by contributing not only to risk reduction of macular diseases but also to
improving visual performance of the healthy eye, which was the original hypothesis to explain the
presence of the macular yellow pigment as mentioned previously.
13.8.1 F
IRST
H
UMAN
S
UPPLEMENTATION
S
TUDIES
WITH
X
ANTHOPHYLLS
Starting in the late 1940s, just after it was realized that xanthophylls occur in the retina and that they
are provided by dietary intake, a number of supplementation studies were conducted with “Helenien,”
a lutein-dipalmitate ester that had been discovered in the l ower
Helenium autumnale
by Nobel
Laureate R. Kuhn (Kuhn and Winterstein 1930). The helenien used for supplementation was extracted
from the marigold l ower
Tagetes patula l ore pleno
, and not from
Tagetes erecta
, the main commercial
source of lutein today. Under the name “Adaptinol,” helenien was commercialized by Bayer from the
late 1940s on (Cüppers and Wagner 1950, Tarpo and Cucu 1961). As the name implies, the effect on
dark adaptation was the main target of its application. The mechanistic basis of this effect had been
evaluated in frogs using electroretinograms (ERG) (Mueller-Limmroth et al. 1958), measuring retinal
oxygen consumption (Schmitt et al. 1959), and the determination of retinal sodium and potassium
contents (Berges et al. 1959). However, the scientii c basis of this application remained weak and was
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