Download Lutein commercial insight

Lutein commercial insight
Lutein
GAYLE DE MARIA
PRODUCTS ON THE MARKET
Anno 18 - No. 2
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March/April 2007
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AgroFOOD industry hi-tech
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Lutein (from Latin lutea meaning "yellow") is one of over 600
known naturally occurring carotenoids. Found in green leafy
vegetables such as spinach and kale, lutein is employed by
organisms as an antioxidant and for blue light absorption.
Lutein was found to be present in a concentrated area of the
macula, a small area of the retina responsible for central vision.
The hypothesis for the natural concentration is that lutein helps
protect from oxidative stress and high-energy light. Various
research studies have shown that a direct relationship exists
between lutein intake and pigmentation in the eye. Several
studies also show that an increase in macula pigmentation
decreases the risk for eye diseases such as Age-related
Macular Degeneration (AMD). Lutein is naturally present in
human diet when fruits and vegetables are consumed. For
individuals lacking sufficient lutein intake, lutein-fortified foods
are available; since 1996, in fact, lutein has been incorporated
into dietary supplements. Its commercial value has recently
exploded with an estimated market value of $139 million in
2004 ending up to be one of the fastest growing areas of
carotenoid market.
Agro Food Industry Hi tech Journal has decided to interview
experts from some of the leading companies in this field to find
out more about this natural molecule.
In the diet, lutein is mostly found in green vegetables,
particularly kale and spinach. Lutein and zeaxanthin esters are
present in small amounts in fruits. A study by Nebeling et al. (1)
showed that 93% of the total amount of lutein and zeaxanthin
found in fruit, vegetables and eggs is present either in free or
ester form of lutein and zeaxanthin. Tropical fruits like: papaya
and oranges are rich in lutein
...lutein helps protect
ester. Kemin Health produces
from oxidative stress and
and commercializes FloraGLO
high-energy light...
Lutein which is a patented
purified free lutein identical to the lutein found in abundance in
the human diet and in the body and naturally containing
zeaxanthin. "DSM Lutein is free lutein, too", affirms Isabelle
Frappa - New Business Development Manager Europe, DSM
Nutritional Products. "According to the scientific evidence",
states Samanta Maci - Technical Services Manager, Europe,
Kemin Health - "only free lutein is found in the human serum
regardless of its original dietary source". "Lutein esters must be
de-esterified (hydrolyzed) before being absorbed by the body
and distributed to the different organs, particularly eyes and
skin", adds Maci. The efficacy of this enzymatic process which
depends on the activity of the human intestinal enzymes is not
clearly established (2, 3). Additionally important factors such as
dietary fat and age may affect the kinetics of these compounds.
"The body deals with lutein esters in the same way that it deals
with many other day to day foods such as dietary fats and
vitamins A and E - in a completely
natural way. Lutein esters are
broken apart as part of the normal
process of digestion, releasing
lutein for absorption into the
Isabelle Frappa
bloodstream", stresses Ralf Zink DSM Nutritional Products
Global R&D Director, Cognis
Nutrition & Health. "The scientific
community recognizes lutein esters
as a source of lutein because
studies consistently show lutein
from lutein esters to have excellent
bioavailability", he explains, adding:
"Lutein from lutein esters and 'free'
lutein are both well-absorbed, but
lutein from lutein esters may
actually be more bioavailable. For
example, recent laboratory
research predicts that when lutein
Samanta Maci
is ingested in the free form it is
Kemin Health
more prone to degradation in the
stomach. This is likely to reduce the amount reaching the
intestine for absorption into the bloodstream" (Molnar P. et al.,
Carotenoid Science 2006;10;1). Fit Ingredients e.K., for
example, is working on Novopure® Lutein Ester because
according to Alexandra Schmid-Riedl - CEO, Fit Ingredients it is of higher bioavailability in comparison to Free-Lutein.
"Lutein found in nature for examples in flower petals is
chemically bound to various types of fatty acids, known as
Lutein Ester", she affirms. Cognis Nutrition & Health also
provides a natural lutein ester, named Xangold®, the first
patented lutein ester product in the market and a concentrate
extracted from marigold flowers grown exclusively for the
company. "There is a high demand for both lutein formulations
in the dietary supplements market", points out Zohar Nir - V.P.
of New Products Development & Scientific Affairs, Lycored Ltd.
LycoRed Ltd's patented lutein line, Lyc-O-Lutein, for example
includes both free lutein and lutein Di Ester the trans isomer
form. Another company that deals with both forms of lutein is
OmniActive Health Technologies, the first, and only company in
the world with international patents for both Free Lutein (US
Patent # 6,743,953, and other patents pending worldwide) and
Lutein Esters (US Patent # 6,737,535, and other patents
pending worldwide).
A vast majority of scientific studies show that high levels of
lutein in diet are to be associated with good eye health and low
incidence of age related macular
...93% of the total
degeneration, and that lutein
amount of lutein and
deficient diets are associated with
zeaxanthin found in fruit,
vision problems. The US RDA data
vegetables
and eggs is present
clearly informs the public that
either
in
free
or ester form of
against the RDA of around 3.7 mg,
lutein and zeaxanthin...
US diets are at barely at 0.7 mg,
Lutein
clearly identifying the need to a
...there is a high demand
for both lutein formulations in the growing population of baby
boomers and the next
dietary supplements market...
generation of enhancing lutein in
diet-through food, or through supplements. A highly respected
and authoritative scientific advisory body like the Joint WHO/
FAO Committee JECFA (Joint Expert Committee on Food
Additives) assessed all the FloraGLO® Lutein safety data and
ruled in September 2004 that lutein (along with its structural
isomer zeaxanthin) are safe for human consumption even at
maximum daily intake levels of 2 mg/kg body weight (i.e.
around 90-150 mg per day for most adults). This clears the way
for higher dosages of lutein being incorporated into
supplements and nutritional foods over and above current
levels. All the information clearly adds up, and appeals the
average consumer, to induce the use of lutein as daily
supplement. Almost all supplementation studies-whether as
lutein esters or free lutein - show a positive correlation with
enhanced serum and tissue concentrations of lutein and
zeaxathin, and with markers of good eye health. And enough
studies keep coming along to show that both forms of lutein in
supplement form are relevant. "Hence", states Sanjaya
Mariwala - Managing Director, OmniActive Health
Technologies, "we strongly believe that both nutritionally
relevant forms of lutein-as lutein esters and free lutein- need to
be made available to the formulators for appropriate product
offerings".
FOCUS ON PRODUCTS
March/April 2007
■
Anno 18 - No. 2
Alexandra Schmid-Riedl
Fit Ingredients
■
Botanic source and extraction / purification
process
Cognis: "The carotenoids in our Xangold® lutein ester products
are extracted from Marigold flowers (Tagetes erecta), as are all
the other commercially available lutein products irrespective of
whether they are in the ester or the free form", says Holger
Becker - Global Product Line Manager Xangold®, Cognis
Nutrition & Health - and he explains
to us that the Xangold® concentrate
also contains small amounts of
naturally-occurring zeaxanthin
esters and undergoes the minimum
processing necessary to give a top
quality, competitively-priced,
natural-source product. Xangold
natural lutein esters are produced
by a patented extraction process.
"Together with our patented product
concentrate, this serves as a
Ralf Zink
quality control seal for our
Cognis Nutrition & Health
customers", he says. The
carotenoids (lutein and zeaxanthin
esters) are extracted from the
marigold flower petals (corollas)
solely with the use of an accepted
and approved food-grade solvent,
which is then evaporated thus
achieving a lutein ester concentrate
(oleoresin). An alcohol mix then
dissolves and separates out any
impurities. This extraction and
purification method results in a
39
AgroFOOD industry hi-tech
We have asked our experts to explain to our readers the
process used to achieve their unique product and formulations
and to give us details on their properties. To simplify the
reading process we have decided to concentrate on one
company at a time.
Anno 18 - No. 2
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March/April 2007
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AgroFOOD industry hi-tech
Lutein
product that contains lutein (and zeaxanthin) in their natural
ester form and brings the desired characteristics of enhanced
purity. The process and composition is patented in Europe
under 1,073,694B1 and in the U.S. under 6,191,293. Cognis'
Xangold® was the first patented lutein ester product in the
market.
DSM: "DSM lutein is originally extracted from tagetes (marigold
petals) and formulated into beadlets with Actilease™, a
proprietary formulation technology", says Frappa.
Fit Ingredients e.K.: Lutein Ester extracted from marigold
flowers is rich, safe and natural source of lutein. Naturallyzeaxanthin esters add to the carotenoid profile of natural lutein
ester. Lutein ester provides a source of lutein and zeaxanthin
preserved in the natural form Lutein-Ester and ZeaxanthinEster from marigold flowers. NovoPure LUTEIN Esters is the
only product available in the market produced through
Supercritical Fluid Extraction process-(SCF). Using CO2 as
media of extraction with the highest concentration of lutein
available in the Nutraceutical industry. It contains 40% lutein
ester, equivalent to 20% lutein ester , zeaxanthin also in its
esterified form. Its solid powder presentation is ideal for
application in food supplements, nutraceuticals, functional and
baby foods. It is a 100% natural lutein ester concentrate
obtained from an extract of marigold flowers (Tagetes erecta)
undergone a special patented process without effecting any
chemical transformation. "It guarantees that the product is free
from pesticides, fungicides and herbicides commonly
associated with products of plant origin; thus making it a
reliable source of natural lutein and other carotenoids which are
easily absorbed by the body", states Schmid-Riedl. "Our
principal Novo Agritech Limited utilizes a state of the art Super
Critical Fluid Extraction method under a patented process in
dissolving Lutein Ester as it exists in marigold flower, utilizing
high pressure super critical fluid CO2 at a low temperature", she
40
concludes.
Kemin Health: FloraGLO® Lutein is a purified lutein extracted
from marigold flower (Tagetes erecta) oleoresin. Marigold
oleoresin, which contains lutein esterified with fatty acids, is
subjected to a saponification process during which esters are
removed. "This saponification process is followed by
purification and crystallization steps in order to obtain purified
lutein crystals according to the highest standard of quality",
says Maci. These steps are based on a unique patented
process owned by Kemin: U.S. Patents 5,382,714, 5,648,564,
and 6,663,900, Canadian Patent 2,239,971, Japanese Patents
2,790,212 and 3,190,686, European Patent Conventions
0672655 and 0904258, Australian Patent 700,719, Austria
Patents 215059 and E191475, Belgium Patents 0904258 and
0672655, Denmark Patent 0672655, France Patents 0904258
and 0672655, Germany Patents 69516031T2 and 69620258,
Ireland Patents 0904258 and 0672655, Israeli Patent 124987,
Italy Patent 0672655, Korea Patent 214430, Netherlands
Patent 0672655, New Zealand Patent 319,825, Mexico Patent
205122, Portugal Patent 0672655, Spain Patent 2147261,
Sweden Patent 95300273, Switzerland Patents 0904258 and
0672655, and United Kingdom Patents
...lutein from lutein
0904258 and 0672655.
esters and 'free' lutein are both Lycored: Lyc-O-Lutein is extracted from
well-absorbed, but lutein from the flower of the marigold (Tagetes
lutein esters may actually be erecta). The dried petals of the flower
more bioavailable...
are rich in lutein and also contain some
zeaxanthin in association with the lutein. LycoRed holds a
patent on lutein extraction which is adopted from its method for
lycopene extraction from tomato solids. Soluble solids are
mechanically separated from the insoluble solids, then the
patented extraction technology is employed to extract either
lutein Di Ester or Free-lutein. "LycoRed's accumulated
experience in natural carotenoids has enabled us to produce a
product which satisfies the requirements and expectations of
our customers", says Nir.
OmniActive Health Technologies:
"Our complete range of Lutemax®
Free Lutein and Lutein Esters
products is obtained from marigold
(Tagetes erecta) grown on our own
contract farms, and marketed
under the brand name Lutemax®.
We will shortly be initiating our
international launch of a
Zohar Nir
Zeaxanthin product based on such
Lycored Ltd
natural plant material as well", says
Mariwala. "We have consciously
developed an entire supply chain
for Lutemax® keeping in mind the
end-use for human nutrition,
completely eliminating the use of
shortcuts to stabilize xanthophylls
as some manufacturers of feed
grade marigold products do, and
using better methods of storage,
dehydration and extraction using
only GRAS solvents", states
Abhijit Bhattacharya, Chief
Sanjaya Mariwala
Operating Officer, OmniActive
OmniActive Health
Technologies
Health Technologies. "Our process
ensures that even the GRAS
solvents used are within extremely low or non-detectable
residual limits. In fact, in order to heighten the need for product
safety, we were the first to highlight the need to have ETQ free,
GMO-free, BSE-/TSE- free , trans-fat free products", he
continues. "Our process ensures high level of stabilization of
lutein in terms of the total actives, and the required isomeric
form: our products have consistently high levels of the
nutritionally desirable trans-isomers of lutein and zeaxanthin.
Further, our products are so stabilized that even after subjecting
to high impact compression, our vegetarian beadlets continue
to show high levels of the trans-lutein isomers, and negligible
levels of the less-desirable cis-isomers" he concludes.
Formulations
Cognis: "The Xangold® range of natural lutein esters is
available in multiple concentrations in both oil suspensions and
micro-encapsulated, free-flowing tablet-grade powders
(beadlets)", says Zink. He adds that in 2001, Cognis was the
first company to launch BSE-free and GMO-free lutein ester
products especially for the European market. Cognis has a
10% vegetarian beadlet and recently launched a highconcentrate 20% beadlet, which enables formulators to follow
the trend and add more potency to the tablet without changing
its size. Stability tests on these formulations are conducted by
Cognis on both oil suspensions in bulk and soft gelatin
capsules, as well as on beadlets in bulk and tablets. "The
sophisticated micro-encapsulation technology used provides
phenomenal stability of the beadlets and only requires 5%
overage in the tabletting process", says Becker.
DSM: "DSM Nutritional Products offers excellent, highly stable
lutein formulations for a wide range of applications: Lutein 5%
CWS/S-TG for direct compression tablets and fortification of
foods and beverages and Lutein 20% FS for soft-gelatine
capsules", informs us Frappa.
...a vast
Lutein 5% CWS/S-TG combines a
majority of scientific
studies show that high cold water soluble form for the
levels of lutein in diet are fortification of effervescent tablets,
to be associated with food and beverage products with
good eye health and low the tablet grade form suitable for a
incidence of age related range of tablet applications. Lutein
macular degeneration, 5% CWS/S-TG delivers excellent
and that lutein deficient performance in regard of stability
diets are associated with
vision problems...
/ multimineral tablets", states Maci.
Lycored: The Lyc-O-Lutein line is available in oil suspensions
for soft-gel formulations and numerous beadlet formulations for
tablets and hard-shell capsules. The centre-piece of the new
product line is a highly stable gelatin-free and allergen-free
beadlet, containing 20% lutein. Lyc-O-Lutein, is available in
vegetarian and gelatin beadlets of various assays for tablets
and hard-shell capsules. "The newly launched Lyc-O-Lutein
20%VBAF, allergen-free, vegetarian beadlet", says proudly Nir,
"is gaining extra attention from the marketplace due to its high
assay which allows manufacturers to save space in the tablet
or capsule, leaving room for other combinations of bioactives
which enhance the bioactivity of lutein". The formulations have
undergone and passed stability testing. The newly developed
vegetarian beadlets are very stable even under the conditions
of high pressure, present during tableting.
OmniActive Health Technologies: Lutemax® Free Lutein and
Lutemax® Lutein Esters are offered in a completely range of
delivery formulations including Beadlets (for tablets, capsules
and dry mixes), Oil Suspensions (for liquid and soft gelatin
capsule formulations) and Cold Water Dispersible Powders.
"OmniActives has pioneered a new -generation delivery
technology", affirms Mariwala, "to offer the world's first
complete range vegetarian beadlets of Free Lutein and Lutein
Esters under the Lutemax® brand". Lutemax beadlets do not
use excipients of animal origin such as gelatin or lactose. They
are therefore completely vegetarian, and free from the risk
associated with BSE/TSE in ingredient source. OmniActive's
proprietary beadlet ingredient system uses a combination of
GMO-free, allergen free plant-based excipients which are
cellulosic and carbohydrate like in nature. These excipients
provide a strong encapsulating matrix and coating for the
carotenoid, and protect it from the impact of moisture, oxygen,
heat etc. "Our technology enables to make vegetarian beadlets
Lutein
and handling properties and furthermore contains no ingredient
of animal origin. "This formulation answers the market need
and consumer requirement for animal- and allergen-free
ingredients", affirms Frappa. DSM formulates its carotenoids
(and other fat soluble health ingredients) into specially
designed beadlets with micro-dispersed carotenoid phase.
Lipophilic substances need to be presented in tiny particles in
order to be absorbed by the digestive tract and provide their
health benefits. "Actilease™ beadlets contain small-sized
particles of lipophilic substances in a water soluble shell,
combining high bioavailability with excellent stability. The
protective matrix prevents tabletting losses and interactions
with other compounds and dissolves in the stomach, releasing
the micronutrient droplets so that they can be absorbed by the
body", adds Frappa. Talking about stability, Frappa says that
their formulations have been tested in numerous applications
and the stability data are available on request.
Fit Ingredients e.K.: Fit Ingredients has two main formulations
available: 1) Granular powder 5%,10%, 15%, 2) Extract 10%,
20%, 30%, 40%. "We must remember that Free Lutein is very
unstable against heat and light", says Schmid-Riedl. "Lutein
Ester, instead, is stable against light and heat. To get exact
information about stability, stability studies in the finished
product should be carried out because there could be an
influence of other ingredients in the finished formulation".
Kemin Health: FloraGLO® Lutein is available in dry and liquid
forms as follows: FloraGLO® Lutein 5% VG Granules and
FloraGLO® Lutein 10%VG tabGrade, FloraGLO® Lutein 20%
into Safflower oil. "All FloraGLO® Lutein are preservative and
BSE/TSE -free, vegetarian grade and do not require allergen
labelling. They are subjected to stability studies performed
under ambient (25C, 60% RH) and accelerated (40C, 75% RH)
conditions. Additionally Kemin has successfully tested under
the same conditions the stability of its dry forms in multivitamins
41
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Anno 18 - No. 2
Lutein
Anno 18 - No. 2
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AgroFOOD industry hi-tech
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...lutein
absorption and
with lutein concentrations ranging
bioavailability is
from the standard 5% up to a highaffected by several
potency 25% beadlet", adds
dietary and non-dietary
Mariwala.
factors such as the food
matrix in which it is
Lutein bioavailability
consumed, the state of
Little information is known about the the food (raw, cooked,
pharmacokinetics of lutein and
processed), presence of
zeaxanthin. A study by DSM
fibres and/or other
Nutritional Products and Kemin Health carotenoids, tobacco
L.C. was conducted with healthy
smoke, malabsorption
humans to measure the effect of
and liver and kidney
lutein (originally extracted from
diseases...
tagetes (marigold petals) and
formulated into beadlets by DSM Nutritional Products) and
zeaxanthin supplementation on blood plasma (4) The time to
reach steady-state plasma concentration, estimation of half-life
elimination of all-trans lutein, and other carotenoid profiles were
compared in this study. Safety parameters were also assessed.
According to the results lutein did not follow dose-linear kinetics,
steady state concentration was reached in approximately 5-6
weeks. Half-life calculations for total lutein, all trans lutein, and
zeaxanthin ranged from 5-7 days. No toxicity was detected in
any of the subjects. Lutein absorption and bioavailability is
affected by several dietary and non-dietary factors such as the
food matrix in which it is consumed, the state of the food (raw,
cooked, processed), presence of fibres and/or other carotenoids,
tobacco smoke, malabsorption and liver and kidney diseases.
"Several studies", informs us Maci, "have evaluated the
bioavailability of supplemental lutein, such as FloraGLO versus
dietary lutein such as that of spinach, and other greens and even
novel food sources fortified with lutein, such as yellow carrots (57)". The data cited from these papers indicate that FloraGLO
Lutein is more bioavailable than lutein from spinach and greenleafy vegetables and lutein-fortified carrots. Another scientific
paper (4) completes the series of pharmacokinetic studies of
xanthophylls manufactured by DSM Nutritional Products, after
publication of the pharmaco-kinetic properties of OPTISHARP™
(Zeaxanthin) early in the year 2004. "In summary", states
Frappa, "similar to OPTISHARP™ (Zeaxanthin), DSM Lutein
beadlets proved also to be readily bioavailable and did not affect
the concentrations of other carotenoids". "Lutein esters, too,
including Cognis´ Xangold® natural lutein esters, have been
used as the lutein source in many human trials - more than 20
have been published, and there are several trials ongoing",
points out Gartner. Also, several studies have been published
from research that was part of a project funded by the European
Union (AAIR-study), and which used lutein esters as lutein
source. This body of research addressed various questions, but
all the trials have proven the excellent bioavailability of lutein
from lutein esters.
The biokinetics of lutein, irrelevant of the source - foods, free
lutein supplements or lutein ester supplements - resemble those
of carotenoids in general: blood levels start to increase within a
few hours of consuming the lutein source and reach a peak after
12 - 24 hours. When consumed for several days in succession,
blood levels will reach a plateau after 2-3 weeks and decrease to
baseline levels within a few days after consumption is
discontinued. Kinetics in tissues may be quite different. For
example, lutein levels in the retina of the eye increase much
more slowly than in blood - only after some weeks of increased
lutein consumption. It is important both for consumers and
scientists to understand the implications: it needs to be made
clear to consumers that in order to benefit from increased lutein
intake - for example for eye health - consumption needs to be
sustained (preferably daily) over a long period of time. "Just
taking a supplement or eating spinach once in a while won't
work!", states Gartner. Scientists need to allow a long enough
study period if they want to measure effects in the eye, such as
macular pigment density or glare sensitivity: four weeks would be
much too short, three to six months is more likely to be adequate.
Data sheet
Every company declares the values of each carotenoid present
into their formulations on a specific data sheet. For example Fit
Ingredients' Novopure® lutein content is analysed by U.V.
spectrophotometer analysis and zeaxanthin content is reported
according to the formulation in %. "We, in OmniActive Health
Technologies, have taken the lead in declaring the total
xanthophyll values along with levels of the main active ingredient
as its trans-isomer and cis-isomers. Further we also declare the
total Zeaxanthin content in our products", states Mariwala.
"Zeaxanthin is a very important part of the Lyc-O-Lutein", affirms
Nir, "and our data sheets reflect its assay accordingly".
FloraGLO® Lutein by Kemin Health, instead, is a natural source
of both lutein and zeaxanthin. FloraGLO® Lutein provides a
lutein: zeaxanthin ratio similar to that found in green vegetables.
"Our specification sheet for each product always document the
minimum level of lutein as well as of zeaxanthin", explains to us
Maci. "Carotenoid values are reported in our data sheets", says
Becker, "expressed as typical profiles with a guaranteed
minimum, rather than being declared as an exact amount in each
batch". "The concentrate contains small amounts of naturallyoccurring zeaxanthin esters in addition to lutein esters and
undergoes the minimum processing necessary to deliver a top
quality, natural-source product", he concludes. In the Xangold®
15% product, for example, the oil contains not less than 15%
lutein esters and related carotenoid esters according to
spectrophotometric analysis. OPTISHARP™ 5% CWS/S-TG by
DSM Nutritional Products, an animal...it needs to
and allergen-free formulation suitable
be made clear to
for the production of tablets by direct consumers that in order
compression and water-soluble for
to benefit from
fortification of select foods and
increased lutein intake beverages, offers pure zeaxanthin.
for example for eye
"Our zeaxanthin is formulated with the health - consumption
Actilease™ beadlet technology and
needs to be sustained
combines excellent stability with high (preferably daily) over a
absorption. Data are available on
long period of time...
request", states Frappa.
Products of all the companies interviewed comply with the
European legislation for foods. All certificates and compliance
statements (absence of irradiation, GMO, allergen…) are
available upon request.
REFERENCES
1.
2.
3.
4.
5.
6.
7.
Nebeling, L.C., et al., Changes in carotenoid intake in the United
States: the 1987 and 1992 National Health Interview Surveys. J
Am Diet Assoc, 1997. 97(9): p. 991-6.
Breithaupt, D.E., A. Bamedi, and U. Wirt, Carotenol fatty acid
esters: easy substrates for digestive enzymes? Comp Biochem
Physiol B Biochem Mol Biol, 2002. 132(4): p. 721-8.
Granado, F., B. Olmedilla, and I. Blanco, Serum depletion and
bioavailability of lutein in type I diabetic patients. Eur J Nutr,
2002. 41(2): p. 47-53.
Thurmann, P.A., et al., Plasma kinetics of lutein, zeaxanthin, and
3-dehydro-lutein after multiple oral doses of a lutein supplement.
Am J Clin Nutr, 2005. 82(1): p. 88-97.
Molldrem, K.L. and S.A. Tanumihardjo, Lutein supplements are
not bioavailable in the Mongolian gerbil while consuming a diet
with or without cranberries. Int J Vitam Nutr Res, 2004. 74(2): p.
153-60.
van het Hof, K.H., et al., Influence of feeding different
vegetables on plasma levels of carotenoids, folate and vitamin
C. Effect of disruption of the vegetable matrix. Br J Nutr, 1999.
82(3): p. 203-12.
Castenmiller, J.J., et al., The food matrix of spinach is a limiting
factor in determining the bioavailability of beta-carotene and to a
lesser extent of lutein in humans. J Nutr, 1999. 129(2): p. 349-55.