Bioavailability of lutein/zeaxanthin isomers and macular pigment optical density response to macular carotenoid supplementation: A randomized double blind placebo controlled study

Abstract

Abstract
Purpose: To examine the bioavailability of Lutein (L) and Zeaxanthin isomers (Zi) concentrations in serum and changes in MPOD over 12 weeks macular carotenoids supplementation in healthy young subjects.
Methods: In a randomized double blind placebo controlled study, twenty eight (N=28) healthy young male and female volunteers were randomized to receive one of three doses (6 mg L/1 mg Zi, 10 mg L/2 mg Zi or 20 mg L/4 mg Zi) for 12 weeks. Blood samples for serum L/Zi and macular pigment optical density (MPOD) were determined every two weeks over the 12 week study period. Serum lutein and zeaxanthin isomers concentration was determined by HPLC and MPOD by heterochromatic flicker photometry (HFP). The area under the curve (AUC) was calculated using the linear trapezoidal rule. Cmax and tmax was determined over 12 weeks of supplementation.
Results: No significant difference in serum L/Zi concentrations of each dose group at baseline visit. Serum levels of L and Zi increased at 2 weeks, and peaked by 12 weeks. Median serum concentrations of 6 mg L, 10 mg L or 20 mg L groups from baseline to month 3 increased from 0.323 to 1.984 μg/dL (6-fold increase),
from 0.353 to 2.234 μg/dL (7-fold increase), and from 0.372 to 3.163 (10-fold increase), respectively (all P<0.001). Median serum concentrations of 1 mg Zi, 2mg Zi or 4 mg Zi groups from baseline to month 3 increased from 0.060 to 0.377 μg/dL (6-fold increase), from 0.096 to 0.350 μg/dL (4-fold increase), and from
0.117to 0.391 (3.3 fold increase), respectively (all P<0.001). Area under curve (AUC) for serum lutein increased (p<0.01) and AUC for serum Zi increased (p<0.03) with increased dose of L/Zi over placebo. AUCL increased in 6 mg of L & 1 mg Zi by 6 fold, 8 fold in 10 mgL and 2 mg, and 12 fold in 20 mg L and 4 mg Zi over
placebo, respectively. AUCZi increased in all three treatments over placebo by 3 fold, 4 fold and 5 fold, respectively. MPOD increased significantly from baseline to month 3 increased for all L/Zi treatments over placebo. No adverse events were observed with any dose of lutein.
Conclusion: Increasing doses of macular carotenoid supplementation significantly increased the serum AUC levels of lutein and zeaxanthin isomers, and doses up to 20 mg were safely administered. A long-term large clinical trial is necessary to investigate the safety and efficacy of macular carotenoids in health and disease

Full text

Research Article
New Frontiers in Ophthalmology
New Front Ophthalmol, 2016 doi: 10.15761/NFO.1000132 Volume 2(4): 140-145
ISSN: 2397-2092
Bioavailability of lutein/zeaxanthin isomers and macular
pigment optical density response to macular carotenoid
supplementation: A randomized double blind placebo
controlled study
Vijaya Juturu1*, James P Bowman2, Nicole T. Stringham3 and James M. Stringham4
1Omni Active Health Technologies Inc. Morristown NJ 07960, USA
2James P Bowman & Associates LLC, 6409 Roth Ridge Loveland, OH 45140, USA
3Interdisciplinary Neuroscience Program, Biomedical Health Sciences Institute, University of Georgia, Athens, GA 30602 USA
4Nutritional Neuroscience Laboratory, Department of Physiology and Pharmacology, USA
Abstract
Purpose: To examine the bioavailability of Lutein (L) and Zeaxanthin isomers (Zi) concentrations in serum and changes in MPOD over 12 weeks macular
carotenoids supplementation in healthy young subjects.
Methods: In a randomized double blind placebo controlled study, twenty eight (N=28) healthy young male and female volunteers were randomized to receive one of
three doses (6 mg L/1 mg Zi, 10 mg L/2 mg Zi or 20 mg L/4 mg Zi) for 12 weeks. Blood samples for serum L/Zi and macular pigment optical density (MPOD)
were determined every two weeks over the 12 week study period. Serum lutein and zeaxanthin isomers concentration was determined by HPLC and MPOD by
heterochromatic icker photometry (HFP). e area under the curve (AUC) was calculated using the linear trapezoidal rule. Cmax and tmax was determined over 12
weeks of supplementation.
Results: No signicant dierence in serum L/Zi concentrations of each dose group at baseline visit. Serum levels of L and Zi increased at 2 weeks, and peaked by
12 weeks. Median serum concentrations of 6 mg L, 10 mg L or 20 mg L groups from baseline to month 3 increased from 0.323 to 1.984 μg/dL (6-fold increase),
from 0.353 to 2.234 μg/dL (7-fold increase), and from 0.372 to 3.163 (10-fold increase), respectively (all P<0.001). Median serum concentrations of 1 mg Zi, 2
mg Zi or 4 mg Zi groups from baseline to month 3 increased from 0.060 to 0.377 μg/dL (6-fold increase), from 0.096 to 0.350 μg/dL (4-fold increase), and from
0.117to 0.391 (3.3 fold increase), respectively (all P<0.001). Area under curve (AUC) for serum lutein increased (p<0.01) and AUC for serum Zi increased (p<0.03)
with increased dose of L/Zi over placebo. AUCL increased in 6 mg of L & 1 mg Zi by 6 fold, 8 fold in 10 mgL and 2 mg, and 12 fold in 20 mg L and 4 mg Zi over
placebo, respectively. AUCZi increased in all three treatments over placebo by 3 fold, 4 fold and 5 fold, respectively. MPOD increased signicantly from baseline to
month 3 increased for all L/Zi treatments over placebo. No adverse events were observed with any dose of lutein.
Conclusion: Increasing doses of macular carotenoid supplementation signicantly increased the serum AUC levels of lutein and zeaxanthin isomers, and doses up
to 20 mg were safely administered. A long-term large clinical trial is necessary to investigate the safety and ecacy of macular carotenoids in health and disease.
Introduction
Lutein and zeaxanthin are 2 of the most abundant carotenoids
present in the diet, and they are the pigments responsible for the
bright colours of many fruits and vegetables. Lutein and zeaxanthin
are isomers that dier by site of a single double bond [1,2]. Zeaxanthin
exists as 3 stereoisomeric forms; (3R, 3’R)-zeaxanthin and (3R,
3’S)-zeaxanthin (also called meso-zeaxanthin) are the main forms
present in the macula of the retina, while small amounts of (3S,
3’S)-zeaxanthin have also been detected [3,4]. Humans are unable
to synthesize lutein and zeaxanthin isomers; thus, these nutrients
are obtained from natural dietary sources or from supplementation.
Circulating and tissue levels of xanthophylls increase with
supplementation with lutein/zeaxanthin [5,6]. However, variability in
their bioavailability has been reported [7-9], andhas been relatedto
factors such as the matrix of the formulation (e.g., presence of fat), the
form in which theywere administered(i.e., freeversus esteried) and
Correspondence to: Vijaya Juturu, Ph.D., F.A.C.N. Director (Global) Scientic
and Clinical Aairs, OmniActive Health Technologies, 67 East Park Place, Suite
500, Morristown, NJ07950, USA, E-mail: v.juturu@omniactives.com
Key words: lutein, zeaxanthin isomers, bioavailability, area under curve
Received: April 16, 2016; Accepted: May 10, 2016; Published: May 13, 2016
interactions with other nutrients [10,11]. Supplementation with lutein
and zeaxanthin [i.e., (3R,3’R)-zeaxanthin and meso-zeaxanthin] is
generally consideredto besafe [12].
Epidemiological data indicate that the average intake of lutein
and zeaxanthin from dietary sources is in the range of 1 to 2 mg/day
(approximately 0.01 to 0.03 mg/kg body weight/day), corresponding
serum concentrations of approximately 0.4 µmol/L have been
measured [10,13,14]. Supplementation with lutein/zeaxanthin has
been shown to increase levels in the blood and tissues where these

Juturu V (2016) Bioavailability of lutein/zeaxanthin isomers and macular pigment optical density response to macular carotenoid supplementation: A randomized
double blind placebo controlled study
New Front Ophthalmol, 2016 doi: 10.15761/NFO.1000132 Volume 2(4): 140-145
xanthophylls are selectively deposited (such as the macula lutea of the
retina) [15,16]. However, considerable inter-individual variability in
serum concentrations and macular pigment density has been reported
following supplementation with lutein/zeaxanthin [17]. Some of the
factors that may contribute to this variation include those that aect
the absorption of xanthophylls, such as the matrix of the formulation,
the form in which they were administered (i.e., free versus esteried).
Lutein occurs as a single stereoisomer [(3R,3’R,6’R)-β,ε-carotene-3,3’-
diol] while zeaxanthin occurs as a mixture of stereoisomers, with the
2 most prominent forms in the macula of the retina being (3R,3’R)-
β,β-carotene-3,3’-diol (referred to as zeaxanthin) and (3R,3’S)-β,β-
carotene-3,3’-diol (referred to as mesozeaxanthin). e physical and
chemical properties of lutein and zeaxanthin isomers are summarized
in Figure 1. Most of the studies are single dose studies [7,18,19]
and a multiple-dose pharmokinetis (PK) study [20] reported in the
literature.e present study was designed to compare, in human
subjects, the bioavailability of lutein and zeaxanthin isomers when
ingested at dierent doses compared with placebo and to study the
changes in MPOD by macular carotenoid dose over three months
supplementation(Figure 2).
Subjects and methods
Twenty eight (28) volunteers participated in this
study recruited from the University of Georgia population in
accordance with the IRB guidelines. is study was reviewed and
approved by the University of Georgia Institutional Review Board.
Informed consent was obtained for each subject, and the study
adhered to the tenets of the Declaration of Helsinki.is study
isregisteredatISRCTN#54990825.Subjects were randomly assigned
to one of four groups: Placebo (Group I, saower oil, N=5),6mgL/1
mgZi(Group II, n = 7), 10 mg L/2 mgZi(Group III, n = 8), or 20 mg
L/4 mgZi(Group IV, n = 8).Identical looking capsules containing only
saower oilwas usedas a placebo.Lutemax 2020 (L/Zi) at dierent
doses (6 mg L/1mg Zi; 10 mg L/2 mg Zi,; 20 mgL/4 mg Zi) and
placebos supplied byOmniActiveHealth Technologies Ltd., Mumbai,
India.Subjectsinstructedto take one capsule per day with a mealfor12
weeks but otherwise to follow their normal diet. Compliance was
ensuredwith weekly phone calls and subjects were requested to return
bottles to count le over pills in the bottle.
Subjects’ anthropometric measurements, health habits and medical
history recordedduring their screening visit. Normal healthy subjects
and no history of smoking includedin the study. Subjects with chronic
conditions excluded such as prescriptions or surgical treatments.
Pregnancy and lactating women and subjects with a BMI higher than
27 and took supplements containing any of the carotenoidsexcluded.
Subjects were instructedtokeep uptheir current diet and not to change
their diet during the study period. In consideration ofMPODtesting,
all subjects had uncorrected or contact lens-corrected visual
acuity of 20/20 or better in the test (right) eye, and had no current
orearlierhistory of ocular pathology.
Subjects were instructed to visit the laboratory every 2 weeks for
blood draws and vision testing. Fasting blood draw samples were
collected to assess serum L/Zi and Macular pigment measurement was
assessed for each subject.
Serum analysis
Serum concentrations of lutein and zeaxanthin isomers were
obtained by HPLC according to a method described in detail [21].
Samples were taken at baseline and every 2 weeks over the 12-week
study period.
Detection wavelengths were λ = 447 nm (lutein) and 450 nm
(zeaxanthin isomers).
Measurement of macular pigment optical density (MPOD)
MPOD in the central retina was assessed with a non-invasive,
perceptual task called customized heterochromatic icker photometry
Figure 1. Molecular Structures of Lutein and Zeaxanthin Isomers.
1.24
7.235
10.03
14.28
P 6mg 10mg 20mg
P 1mg 2mg 4mg
0.46
1.25
1.84
2.18
2.5
1
1.5
1
0.5
0
16
14
12
10
8
6
4
2
0
2A. AUC
L
2B. AUCZi
P<0.0259
P<0.0081
Dose
Dose
µg/ml µg/ml
Figure 2. A and 2 B Lutein and zeaxanthin isomers bioavailability measured by AUC (µg/
mL) over 12 weeks of supplementation.

Juturu V (2016) Bioavailability of lutein/zeaxanthin isomers and macular pigment optical density response to macular carotenoid supplementation: A randomized
double blind placebo controlled study
New Front Ophthalmol, 2016 doi: 10.15761/NFO.1000132 Volume 2(4): 140-145
[22]. A densitometer (Macular Metrics Corp., Rehoboth, MA) described
by Wooten et al.[23] was used for this purpose.e densitometer,
detailed measurement procedures, and the principle of HFP have been
fully described in earlier publications [23].Measurements were taken at
baseline and every 2 weeks over the 12 week study period.We obtained
spatial proles of MPOD at each visit, with measures at 10’, 20’, 30’,
1.75 degrees, and 2.75 degrees of retinal eccentricity.
e primary study endpoint was the 12 week area under the curve
for plasma lutein (AUC). Secondary endpoints included the maximum
concentration (Cmax), the time at which the maximum concentration
was observed for plasma lutein (Tmax) and Cmax, and Tmaxwas also
calculated for zeaxanthin. e area under the curve was calculated
using the linear trapezoidal rule. In order to meet the assumption of
normality, statistics on AUC andCmaxwere based on log transformed
values for individual subjects
Statistical analysis
Descriptive statistics (mean and standard deviation) were reported.
One-way and repeated-measures analysis of variance, curve tting,
and correlational analyses were conducted. All statistical analyses
performed with SAS (NC). Tukey-Kramer adjustedPvalues were used
to nd where the post hoc dierences occurred within statistically
signicant interaction or main eects, with signicance set atP<0.05.
Multiple models comparing group dierences analyzed (raw values at
all time points, raw values adjusted for baseline, and change scores).
Statistical signicance determined at p<=0.05 level.Interaction and
main eects were considered statistically signicant at P<0.05 and
trends atP<0.1.
Results
Baseline characteristics
Table 1 provides baseline characteristics of the study. No signicant
dierence was found in any of the groups.
Lutein bioavailability
e mean serum plasma and AUCL concentrations were
signicantly higher (p<0.001) compared to placebo. Highly signicant
dierence in AUCLwas observed between Group I (placebo) and Group
IV (20 mg L, p<0.001) followed by group III (10 mg L, p<0.019) and
a trend of signicant dierence in AUCL between Group I (placebo)
and Group II (6 mgL, p<0.1) was observed. ere was a signicant
dierence between Group II (6 mg L and 20 mg) and Group IV over 12
week period (p<0.03) (Table 2).
Between treatment analysis of covariance, signicant dierences
were observed between Group I and II (placebo vs. 6 mg L, p<0.0494),
Group I and Group III (placebo vs. 10 mg L, p<0.034) and Group I and
Group IV (placebo vs. 20 mgL, p<0.0002). Signicant dierence in Cmax
was observed between Group I and Group IV (p<0.015) and Group
III and Group IV (10 mg L vs. 20 mg, p<0.023,Table 3). e time to
reach maximum concentration (Tmax) for lutein was not signicantly
dierent fortreatments.
Zeaxanthin isomers bioavailability
Highly signicant dierence in AUCZiwas observed between
placebo and Group IV (4 mg Zi, p<0.005) followed by group III (2
mg Zi, p<0.02) and a trend of signicant dierence in AUCZi between
Group I and Group II (placebo and 6 mg L, p<0.1) observed. ere was
a trend of signicant dierence between Group I and IV (6 mg L and
20 mgL) over 12 week period (p<0.07).
Between treatment analysis of covariance, signicant dierence
between Group I and II (placebo vs.1 mg Zi, p<0.0541), Group I and
Group III (placebo vs. 2mg Zi, p<0.0114) and Group I and Group IV
(placebo vs. 4 mg Zi, p<0.0005) was observed. Signicant dierence in
Cmax was observed between Group I and Group IV (p<0.0363, Table
3) and no signicance in other groups was observed. e time to reach
maximum concentration (Tmax) for Zi was not signicantly dierent
fortreatments.
Change in MPOD
MPOD responses were detected at 4 weeks in Group II and Group
III (NS) at the standard, 30’ retinal locus followed by a signicant
change in MPOD in Group II at 12 weeks. A non-signicant change
in MPOD was observed in Group III and IV at week 6. Signicant
change in MPOD was observed in Group III and IV at week 8 to week
12 (p<0.001). No signicant dierence between Group III and IV were
observed.
Discussion
In several conducted studies where lutein preparations were
repeatedly administered at doses ranging from 4 to 20 mg/day for up
to 20 weeks, plasma concentrations of lutein increased by 3- to 8-fold
compared to controls or baseline, with levels back to baseline by 3 to
4 weeks following cessation of treatment [9,24-26]). is is our rst
Variables Group I, Placebo Group II, 6 mgL/1 mg Zi Group III,
10 mg L/2 mg Zi
Group IV,
20 mg L/4 mg Zi
Age,y 21.4 ± 2.07 20.0 ± 1.195 20.63 ± 0.92 21.56 ± 3.20
BMI, kg/m226.2 ± 1.5 19.7 ± 0.50 21.54 ± 2.63 21.53 ± 3.33
Males/Females 3M/2 F 3M/5F 3M/5F 3M/5F
Smokers None None None None
Table 1. Baseline characteristics.
Baseline Week 2 Week 4 Week 6 Week 8 Week 10 Week 12
Group I, Placebo 0.44 ± 0.29 0.45 ± 0.27 0.48 ± 0.33 0.48 ± 0.34 0.54 ± 0.40 0.49± 0.33 0.47 ± 0.29
Group II, 6 mgL/1 mg Zi 0.73 ± 0.15 0.75 ± 0.11 0.75 ± 0.12 0.79 ± 0.10 0.81 ± 0.13 0.82± 0.14 0.82 ± 0.11
Group III, 10 mgL/2 mg Zi 0.42 ± 0.25 0.45 ± 0.24 0.49 ± 0.26 0.51 ± 0.29 0.54 ± 0.33 0.54± 0.31 0.56 ± 0.31
Group IV, 20 mgL/4 mg Zi 0.43 ± 0.15 0.45 ± 0.15 0.48 ± 0.16 0.48 ± 0.18 0.50 ± 0.19 0.57± 0.17 0.55 ± 0.17
MPOD: Macular Pigment Optical Density; OD: Optical Density
Table 2. MPOD (OD Units) Response by Week and Dose (Mean ± SD).

Juturu V (2016) Bioavailability of lutein/zeaxanthin isomers and macular pigment optical density response to macular carotenoid supplementation: A randomized
double blind placebo controlled study
New Front Ophthalmol, 2016 doi: 10.15761/NFO.1000132 Volume 2(4): 140-145
attempt to study the concentrations of L/Zi in serum at dierent doses
for a period of 12 weeks to see consistent increase of serum levels of
macular carotenoids and MPOD response for each dose. L/Zi capsules
are a concentrate containing at least 80% carotenoids, with a minimum
of 63.75% lutein and 11.25% zeaxanthin isomers in the free form.
(3R,3’R)- zeaxanthin and (3R,3’S)-zeaxanthin (i.e.,meso-zeaxanthin)
are present at a ratio of approximately 50:50, and batch analytical data
suggest the ratio of these 2 isomers may vary between 40:60 to 60:40.
In general, the ratio of lutein to zeaxanthin in natural dietary sources
is about 5:1 [27].
In a study where volunteers (4/sex/group) were administered
capsules containing crystalline lutein (4 to 20 mg) plus zeaxanthin
(0.34 to 1.7 mg) for 42 days and monitored further for 25 days, steady
state concentrations of lutein and zeaxanthin were reached between
days 38 to 43, and the elimination half-life was determined to be 5 to
7 days for both compounds [28]. In this study, greater the dose of L/Zi
greater the response in serum macular carotenoids. Increase in serum
levels of L and Zi are consistent with the dose. At week 12 the higher
dose appears to plateau. ese results suggest the macular carotenoids
are being taken up by the tissues. Hence we saw signicance in change
in MPOD at 12 weeks in all doses. ese results suggestthe presence
ofa strikingtreatmenteectwhere relative to placebo,greater Lutein
and Zeaxanthin isomer bioavailability was observed in one or more
of the active treatments.Because these dierences were observed at
a statistically signicant level in a study of modest sample size, the
strength of the treatment eect and the potential clinical importance of
these ndingsare underscored.Further studies are required to explore
further in a large population.
e pharmacokinetics of lutein in humans was assessed in two
studies utilising [14C] and [13C] labelled lutein from spinach and
kale, respectively [29,30]. e 14C-lutein concentrations reached its
peak (Cmax) of 2.08% of dose/L at 14 hours aer administration with
a calculated half-life of approximately 10 days [29].e primary route
of elimination was through faeces, which accounted for 45% of the
eliminated lutein, whereas, 10% of the lutein was eliminated in the
urine within the rst 2 days. In the study by Novotny et al.[30], the
mean AUC over 28 days was calculated to be 42.8 µM x h, with the
Cmax containing 3.6% of the administered dose. is study attempted to
see the changes of AUC L/Zi over 12 weeks. Maximum concentrations
(Cmax) were determined based on the concentrations of L and Zi from
individual data sets(Table 3). Ocular tissues, particularly the retina,
selectively retain high concentrations of lutein and zeaxanthin [31,32].
e levels of these xanthophylls are up to 1,000-fold higher than in
other tissues, and other carotenoids are only present in trace amounts
[31,32]. In studies where lutein (extracted from marigold petals)
administered as either the free or esteried form for durations ranging
from 12 to 42 weeks, an accumulation of lutein in the macula was
observed, as demonstrated by the increase in macular pigment density
[33-35]. Carotenoids have also been found in variable amounts in other
tissues in humans, including the kidneys, buccal mucosal cells, adrenal
glands, adipose tissue and liver [6,36].
Several clinical trials have compared bioavailability of free lutein/
zeaxanthinversus their esteried forms, though the results from these
studies been mixed. Norkus et al. [37] reported bioavailability of free
lutein greater than esteried lutein.Seventy-two healthy volunteers
administered capsules containing free lutein (12.2 mg) or lutein esters
(equivalent to 13.5 mg free lutein) for 28 days. e test articles formulated
as beadlets in identical hard-shell capsules, and administered with a
standard breakfast cereal and an 8 oz. serving of 2% cow milk.Subjects
administered the formulation containing free lutein had signicantly
greater changes in serum lutein levels, and a signicantly higher AUC
(by 17%), compared to those consuming esteried lutein.In addition,
regression modelling indicated that the form of lutein (i.e., free
versusesteried) remains a signicant contributing factor to the serum
lutein response, even aer controlling for factors including age, gender,
body mass index, and serum lipids.In this study, AUC increased as the
dose increased over placebo. AUCL increased 6 folds higher in Group II
over placebo (Group I), 8 folds higher Group III and 12 folds higher in
Group III over placebo (allP<0.01). AUCZiincreased by 3, 4 and 5 folds
inGroup II, III and IV over Group I (allP<0.05). e dierence isdue
to dierential spatial accumulation of lutein relative to zeaxanthin may
be relevant to retinal health.
Conversely, no signicant dierences in serum lutein levels were
reported following supplementation with free lutein (6.0 mg) or
esterified lutein (5.5 mg of free lutein) for 9 days in a cross-over
study with 10 healthy males [11]. In this study, both formulations
were provided as crystalline suspensions in oil in so gel capsules and
administered with a test meal. In another cross-over study, subjects
administered a single dose of a formulation containing unesteried
lutein or lutein diesters (0.5 and 0.67 µmol lutein/kg body weight
in 10 and 8 subjects, respectively), along with a test meal [38].
Supplementation with lutein diesters produced a signicantly higher
maximum serum concentration of lutein and a higher mean AUC (by
61.6%), compared to supplementation with free lutein.It should be
noted, though, that dierent formulations were used for the test articles,
with free lutein administered as a crystalline oil suspension in so gel
capsules, whereas esteried lutein was administered as a powder in
hard gel capsules.As such, the interpretation of these ndings is unclear
as they may have been confounded by dierences in formulation
dissolution.In the current study, median serum concentrations of6 L,
10 mg L or 20 mg L groups from baseline to month 3 increased from
0.323 to 1.984 μg/dL (6-fold increase), from 0.353 to 2.234 μg/dL (7-
fold increase), and from 0.372 to3.163 (10-fold increase), respectively
(allP<0.001). Median serum concentrations of1mg Zi, 2 mg Zi or 4 mg
Zi groups from baseline to month 3 increased from 0.060 to 0.377 μg/
dL (6-fold increase), from 0.096 to 0.350 μg/dL (4-fold increase), and
from 0.117 to 0.391 (3.3 fold increase), respectively (allP<0.001).
e bioavailability of esteried versus free zeaxanthin has also
been evaluated in 1 study where a single dose of esteried or free
3R,3’R-zeaxanthin (5mg) was administered to 12 healthy volunteers
in a cross-over study design [39]. Both test articles were suspended in
sunower oil and mixed with a yogurt which was consumed along with
a standardized breakfast. Supplementation with 3R,3’R-zeaxanthin
Groups BL (Before
supplementation)
After Supplementation
Cmax Cmax
Serum Lutein, µg/mL (Mean ± SD)
Group I, Placebo 0.343 ± 0.154 0.539 ± 0.113
Group II, 6 mgL/1 mg Zi 0.359 ± 0.281 2.353 ± 0.609
Group III, 10 mgL/2 mg Zi 0.388 ± 0.177 2.509 ± 0.634
Group IV, 20 mgL/4 mg Zi 0.817 ± 1.379 4.374 ± 2.774
Serum Zi, µg/mL (Mean ± SD)
Group I, Placebo 0.141 ± 0.062 0.189 ± 0.056
Group II, 6 mgL/1 mg Zi 0.087 ± 0.064 0.406 ± 0.078
Group III, 10 mgL/2mg Zi 0.101 ± 0.026 0.482 ± 0.132
Group IV, 20 mgL/4mg Zi 0.193 ± 0.212 0.614 ± 0.318
BL: Baseline; CMax: Maximum concentration; L: Lutein; Zi: Zeaxanthin isomers
Table 3. Maximum Concentrations (CMax) for L and Zi in different groups (Mean ± SD).

Juturu V (2016) Bioavailability of lutein/zeaxanthin isomers and macular pigment optical density response to macular carotenoid supplementation: A randomized
double blind placebo controlled study
New Front Ophthalmol, 2016 doi: 10.15761/NFO.1000132 Volume 2(4): 140-145
palmitate (esteried) produced approximately 2-fold higher AUC
values compared to supplementation with free 3R, 3’R-zeaxanthin
(p<0.05). Supplementation with L/Zi (free) had higher AUC values
and very quick response and MPOD also detectable at 4 weeks but
signicance observed at 8 to 12 weeks.
e role of lutein and zeaxanthin in eye health has been further
supported by some epidemiological studies reporting an inverse
relationship between lutein/zeaxanthin intake and eye disease,
particularly AMD and cataracts [16,40-44]. Several controlled
intervention studies have also indicated that macular pigment density
or dietary supplementation with lutein improves parameters of visual
function, such as visual acuity [45,46], glare recovery, and contrast
sensitivity [26,45,47-49]. A number of clinical studies have evaluated
the pharmacokinetic properties of lutein and zeaxanthin.Overall,
an increased intake of lutein and zeaxanthin, either through natural
dietary sources or supplementation, produces corresponding increases
in levels of these carotenoids in systemic circulation.
Acknowledgements
We wish to thank the volunteers who participated in this study for
their willingness and diligence in complying with the protocol. e
study was sponsored by OmniActive Health Technologies Ltd, India.
Conict of interest
VJ is an employee of OmniActive Health Technologies.
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