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Exploring the role of
Lutein in maternal and
infant health
IMG-KI-00508
Seminar – Nutrition for Maternal and Infant Health
November 21st 2018
Filipa Quintela
Technical Services Associate | Pharm.D.
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Overview Diet recommendations and Lutein/Zeaxanthin intake
Role of Lutein during pregnancy, infancy and childhood
The science on Lutein for prenatal and infants
FloraGLO Lutein’s unique position
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Lutein & Zeaxanthin and the Macular Pigment
Macular Pigment (MP) – Comprised of L, Z
and meso-zeaxanthin (MZ)1-5
• While L and Z are exclusively of dietary origin,
MZ originates from the conversion of L
exclusively in the macula
• The macula lutea has the highest
concentration of carotenoids in the human
body: 0,1- 1mM
• Active uptake mediated by specific
xanthophylls-binding proteinso GSTP1 – Zeaxanthin and Meso-zeaxanthin
o StARD3 – Lutein
1. Krinsky et al. Annu Rev. Nutr 2003,23:171-201; 2, Johnson et al. Inves Ophthalmol Vis Sci 2005;46(2):692-702
3, Bernstein et al Vision Res.2010;50:716-728 Oct 23; 4, Neuringer M., et al IOVS 2004; 45(9):3234-3243;
5, Shyam e al. Proc. Natl Acad Sci USA.2017Oct 10;114/41):10882-10887
Lutein (L) and zeaxanthin (Z) are carotenoids that the body naturally and
selectively deposits in the macula of the eye to create a protective layer known
as MACULAR PIGMENT.
Photomicrograph under license from Dr. Max Snodderly
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How well do we eat?
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Global Diet Recommendations: UK, WHO, Singapore
1. National Health Service, UK.
2. Healthy diet, World Health Organization Fact sheet N°394, updated September 2015
3. Singapore Heart Foundation, http://www.myheart.org.sg/article/a-heart-healthy-lifestyle/diet-and-nutrition/the-healthy-diet-pyramid/214
Image adapted from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/528193/Eatwell_guide_colour.pdf
UK: Five fruit and vegetables per day1
World Health Organization:
Eat at least 400 g, or 5 portions,
of fruits and vegetables per day2
Singapore Heart Foundation
servings per day3
Food Group Children Adolescents
Fruits &
Vegetables*
2+2 (of
each type)
2+2
*Vegetable = leafy vegetables as well as
non-leafy, cruciferous, or root vegetables
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Children Eat Few Dark Green Vegetables
Source: (1) What We Eat in America, NHANES 2013-2014, individuals 2 years and over (excluding breast-fed children), day 1 dietary intake data, weighted. Food Patterns Equivalents
Database (FPED) 2013-2014. https://www.ars.usda.gov/ARSUserFiles/80400530/pdf/fped/Table_1_FPED_GEN_1314.pdf
(2) Source EU data: https://ec.europa.eu/jrc/en/health-knowledge-gateway/promotion-prevention/nutrition/fruit-vegetables#ftna
National Nutrient Database for Standard Reference Release 28 slightly revised May, 2016 SHUTTERSTOCK: 139259597, 279924581
Average Intake of Food Group (g/day)
Dark Green Vegetables in US1
Age (y) Boys
2 to 5 14
6 to 11 11
12 to 19 16
Age (y) Girls
2 to 5 9
6 to 11 14
12 to 19 23
Mean children intake (g/day)
36 months up to 9 years of age2
EU country Vegetables Fruits intake
France 84 89
Spain 64 104
UK 59 102
Germany 82 124
Italy 142 129
“EU citizens fail to consume the recommended 400
grams a day of Fruits and Vegetables.”2
Indicates an estimate with a relative standard error
greater than 30. Grams calculated considering 1 cup of
cooked vegetables equivalent to 225 grams
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• Children eat less than 1 mg lutein from diet.
• Greater lutein intake with age.
• Younger woman have lower Lutein intake than older one.
U.S. Lutein Intake (mg/d)
Johnson et al. J Am Diet Assoc 2010;110(9):1357-62
Lutein
mg
/day
Lutein
mg
/day
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Diet Recommendations and Status
• Worldwide recommendation for vegetables consistently 2 servings per day.
• Dietary intake is below recommendations in EU countries for children.
• American children eat less than 1 mg lutein and 0.1 mg or less zeaxanthin from diet per day.
• Dietary supplementation is a viable option to fill the gap in addition to nutritional recommendation.
Sources: Johnson et al. J Am Diet Assoc 2010;110(9):1357-62, Mean Amounts of Food Patterns Cup Equivalents Consumed per Individual, by Gender and
Age, in the United States, 2013-2014. https://www.ars.usda.gov/ARSUserFiles/80400530/pdf/fped/Table_1_FPED_GEN_1314.pdf
Shutterstock: 289525484
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Role of Lutein in
Pregnancy, Infancy and Childhood
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Lutein and Zeaxanthin Deposit in Critical Locations
1.Oostenbrug GS, et al. Br J Nutr 80:67-73, 1998.; 2.Kiely M, et al. Eur J Clin Nutr 53: 711-715, 1999; 3.Yeum KJ, et al. J Am Coll Nutr 17: 442-447, 1998; 4. Yamini S, et al. Eur J Clin
Nutr 55: 252-259, 2001; 5. Sherry C, et al. J Nutr. 144: 1256-1263, 2014; 6. Zielinska Nutrients. 2017 Aug 4;9(8) 7. Vishwanathan R. et al. J Pediatr Gastroenterol Nutr. 2014; 8.Bone
RA, et al Invest Ophthalmol Vis Sci 29: 843-849, 1988; 9. Johnson E. Nutr Rev. 2014 Sep;72(9):605-12
Shutterstock 685908817; 567102439; 164818436
Mother ↑ plasma L/Z during 2nd & 3rd trimester1
L/Z are present in cord blood1-3
L in maternal plasma persists in postpartum 1-2,4
Breast milk lutein is dependent on maternal intake5,6
L in plasma & breast milk decreases during lactation5,6
Child L/Z are deposited in specific areas of the baby’s body.6-8
High in polyunsaturated fatty acids9
High metabolic activity9Eye Brain
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(1) Patton S, et al. Lipids 25: 159-165, 1990. (2)Khachik F, et
al. Anal Chem 69: 1873-1881, 1997. (3)Schweigert FJ, et al.
Eur J Nutr, 43(1): p. 39-44, 2004. (4)Cena, H., et al. Public
Health Nutr, 12(10): p. 1878-84 ; (5)Sherry et al., Journal
Nutr. 2014. . First published ahead of print June 4, 2014 as
doi: 10.3945/jn.114.19 Shutterstock: 249288211
Lutein is a major carotenoid in colostrum and breast milk.1,2
Lutein levels in mom’s blood and
breastmilk decreases during
breast feeding.3,5
Lutein concentrations in
breast milk are proportional
to maternal intake.4
Lutein is 2 to 3 times
more concentrated than
β-carotene in breast milk.2
Nature Provides Lutein and Zeaxanthin
The colostrum is heavily
fortified with critical
antibodies, proteins, L & Z.
The yellow of colostrum is
due to the high
concentration of carotenoids.1
Nature puts L & Z in the colostrum
to help deliver an initial boost of
protection that the baby needs for
healthy development.
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Eye Development
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Early Need for Lutein and Zeaxanthin
(1) Bone RA, et al. Invest Ophthalmol Vis Sci 29: 843-849, 1988. (2) Handelman GJ, et al. Invest Ophthalmol Vis Sci 29: 850-855, 1988.
(3) Hendrickson (2016) Am J Ophthalmol. 2016 Jan;161:29-35.e1.
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Lutein is present in the
fetal retina.1,2
17 to 22 weeks of
gestation
Cone cells gradually become predominant in the
fovea resulting in improved visual acuity.2
The outer plexiform layer becomes discernible
within the retina (layer that contains the highest
concentration of L & Z).3
First 16 weeks of life
The photoreceptors have
reached near-adult lengths and
the outer plexiform layer is fully
formed and visual acuity is
approaching adult levels.2
By 4 years of age
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Infant Versus Adult Eye
In infants
L & Z concentration in the fovea
increase during childhood1,2
Lutein is the dominant
carotenoid in infant retina
Premature infants have undetectable MP
In adults
ratio of L to Z in
the central macula
are approximately
equivalent.1
The changes in L/Z ratio in the macula appear to be closely
related to steps in anatomical development.1,2
(1) Bone RA, et al. Invest Ophthalmol Vis Sci 29: 843-849, 1988. (2) Berstein PS et al. IOVS;54:4034-4040, 2013 Shutterstock: 153205802
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Why are children particularly susceptible?
1.Hammomd BR. Nutr Rev. 66(12):695-702, 2008; 2. Quigley et al, Invest Ophthalmol Vis Sci. 2018 Aug 1;59 3.Abramov I, et al. Science, 217:265-7, 1982. (SA-09-04489)
4. Wing GL et al. IOVS.17:601-607, 1978 5.Bone RA, et al. Invest Ophthalmol Vis Sci 29: 843-849, 1988. 6. Hendrickson et al, Ophthalmology. 1984 Jun;91(6):603-12; 7. Zielinska
Nutrients. 2017 Aug 4;9(8); (8) Hendrickon et al, Ophthalmology. 1984 Jun;91(6):603-12 Images Adapted from SCENIHR Health Effects of Artificial Light, European Commission,
2012
Orbital Size The size and length of the eye is smaller in
infant1
Increases significantly during the first 4 to 6y1
Increased retinal light dose2
Lens Infant lens is transparent to light1
More susceptible to UVA and blue light
damage1
FoveaPoorly developed and nonfunctional at birth1,3-5
Immature cone receptors, maturity of the fovea
but the third to forth postnatal year 5,8
Cone density increases 80% from birth to 4-5y1
Rapid changing area, maturation in the first 4y6
Increased metabolic activity →Oxidative stress7
Accumulation of lipofuscin in the first years4
Blue Visible >500nm
Absorption
Transm
itted
Adult
60-70y
Blue Visible >500nm
Child
<9y Absorption
Transm
itted
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Brain Development
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Preferential Uptake of Lutein into the
Infant Brain
Department of Health and Human Services. CDC. Vital and Health Statistics, Series 11, Number 245. July 2002
Vishwanathan R, et al., J Pediatr Gastroenterol Nutr 2014, 59(5):659-665.
Reviewed in Maci S. at al. Nutrafoods 2016. 3:179-188
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Study Participants Key Findings
56 preadolescent (8-9y)Retinal L and Z, measured as MPOD, is positively related to academic
achievement, mathematics and written language in children
40 preadolescent (7-10y)
MPOD positively and significantly predicted hippocampal-dependent
memory performance
MPOD positively and significantly associated with a spatial
reconstruction task designed to assess hippocampal-dependent
relational memory performance
51 healthy children (49%
female) from 7 – 13y
Link between higher carotenoid status and improved cognitive
functioning
MPOD was significantly correlated to:
• Global Intelligence (p<0.05)
• Executive Processes (p<0.05)
• Spatial Relations subtest (p=0.035)
• Approached significance in Cognitive Efficiency (p=0.074)
Lutein and Cognitive PerformanceKey Findings Children
Shutterstock:
MPOD – Macular pigment optical density
L, Z – Lutein and Zeaxanthin
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Lutein & ZeaxanthinKey Findings - Children
Lutein is the predominant carotenoid in infant brain1
Preterm infants have decreased concentrations of brain carotenoids1
Higher carotenoid status linked to improved cognitive functioning in preadolescent children2
L and Choline work together in support of infant brain development and subsequent cognitive development3
Intake of L by the mother prior to conception along with folate may help reduce risk of neural tube defect-affected pregnancies4
L is concentrated in regions important for learning and memory (FC, HIP, OC), and is correlated with fatty acids, phospholipids and amino acid neurotransmitters in the brain5
Associations between MPOD, and cognitive performance6, memory7
and academic achievement8
Vishwanathan R. et al. J Pediatr Gastroenterol Nutr. 2014
2. Saint et al. Nutrients. 2018 Feb 10;10(2). pii: E193. doi:10.3390/nu10020193.
Cheatham et al. Nutrients 2015, 7 9079-9095.
4, haw GM, et al. Epidemiol. 10:711-716, 1999.
Lieblein-Boff et al. PloS ONE 2015, 10 e0136904
6. Walk A et al., childhood International Journal of Psychophysiology 118 (2017) 1–8
7. Hassevoort K et al J Pediatr. 2017 Apr;183:108-11
8. Barnett S et al., 2017 Nutritional Neuroscience.
FC – Frontal Cortex
HIP - Hippocampus
OC – Occipital Cortex
L – Lutein
MPOD – Macular Pigment Optical Density
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Mechanisms of Action Lutein and Zeaxanthin
Increases visual
processing speed
and vision under
dim light3-5
May increase the
speed with which
messages are
transmitted across
neurons1,2
1. Gruszecki WI, Carotenoids in Health and Disease. New York: Marcel Dekker, Inc. 151-163, 2004. 2. Stahl W, Biofactors, 15:95-98, 2001. 3. Hammond BR, et al., Ophthalmic
Physiol Opt. 25:315-9, 2005. 4. Renzi LM, et al. Ophthalmic Physiol Opt. 30:351-7, 2010. 5. Renzi LM, et al. Exp Eye Res, 91:896-900, 2010. 6. Mares J. Lutein and Zeaxanthin
Isomers in Eye Health and Disease Annu Rev Nutr. 2016 Jul 17; 36: 571–602; Photos: IMG-KH-00044 (eye) and shutterstock_312413090 (brain).
Antioxidant and anti-
inflammatory
properties6
Lutein integrates into cellular membranes into specific
directions, likely influencing the functional properties of
synaptic membranes.1
Enhances gap junction communication2
• Light processing in the retina
• Helps improve reaction time and
processing of rapidly moving
objects
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Clinical Studies - Sherry C, et al.
Sherry C, et al. J Nutr. 144: 1256-1263, 2014.
Effects of FloraGLO Lutein supplementation in lactating women1
• 82 breastfeeding women, 4-6 weeks postpartum
• 6 week supplementation of placebo, 6 mg or 12 mg FloraGLO Lutein
• Assessed maternal plasma, maternal breast milk, infant plasma
• Total lycopene was the most abundant in maternal plasma.
• Total L + Z was most abundant carotenoid in breast milk.
• Infant plasma carotenoids most closely matched that of breast milk.
Ba
se
lin
e v
alu
es
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Clinical Studies - Sherry C, et al.
FloraGLO Lutein Supplementation increases the amounts of L & Z in
bloodstream and breast milk of healthy pregnant women.
* p < 0.05 compared to baseline., ** p < 0.0001 compared to baseline, • p < 0.05 between treatments.
Results :
• Total L + Z significantly increased with both lutein dosages compared to baseline in
maternal plasma and in breast milk.
• At 6 weeks the change in total L + Z concentration was significant between groups for the
12 mg/day dosage for both maternal plasma and breast milk.
Sherry C, et al. J Nutr. 144: 1256-1263, 2014.
To
tal L
+ Z
in
Mate
rnal P
lasm
a
( mg
/dL
)
Baseline 6 Weeks Change
-10
0
10
20
30
40
50
60
**
**
**
**#
#
To
tal L
+ Z
in
Bre
ast
Milk
( mg
/dL
)
Baseline 6 Weeks Change
-4
-2
0
2
4
6
8
10
12
14
16
18
Placebo
6 mg Lutein Per Day
12 mg Lutein Per Day
**
**
**
*
#
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• Increase in total L+Z concentration in infant plasma
o 180% and 330% greater concentrations for the
low and high dose, respectively, at the end of
the study vs the placebo group (p < 0.05)
• No differences in other non lutein carotenoids in
infant plasma
• Breast milk total L+Z was significantly correlated with
both maternal and infant plasma at the end of the
study
o r = 0.74 and r = 0.81, respectively p<0.0001 for
both
• Maternal and infant plasma total L+Z were also
significantly correlated (r =0.82, p < 0.0001).
Sherry C, et al. results - Effect of Supplementation in Infants
Sherry et al., Journal Nutr. 2014. . First published ahead of print June 4, 2014 as doi: 10.3945/jn.114.19
0
10
20
30
40
50
60
Placebo Low Dose (6mgL/Day)
High Dose(12mg L/Day)
To
tal L
+Z
in in
fan
t p
lasm
a (µ
g/d
L)
6 weeks after maternal lutein supplementation
*
*
* p<0,05 versus placebo
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Safety, Bioavailability and Suitability of FloraGLO
Lutein for Infant- and Follow-on Formulae
EFSA Opinion (2008) on the Safety, bioavailability and suitability of lutein for
the particular nutritional use by infants and young children
“ The Panel considers that the information provided in the dossier does not raise concerns
about the safety of lutein in infant formulae at the levels achieved through the natural content
of ingredients nor at the level of use (concentration of added lutein 250µg/l) proposed by the
applicant for infant formulae with a low natural lutein content (about 20 µg/l or lower).
Based on the studies provided, the Panel concludes that lutein from FloraGLO is bio-
available in infant formulae. …”
http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2008.823/epdf
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The Most Clinically Researched Lutein
Brand Worldwide*
Over 80 human clinical trials published in peer-reviewed journals
FloraGLO
Supplementation doses
clinically tested: 1.7 to
40mg/day for periods of
up to 5 years
*Review of the scientific literature available through PubMed as of November 1, 2017
KHTL-017-083 Human Clinical trials with FloraGLO Lutein
Maternaland Infant Nutrition
Brain Health and Cognitive Function
Macular Pigment Optical Density
(MPOD)
Absorption and Bioavailability
Visual FunctionAnd
Performance
Serum LuteinConcentrations
AMD Progression
(AREDS2)
Skin Health
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• The L brand clinically proven
safe for use in infant
nutrition1
• The only L brand GRAS for
infant formula1
• Kemin owns a patent showing
how lutein protects
individuals with three
common ocular disorders
from blue light or light-
induced damage associated
with computers, smartphones
and sunlight5
• The #1 doctor
recommended
lutein brand (USA)4
• The most researched L brand
worldwide2
• The lutein brand chosen by
the US National Eye Institute
for use in AREDS2, the largest
L supplemental trial to date3
1.U.S. Food & Drug Administration, 2004. GRAS Notice Inventory, GRN No. 140, 221 and 390. 2. PubMed, 2017. 3. Age-Related Eye Disease Study 2 Research Group. Lutein +
zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA 309, 2005–2015
(2013). 4. Based on the results of the US Quintiles IMS National Disease and Therapeutic (NDTI) syndicated report among US physicians who recommend a dietary supplement
with lutein for eye health between April 1, 2016 to March 31, 2017. 5. US Patent 9,226,940 B2, Method of Treating Ocular Disorders, Issued Jan. 5, 2016 to Kemin Industries
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease. This business-to-
business communication is not intended to be directed to the final consumer.
Why FloraGLO Lutein?
GRAS – Generally recognized as safe
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Thank [email protected]