Exploring the role of Lutein in maternal and infant health€¦ · 5, Shyam e al. Proc. Natl Acad Sci USA.2017Oct 10;114/41):10882-10887 Lutein (L) and zeaxanthin (Z) are carotenoids

© Kemin Industries, Inc. and its group of companies 2018. All rights reserved. ® ™ Trademarks of Kemin Industries, Inc., U.S.A.

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.


Shutterstock: 236885392

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


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


How well do we eat?



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

http://www.myheart.org.sg/article/a-heart-healthy-lifestyle/diet-and-nutrition/the-healthy-diet-pyramid/214

https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/528193/Eatwell_guide_colour.pdf


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

https://www.ars.usda.gov/ARSUserFiles/80400530/pdf/fped/Table_1_FPED_GEN_1314.pdf

https://ec.europa.eu/jrc/en/health-knowledge-gateway/promotion-prevention/nutrition/fruit-vegetables#ftna


• 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


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


https://www.ars.usda.gov/ARSUserFiles/80400530/pdf/fped/Table_1_FPED_GEN_1314.pdf


Role of Lutein in

Pregnancy, Infancy and Childhood

Shutterstock: 567102439; 164818436


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


(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.


Eye Development


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.


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


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


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


Brain Development


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


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


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

https://www.ncbi.nlm.nih.gov/pubmed/29439387


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


Shutterstock: 567102439; 164818436


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


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

**

**

**

*

#


• 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


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

http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2008.823/epdf


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


• 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


Thank [email protected]

mailto:[email protected]

Exploring the role of Lutein in maternal and infant health€¦ · 5, Shyam e al. Proc. Natl Acad Sci USA.2017Oct 10;114/41):10882-10887 Lutein (L) and zeaxanthin (Z) are carotenoids

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