Emerging Science on Lutein in the Brain

Elizabeth J. Johnson, Ph.D.

Jean Mayer USDA Human Nutrition Research Center on AgingTufts University

Boston, Massachusetts USA

A Consideration for a Role for Lutein in Early Life.

Structure of the eye adapted from Sung C and Chuang. The cell biology of vision. J Cell Biol 2010;190:953-963

Presence of lutein and zeaxanthin in the neural retina

Macula

Purves D, Augustine GJ, Fitzpatrick D et al., editors. The Retina. Neuroscience 2nd edition, Sunderland (MA): Sinauer Associates, 2001

Lutein and Zeaxanthin

Lutein and Zeaxanthin

Lutein and Zeaxanthin

Adapted from Purves D, Augustine GJ, Fitzpatrick D et al., editors. The Retina. Neuroscience 2nd edition, Sunderland (MA): Sinauer Associates, 2001

Presence of lutein and zeaxanthin in the neural retina

Lutein and Zeaxanthin

Lutein and zeaxanthin

Carotenoid concentrations in Serum and Brain

Serum, nmol/L Brain, pmol/g

(mean + se, n=48)

Xanthophylls

Carotenes

a a

aSignificantly greater than other carotenoids

Lutein ZeaxanthinCryptoxanthinb-Carotene Lycopene0

100

200

300

400

500

Lutein Zeaxanthin Cryptoxanthin b-Carotene Lycopene0

20

40

60

80

100

120

Johnson EJ et al. Abstract FASEB J 2011;25:975.21

Cryptoxanthin is the sum of α- and β-cryptoxanthin

Correlations - serum carotenoids/tocopherol and cognitive function measures

  Lutein Zeaxanthin β-carotene α-tocopherol

MMSE (n=305) 0.232p=0.001

0.160p=0.007

0.005p=0.947

0.047p=0.565

BDS (n=305) 0.214p=0.001

0.146p=0.014

0.034p=0.677

0.071p=0.380

FOME Recall (n=305) 0.237p=0.001

0.162p=0.006

0.106p=0.188

-0.012p=0.884

Values are age, sex, education, BMI, diabetes and hypertension adjusted partial correlation coefficients ‘r’ . Significant relations are shown in yellow.

Verbal fluency (n=37) 0.355p=0.075

0.346p=0.084

0.409p=0.146

0.547p=0.043

Word list learning (n=34) 0.306p=0.202

0.241p=0.320

0.470p=0.145

0.561p=0.073

Correlations - brain lutein, zeaxanthin, β-carotene and α-tocopherol concentrations and pre-mortem cognitive

function measures

 MMSE BDS Verbal

Fluency Word List Learning

Lutein 0.638 p=0.035

0.704 p=0.016

0.577 p=0.063

0.542 p=0.085

Zeaxanthin 0.437 p=0.143

0.149 p=0.663

0.495 p=0.121

0.127 p=0.710

β-carotene 0.380 p=0.249

0.178 p=0.600

0.489 p=0.127

0.200 p=0.556

α-tocopherol 0.195 p=0.566

0.030 p=0.930

0.183 p=0.590

0.171 p=0.615

Values are age, sex, education, diabetes and hypertension adjusted partial correlation coefficients ‘r’

n=16

Johnson EJ et al. Abstract FASEB J 2011;25:975.21

Study design: randomized, double-blinded, placebo-controlled, intervention trial

Subjects: Healthy women (60-80 years)

Intervention (4 months): Placebo (n = 10) Lutein, 12 mg/d (n = 11)

DHA, 800 mg/d (n = 14) Lutein + DHA (n = 14)

Johnson et al. J Nutr Neuroscience 2008;11(2):75-83

Executive FunctionVerbal Fluency (more = better)

50

70

90

110

130

Placebo DHA Lutein Lutein+DHA

** *

*significantly increased from baseline

Johnson et al. J Nutr Neuroscience 2008;11(2):75-83

% o

f bas

elin

e

Learning(Shopping List, change in the number of trials to learn list, less =

better)

*

*significantly decreased from baseline

50

55

60

65

70

75

80

85

90

95

100

P l ac ebo DHA Lutei n Lutei n+DHA

*% o

f bas

elin

e

Johnson et al. J Nutr Neuroscience 2008;11(2):75-83

Short-Term Memory(Memory in Reality Apartment test, more = better)

*significantly increased from baseline

50

60

70

80

90

100

110

Placebo DHA Lutein Lutein+DHA

*

% o

f bas

elin

e

Johnson et al. J Nutr Neuroscience 2008;11(2):75-83

Lutein in Early Life

Lutein and Zeaxanthin intake (mg/d) differs with Age (NHANES 2003-2004 data)

1-3 4-8 9-13 14-18 19-30 31-50 51-70 71+0

20

40

60

80

100

120

140

160femalemale

1-3 4-8 9-13 14-18 19-30 31-50 51-70 71+0

200

400

600

800

1000

1200

1400

1600

1800femalemale

Lutein Zeaxanthin*

Age, years Age, years

*Note the 10-fold difference in the y-axis scale between lutein and zeaxanthin

Johnson et al. J Am Diet Assoc 2010;110(9):1357-62

Plasma lutein and zeaxanthin concentrations in breast fed and formula fed infants

Zimmer JP and Hammond BR. Clinical Ophthalmol 2007;1(1):25-35. Original study data presented in Johnson et al. FASEB (abstract) 1995;9:1869

Lutein in infant formula has lower bioavailability compared to lutein in breast milk

Bettler J et al. Eur J Nutr 2010;49:45-51

Serum lutein concentrations in infants fed either breast milk, control formula and formula supplemented with lutein for 12 weeks

~20 mcg/L

225 mcg/L

120 mcg/L

45 mcg/L

20 mcg/L

Infants fed formula (without lutein) may be at a greater risk of low lutein status

Possible implications of low lutein status early in lifeLower macular pigment levelsInfluence early visual developmentAffect maturation of retinal pigment epithelial cellsExpose the retina to damage from short wavelength blue light and oxidative stress

(Hammond BR, Jr. Nutr Reviews 2008;66(12):695-702)

Can low lutein status early in life also affect cognitive development?

Study Objective

Determine carotenoid concentration in infant brain during the first year of life

4 regions of the brain (hippocampus, frontal cortex, auditory cortex and occipital cortex) were analyzed

Vishwanathan et al. Poster at 16th International Symposium on Carotenoids, Poland, July 2011

Subjects

Subject characteristics (n=30)

Age, in days 113 + 13 (Mean + SEM)

Sex Males 21 (70%)Females 9 (30%)

Race Caucasian 16 (53%)African American 12 (40%)Hispanic 2 (7%)

Cause of death SIDS 15 (50%)Others 15 (50%)(Bronchopneumonia, dehydration, asthma, drowning, hyperthermia, cardiac disorders, complications of prematurity)

Voluntarily donated samples were obtained from the NICHD Brain and Tissue Bank, of otherwise healthy infants who died during the

first year of life from SIDS or other conditions

Carotenoid concentration in the brain (mean of the 4 regions)

0

10

20

30

40

50

60M

ean

brai

n ca

rote

noid

con

cent

ratio

n (p

mol

/g)

Lutein Zeaxanthin Crypto β-car Lycopene

*

*significantly different from all other carotenoids at p<0.05

No alpha-carotene was detected. Lycopene detected only in 2 decedents

Diet (NHANES 1988-1994, 2-11 mo)

Dietary intake versus brain uptake (Percentage of total carotenoids)

Lutein Zeaxanthin Cryptoxanthin beta-carotene Lycopene

7%

Brain carotenoids (0-11 mo)

No alpha-carotene

LuteinZeaxanthinCryptoxanthinalpha-carotenebeta-caroteneLycopene

59%16%

43%

28%

12%

13%

Xanthophylls are more prevalent in breast milk compared to carotenes

Adapted from Khachik F et al. Anal Chem 1997;69:1873-1881

Adapted from Lietz G et al. J Nutr 2006;136:1821-1827

Data suggest that lutein is actively transported into breast milk and not acquired by passive diffusion

Lutein

Zeaxanthin

Cryptoxanthin

alpha-carotene

beta-carotene

Lycopene

Other carotenoids

Breast milk carotenoids (3 lactating women in US) Carotenoids Milk (nmol/g fat)

n=30 1 month postpartum

3 month postpartum

Lutein 7.41 (5.97-9.20)

9.77 (7.75-12.32)

Zeaxanthin 1.04 (0.82-1.31)

1.23 (0.98-1.55)

α-carotene 0.03 (0.00-0.07)

0.02 (0.00-0.05)

β-carotene 0.82 (0.66-1.03)

0.89 (0.69-1.13)

27%

22%

Brain carotenoid profile in infants and centenarians

Vishwanathan et al. Poster at 16th International Symposium on Carotenoids, Poland, July 2011Johnson EJ et al. Abstract FASEB J

2011;25:975.21

Lutein Zeaxanthin Cryptoxanthin beta-carotene Lycopene Others

Lutein Zeaxanthin Cryptoxanthin beta-carotene Lycopene

55%15%

18%

31%

22%10%

18%

Others: cis lutein isomers (1%), 9 cis beta-carotene (4%) and

unknown (8%)

Infant Brain (n=30)

Centenarian Brain (n=48)

Conclusions

• Lutein is the predominant carotenoid in infant brain accounting for more than half the concentration of carotenoids– Lutein may be important for early neural development

• A meta-analysis of 11 studies showed breast feeding was associated with significantly higher scores for cognitive development than was formula feeding

(Anderson JW et al. Am J Clin Nutr 1999;70:525-35)

• As infant formula is not routinely supplemented with lutein, further investigation of the impact of lutein intake on neural development is warranted

Acknowledgements

Tufts HNRCARohini Vishwanathan, Ph.D.Tammy M. Scott, Ph.D.Emily Eggert (Rice University, Houston, TX)

Alessandro Iannaccone, M.S., M.D., Univ. of TN Martha Neuringer, Ph.D. Oregon Science & Health Univ.Leonard Poon, Ph.D., University of Georgia-AthensLisa Renzi, Ph.D., University of Georgia-Athens D. Max Snodderly, Ph.D., University of Texas-AustinWolfgang Schalch, Ph.D., DSM NutritionalsMatthew Kuchan, Ph.D., Abbott Nutrition