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Page 1: Tanumihardjo nutrition vit a

Taking Stock of the Evidence on

Biofortification of Food Crops with

Provitamin A Carotenoids: Situation

Analysis of What We KnowSherry A. Tanumihardjo

Associate Professor

University of Wisconsin-Madison, USA

Department of Nutritional Sciences

Page 2: Tanumihardjo nutrition vit a

Parker, FASEB J 10:543, 1996

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Definitions

Bioaccessibility: how much carotenoid is released from the food matrix and available for absorption.

Bioavailability: fraction of ingested nutrient available for utilization or storage.

Bioconversion: proportion of bioavailable carotene converted to retinol.

Bioefficacy: efficiency ingested carotenoids are absorbed and converted to retinol.

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Intestinal

wall

b-Cabsorbed

Cleaved

Retinal

Reduced

Retinol

Food

b-Ctotal

b-Cfreed

Bioaccessibility = b-Cfreed / b-Ctotal

Bioavailability = b-Cabsorbed / b-Ctotal

Bioconversion = Retinol / b-Cabsorbed

Bioefficacy = Retinol / b-Ctotal

Tanumihardjo, IJVNR 72: 41, 2002

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SLAMENGHI - 1996

Species of carotenoids

molecular Linkage

Amount of carotenoids consumed in a meal

Matrix in which the carotenoid is incorporated

Effectors of absorption and bioconversion

Nutrient status of the host

Genetic factors

Host-related factors

mathematical Interactions

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Advantages of Biofortification:

Enhancing micronutrients in crops

Targets the poor: eat high levels of food

staples

Rural-based: complements fortification

and supplementation

Cost-effective: research at a central

location can be multiplied across countries

and time

Sustainable: investments are front-loaded,

low recurrent costs

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The Sherry Factors!!!

S – Species of carotenoid

H – Host related factors

E – Effectors of absorption

R – Relative amounts of carotenoids

R – Resistant starch

Y – Yet to be determined

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S – Species of carotenoid

Hydrocarbon or not…

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S – Species of carotenoid

OH

OH

-carotene

b-carotene

b-cryptoxanthin

retinol

Page 10: Tanumihardjo nutrition vit a

-Carotene equivalents

5.5 mg:1 mg

Treatment

group

n Serum retinol

(mmol/L)

Liver retinyl

palmitate

(mmol/g)

Liver total retinol2

(mmol/g)

Baseline3 6 1.30 + 0.35 0.123 + 0.024b 0.170 + 0.027b

Vitamin A 9 1.44 + 0.21 0.198 + 0.051a 0.267 + 0.071a

-Carotene 9 1.39 + 0.09 0.110 + 0.026b 0.155 + 0.033b

b-Carotene 9 1.40 + 0.17 0.109 + 0.051b 0.153 + 0.066b

Oil control 5 1.57 + 0.38 0.061 + 0.029c 0.091 + 0.041c

Tanumihardjo & Howe. J. Nutr. 135: 2622–6, 2005

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Bioconversion for

b-cryptoxanthin

was 2.8 mg to 1 mg

retinol and almost

identical to b-

carotene.

aab

bc

c

ab

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

Base Ctl bC bCX VA

µm

ol

RE

/ g

liv

er

ab

c

bc

a

a

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

Base Ctl bC bCX VA

µm

ol

RE

/ l

iver

Davis et al., BJN, 2008

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Biofortified b-cryptoxanthin maize

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6m

mo

l R

E / liv

er

Base Control bC Maize VA

bc bc

c

b

a

Davis et al., BJN, 2008

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Bioefficacy of biofortified b-carotene maize

High-b-carotene maize did not differ from b-carotene .

Bioconversion: ~3 mg b-carotene to 1 mg retinol.

0.0

0.5

1.0

1.5

2.0

Control Maize BC VA

Treatment

Liv

er

VA

(m

mo

l)

a

bb

c

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What about bioconversion

factors in human studies? Li et al. Am J Clin Nutr 2010

• 6.48 ± 3.51 mg bC:1 mg retinol in 6 young

women in Iowa

Muzhingi et al. FASEB J. 2009

• 3.0 ± 1.5 mg bC:1 mg retinol in 9 healthy

Zimbabwean men

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S – Species of carotenoid

Cis or trans

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Cassava: Comparable to

b-carotene supplement

even with substantial

cis-b-carotene

a

bb

c

bc

0

0∙2

0∙4

0∙6

0∙8

1

1∙2

1∙4

1∙6

1∙8

Base Control BC Cassava VA

Treatments

mm

ol V

itam

in A

/ liv

er

A

a

bcb

c

bc

0

0∙1

0∙2

0∙3

0∙4

0∙5

0∙6

0∙7

0∙8

Base Control BC Cassava VA

Treatments

mm

ol V

itam

in A

/ g

liv

er

B

c c ca b

b b

a

a

b

0

1

2

3

4

5

6

7

8

9

Base Control BC Cassava VA

Treatments

nm

ol b

-Caro

ten

e / liv

er

trans

cis

C

Page 17: Tanumihardjo nutrition vit a

Erdman’s group All-trans b-carotene appears to be more

bioavailable than 9-cis or 13-cis b-carotene in

gerbils given single oral doses of each isomer

• Deming et al., J. Nutr. 132: 2700-8, 2002.

The relative vitamin A value of 9-cis b-carotene

is less and that of 13-cis b-carotene may be

greater than the accepted 50% that of all trans-

b-carotene in gerbils

Deming et al., J. Nutr. 132: 2709-12, 2002.

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Cis/trans b-carotene

Bresnahan et al. FASEB J 2011

a

c bc bc b b

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H – Host related factors

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Polymorphisms

Single nucleotide polymorphisms in the

human BCMO1 gene have been

discovered causing observably reduced

BCMO1 activity.

We do not know how this will influence

biofortification efforts at the population

level.

Lietz et al., Arch Biochem Biophys, 2010

Page 21: Tanumihardjo nutrition vit a

R = 0.885

0

5

10

15

20

25

0 0.5 1 1.5 2

Co

nv

ers

ion

fa

cto

r (m

g:m

g)

Total vitamin A liver reserves (mmol)

Vitamin A status of the host

High b-carotene

orange carrots

Orange and

purple carrots

Kale, spinach,

and brussels

sprouts

Sweet Potato

Red carrots and Cassava

Maize

Total vitamin A liver reserves (mmol)

Co

nvers

ion

facto

r (m

g:m

g)

Page 22: Tanumihardjo nutrition vit a

H – Host related factors

Other nutrient status

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How are iron and vitamin A related?

Hematopoiesis and erythropoiesis: formation

of red blood cells

Modulation in the anemia of infection

Iron absorption and metabolism: iron

mobilization and transport

Immune modulation: Reduced morbidity and

mortality of some infectious diseases

Page 24: Tanumihardjo nutrition vit a

Vision retinol retinal

Zn

monooxygenase

Digestion b-carotene 2 retinal

Zn

Protein synthesis

Zn retinol binding protein retinol:RBP in blood

(RBP)

Synergism between vitamin A and Zn

dehydrogenase

Page 25: Tanumihardjo nutrition vit a

E – Effectors of absorption

Fat

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Ribaya-Mercado et al. AJCN

2007;85:1041-9

Schoolchildren fed 4.2 mg provitamin A

carotenoids in the form of vegetables for

9 weeks with 2.4, 5 or 10 g fat/meal.

Low liver reserves (< 0.07 mmol/g) fell

from 35% to 7% and the amount of fat

did not influence the results.

Page 27: Tanumihardjo nutrition vit a

Influence of fat on bioconversion Mills et al. J. Nutr. 139: 44-50, 2009

mg b

-caro

ten

e to

ret

inol

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Emerging data: Type of fat

Dietary fats with increased unsaturated

to saturated fat enhance absorption of

carotenoids by increasing efficiency of

micellarization and lipoprotein secretion

Unsaturated fat enhances carotenoid

bioavailability

• Chitchumroonchokchai et al., FASEB J.

2010; Abstract 539.3.

Page 29: Tanumihardjo nutrition vit a

R – Relative amounts of carotenoids

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Conversion factors

ranged from 9 to 11

mg b-carotene to 1 mg

retinol for typical

orange and 23 mg b-

carotene to 1 mg

retinol for biofortified

carrots.

0

50

100

150

200

250

300

350

high orange orange purple white

To

tal li

ver b

-caro

ten

e (

nm

ol)

a

b

b

c

(A)

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

high orange orange purple white

To

tal

liv

er v

ita

min

A (m

mo

l)

a

b b

c

(B)

Dosti et al., BJN. 2006

Page 31: Tanumihardjo nutrition vit a

Cassava:Varying the level

of cassava

a

abab

b

aa

0

0∙3

0∙6

0∙9

Base Control 15% #2 17% #1 35% #2 40% #1Treatments

mm

ol V

itam

in A

/ liv

er

A

abab

ab

b

ab a

0

0∙1

0∙2

0∙3

Base Control 15% #2 17% #1 35% #2 40% #1Treatments

mm

ol V

itam

in A

/ g

liv

er

B

bb a

bb

a

a

bb

cc

a

0

1

2

3

4

5

6

7

8

Base Control 15% #2 17% #1 35% #2 40% #1

Treatments

nm

ol b

-Caro

ten

e / liv

er

trans

cis

C

Page 32: Tanumihardjo nutrition vit a

b-Carotene assessment

0

10

20

30

40

Control Maize BC VA

Treatment

Liv

er b

-caro

ten

e (

nm

ol)

a

b

Liver bC is ~100%

greater in maize

treatment group

Page 33: Tanumihardjo nutrition vit a

VA status with increasing b-carotene. Liver

VA from orange maize was greater than

yellow, regardless of % (P < 0.05).

0

0.2

0.4

0.6

0.8

30% typical 60% typical 30% high BC 60% high BC

Maize Treatment

Liv

er

VA

(m

mo

l)

abbc

c

a

Page 34: Tanumihardjo nutrition vit a

Provitamin A from

cassava, maize, or

supplements of

vitamin A, β-carotene,

and β-cryptoxanthin

Page 35: Tanumihardjo nutrition vit a

Conclusions:

Not all provitamin A carotenoids are equivalent,

one conversion factor does not fit all foods and is

related to vitamin A status.

Biofortified maize not only maintained vitamin A

status, but was as efficacious as b-carotene

supplements.

In populations consuming maize, using orange

instead of white maize may impact vitamin A

status.

Page 36: Tanumihardjo nutrition vit a

A male child eating maize

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

0.5 1 1.5 2 2.5 3 3.5 4 4.5

Age of child (y)

Liv

er

vit

am

in A

ac

cu

mu

lati

on

m

mo

l/g

)

Sugar

Maize

Supplements

Bioconversion slows

Tanumihardjo, Comp. Rev. Food Sci. & Food Safety, 2008;7:373-81.

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Setting up kitchens

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Grinding the maize

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Food Details

Standardized recipes

with a rotating menu

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Cooking the maize

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Stirring and stirring….

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Food Details

Serving sizes weighed

for each menu item

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Food Details

Children Eating!

All uneaten food weighed for each subject

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Cleaning up the mess

And the data!

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**

A

B

C

D

Page 46: Tanumihardjo nutrition vit a

R – Resistant starch

Sweet potato, Golden Rice and

banana

Page 47: Tanumihardjo nutrition vit a

Orange Fleshed Sweetpotato

Page 48: Tanumihardjo nutrition vit a

• Using the paired isotope dilution test, final

vitamin A was higher in the spinach, vitamin A and

b-carotene groups compared to the control group.

• Vitamin A equivalency factors were estimated:

~13:1 for sweet potato

~10:1 for Indian spinach

~6:1 for b-carotene

Vitamin A provided with meals

Haskell et al. Am J Clin Nutr. 2004;80:705-14

Page 49: Tanumihardjo nutrition vit a

Mills et al. J. Nutr. 139: 44-50, 2009

Influence of dry matter on bioconversion

mg b

-caro

ten

e to

ret

inol

Page 50: Tanumihardjo nutrition vit a

South African Trial Supervised feeding; 125 g x 5 d/wk for 10.5 wk; 1030 mg RAE OFSP

vs 0 mg RAE WFSP; 90% compliance; 250% RDA

Page 51: Tanumihardjo nutrition vit a

Infants eating sweet potato

Sweet potato

Sachets or tablets

?

0

0.2

0.4

0.6

0.8

6 7 8 10 11 12 13

Age of child (mo)

Liv

er

vit

am

in A

ac

cu

mu

lati

on

(mm

ol/

g)

Sweet potato

Tablets or sachets

Tanumihardjo, Comp. Rev. Food Sci. & Food Safety, 2008;7:373-81.

Page 52: Tanumihardjo nutrition vit a

-0.004

0.004

-0.006-0.005-0.004-0.003-0.002-0.0010.0000.0010.0020.0030.0040.0050.006

Intervention effect: -0.008 (-0.015, -0.001)

P = 0.0203

Change in liver stores of vitamin A

Intervention Control

Page 53: Tanumihardjo nutrition vit a

Sweet potato in Mozambique

Effectiveness study using an integrated

agricultural and nutrition intervention

2 year intervention covering 2 agricultural

cycles

90% of intervention households produced

sweet potato

Intervention children (n = 498) ate more sweet

potato and had higher serum retinol than

controls (n = 243)

Low et al. J Nutr. 2007;137:1320-7.

Page 54: Tanumihardjo nutrition vit a

.

Towards Sustainable Nutrition Improvement

in Rural Mozambique

Taste tests were conducted at every adaptive trial

harvest to determine preferences of local consumers.

Page 55: Tanumihardjo nutrition vit a

.

Towards Sustainable Nutrition Improvement

in Rural Mozambique

Sweet potato bread maker making his bread at home and

selling it in the nearby market of Lualua. Bread is marketed

under the name of Golden Bread.

Page 56: Tanumihardjo nutrition vit a

Orange sweet potato

in Africa – a Success Story

Active behavior change

Agronomic ‘equality’ crucial

Assistance to understanding and overcoming constraints to adoption crucial

• Farmer participation in breeding and varietal selection

• Seeds systems, product, and market development

Page 57: Tanumihardjo nutrition vit a

Progress with Golden Rice

Page 58: Tanumihardjo nutrition vit a

Ready for golden rice?

Page 59: Tanumihardjo nutrition vit a

Bioconversion factor:

The conversion factor for Golden Rice

was 3.8 + 1.7 mg to 1 mg with a range of

1.9–6.4:1 in 5 healthy adults

• Tang et al. Am J Clin Nutr 2009;89:1776–83

Pure βC, GR βC, and spinach βC to

retinol were 2.0, 2.1, and 7.3 mg to 1 mg,

respectively

• Tang et al. FASEB J 2010 Abstract

Page 60: Tanumihardjo nutrition vit a

Do favorable bioconversion

factors result in efficacy to

improve vitamin A status?

Page 61: Tanumihardjo nutrition vit a

No change in serum retinol

Page 62: Tanumihardjo nutrition vit a

Both groups lost liver stores as

predicted by the numbers

Page 63: Tanumihardjo nutrition vit a

What do the numbers predict?

6 mg/g X 0.75 retention factor

4.5 mg/g X158 g/day

711 mg with an optimistic 3:1

conversion

237 mg with a 275 mg/d EAR = - 38 mg

Potential loss during the trial is 28

mg/g liver with maize feeding

Page 64: Tanumihardjo nutrition vit a

MRDR versus liver reserves

Liver reserves in mg/g liver

MR

DR

va

lue

Page 65: Tanumihardjo nutrition vit a

BN MN OR TN PP VA

Vit

am

in A

mo

l / li

ve

r)V

ita

min

A (μ

mo

l / g

liv

er)

Values are means + SD; n = 10. Means with different letters are

different, P < 0.05. ND, not detected

VA Concentration

Total Liver VA

All fruits maintained

baseline liver VA

concentrations.

All fruits prevented VA

depletion as compared to

control, except banana.

Liver carotenoids

present in respective

groups.

Arscott et al., Exp. Biol. Med, 2009

Fruit – Banana?

Page 66: Tanumihardjo nutrition vit a

r = 0.88

Banana r = 0.44 with banana

Dark orange carrot

Orange and

purple carrots

Kale, spinach

brussels Red carrots

sprouts Maize

Mango, orange, tangerine, papaya

Conversion efficiency improves as VA status declines

Page 67: Tanumihardjo nutrition vit a

Interesting Observations

Daily Diet and VA Intake

DietDaily Diet Intake

(g)VA Intake (nmol)

VA- 6.77 0.00

VA+ 6.64 19.11

VA+ Banana 8.12 30.38

60CG 9.16 32.47

60CR 8.99 37.50

60LG 8.28 29.72

60LR 7.67 48.84

15KBG 7.55 56.16

30KBG 7.61 103.70

Page 68: Tanumihardjo nutrition vit a

More studies with banana

All gerbils vitamin A deficient!

Page 69: Tanumihardjo nutrition vit a

Study 2:

Total liver vitamin A (nmol)

Page 70: Tanumihardjo nutrition vit a

Y – Yet to be determined

Page 71: Tanumihardjo nutrition vit a

Another

reason to feed

whole foods!

Mills et al. J. Nutr.

2008.;138:1692-8

c

aababab

bc

d

0

2

4

6

8

10

12

Bas

eline

Contr

olPO O O

RPO

R VA

mm

ol T

EA

C/g

Hydrophilic Extracts Lipophilic Extracts

ba a a a a a

0

1

2

3

4

5

6

Bas

eline

Contr

olPO O O

RPO

R VA

mm

ol T

EA

C/L

Page 72: Tanumihardjo nutrition vit a

Vision retinol retinal

Zn

monooxygenase

Digestion b-carotene 2 retinal

Zn

Protein synthesis

Zn retinol binding protein retinol:RBP in blood

(RBP)

Biofortification: vitamin A and Zn

dehydrogenase

Page 73: Tanumihardjo nutrition vit a

LET’S FEED PEOPLE:

Jejunal Morphology

ORAL TPN

Peterson, C.A. et al. Am J Physiol 272:G1100, 1997

Supports biofortification efforts!

Page 74: Tanumihardjo nutrition vit a

Situation analysis of what we know

Page 75: Tanumihardjo nutrition vit a

The Current VAAL Team

Sara Arscott

Kara Bresnahan

Ashley Valentine

Emily Nuss

Chris Davis

Harold Furr

David Liu

Napaporn Riabroy

Margertha McLean

Sammie Schmalzle

Jacob Tanumihardjo

Collaborators:

Philipp Simon

Torbert Rocheford

Kevin Pixley

Natalia Palacios

Past members whose

work was cited:

Mandy Porter Dosti

Hua Jing

Julie Howe

Jordan Mills

Page 76: Tanumihardjo nutrition vit a

Thanks for your attention


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