Brown nutrition fe zn

Mainstreaming iron and zinc biofortification

programs

Kenneth H Brown

Shawn K Baker

Program in International and Community Nutrition

University of California, Davis

Helen Keller International

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Perspectives on nutrition intervention programs:

health scientist, policy maker, program manager

Health scientist

Prevalence

Severity

Efficacy of

interventions

Formative research

Operational research

Policy maker

Scientific consensus

Political constituency

Response time

Cost

Program manager

Logistics, finances

Delivery platform

Institutional base

Personnel recruitment,

training & supervision

IEC/BCC

M&E

Industry, agriculture, trade, civil society, …….

Steps in scaling up nutrition intervention

programs – advocacy issues

Establish

scientific

consensusSelect

intervention

strategy(ies)

Identify sector(s)

& institutional

base(s) for

program

management

Determine

appropriate

delivery

platform(s)

Conduct advocacy,

establish political

consensus; mobilize

financial resources

Initiate and

monitor

program

• Agricultural specialists primarily

responsible for intervention

• Dual targets

– Farmers

– Consumers

• Invisible

Special aspects/challenges of biofortification

programs

Activities required for scaling up biofortification

programs, and responsible parties

Activity Discipline Sector

Population nutr assessment Nutrition Academia





Establish breeding targets Nutr, Agr Academia






Development, selection of

cultivars

Plant science Academia







cultivars


Measure nutrient absorption,

product efficacy

Nutrition Academia







cultivars



product efficacy

Nutrition Academia

Assess yields, consumer

acceptance

Agr, marketing Academia







cultivars



product efficacy

Nutrition Academia

Assess yields, consumer

acceptance

Agr, marketing Academia

Advocacy, resource mobiliz-

ation

Nutr, Agr,

public admin

Public, CSO


Produce, distribute seeds Plant science,

commerce

Public, pvt





commerce

Public, Pvt

Social mobilization (farmers,

consumers)

Communicat/

mkting, Agr

Public, CSO





commerce

Public, Pvt


consumers)

Communicat/

mkting, Agr

Public, CSO

Training, supervision Agr, Nutr Public, Pvt





commerce

Public, Pvt


consumers)

Communicat/

mkting, Agr

Public, CSO


Monitoring Agr, Nutr, Mkt Public,

Acad, Pvt





commerce

Public, Pvt


consumers)

Communicat/

mkting, Agr

Public, CSO


Monitoring Agr, Nutr, Mkt Public,

Acad, Pvt

Evaluation Agr, Nutr Public, Acad



How nutrients in fortified foods reach

young children

Directly via food

Indirectly via

breast milk

Krebs et al, AJCN 1995;61:1030-6. Women supplemented with 15 mg zinc per day.

Breast milk zinc concentrations of zinc-

supplemented and control mothers, by infant age

Median rice and zinc intakes, Bangladeshi

children and women

Children Women

Rice (g/d) 134 420

Zinc (mg/d) 2.5 5.4

Phytate (mg/d) 272 643

P:Z molar ratio 11.2 12.0

% inadeq zinc* 22% 94%

% zinc from rice 49% 69%

Based on IZiNCG dietary requirements: 2 mg/d, children; 8 mg/d women, considering low

bioavailability

Data from Arsenault J et al, J Nutr, 2010

Estimated prevalence of inadequate zinc

intakes by assumed coverage of biofortification

Baseline 15% 35% 70%

Children 22 19 15 9

Women 94 78 40 20

Data from Arsenault J et al, J Nutr, 2010

Pre-schoolers

Adolescents

Adult males

Pregnant women

Elderly

Schoolers

Efficacy research Flour consumption Pgm impact?

Population sub-groups that might benefit from

iron and zinc biofortification

Mean change in plasma zinc concentration (ug/dL),

following 6 months of zinc supplementation or

fortification* among young Peruvian children

-5

-4

-3

-2

-1

0

1

2

3

4

5

Ch

an

ge

in

pla

sm

a z

inc c

on

c

(ug

/dL

)

Placebo Zn Suppl Zn Fort

b

a

a

P<0.01*

* Zinc supplementation and fortification (wheat porridge)

provided 3 mg additional zinc/d as ZnSO4.

Data from: Brown KH et al. Am J Clin Nutr, 2007.

Time line for developing nutrition

intervention programs

Development

of scientific

evidence

Development

of scientific &

political

consensus

Implementation

of pilot

intervention

Modifying,

scaling up

intervention

Monitoring &

evaluation

10-20 yrs

3-5 yrs

Conclusions

• Epidemiology of iron and zinc deficiency uncertain– Information needed!

• Biofortification interventions are extremely complex operations involving multiple technical disciplines and both public and private sector agencies– Coordination essential!

• Biofortification interventions are currently in their very early stages– Patience required!

• Uncertainty regarding impact on different target groups– Evaluation important!

• Potential for broad coverage and sustainability– They deserve a try!

Thanks!

Children consumed ~22-25 g porridge/d

(~3.3 mg additional zinc in zinc-fortified group)

Can mass fortification programs improve young

children’s nutritional status health and survival?

So…, can

fortified foods

enhance young

children’s nutritional

status?

Steps in the development of

biofortification programs

• Population nutritional status assessment

• Establishing plant breeding targets, producing local cultivars

• Determining nutrient absorption, product acceptance, efficacy

• Advocacy, resource mobilization

• Social mobilization, BCC (food production and consumption)

• Monitoring and evaluation

Simulations of potential impact of fortified

foods on young children’s nutrient intakes

Effect of zinc supplementation on change in

mean serum zinc concentration

(n = 30 comparisons; 4,571 children)

Zinc supplementation

produced a significant

increase in mean serum

zinc concentration

Mean effect size = 0.60

(CI = 0.44, 0.77), p<0.001

Data from Brown KH et al,

Food Nutr Bulletin, 2009

Results of EURRECA systematic review

Data from Lowe NM. AJCN, 2009

Change in plasma zinc concentration by

dose of zinc supplement, Ecuador

0 3 7 10-10

0

10

20

30

Zinc dose (mg/d)

Ch

an

ge i

n p

lasm

a z

inc (

ug

/dl)

Wuehler S et al, Am J Clin Nutr, 2008

0

20

40

60

80

100

120

0 20 40 60 80 100 120Zinc concentration, Day -7 (ug/dL)

Zin

c c

on

ce

ntr

ati

on

, D

ay

0 (

ug

/dL

)Within-subject comparison of two

measurements of fasting plasma zinc

concentration obtained one week apart*

Y = 0.998; r2 = 0.65; p<0.01;

Paired t-test NS (p = 0.97)

* Data from Wessells KR

et al, J Nutr, in press.

(N=58)

Individuals have a fairly stable

fasting serum zinc concentration

70

75

80

85

90

95

0 5 10 15 20 25 30 35 40 45

Study Day

Pla

sm

a Z

inc

Co

nc

en

tra

tio

n (

ug

/dL

)

placebo

10 mg zinc

20 mg zinc

Mean plasma zinc concentration, by study

group and day of study, n = 58

Data from Wessells KR


Period of supplementation

* Groups were significantly different on days 5, 9, 14, 21, 22, 23, 26, 30, and 35

***

**

*

*

*

*

Change in plasma zinc concentration (PZC), by

initial PZC and study group, day 14 of study

N = 58. Data from Wessells KR


*

Placebo group

Mean change in plasma zinc concentration (μg/dL)

following 15 days of zinc supplementation or

fortification* among young Senegalese children

Data from: Ba Lo N et al, unpublished.

*Zinc supplementation: 6 mg Zn/d as ZnSO4;

Zinc fortification (maize porridge): 6 mg Zn/d as ZnO.

-6

-4

-2

0

2

4

6

Control Zinc supplement Zinc fortification

Ad

just

ed c

han

ge in

zin

c co

nc.

(µ

g/d

L)

Effects of meals and time of day on plasma

zinc concentration

King J et al. J Nutr, 1994.

Factors affecting serum zinc concentration

in a community-based trial among young

Peruvian children

Variable Beta (significance)

Hours since last meal +1.0 (p<0.004)

Time of day of

sampling

-1.9 (p<0.004)

Elevated CRP -4.3 (p<0.002)

Reported fever -6.1 (p<0.01)

Arsenault J et al, Europ J Clin Nutr, in press.

Suggested cutoffs for assessing serum zinc

concentration (NHANES II)

Time of day

and fasting

status

Serum zinc concentration

(ug/dL) by age and sex

<10 yrs > 10 years

Males &

femalesMales

Non-

pregnant

females

Morning

fastingna 70 74

Morning other 65 66 70

Afternoon 57 59 61

Hotz C et al. AJCN, 2004

Rationale for using serum zinc concentration for

assessing population risk of zinc deficiency

• Reflects zinc intake over past few days/weeks, hence risk of zinc deficiency (not necessarily zinc “status”)

• Changes occur during depletion in relation to changes in total body zinc

• Responsive to zinc supplementation in dose-dependent fashion

• Fairly small intra-individual (day-to-day) variability while consuming usual diet

• Reference data available from presumably healthy population

Some caveats…

• Issues of confounders and contamination

– Samples should be collected at fixed time of day and

in relation to meals (or adjusted statistically)

– Need to control for effect of infection/inflammation

• To assess program impact, samples should be

collected while intervention is still in progress

• Need control group to assess intervention effect

(note issue of “regression to mean”)

Acknowledgements

UC Davis/WHNRC/CHORI

Grant Aaron

Joanne Arsenault

Reina Engle-Stone

Sonja Hess

Josh Jorgenson

David Killilea

Janet King

Jan Peerson

Ryan Wessells

Leslie Woodhouse

Sara Wuehler

UCAD, Senegal/

IRSS, Burkina Faso

Nafisatou Ba Lo

Amadou Guiro

Jean-Bosco Ouédraogo

Zinewendé Ouédraogo

Noel Rouamba

Salimata Wade

IZiNCG

Christine Hotz

Rosalind Gibson

Impact of zinc fortification of wheat flour* on

mean serum zinc conc (μg/dL), China

Month of

study

EDTA arm Elemental iron arm

Control EDTA iron

+ zinc

Control Elem iron +

zinc

0 73+25 75+27 73+16 72+17

12 72+24 75+28 72+14 74+18

24 72+19 78+16 74+13 76+12

36 71+19 79+16 75+13 78+11

* Wheat fortified with 25 mg/kg flour as zinc oxide (Huo Junsheng, China CDC, unpublished)

IZiNCG Publications

Available on the IZiNCG web site:

www.izincg.org

Relation between elevated CRP or clinical signs of

illness and serum zinc concentration in a community-

based trial among young Peruvian children

Zn conc (μg/dL) % low

(<65μg/dL)

All 78 14 16

Elev CRP, yes

no

74 15

79 14

28

12

Fever yes

no

72 15

78 14

33

14

Diarrhea yes

no

76 18

78 14

33

14

Data from: Arsenault et al. Europ J Clin Nutr, in press.

Serum zinc concentration in relation to acute

phase proteins (Bangladesh; n = 279 children)

Nl CRP,

AGP

(n=211)

↑CRP only

(n=5)

↑AGP only

(n=40)

↑ CRP

and AGP

(n=23)

Serum

zinc conc

(μg/dL)

74

13

70

9

71

11

68

12

% <65

μg/dL

Mean change in plasma zinc concentration (μg/dL)

following 15 days of zinc supplementation or

fortification* among Senegalese men

-3.0

-2.0

-1.0

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

Ch

ange

in p

lasm

a zi

nc

con

c (

mg/

dL)

Control Zinc supplement Mod-Zn-fort High-Zn-fort

Data from Aaron GJ et al, unpublished.

* Zinc supplementation: 7.5 mg/d as ZnSO4;

Zinc fortification (wheat bread): 7.5 mg/d or 15 mg/d as ZnO

The roles of zinc transporters in maintaining

intracellular zinc concentration

[Zn]

ZnT family of

transporters

[Zn]

ZIP family of

transporters

[Zn]

[Zn]

Zn Zn

Zn

Zn

ZnZn

[Zn]

Am J Clin Nutr 80:1570-3, 2004

Estimation of zinc absorption

Based on model by Miller LV et al model (J Nutr,

2007), which uses physiological assumptions

(saturation kinetics) and empirical data from 32

data sets*

Dietary zinc and phytate are two dietary factors

that affect total absorbed zinc (TAZ)

Model fit, r2 = 0.86

*Revised model parameters as per Hambidge et al, FASEB J, 2008

www.IZiNCG.org

Global prevalence of zinc deficiency

• Little information available based on biomarkers of zinc status

• Current estimates based of prevalence of child stunting

• Assessments should be added to all planned nutritional status

surveys in countries with an elevated risk of zinc deficiency!

< 20 %

20-30 %

30-40%

> 40 %st unt cat 1 2 3 4 9

Supplementation recommended for…

Treatment of diarrhea - twice age-specific RDA/day (10-20

mg) X 10-14 day, distributed with ORS

Components needed for scaling up – tablet production,

communication, training, formative research, evaluation,

(financing)

Baq

ui

(2003)

Baq

ui

(2003)

Fe

Casti

llo

-Du

ran

(1995)

Bro

wn

(2007)

Wu

eh

ler

(2007)

3 m

gO

sen

darp

(2002)

Wu

eh

ler

(2007)

7 m

gH

on

g (

1992)

Cavan

(1993)

Bro

oks (

2005)

Lin

d (

2004)

Lin

d (

2004)

Fe

Pen

ny (

2004)

Ru

z (

1997)

Sazaw

al (1

996)

Sem

pert

eg

ui (1

996)

Wu

eh

ler

(2007)

10 m

gR

osad

o (

1997)

Ro

sad

o (

1997)

Fe

San

dste

ad

(1998)

Ud

om

kesm

ale

e (

1992)

Fri

is (

1997)

Rah

man

(2001)

Rah

man

(2001)

Vit

. A

Ro

sad

o (

2006)

Ro

sad

o (

2006)

Fe

All

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

Effect of zinc supplementation on change in

serum zinc concentration

0.60

0.43, 0.76

Consistent increase in serum zinc

concentration following zinc

supplementation

Conclusions

• Consistent, moderately large increase in

serum zinc concentration

• Decreased incidence of diarrhea

• Decreased incidence of pneumonia

• Decreased mortality among LBW infants,

older children

0

0.2

0.4

0.6

0.8

1

1.2

TA

Z (

mg)

0

0.5

1

1.5

2

TA

Z (

mg)

Effect of zinc fortification

on total absorbed zinc (TAZ) Hansen, 2001Lopez de Romaña, 2005

0

0.2

0.4

0.6

0.8

1

TA

Z (

mg)

0

0.1

0.2

0.3

0.4

TA

Z (

mg)

Sandström, 1980

Refined wheat

Sandström, 1980

Whole wheat

0.4 3.6 1.3 3.5

1.2 3 0 3 9Level of zinc fort.(mg/1-2 servings)

Level of zinc fort.(mg/1-2 servings)

Increased total zinc absorption when foods

are supplemented with zinc

FAZ and TAZ, by amount of zinc intake

from meals containing fortified foods

0 2 4 6 8 10 120.0

0.5

1.0

1.5

2.0

2.5

3.0

Zinc intake at breakfast and lunch (mg)

Ab

so

rbe

d z

inc

(m

g)

y = 0.45 + 0.148x - 0.0056x2

( )( )

0 2 4 6 8 10 120.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

Zinc intake at breakfast and lunch (mg)

Fra

cti

on

al

ab

so

rpti

on

of

zin

c y = 0.50 - 0.079x + 0.0042x2

( )

López de Romaña et al. Am J Clin Nutr, 2005

Factors affecting serum zinc concentration

• Serum zinc concentration vary by

– Age group

– Sex

– Time of day of blood collection

– Fasting status

– Presence of inflammation

Use respective cutoff

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