1. 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
5. 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, …….
6. Steps in scaling up nutrition intervention
programs – advocacy issues
Establish
scientific
consensus
Select
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
7. • Agricultural specialists primarily
responsible for intervention
• Dual targets
– Farmers
– Consumers
• Invisible
Special aspects/challenges of biofortification
programs
8. Activities required for scaling up biofortification
programs, and responsible parties
Activity Discipline Sector
Population nutr assessment Nutrition Academia
9. Activities required for scaling up biofortification
programs, and responsible parties
Activity Discipline Sector
Population nutr assessment Nutrition Academia
Establish breeding targets Nutr, Agr Academia
10. 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
11. 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
Measure nutrient absorption,
product efficacy
Nutrition Academia
12. 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
Measure nutrient absorption,
product efficacy
Nutrition Academia
Assess yields, consumer
acceptance
Agr, marketing Academia
13. 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
Measure nutrient absorption,
product efficacy
Nutrition Academia
Assess yields, consumer
acceptance
Agr, marketing Academia
Advocacy, resource mobiliz-
ation
Nutr, Agr,
public admin
Public, CSO
14. Activity Discipline Sector
Produce, distribute seeds Plant science,
commerce
Public, pvt
Activities required for scaling up biofortification
programs, and responsible parties
15. Activity Discipline Sector
Produce, distribute seeds Plant science,
commerce
Public, Pvt
Social mobilization (farmers,
consumers)
Communicat/
mkting, Agr
Public, CSO
Activities required for scaling up biofortification
programs, and responsible parties
16. Activity Discipline Sector
Produce, distribute seeds Plant science,
commerce
Public, Pvt
Social mobilization (farmers,
consumers)
Communicat/
mkting, Agr
Public, CSO
Training, supervision Agr, Nutr Public, Pvt
Activities required for scaling up biofortification
programs, and responsible parties
19. How nutrients in fortified foods reach
young children
Directly via food
Indirectly via
breast milk
20. 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
21. 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
22. 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
24. 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
Changeinplasmazincconc
(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.
25. 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
26. 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!
32. 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
35. 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
37. Change in plasma zinc concentration by
dose of zinc supplement, Ecuador
0 3 7 10
-10
0
10
20
30
Zinc dose (mg/d)
Changeinplasmazinc(ug/dl)
Wuehler S et al, Am J Clin Nutr, 2008
38. 0
20
40
60
80
100
120
0 20 40 60 80 100 120
Zinc concentration, Day -7 (ug/dL)
Zincconcentration,Day0(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
39. 70
75
80
85
90
95
0 5 10 15 20 25 30 35 40 45
Study Day
PlasmaZincConcentration(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
et al, J Nutr, in press.
Period of supplementation
* Groups were significantly different on days 5, 9, 14, 21, 22, 23, 26, 30, and 35
***
*
*
*
*
*
*
40. Change in plasma zinc concentration (PZC), by
initial PZC and study group, day 14 of study
N = 58. Data from Wessells KR
et al, J Nutr, in press.
*
Placebo group
41. 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
Adjustedchangeinzincconc.(µg/dL)
42. Effects of meals and time of day on plasma
zinc concentration
King J et al. J Nutr, 1994.
43. 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.
44. 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 &
females
Males
Non-
pregnant
females
Morning
fasting
na 70 74
Morning other 65 66 70
Afternoon 57 59 61
Hotz C et al. AJCN, 2004
45. 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
46. 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”)
47. 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
48. 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)
50. 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.
51. 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
52. 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
Changeinplasmazincconc(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
53. 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
Zn
Zn
[Zn]
55. 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
57. 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
58. 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)
60. Conclusions
• Consistent, moderately large increase in
serum zinc concentration
• Decreased incidence of diarrhea
• Decreased incidence of pneumonia
• Decreased mortality among LBW infants,
older children
61. 0
0.2
0.4
0.6
0.8
1
1.2
TAZ(mg)
0
0.5
1
1.5
2
TAZ(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
TAZ(mg)
0
0.1
0.2
0.3
0.4
TAZ(mg)
Sandström, 1980
Refined wheat
Sandström, 1980
Whole wheat
0.4 3.6 1.3 3.5
1.2 30 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
62. FAZ and TAZ, by amount of zinc intake
from meals containing fortified foods
0 2 4 6 8 10 12
0.0
0.5
1.0
1.5
2.0
2.5
3.0
Zinc intake at breakfast and lunch (mg)
Absorbedzinc(mg)
y = 0.45 + 0.148x - 0.0056x2
( )( )
0 2 4 6 8 10 12
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
Zinc intake at breakfast and lunch (mg)
Fractionalabsorptionofzinc
y = 0.50 - 0.079x + 0.0042x2
( )
López de Romaña et al. Am J Clin Nutr, 2005
63. 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
