Mainstreaming iron and zinc biofortification
programs
Kenneth H Brown
Shawn K Baker
Program in International and Community...
Navajo rugs
Navajo rugs – tourists’ perspective
Navajo rugs – Navajo perspective
Perspectives on nutrition intervention programs:
health scientist, policy maker, program manager
Health scientist
Prevalen...
Steps in scaling up nutrition intervention
programs – advocacy issues
Establish
scientific
consensus
Select
intervention
s...
• Agricultural specialists primarily
responsible for intervention
• Dual targets
– Farmers
– Consumers
• Invisible
Special...
Activities required for scaling up biofortification
programs, and responsible parties
Activity Discipline Sector
Populatio...
Activities required for scaling up biofortification
programs, and responsible parties
Activity Discipline Sector
Populatio...
Activities required for scaling up biofortification
programs, and responsible parties
Activity Discipline Sector
Populatio...
Activities required for scaling up biofortification
programs, and responsible parties
Activity Discipline Sector
Populatio...
Activities required for scaling up biofortification
programs, and responsible parties
Activity Discipline Sector
Populatio...
Activities required for scaling up biofortification
programs, and responsible parties
Activity Discipline Sector
Populatio...
Activity Discipline Sector
Produce, distribute seeds Plant science,
commerce
Public, pvt
Activities required for scaling u...
Activity Discipline Sector
Produce, distribute seeds Plant science,
commerce
Public, Pvt
Social mobilization (farmers,
con...
Activity Discipline Sector
Produce, distribute seeds Plant science,
commerce
Public, Pvt
Social mobilization (farmers,
con...
Activity Discipline Sector
Produce, distribute seeds Plant science,
commerce
Public, Pvt
Social mobilization (farmers,
con...
Activity Discipline Sector
Produce, distribute seeds Plant science,
commerce
Public, Pvt
Social mobilization (farmers,
con...
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-
sup...
Median rice and zinc intakes, Bangladeshi
children and women
Children Women
Rice (g/d) 134 420
Zinc (mg/d) 2.5 5.4
Phytate...
Estimated prevalence of inadequate zinc
intakes by assumed coverage of biofortification
Baseline 15% 35% 70%
Children 22 1...
Pre-schoolers
Adolescents
Adult males
Pregnant women
Elderly
Schoolers
Efficacy research Flour consumption Pgm impact?
Pop...
Mean change in plasma zinc concentration (ug/dL),
following 6 months of zinc supplementation or
fortification* among young...
Time line for developing nutrition
intervention programs
Development
of scientific
evidence
Development
of scientific &
po...
Conclusions
• Epidemiology of iron and zinc deficiency uncertain
– Information needed!
• Biofortification interventions ar...
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 bree...
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 supple...
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)
Changeinp...
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-subjec...
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 ...
Change in plasma zinc concentration (PZC), by
initial PZC and study group, day 14 of study
N = 58. Data from Wessells KR
e...
Mean change in plasma zinc concentration (μg/dL)
following 15 days of zinc supplementation or
fortification* among young S...
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 (signifi...
Suggested cutoffs for assessing serum zinc
concentration (NHANES II)
Time of day
and fasting
status
Serum zinc concentrati...
Rationale for using serum zinc concentration for
assessing population risk of zinc deficiency
• Reflects zinc intake over ...
Some caveats…
• Issues of confounders and contamination
– Samples should be collected at fixed time of day and
in relation...
Acknowledgements
UC Davis/WHNRC/CHORI
Grant Aaron
Joanne Arsenault
Reina Engle-Stone
Sonja Hess
Josh Jorgenson
David Killi...
Impact of zinc fortification of wheat flour* on
mean serum zinc conc (μg/dL), China
Month of
study
EDTA arm Elemental iron...
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 ...
Serum zinc concentration in relation to acute
phase proteins (Bangladesh; n = 279 children)
Nl CRP,
AGP
(n=211)
↑CRP only
...
Mean change in plasma zinc concentration (μg/dL)
following 15 days of zinc supplementation or
fortification* among Senegal...
The roles of zinc transporters in maintaining
intracellular zinc concentration
[Zn]
ZnT family of
transporters
[Zn]
ZIP fa...
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...
www.IZiNCG.org
Global prevalence of zinc deficiency
• Little information available based on biomarkers of zinc status
• Current estimates...
Supplementation recommended for…
Treatment of diarrhea - twice age-specific RDA/day (10-20
mg) X 10-14 day, distributed wi...
Baqui(2003)
Baqui(2003)FeCastillo-Duran(1995)
Brown(2007)Wuehler(2007)3mgOsendarp(2002)Wuehler(2007)7mg
Hong(1992)
Cavan(1...
Conclusions
• Consistent, moderately large increase in
serum zinc concentration
• Decreased incidence of diarrhea
• Decrea...
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, 20...
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
Zi...
Factors affecting serum zinc concentration
• Serum zinc concentration vary by
– Age group
– Sex
– Time of day of blood col...
Brown nutrition fe zn
Brown nutrition fe zn
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Brown nutrition fe zn

  1. 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
  2. 2. Navajo rugs
  3. 3. Navajo rugs – tourists’ perspective
  4. 4. Navajo rugs – Navajo perspective
  5. 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. 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. 7. • Agricultural specialists primarily responsible for intervention • Dual targets – Farmers – Consumers • Invisible Special aspects/challenges of biofortification programs
  8. 8. Activities required for scaling up biofortification programs, and responsible parties Activity Discipline Sector Population nutr assessment Nutrition Academia
  9. 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. 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. 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. 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. 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. 14. Activity Discipline Sector Produce, distribute seeds Plant science, commerce Public, pvt Activities required for scaling up biofortification programs, and responsible parties
  15. 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. 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
  17. 17. 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 Monitoring Agr, Nutr, Mkt Public, Acad, Pvt Activities required for scaling up biofortification programs, and responsible parties
  18. 18. 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 Monitoring Agr, Nutr, Mkt Public, Acad, Pvt Evaluation Agr, Nutr Public, Acad Activities required for scaling up biofortification programs, and responsible parties
  19. 19. How nutrients in fortified foods reach young children Directly via food Indirectly via breast milk
  20. 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. 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. 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
  23. 23. 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
  24. 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. 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. 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!
  27. 27. Thanks!
  28. 28. Children consumed ~22-25 g porridge/d (~3.3 mg additional zinc in zinc-fortified group)
  29. 29. Can mass fortification programs improve young children’s nutritional status health and survival?
  30. 30. So…, can fortified foods enhance young children’s nutritional status?
  31. 31. 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
  32. 32. Simulations of potential impact of fortified foods on young children’s nutrient intakes
  33. 33. 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
  34. 34. Results of EURRECA systematic review Data from Lowe NM. AJCN, 2009
  35. 35. 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
  36. 36. 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
  37. 37. 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 *** * * * * * *
  38. 38. 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
  39. 39. 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)
  40. 40. Effects of meals and time of day on plasma zinc concentration King J et al. J Nutr, 1994.
  41. 41. 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.
  42. 42. 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
  43. 43. 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
  44. 44. 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”)
  45. 45. 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
  46. 46. 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)
  47. 47. IZiNCG Publications Available on the IZiNCG web site: www.izincg.org
  48. 48. 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.
  49. 49. 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
  50. 50. 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
  51. 51. 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]
  52. 52. Am J Clin Nutr 80:1570-3, 2004
  53. 53. 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
  54. 54. www.IZiNCG.org
  55. 55. 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
  56. 56. 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)
  57. 57. Baqui(2003) Baqui(2003)FeCastillo-Duran(1995) Brown(2007)Wuehler(2007)3mgOsendarp(2002)Wuehler(2007)7mg Hong(1992) Cavan(1993) Brooks(2005) Lind(2004) Lind(2004)Fe Penny(2004) Ruz(1997) Sazawal(1996)Sempertegui(1996)Wuehler(2007)10mg Rosado(1997)Rosado(1997)FeSandstead(1998)Udomkesmalee(1992) Friis(1997) Rahman(2001)Rahman(2001)Vit.A Rosado(2006)Rosado(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
  58. 58. Conclusions • Consistent, moderately large increase in serum zinc concentration • Decreased incidence of diarrhea • Decreased incidence of pneumonia • Decreased mortality among LBW infants, older children
  59. 59. 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
  60. 60. 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
  61. 61. 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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