Jere D. HaasCornell University

Ithaca, NY, USA

First Global Conference on BiofortificationWashington, DC

November 9, 2010

(From Hotz & McClafferty, Food and Nutrition Bulletin, 2007;28:S271-79) 2

Challenges for Iron and Zinc Biofortification

Measuring biological response to changes in iron and zinc ingestion

Testing efficacy and effectiveness of iron and zinc biofortification interventions

Demonstrating benefits versus costs of iron and zinc biofortification intervention strategies

3

Measuring biological response to changes in iron and zinc ingestion

Constraints to observing significant improvements in iron and zinc status from consumption of biofortified staple foods

Low concentrations of nutrients in biofortified

staple crops

Post harvest processing reduces iron and zinc content in some staple foods

Low bioavailability of iron and zinc in plant based diets

4

Assessing Bioavailability

Methodological constraints for assessing bioavailability

Conceptual constraints affecting the assessment bioavailability

Conceptual constraints affecting response to low nutrient bioavailability

5

Methodological constraints to assessing bioavailability

Intrinsic versus extrinsic labeling with stable isotopes

Use of animal models and in vitro methods to screen staple crop varieties

Use of algorithms to evaluate diets containing biofortified foods

6

Conceptual constraints for assessing bioavailability

Should we concentrate only on the upper small intestine?

Are there other methods that can estimate bioavailability?

Do we have sufficient information on bioavailability for the high risk populations and high risk segments of these population?

7

Conceptual constraints affecting the response to low nutrient bioavailability

How much can food processing of staple foods affect mineral bioavailability ?

Should plant breeding objectives focus more on modifying inhibitors and enhancers of absorption?

8

Measuring biological response to biofortificationWide array of iron status indicators reflecting

various stages of iron metabolism

Very limited biomarkers to assess zinc status

Some conventional markers are not sufficiently sensitive to changes in status in response to increased iron and zinc intakes

intrinsic environmental factors like inflammation and parasitic infections confound interpretation of biomarkers

Measuring functional outcomes of changes in iron and zinc status 9

Figure 1

Fe stores

Ferritin

Hemoglobin

anemiaIDNA

IDNA=Iron Deficient Non-Anemic

FEP & sTfR

TS

Relationship between various indicators of iron status and the body’s level of iron stores

Modified from Guthrie and Picciano, Human Nutrition, 1995

Measuring biological response to biofortificationWide array of iron status indicators reflecting

various stages of iron metabolism

Very limited biomarkers to assess zinc status

Some conventional markers are not sufficiently sensitive to changes in status in response to increased iron and zinc intakes

intrinsic environmental factors like inflammation and parasitic infections confound interpretation of biomarkers

Measuring functional outcomes of changes in iron and zinc status 11

Assessing efficacy and effectiveness Efficacy requires strict controls on the experimental

situation which is required given low nutrient density and bioavailability

Efficacy must be shown in order to justify effectiveness studies.

How can we expand the scope of efficacy studies to better inform subsequent effectiveness studies?

Efficacy studies could be the best place to study the relation of functional outcomes to change in biomarkers

Can populations consume enough of the biofortified staple food under real life conditions to achieve a measurable difference in iron or zinc status?

What are reasonable expectations for response to biofortification in effectiveness studies? How much time is required to observe effectiveness?

12

Assessing efficacy and effectiveness Efficacy requires strict controls on the experimental

situation which is required given low nutrient density and bioavailability

Efficacy must be shown in order to justify effectiveness studies.

How can we expand the scope of efficacy studies to better inform subsequent effectiveness studies?

Efficacy studies could be the best place to study the relation of functional outcomes to change in biomarkers

Can populations consume enough of the biofortified staple food under real life conditions to achieve a measurable difference in iron or zinc status?

What are reasonable expectations for response to biofortification in effectiveness studies? How much time is required to observe effectiveness?

13

14

1

1.5

2

2.5

3

3.5

4

4.5

Fin

al

ferr

itin

(ln

ug

/L)

1 2 3Ferritin at baseline (ug/L)

Plasma ferritin after 9 months of consuming

high iron (IR68144) or control (C4) rice

non-anemic at baseline (n=137 )

C4 IR68144

Iron

deficiency

(<12ug/L)

15 33 65

p=.01 p=.02 p=.13

14.418.9

28.4

59.749.9

35.4

15

Changes in body iron (mg/kg) by level of

iron intake from rice over nine months

-10

-5

0

5

10

0 0.5 1 1.5 2 2.5 3

Iron Intake from Rice (mg/day )

Ch

an

ge

in

Bo

dy

Iro

n

(mg

/kg

)

OX

Control Rice High Iron Rice

O,X = mean change in body iron at the mean

value of iron intake from rice

r=.35

Assessing efficacy and effectiveness Efficacy requires strict controls on the experimental

situation which is required given low nutrient density and bioavailability

Efficacy must be shown in order to justify effectiveness studies.

How can we expand the scope of efficacy studies to better inform subsequent effectiveness studies?

Efficacy studies could be the best place to study the relation of functional outcomes to change in biomarkers

Can populations consume enough of the biofortified staple food under real life conditions to achieve a measurable difference in iron or zinc status?

What are reasonable expectations for response to biofortification in effectiveness studies? How much time is required to observe effectiveness?

16

Production efficiency (PE) of Chinese

female cotton mill workers before and

after 12 weeks of iron suplementation

1.6

1.7

1.8

1.9

2

2.1

2.2

Baseline After 12 weeks

PE

(y

ua

n/M

J)

Placebo Control

Iron Supplemented

From Li et al., AJCN 59:908;1994

1.86 1.83 1.85 2.15

P=.001

5% increase in earnings16% improvement in PE

Assessing efficacy and effectiveness Efficacy requires strict controls on the experimental

situation which is required given low nutrient density and bioavailability

Efficacy must be shown in order to justify effectiveness studies.

How can we expand the scope of efficacy studies to better inform subsequent effectiveness studies?

Efficacy studies could be the best place to study the relation of functional outcomes to change in biomarkers

Can populations consume enough of the biofortified staple food under real life conditions to achieve a measurable difference in iron or zinc status?

What are reasonable expectations for response to biofortification in effectiveness studies? How much time is required to observe effectiveness?

18

19

Dietary source of iron during

9 month feeding trial in Philippine women

0

2

4

6

8

10

12

14

16

18

Control High Iron

Rice group

Iro

n c

on

su

mp

tio

n

(mg

/da

y)

Rice iron

Non-rice iron

RDA for

women

44% to

46% of

RDA

46% to

56% of

RDA

+0.36 mg

+1.77 mg

n=138

20

Fe required (mg/d)

0

2

4

6

8

10

12

14

16

18

20

0 10 20 30 40 50 60 70 80 90 100

Estimated percentile of Requirement

Fe

re

qu

ire

me

nt

(mg

/d)

range of habitual intakes

in Filipino women

The distribution of Fe requirements is modeled from a factorial accounting for body size, age, menstrual blood loss, and contraceptive use (IOM 2001). A Monte Carlo simulation with n>1000 was used.

8 mg/d intake is sufficient for only 50% of women

10 mg/d is sufficient for 73% of women

Meeting dietary iron requirements at two levels of intake from rice

Assessing benefits relative to costs

There is a need to updated estimates from previous ex ante analysis of the impact of biofortification

Better measures of benefit (functional outcomes) can strengthen assumptions and calculations of benefit-cost ratios

Policy makers need thoughtful and understandable translation of good science to inform their decisions.

21

Relationship between work output and work input in iron deficient and healthy subjects.

Constant Work Output

Lo Work input (kcals) Hi

Wo

rk o

utp

ut

(w

att

s)

Healthy

Fe Def

An iron deficient person performs the same amount of work as a healthy person but at higher energetic cost (effort)

It follows that for the same amount of effort the iron deficient person produces less than the healthy person

Iron deficiency effects on work output (productivity) must also consider work input (kcals) and efficiency

23

Differences in dietary iron intake between control

and high iron rice groups

Iron concen-tration1

(ppm)

Rice intake1

(g/d)

Iron intake

from rice1

(mg/d)

Iron intake-

total diet1

(mg/d)

Control Rice

(n=69)0.57+0.08 623+133 0.36+0.09 8.3+1.8

High Iron Rice

(n=69)3.21+0.26 553+120 1.77+0.41 10.0+1.9

Difference

(relative to control rice)

2.80 ppm

5.6-fold increase

-70 g

11% less

1.41 mg

5-fold increase

1.69 mg

20% increase

1Means+SD

JB

24

Probability of inadequate intake v. usual intakes

0

2

4

6

8

10

12

14

16

18

20

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

probability of inadequate intake

Fe

in

tak

es

(m

g/d

)

without biofortification

43% probability of

inadequate intake

21% probability

of inadequate

intake

with biofortification

The probability of an inadequate intake of iron is reduced as iron intake increases. The “gain” however is not equivalent in all parts of the distribution curve.

a probability of 1 has been assigned for all usual intakes<2.5% of requirement and a

probability of 0 has been assigned to all usual intakes >97.5 percentile of requirement.

Probability of inadequate total daily iron intake at two levels of iron from rice