Haskell nutrition vit a

Research gaps and constraints to

mainstreaming biofortification as a

public health and nutrition

intervention

Marjorie HaskellProgram in International and Community NutritionUniversity of California, Davis

Biofortification as a strategy for improving

vitamin A status in populations at risk of

vitamin A deficiency

– Biofortification increases the provitamin A (PVA) carotenoid content of staple crops

– Dietary intake of PVA-carotenoids increases in populationsconsuming biofortified staple foods

– Vitamin A status improves in populations consumingbiofortified staple foods

Biofortified staple foods for improving

vitamin A status

Traditional breeding techniques:

High provitamin A sweet potatoes ~100 µg/g

High provitamin A maize ~ 15 µg/g (target level)

High provitamin A cassava ~ 15.5 µg/g (target level)

Transgenic techniques:

High provitamin A rice Golden rice ~37 µg/g

Populations at risk of vitamin A deficiency

Low-income populations in developing countries:

– Infants and young children 6-24 months of age

– Preschool-age children (2-5 y of age)

– Pregnant women

– Lactating women

Can PVA-carotenoid biofortified staple foods

improve vitamin A status in populations at risk

of vitamin A deficiency?

Efficacy/Effectiveness of biofortified foods for

improving vitamin A status in populations at risk of

vitamin A deficiency

Groups at high-risk of Evidence of

VA deficiency: Efficacy/Effectiveness

Infants and young children No data

Preschool-age children OFSP Effective

Pregnant women No data

Lactating women No data

Assessing efficacy of PVA-biofortified staple foods for

improving vitamin A status

Initial

vitamin A

status

Intervention

-biofortified food group

-negative control group

Final

vitamin A

status

Outcome: mean change in vitamin A status

Intervention effect:

Mean change in vitamin A status in biofortified food group

vs.

Mean change in vitamin A status in negative control group

Challenges in evaluating the efficacy of biofortified

foods for improving vitamin A status

1. Biofortified staple foods tend to provide small to

moderate amounts of provitamin A carotenoids

2. Which target groups are most likely to demonstrate

a measureable change in vitamin A status in response

to consumption of biofortified foods?

– infants/young children have small gastric capacity;

limits intake

– initial vitamin A status is important; marginally

deficient individuals more likely to respond

Challenges in evaluating efficacy of food-based

interventions for improving vitamin A status

3. What is the expected impact on vitamin A status in the

selected target group?

– infection may reduce the expected impact; reduced

absorption of PVA-carotenoids/increased utilization of

vitamin A; infection rates tend to be high

4. Which vitamin A status indicator(s) can detect the

expected impact on vitamin A status?

Serum retinol concentration

Olson, 1981

Serum retinol concentration homeostatically controlled;

not an optimal indicator of change in vitamin A status

Serum retinol concentration declines transiently in infection;

difficult to interpret; high infection rates in target populations

Relative dose response tests

Relative dose response tests assess adequacy of liver

vitamin A stores:

– more sensitive than serum retinol concentration

– dichotomous outcome (adequate/inadequate)

– do not provide information on magnitude of change

in vitamin A status in response to an intervention

Stable isotope dilution technique

Stable isotope dilution technique provides a quantitative

estimate of total body vitamin A stores

– provides a quantitative estimate of change in total body

vitamin A stores in response to an intervention

– method is not validated in pregnant or lactating women

or infants

– costly, requires analysis by mass spectrometry

Breastmilk retinol concentration

Breastmilk retinol concentration provides information on

the mother’s vitamin A status

– may also be useful for assessing adequacy of vitamin A

intake in breastfed infants

– milk vitamin A reflects maternal dietary vitamin A intake;

recently absorbed dietary vitamin A is taken-up

directly by the mammary gland

– milk vitamin A is not under homeostatic control; likely

to be more sensitive than serum retinol

Dietary vitamin A rapidly affects milk vitamin A

Akohoue SA, Green JB and Green MH, J Nutr. 136:128-132, 2006

days of lactation

Dietary treatments – Pregnancy/Lactation:

Plasma and liver vitamin A concentrations of pups

of dams fed different levels of vitamin A during

pregnancy and lactation

-VA/-VA -VA/+VA +VA/+VA +VA/-VA

Plasma,

µmol/L 0.78 0.08c 1.02 0.14b 1.15 0.15a 1.02 0.12b

Liver,

nmol/g 38.3 7.29d 143 16b 204 24a 63.6 11.7c

Means SD, means in a row without a common letter differ, P<0.001

Akohoue SA, Green JB and Green MH, J Nutr. 136:128-132, 2006

Breastmilk vitamin A response to vitamin A

fortified MSG in lactating Indonesian women

Muhilal, AJCN, 1988

Dark adaptation as a functional indicator of

vitamin A status

– Nightblindness (impaired dark adaptation) is prevalent

in areas where vitamin A deficiency is endemic

– Dark adaptation can be measured objectively using the

pupillary threshold test

– Nightblindness (impaired dark adaptation) responds to

treatment with small daily amounts of vitamin A

Initial and final pupillary thresholds of pregnant

Nepali women initially reporting nightblindness

= proposed cut-off for abnormal dark adaptation (>-1.11 log cd/m2)

= mean value for non-pregnant US women (-1.35 log cd/m2)

= mean value for non-nightblind Nepali women (-1.42 log cd/m2)

Final means with different superscript letters are different, p<0.02, n=353

Hi Vi t A Lo Vi t A Ul tra-ri ce Li ver Greens Carrots-2.50

-2.25

-2.00

-1.75

-1.50

-1.25

-1.00

-0.75

-0.50

-0.25

0.00

Log c

andela

/m2

In i tial

Final

a,b a,b a,b a,bb

a

0.00

0.03

0.06

0.08

0.11

0.14

0.17

0.19

0.22

Initial

Final

HiVA LoVA Ultra-rice Liver Greens Carrots

Mean value for comparison women (0.087 µmol/L)


Initial and final plasma β-carotene in pregnant

Nepali women initially reporting night blindness

Pla

sm

a β

-caro

ten

e µ

mo

l/L

Haskell et al., AJCN, 2005

Initial and final plasma retinol in pregnant Nepali

women initially reporting night blindness

= mean value for comparison women (1.03 mol/L)


Hi Vi t A Lo Vi t A Ul tra-ri ce Li ver Greens Carrots0.00

0.30

0.60

0.90

1.20

1.50

Pla

sm

a r

eti

no

l, µ

mo

l/L

Initial

Final

a

b,ca a,b

c

aa

Haskell et al., AJCN, 2005

Summary

1. The effectiveness of OFSP for improving vitamin A status in preschool children has been demonstrated.

2. Further evidence on efficacy and effectiveness of the other biofortified staple crops (maize, cassava, golden rice) is needed in populations at risk of deficiency.

3. Target groups and indicators of vitamin A status should be chosen carefully to optimize chances of demonstrating efficacy or effectiveness.

Summary

4. Targeting lactating women may be advantageous because milk vitamin A is likely to be responsive to consumption of biofortified staple foods; and their breastfed infants are likely to benefit from increased milk vitamin A.

5. Dark adaptation is a functional indicator of vitamin A status that is likely to be useful for evaluating the efficacy/effectiveness of biofortified foods.

Thank you

Biofortification is a complementary strategy for

improving vitamin A status

Existing strategies for improving vitamin A status:

– supplementation

– high-dose vitamin A capsules

– children 6 mo to 5 y of age

– women in first 8 wk post-partum

– food fortification

– universal vitamin A fortification of cooking oil, sugar

– targeted vitamin A fortification (infant foods)

– diet diversification; other food-based interventions

Evaluate biofortified staple foods in the context of other

intervention strategies in selected target population

Haskell nutrition vit a

Health & Medicine