1. Research gaps and constraints to
mainstreaming biofortification as a
public health and nutrition
intervention
Marjorie Haskell
Program in International and
Community Nutrition
University of California, Davis

2. 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 populations
consuming biofortified staple foods
– Vitamin A status improves in populations consuming
biofortified staple foods

3. 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

4. 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

5. Can PVA-carotenoid biofortified staple foods
improve vitamin A status in populations at risk
of vitamin A deficiency?

6. 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

7. 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

8. 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

9. 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?

10. 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

11. 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

12. 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

13. 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

14. 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:

15. 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

16. Breastmilk vitamin A response to vitamin A
fortified MSG in lactating Indonesian women
Muhilal, AJCN, 1988

17. 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

18. 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
Logcandela/m2
Initial
Final
a,b a,b a,b a,b
b
a

19. 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)
Final means with different superscript letters are different, p<0.02, n=353
Initial and final plasma β-carotene in pregnant
Nepali women initially reporting night blindness
Plasmaβ-caroteneµmol/L
Haskell et al., AJCN, 2005

20. Initial and final plasma retinol in pregnant Nepali
women initially reporting night blindness
= mean value for comparison women (1.03 mol/L)
Final means with different superscript letters are different, p<0.05, n=353
Hi Vi t A Lo Vi t A Ul tra-ri ce Li ver Greens Carrots
0.00
0.30
0.60
0.90
1.20
1.50
Plasmaretinol,µmol/L
Initial
Final
a
b,c
a a,b
c
a
a
Haskell et al., AJCN, 2005

21. 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.

22. 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.

23. Thank you

24. 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