Kathryn G. Dewey, PhD Program in International & Community Nutrition

1. Design and evaluation of a lipid-based nutrient supplement to enrich local complementary foods: Results from Ghana Kathryn G. Dewey, PhD Program in International & Community Nutrition University of California, Davis

2. Complementary feeding (6-24 mo): need for fortified products • Difficult to meet nutrient needs of infants (especially iron & zinc) without fortified foods • Commercially produced fortified complementary foods are being evaluated in several countries – key issue is cost • Home-fortification of complementary foods is a less costly alternative • Sprinkles (micronutrients only) • Lipid-based products (e.g. “Nutributter”)

3. Advantages of lipid-based products for home fortification • Stable, resistant to spoilage, prevent micronutrients from interacting • Provide some additional energy (and increase energy density of complementary foods) • Provide essential fatty acids • May enhance absorption of fat-soluble vitamins • Taste good; can mask taste of other nutrients such as B vitamins • Can be consumed alone or mixed with other foods • Can easily divide the dose during the day • Can be locally produced & stimulate local economy

4. Randomized controlled trial of home fortification of complementary foods with 3 types of micronutrient supplements in Ghana S Adu-Afarwuah1, A Lartey2, KH Brown1, A Briend3, S Zlotkin4, KG Dewey1 1Prog. Intl. Nutr., UC Davis 2 Univ. of Ghana, Legon 3 Inst. de Recherche pour le Développement, Paris, France 4 Hospital for Sick Children, Univ. of Toronto, Canada

5. Study design • At 6 mo, infants (n=313) randomly assigned to receive supplement daily, 6-12 mo • Sprinkles (Fe, Zn, Vit A, Vit C, folate) • Nutritabs (all of the above plus 11 other micronutrients) • Nutributter (19 micronutrients plus fat; 108 kcal/d) • Anthropometric & biochemical assessment at 6 & 12 mo; diet & morbidity assessed weekly; motor development observed at 12 mo • Non-intervention group (n=96), eligible but not randomly selected for the intervention, assessed at 12 mo only

6. Sprinkles (SP) (per sachet/d) • Vitamin A (μg RE) 300 • Vitamin C (mg) 50 • Vitamin D3 (μg) 7.5 • Folic acid (μg) 150 • Iron (mg) 12.5 (microencapsulated, fumarate) • Zinc (mg) 5 (gluconate)

7. Nutritabs (NT) (per tablet/d) • Vitamin A (μg RE) - 400 • Vitamin C (mg) - 30 • Folic acid (μg) - 80 • Vitamin B1(mg) - 0.3 • Vitamin B2(mg) - 0.4 • Vitamin B3(mg) - 4.0 • Pantothenic acid (mg)- 1.8 • Vitamin B6(mg) - 0.3 • Vitamin B12 (μg) - 0.5 • Iron (mg) - 9.0 (sulfate) • Zinc (mg) - 4.0 (oxide) • Calcium (mg) - 100 (carbonate) • Potassium (mg) - 152 (chloride) • Copper (mg) - 0.2 (sulfate) • Selenium (μg) - 10 (sodium selenite) • Iodine (μg) - 90 (potassium iodate)

8. Nutributter (NB) (per 20 g dose/d) Based on RNI, 6-12 mo • Vitamin A (μg RE) - 400 • Vitamin C (mg) - 30 • Folic acid (μg) - 80 • Vitamin B1 (mg) - 0.3 • Vitamin B2 (mg) - 0.4 • Vitamin B3 (mg) - 4.0 • Pantothenic acid (mg) - 1.8 • Vitamin B6 (mg) - 0.3 • Vitamin B12 (μg) - 0.5 • Iron (mg) - 9.0 (sulfate) • Zinc (mg) - 4.0 (sulfate) • Copper (mg) - 0.2 (sulfate) • Selenium (μg) - 10 (sodium selenite) • Iodine (μg) - 90 (potassium iodate) • Calcium (mg) - 100 (phosphate) • Potassium (mg) - 152 • Total energy (kcal) - 108 • Linoleic acid (g) - 1.29 • Linolenic acid (g) - 0.29 RNI minus amount from other sources RNI minus amount from other sources Plus some P, Mg and Mn, mainly from the ingredients

9. Study design Potential participants: n=612 Approx. 75% randomly selected for intervention at 5 mo (n=442) Not selected at 5 mo (n=170) Randomized into 3 Intervention groups at 6 mo (n=313) SP: n=105 NT: n=105 NB: n=103 SP: n=98 NT: n=102 NB: n=98 NI: n=96 SP= Sprinkles; NT=Nutritabs; NB= Nutributter; NI=Non-intervention

10. Seth Adu-Afarwuah explains some details to study mother Picture by Dr. K.H. Brown

11. A child at 9 mo being weighed in her home Picture by Seth Adu-Afarwuah, UCD and Univ. of Ghana,

12. Measuring the head circumference of a nine-month-old boy in his home Picture by Seth Adu-Afarwuah, UCD and Univ. of Ghana,

13. A field worker demonstrates to a study mother how she should administer Nutritabs to her child. We provided a plastic cup and a stainless steel spoon to the mother to help her measure the appropriate amount of food (about 3 spoonfuls) and mix it with the supplement. Picture by Dr. K H Brown, UCD

14. Assessment of motor development at 12 mo at the laboratory. The little girl holding the table is going through the “standing with assistance” procedure, whilst the other boy has already been through all the assessment procedures. Picture by Seth Adu-Afarwuah, UCD and Univ. of Ghana,

15. Iron status: Ferritin < 12 ug/L at 12 mo b a a a

16. Anemia: Hemoglobin < 100 g/L at 12 mo b a a a

17. Growth and energy intake from CF, 6-12 mo SP = Sprinkles; NT= Nutritabs; NB = Nutributter; CF = Complementary foods.

18. Length-for-age z-scores of intervention (SP, NT, NB) and non-intervention (NI) groups NB SP, NI NT SP=Sprinkles; NT=Nutritabs; NB=Nutributter; NI=Non-intervention

19. Motor development: % walking at 12 mo a a a b

20. What is responsible for improved outcomes in the Nutributter group? Possible explanations: • Increased energy intake • Favorable ratio of essential fatty acids • Inclusion of milk

21. Path analysis of observed effects Potential intermediary variables: -Energy from CF -FA status Dependent variables: -Weight gain -Length gain Exogenous variable: Group assignment

22. Does increased energy from CFs explain effect of Nutributter on weight and length gain? Controlling for baseline values, child sex and maternal height. SP=Sprinkles, NT=Nutritabs, NB=Nutributter. Answer: Yes (partially) for weight gain; No for length gain

23. Plasma fatty acid analyses • Individual fatty acids and fatty acid classes • 14:0, 16:0, 18:0, 20:0, 22:0 and 24:0 • 16:1n7, 18:1n7, 18:1n9, 20:1n9 and 24:1n9 • 18:2n6, 18:3n6, 20:2n6, 20:3n6 and 20:4n6 • 18:3n3, 20:5n3, 22:5n3 and 22:6n3 • Total fatty acids • Saturated fatty acids (SFA) • Monounsaturated fatty acids (MUFA) • n-6 fatty acids • n-3 fatty acids • Polyunsaturated fatty acids (PUFA) • Ratios • PUFA:SFA • n-6:n-3 PUFA

24. Plasma α-linolenic acid (mg/L) at 12 mo 1 Mean ± SD adjusted for baseline values, mean BF frequency at 6-12 mo and sex; 2 Mean ± SD adjusted for BF frequency in the week prior to 12 mo and sex. ** Different from NB, p< 0.05; * Different from NB, p <0.08.

25. Plasma DHA (mg/L) at 12 mo 1 Mean ± SD adjusted for baseline values, mean BF frequency at 6-12 mo and sex; 2 Mean ± SD adjusted for BF frequency in the week prior to 12 mo and sex.

26. Plasma saturated fatty acids (% total) at 12 mo 1 Mean ± SD adjusted for baseline values, mean BF frequency at 6-12 mo and sex; 2 Mean ± SD adjusted for BF frequency in the week prior to 12 mo and sex. ** Different from NB (p< 0.05).

27. Correlations of plasma fatty acids at 12 mo with weight and length gain 6-12 mo 1 Pearson correlation coefficient for all children in intervention groups. Adjusted for baseline FA values, mean BF frequency at 6-12 mo of age and child sex

28. Do changes in fatty acid status explain the effect of Nutributter on growth 6-12 mo? Controlling for baseline values, child sex and maternal height. SP=Sprinkles, NT=Nutritab, NB=Nutributter Answer: Yes (partially) for length gain; No for weight gain

29. Summary of potential explanations • Nutributter increased energy intake from comp. foods, increased blood PUFA levels (+33-40% in ALA) and decreased blood SFA levels. • Path analysis suggests that • Increased energy intake from CFs explained (part of) the impact on weight gain, but not length gain • The shift in plasma FA explained (part of) the impact on length gain, but not weight gain • However, growth effect could also be due to milk content

30. Acceptability • Supplement consumption (% of days, 6-12 mo): SP 86%, NT 88%, NB 88% • Child accepted food “well” when mixed with supplement: SP 90%, NT 78%, NB 86% • > 97% of mothers in all 3 groups a) liked giving the supplement, b) thought it helped child’s health & c) wanted to purchase in future

31. How much willing to pay? (US cents/day) * p < 0.05; ** p < 0.01

32. Summary of results • All 3 supplements were well accepted • All 3 supplements improved iron status compared to the Non-Intervention group • Only Nutributter improved growth • Motor development was improved by all 3 supplements, but the effect was largest with Nutributter • Providing a larger set of micronutrients in a lipid-based product (with milk powder?) confers benefits beyond those of providing just a few selected key micronutrients

33. Lipid-based Nutrient Supplements (LNS): Convergence of approaches for treatment (SAM/mod malnut) & primary prevention? • RUTF (LNS in large doses) effective & feasible for treatment of SAM in the community • LNS (moderate dose) more effective than cereal-legume blends for supplementary feeding of moderately malnourished children • LNS for home fortification (small daily dose) more effective than preparations with micronutrients only Daily ration of LNS can be chosen based on needs of target population & cost constraints Goal: integrate CTC with programs for prevention of malnutrition

34. LNS Network • Development and evaluation of lipid-based nutrient supplements (LNS) for prevention of malnutrition: an innovative food-based approach • University of California, Davis, USA • University of Tampere, Finland • University of Malawi • University of Ghana • Many advisors and observers

35. Research agenda, LNS Network • Development and testing of new LNS formulations and doses for children 6-24 mo • EFA content, zinc content, milk + / -, ration/day • Supplementation of pregnant and lactating women • Large-scale effectiveness trials (primary outcome: stunting) • Socio-economic studies; cost-benefit evaluation • Partnerships and scaling up LNS interventions

36. Publications (Ghana study) • Adu-Afarwuah, S., Lartey, A., Brown, K. H., Zlotkin, S., Briend, A. and Dewey, K. G. (2007), Randomized comparison of 3 types of micronutrient supplements for home fortification of complementary foods in Ghana: effects on growth and motor development, Am J Clin Nutr, 86: 412-20. • Adu-Afarwuah, S., Lartey, A., Brown, K. H., Zlotkin, S., Briend, A. and Dewey, K. G. (2008), Home fortification of complementary foods with micronutrient supplements is well accepted and has positive effects on infant iron status in Ghana, Am J Clin Nutr, 87: in press.

37. Acknowledgments (Ghana study) • Nestle Foundation and the Human Nutrition Institute of the International Life Sciences Institute (via USAID) for funding • Regional and municipal health administration, and laboratory staff in Koforidua, Ghana • Study team, nurses, mothers in Ghana • Laboratory of Dr. Bruce German at UC Davis for fatty acid analyses • Diane Vandepeute for administrative support at UC Davis • Jan Peerson for statistical support at UC Davis

38. Project staff in Koforidua, Ghana Picture by Unknown