Design and evaluation of a lipid-based nutrient supplement to enrich local

complementary foods: Results from Ghana

Kathryn G. Dewey, PhDProgram in International & Community NutritionUniversity of California, Davis

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”)

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

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

1 Prog. Intl. Nutr., UC Davis2 Univ. of Ghana, Legon3 Inst. de Recherche pour le Développement, Paris, France 4 Hospital for Sick Children, Univ. of Toronto, Canada

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

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)

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)

Nutributter (NB) (per 20 g dose/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 (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

Plus some P, Mg and Mn, mainly from the ingredients

Based on RNI, 6-12 mo

RNI minus amount from other sources

RNI minus amount from other sources

Study design

Potential participants: n=612

Approx. 75% randomly selected for intervention at 5 mo (n=442)

Not selectedat 5 mo (n=170)

SP: n=98 NT: n=102 NB: n=98 NI: n=96

SP: n=105 NT: n=105 NB: n=103

Randomized into 3 Intervention groups at 6 mo (n=313)

SP= Sprinkles; NT=Nutritabs; NB= Nutributter; NI=Non-intervention

Seth Adu-Afarwuah explains some details to study mother

Picture by Dr. K.H. Brown

A child at 9 mo being weighed in her home

Picture by Seth Adu-Afarwuah, UCD and Univ. of Ghana,

Measuring the head circumference of a nine-month-old boy in his home

Picture by Seth Adu-Afarwuah, UCD and Univ. of Ghana,

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

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,

Iron status: Ferritin < 12 ug/L at 12 mo

0

10

20

30

40

50

60

SP NT NB Control

% lowa

aa

b

Anemia: Hemoglobin < 100 g/L at 12 mo

0

10

20

30

40

50

60

SP NT NB Control

% lowaa

a

b

Growth and energy intake from CF, 6-12 mo

SP (n=96)

NT (n=101)

NB (n=97)

p

Wt gain (kg) 1.39 ± 0.50ab 1.35 ± 0.48a 1.57 ± 0.73b 0.02

Ln gain (cm) 7.9 ± 1.4ab 7.8 ± 1.4a 8.3 ± 1.4b 0.04

Energy from CF(kcal/d, 7-12 mo)

139 ± 76a 133 ± 69a 224 ± 71b <0.0001

SP = Sprinkles; NT= Nutritabs; NB = Nutributter; CF = Complementary foods.

Length-for-age z-scores of intervention (SP, NT, NB) and non-intervention (NI) groups

-0.6

-0.4

-0.2

0

0.2

0.4

0.6

6 12

Age (mo)

LA

Z

NB

NT

SP

NI

SP=Sprinkles; NT=Nutritabs; NB=Nutributter; NI=Non-intervention

SP, NI

NB

NT

Motor development: % walking at 12 mo

0

10

20

30

40

50

60

SP NT NB Control

%

aa

a

b

What is responsible for improved outcomes in the Nutributter group?

Possible explanations: Increased energy intake Favorable ratio of essential fatty acids Inclusion of milk

Path analysis of observed effects

Exogenous variable:

Group assignment

Dependent variables:

-Weight gain

-Length gain

Potential intermediary variables:

-Energy from CF -FA status

Does increased energy from CFs explain effect of Nutributter on weight and length gain?

MeanDiff. from NB

Mean Diff.from NB, with CF energy in model

% Diff. due to CF energy

Mean p Mean p %

Weight gain, kg1

SP group NT group

-0.18-0.20

0.040.02

-0.10-0.11

0.280.25

4346

Length gain, cm1

SP group NT group

-0.39-0.44

0.040.02

-0.46-0.50

0.030.02

N/A

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

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

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.

NI SP NT NB p

3-group comparison1

n/a 5.5 ± 4.9**(n=70)

5.2 ± 2.9**(n=74)

7.3 ± 5.0(n=70)

0.03

4-group comparison2

6.2 ± 5.5*(n=72)

5.6 ± 5.5**(n=76)

5.6 ± 5.5**(n=78)

7.9 ± 5.6(n=71)

0.05

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.

NI SP NT NB p

3-group comparison1

n/a 117 ± 53(n=70)

120 ± 53(n=75)

131 ± 54(n=70)

0.24

4-group comparison2

128 ± 61(n=72)

122 ± 61(n=76)

127 ± 61(n=78)

136 ± 62(n=71)

NS

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).

NI SP NT NB p

3-group comparison1

n/a 38.3 ± 2.1**( n=70)

38.4 ± 2.1**(n=72)

37.5 ± 2.1(n=68)

0.02

4-group comparison2

38.5 ± 2.2**(n=72)

38.2 ± 2.2(n=76)

38.6 ± 2.2**(n=77)

37.7 ± 2.2(n=71)

0.09

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

 Fatty acids Length gain Weight gain

18:3n3 (mg/L) 0.20[p = 0.003]

0.03[p = 0.61]

SFA (% of total) -0.13[p = 0.05]

-0.10[p = 0.45]

Controlling for baseline values, child sex and maternal height.SP=Sprinkles, NT=Nutritab, NB=Nutributter

Mean Diff. from NB

Mean Diff. from NB with ALA in

model

% Diff. due to ALA

Mean Diff. from NB with SFA in model

% Diff. due to SFA

p p % p %

Length gain,cm1

SP group NT group

-0.39-0.44

0.040.02

-0.12-0.29

0.600.19

6934

-0.16-0.35

0.490.12

5921

Weight gain,kg1

SP group NT group

-0.18-0.20

0.040.02

-0.19-0.24

0.060.02

N/A -0.20-0.27

0.050.01

N/A

Do changes in fatty acid status explain the effect of Nutributter on growth 6-12 mo?

Answer: Yes (partially) for length gain; No for weight gain

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

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

How much willing to pay? (US cents/day)

SP NT NB

~5 cents/d 93% 89% 99%*

~8 cents/d 69% 53% 81%**

Mean (SD) 8 (5) 8 (5) 10 (7)**

* p < 0.05; ** p < 0.01

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

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

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

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

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.

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

Project staff in Koforidua, Ghana

Picture by Unknown