Are we overdoing it with micronutrient supply to pre-

schoolers?Omar Dary USAID, Bureau for Global Health, Nutrition

DivisionMicro-University

Washington DCMarch 7th, 2014

OD-2014-6

2

Types of nutrients needed for a healthy life

MacronutrientsFats

ProteinsCarbohydrates

EnergyBuilding Blocks

Semi-micro nutrients

Essential fatty acids and

amino acids,Ca, Mg, P

MembranesEnzymes

Hard structuresGenetic material

MicronutrientsVitamins and

Minerals

CatalysisRegulation

Function, Vision

3

Specific nutritional deficiencies (old name)

CharacteristicsConsequences are independent from the protein-energy intake (i.e. quality

of the diet is essential)*

Traditional(1990 Children Summit)

Iodine, Vitamin A, Iron (the “big three”)

Nowadays(in addition to the big 3)

Developed Developing

Folate, Vit. D,Vit. C

Zinc, Vit. B12, Vit. B2

Calcium

* “Hidden Hunger”

Fetus Abortion Stillborn Congenital abnormalities Perinatal mortality Infant mortality Neurologic cretinism: Mutism, mental retardation – deafness Endemic cretinism: dwarfism/ mental deficiency Psychomotor impairment

Infant Hypothyroidism / Irreversible mental retardation Children and adolescent

IQ reduced / Goiter / Hypothyroidism / Impaired physical and mental development

Adult Goiter and complications Hypothyroidism

Consequences of iodine deficiency

4 4

5

Consequences of vitamin A deficiency

• Deterioration of ocular conjunctive and cornea

• Less capacity to fight infections

• Alterations in growth and development

• Impaired visual and reproductive capability

• Night blindness• Permanent blindness• Death

Neural tube defects within 28 days after conception.

Discapacities:• Leg paralysis• Anencephaly• Bad control of bladder and

intestinal evacuations• Learning difficulties

Modified from Jorge Rosenthal

Consequences of folate and B12 deficiencies

6 6

7

Do these nutrients have any adverse effect?

Nutrient Temporal Permanent

IodineHyperthyroidism

(in population that were iodine deficient)

Thyroid Cancer(in adults from all sources

of iodine)

Vitamin A (as retinol)

Intra-craneal pressure (infants and young children)

Teratogenic Effects (fetus)

Bone fragility (adults)

Folic acid*(*precursor of folate that requires B2, B6,

B12, niacin)

Triggering of certain cancers (colon, prostrate)

Antagonist of anti-cancer, and eczema

treatments

Brain damage due to masking of

megaloblastic anemia due to B12 deficiency

(elderly)

Lack of evidence does not mean absence of adverse effects.

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Cumulativerisk of deficiency

Cumulativerisk of toxicity

Distributionof requirements

Distribution ofrisk of toxicity

Acceptable Rangeof Oral intake

(AROI )

Total oral intake

NormalHomeostasis

A BDose

Perc

enta

ge o

f po

pula

tion

at r

isk 100 100

50 50

EAR

RNI

LOAEL

NOAEL

UF

UL

Modified from the International Programme on Chemical Safety (IPCS), 2002.

How to estimate safety?

9Figure modified from Institute of Medicine, the Academies of Science, USA..

An example with iodine (DRI values for 1-3 year old children)

65 90 200 Iodine: µg/d

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Estimating efficacious iodine content for salt

Parameter Ch 1-3 F 19-30 Pregnant Lactating M 19-30

“EAR” (µg I/d) 65 95 160 209 95

Energy (kcal/d) 1100 2400 2637 2804 3050

If salt intake by adult male is 10 g/d

3.6 7.8 8.6 9.2 10.0

[I] in salt (mg/kg) 18.0 12.2 18.6 22.7 9.5

Information: In 1996, WHO estimated the iodine content in salt at homes as 15 mg/kg, based on RNI of 150 µg/d of adults and 10 g/d salt intake. For factories, a 33% overage was calculated (15 x 1.33 = 20 mg/kg). Notice that this calculations are for averages and not for minimum values.

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However, the criteria of success is 90% or more samples with a content

of 15 mg iodine/kg

10 40 60

0.15

0.30

0.45

0.60

Content (mg/kg)

Fre

quen

cy

20 50 70 8030

Low variation

Moderate variation

Large variation

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Values of urinary iodine concentration vs performance of the salt iodization

programsCountry

UIC(µg/L)

Median iodine content (mg I/kg)

% salt samples iodine >15 mg/kg

Germany-2004-6(sch. age)

110 15-25 (80% users)

USA 2007-8(6-11 y. old)

215 ? ?

Cambodia-2008(8-10 y. old)

222 7.1 62 %

Guatemala-2011(women)

139 12.2 43 %

Dominican Rep.-15-19 y women

409 21 35 %

In many countries in the world, more than 80% of salt samples contain iodine, and the average content is around 30 mg/kg, and for some 60 mg/kg. Nevertheless, MNP are “universally” formulated with iodine.

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Source : Menchú et al. (INCAP). Estudio complementario la ENCOVI-2006 de Guatemala; 2013.

Dietary availability of vitamin A, Guatemala-2006

Diet adequacy (density)

Safety of retinol (density)

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Source : Menchú et al. (INCAP). Estudio complementario la ENCOVI-2006 de Guatemala; 2013.

Total supply vitamin A (diet+fortified sugar 9 mg/kg)

Diet adequacy (density)

Safety of retinol (density)

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Source : Menchú et al. (INCAP). Estudio complementario la ENCOVI-2006 de Guatemala; 2013.

Total supply vitamin A (diet+fortified sugar+suppl)

Diet adequacy (density)

Safety of retinol (density)

And… the country also introduced MNP with vitamin A !!!

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Reference: Daly LE et al.,J Am Med Sci 1995;274:1698-1762. Data from Ireland.

Folic acid has reduced NTD-affected pregnancies

0

10

20

30

40

0 5 10 15 20 25 30 35 40 45NT

D I

nci

de

nce

/10,

000

Plasma folate (nmol/L)

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Reference: Hirsch et al., J Nutr 2011.

The change of serum folate in Chile after fortification of wheat flour

0

5

10

15

20

25

30

35

40

4 6 8 10 12 14 16 18 20

beforeafter

Serum folate (ng/ml*)

* ng/mL x 2.273 = nmol/L

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Median of serum folate (nmol/L) before and after flour fortification

with folic acidCountries Chile USA C.Rica W.Bank Ecuador

Before 9 10 22 18.5-23.814

After 38 22 25 -

Information: The cut-off point for deficiency of folate is 6.8-10 nmol/L; the cut-off point of 15.9 nmol/L has been proposed for identifying risk of NTD.

Women of child-bearing age

However, folic acid is being incorporated into MNP for children. Do we know that it is needed? Do we know that it is safe?

Countries Ecuador

Before25.4

After

Children 1-5 years oldReference: Data no published of the National Survey of Nutrition, 2013.

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