IRON ABSORPTION FROM INTRINSICALLY LABELED MICROENCAPSULATED FERROUS FUMARATE (SPRINKLES) IN ANEMIC & NON-ANEMIC INFANTS
M. Tondeur, S. Zlotkin, C. Schauer, S Newton, S Owusu-Agyei: Departments of Paediatrics, Nutritional Sciences, and Centre for International Health, University of Toronto; The Hospital for Sick Children, Research Institute, Canada; The Kintampo Health Research Centre Health Research Unit, Ministry of Health, Ghana.

Microencapsulated ferrous fumarate (Sprinkles) is a new supplement for
‘home-fortification’. The contents of a sachet can be added to any
complementary food without changing the colour or taste. We believe this
intervention may decrease the burden of iron deficiency anemia (IDA) in
the developing world. However, the most appropriate dose of iron (Fe) to
include is not known since its bioavailability has not been studied. Aim:
To determine the absorption of 2 doses of Sprinkles when added to a
complementary food provided to anemic and non-anemic infants.
Methods: In a prospective triple-masked, randomized …

Impact of “Micronutrient Sprinkles” for the Treatment and Prevention of Iron Deficiency in Canadian First Nations and Inuit Infants 4-18 months old.

A. Christofides, S. Zlotkin, C. Schauer. Departments of Paediatrics and Nutritional Sciences, University of Toronto; The Hospital for Sick Children, Research Institute, Canada.

Iron deficiency (ID) is a concern in First Nation (FN) and Inuit infants. H. Pylori infection may contribute to ID. Standard treatment of anemia in infants is ferrous sulphate (DROPS), however, compliance is universally poor. SPRINKLES containing microencapsulated iron in powder form can be easily added to food without organoleptic changes.
Aim: To compare DROPS and SPRINKLES for the treatment and prevention of anemia in FN and Inuit infants.

Methods: A multi-center RCT was performed in Attawapiskat, Fort Albany and Igloolik (total N=94). Anemic infants (Hb?100 g/L) were randomized to DROPS (30 mg Fe/day) or SPRINKLES (60 mg Fe/day) for 3 mo. Non-anemic infants (Hb>100 …

Fortification:

The fortification of staple foods such as wheat or other grains is likely to increase iron intake for those populations that have
access to them. However, infants and children who have a limited capacity to eat large quantities of fortified food are not likely
to benefit significantly form this strategy. Targeted fortification (for example, the fortification of weaning foods specifically
eaten by infants and children) as is practiced by the developed world, is an excellent way to increase the intake of iron in children.
However, fortified commercially prepared infant foods are relatively expensive and may not be affordable for many families with
children at highest risk of iron deficiency (Taken from Zlotkin, 2002-Editorial Current Issues for the prevention of iron deficiency
anemia).

Dietary Diversification:

Dietary diversification involves promotion of a diet with a wider variety of iron-containing foods, especially meat or fish. This
intervention is often not possible …

Iron is involved in the transport of oxygen and cellular respiration as a component of hemoglobin, myoglobin and the enzymes: cytochrome oxidase, peroxidase and catalase.

Physiology

In the gut, ferric iron is converted to ferrous iron (the soluble form) in the presence of the acidic pH of the stomach. Luminal iron-binding proteins facilitate the absorption of iron across the intestinal mucosa. Iron is stored in the body as ferritin and hemosiderin in the liver, bone marrow and spleen. A significant portion of iron in the body is a component of hemoglobin and myoglobin. The remainder is bound to iron transport proteins and enzymes.

Food Sources

Heme iron is best absorbed and is found in red meats and liver, heart and kidney. Less bioavailable sources of iron include green leafy vegetables and whole grain cereals.

Deficiency

A deficiency of iron may lead to anemia with physical signs including weakness, fatigue, poor …

Articles:

2) Presented at the FASB Experimental Biology conference in Orlando, Florida, 2001:

PART 1. RANDOMIZED PROSPECTIVE CONTROLLED TRIAL OF FERROUS SULFATE DROPS VERSUS MICRONENCAPSULATED FERROUS FUMARATE ‘SPRINKLES’ FOR TREATMENT OF ANEMIA IN GHANAIAN INFANTS AND YOUNG CHILDREN. Stanley Zlotkin, Paul Arthur, Kojo Yeboah Antwi, George Yeung. Dept of Paediatrics and Nutr Sci, Hosp For Sick Children, U of Toronto, Toronto, Canada M5R1L9, London School of Hygiene & Trop Med, London, UK, Kintampo Health Res. Centre, Min. of Health, Ghana.>> Background: The standard therapy for anemia in infants is ferrous sulfate drops (DROPS) administered 3-times daily. Unfortunately, adherence to treatment is often poor in both developed and developing countries. One reason for the lack of success is the unpleasant side-effects associated with the use of this form of iron. AIM: In this study we evaluated the use of a new form of iron,
dosing schedule and delivery system to treat …

Function

Folate is involved in DNA synthesis. It is involved in cell division and replication. The active form in the body is tetrahydrofolic acid (THFA), which is involved in certain biological reactions including amino acid conversions.

Physiology

Folic acid is synthesized by intestinal microflora of the colon. It is stored in the liver and other body tissues. Excretion occurs through feces and urine.

Food Sources

Sources of folate include liver, organ meats, yeast, dark green leafy vegetables, legumes, nuts, whole grain cereals, eggs and fruit.

Deficiency

Deficiencies result in fatigue, insomnia, and anemia. Folate deficiency is particularly high in developing countries such as India, especially in pregnant and lactating women. Deficiency results in anemia (megaloblastic neurocytic), glossitis (inflammation of the tongue), gastrointestinal disturbances, diarrhea, malabsorption and mood changes. Deficiency during pregnancy may result in neurotube defects in newborns.…

Effectiveness Study:

A study looking at the operational feasibility of an intervention under normal or field conditions.

Efficacy Study:

A study looking at the technical feasibility, where a meaningful response to treatment or intervention is sought under closely supervised conditions.

Dissolution Studies:

Laboratory based studies looking at the solubility of pharmaceutical compounds.

Bitot’s Spots:

Superficial foamy patches forming on the eye. These resemble small dark spots on the whites of the eyes.

Xerophthalmia:

Dryness resulting from inadequate function of the lacrimal glands, which supply water to produce tears.

Bioavailability

The amount of a compound absorbed into the body.…

Study 1: Efficacy of Sprinkles to treat anemia (Completed)

A clinical trial testing the efficacy of Sprinkles in treating iron deficiency anemia (IDA) was conducted in Ghana where more than 80% of children are anemic. This trial was performed in the field study area of the Kintampo Health Research Centre, located in the Kintampo district of Ghana, West Africa.

557 infants, 6-18 months of age with hemoglobin levels between 70-99 g/L, were randomized to receive either iron Sprinkles plus ascorbic acid (80 mg elemental iron) once per day or ferrous sulphate drops (40 mg elemental iron) 3 times per day for a total of 2 months. Hemoglobin and serum ferritin concentrations were assessed at baseline and after two months of treatment.

At the end of the treatment period, it was found that iron Sprinkles were as efficacious as ferrous sulphate drops, the gold standard, in treating IDA. Successful treatment of …

For the past 150 years or more, oral ferrous sulphate drops or syrup has been the primary source of iron for the treatment (and prevention) of iron deficiency anemia. When a soluble form or iron (such as ferrous sulphate) is ingested in the proper dose, this intervention is effective. However, adherence to long-term ingestion of oral drops is often poor because of the unpleasant metallic taste of drops; drops can stain a baby’s teeth unless wiped off immediately after use; and if the dose is high, the infant may complain of abdominal discomfort.

Supplefer Sprinkles was specifically developed to improve adherence (ie. acceptance and use). Compared to drops or syrup,
Sprinkles are easier to use. The table below exemplifies this point. Sprinkles may provide a possible
solution to the problem of adherence and a valuable supplementation method (Taken from Zlotkin, 2002-Editorial).

Supplefer Sprinkles	Drops/Syrups
No taste or after-taste	Strong

…

Mathematical Modeling

Once efficacy is demonstrated by conducting numerous studies in different geographical areas, program planning and implementation must be examined. Owing to the high prevalence of anemia in most developing countries, such a program must be targeted to all children less than three years of age. For large scale community based intervention, individualized screening procedure for IDA is not possible because: (a) there is no single marker for IDA; and (b) multiple marker studies will be very expensive. Therefore all children will receive iron intervention and a single safe dose is desired that is effective for all ‘at risk’ children under the age of 3 years. Such an ideal dose is challenging to compute, particularly because of the unique and complex metabolism of iron, and the changing needs of iron in rapidly growing children.

While dosing and frequency issues remain unresolved, the conventional approach to these challenges has been …