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Developing food supplements for moderately malnourished children: lessons learned from RUTF

Appetite test with RUTFSummary of research1

Location: Global

What we know: RUTF is as effective as F100 in treating SAM, where weight gain is the recovery outcome. Food supplements for moderate malnutrition treatment, including adapting standard RUTF, are being explored. The prevalent number of children with MAM is (under) estimated at 32.8 million, nearly double that of SAM; this has significant cost implications for their treatment.  

What this article adds: Standard RUTF formulation has limitations with regard to vitamin and mineral levels and bioavailability, protein quality, amino acid profiles, phytate levels, anti-nutrients and cost. Different RUTF formulations may benefit vitamin and mineral status; functional and growth outcomes; and impact stunting in treated children but have not been explored. Cheaper ingredients may compromise RUTF effectiveness. To optimise RUTF formulation for both SAM and MAM treatment, priority research includes precise assessment of ‘normal’ food consumption during rehabilitation, investigation of processing options to improve product nutritional quality, and assessment of vitamin and mineral status of children post treatment. 

 

The physiology of weight gain is not fundamentally different in children with moderate acute malnutrition (MAM); standard RUTF could be used in theory and has been used to treat successfully large numbers of children with MAM. Standard RUTF, however, was designed to be given as the only food that a child consumes while being treated for SAM. This approach may not be appropriate and is unlikely in practice in children with MAM, unless the household is severely food insecure. When special nutritious foods are required for treating children with MAM, cost considerations usually prohibit the use of standard RUTF; globally there are about 32.8 million children with MAM, compared with about 18.7 million with SAM.2 So there is a need to adapt the RUTF formulation to lower its cost by using less expensive ingredients. Using locally available ingredients is another important factor to consider; they are not always less expensive but may have political and other local benefits.

When trying to further adapt the current RUTF formulation for children with MAM, two important aspects of RUTF development should be taken into account. First, the current RUTF formulation has not been fully optimised and may need improvement. Second, cost reduction by using less expensive ingredients may lead to less effective formulations, for reasons that are not fully understood. The goal of a recently published paper is to highlight the questions remaining in RUTF development and research, which may also be relevant for development of effective foods for children with MAM.

RUTF development

The first RUTF (Plumpy’Nut®) was formulated by replacing about half of the dried skimmed milk in F-100 formula with peanut paste. The resulting food paste did not require the addition of water, eliminating bacterial proliferation risk. Whey powder was included to achieve an equivalent level of lactose to F-100; similarly maltodextrins (used to reduce osmolarity) were also added. This approach, aimed to closely reproduce the existing reference diet, to minimise the risk of not obtaining similar programme results. This proved successful, as clinical trials showed that this RUTF formula was at least as effective in promoting weight gain as the existing F-100 diet. However, this approach has its limitations. First, weight gain is not the best criterion to assess recovery. Evaluation of the efficacy of RUTF according to other criteria, including functional outcomes, is needed. Second, it assumes that F-100 is a gold standard. F-100, however, was formally tested in only a small number of children in one setting, and it is possible that its contents of some nutrients are not optimal to reverse stunting, which is often associated with wasting.

F-100 was designed to be consumed as the only food during the nutrition rehabilitation phase; therefore, its mineral and vitamin contents were adjusted to take into account pre-existing deficiencies, rapid growth requirements, and to cover requirements of a child consuming 150 to 200 kcal/kg/day of this diet and having a weight gain of up to 15 to 20 g/kg/day. Most RUTF protocols, that recommend 175 to 200 kcal/kg/day, assume implicitly that RUTF is the only food consumed during treatment. However average weight gain in the community (4 to 6 g/kg/day or less) versus in clinical trials (0 to 15 g/kg/day) suggests this is rare; in reality, RUTF may be shared or children also consume local, less nutrient dense food.  The level of consumption of local foods along with RUTF has never been precisely estimated so that substantial and consistent increased RUTF fortification may be needed to compensate.

The most common RUTF contains about 25% peanut paste; this contains 1% to 2% phytates that may potentially inhibit the absorption of divalent ions, such as iron, zinc, or calcium. The lipid matrix in RUTF, has unknown effects on their absorption, in particular of iron3 and also of phosphorus, which is likely in phytate form and less well absorbed than dairy sources. The 2007 World Health Organisation (WHO)/UNICEF/World Food Programme/United Nations Standing Committee on Nutrition Joint Statement requires a minimum of 300 mg of non-phytate phosphorus per 100g of RUTF (520 mg minimum for 1,000 kcal), substantially less than the 850 mg of phosphorus derived from milk in 1,000 kcal of F-100 and the 850 to 1,400 mg/1,000 kcal recommended by the 2012 WHO technical note on foods for moderately malnourished children.

Studies comparing the effect of different RUTF mineral fortification levels, in particular zinc, phosphorus, iron and calcium, used in real-life conditions are needed to optimise RUTF. For some nutrients that have stable isotopes, such as zinc, absorption could be measured and compared with their levels of absorption in F-100 and/or with calculated requirements for lean tissue synthesis. For nutrients that do not have stable isotopes, such as phosphorus, comparison of lean tissue synthesis and linear growth with different formulations is needed.

No study has ever assessed the vitamin status of children after treatment with RUTF. Ideally, this should be done in different contexts with children having different pre-existing nutritional deficiencies.

The vitamin A content of RUTF is a particular concern. Currently, it is added within narrow limits (between 0.8 and 1.1 mg/100 g) and to the maximal level given its instability and potential loss during storage. Pre-consumption levels of RUTF vitamin A and the vitamin A status of treated children have never been checked, although the current recommendation is to rely only on RUTF and to no longer provide a high-dose vitamin A capsule as part of SAM treatment. Despite uncertainties regarding iron absorption and the fortification levels of vitamins needed for haemoglobin synthesis, a proper evaluation of the haematological status of children after treatment is also lacking and overdue.

Following initial success with RUTF, attempts were made to simplify its formulation to make it easier to produce locally. A first successful step was to replace imported maltodextrin with locally available sucrose. Attempts to remove or to decrease the proportion of dried skimmed milk, the most expensive ingredient in RUTF, have been less successful (see Box 1).

 

Box 1: Attempts to replace dried skimmed milk in RUTF formulation

A first attempt in Malawi to replace milk powder by a mixture of roasted chickpea and sesame led to a product that was well accepted by young children in tasting sessions but gave them abdominal pains when given several days in a row, apparently as a result of inadequate starch gelatinisation. Two other products in which starch gelatinisation was obtained by extrusion cooking were better tolerated.

A first study with RUTF in Malawi compared RUTF containing 10% dried skim milk with RUTF containing 25% dried skim milk in the standard formulation. The RUTF with reduced milk content, however, was less successful in treating children with SAM, achieving 57% recovery after four weeks, compared with 64% for RUTF with 25% milk. Weight gain, height gain and increases in mid-upper arm circumference (MUAC) were also higher for the RUTF with 25% milk.

A second RUTF made without milk, containing soy, maize, and sorghum (SMS-RUTF), was tested in Zambia and also proved less successful than the milk-based original formula, at least in children under 2 years of age, achieving a 53.3% recovery rate versus 60.8% for the standard RUTF. 

 

Replacing milk proteins with proteins derived from other sources is likely to impact protein quality but this effect is not clearly quantified. A comparison of the protein digestibility-corrected amino acid score (PDCAAS) between RUTFs containing 25% and 10% milk suggested that PDCAAS decreases from 1.11 to 1.00. For SMS-RUTF,

PDCAAS was estimated at 0.86, clearly inferior to that for the reference RUTF. These estimates of RUTF protein quality are based, however, on a method that is no longer recommended by the Food and Agriculture Organisation (FAO) and WHO. The recently proposed method is based on true ileal protein digestibility (digestible indispensable amino acid score (DIAAS)), and not on faecal crude digestibility, which may give different results. The impact of this change on assessment of RUTF protein quality is unknown. Current efforts to measure DIAAS on different RUTF formulations may shed light on potential differences.

There is also an uncertainty regarding the amino acid profile that should be used to assess protein quality in RUTF. The amino acid requirements of children depend on those amino acids needed for body maintenance and those needed for new tissue deposition. After the age of 6 to 12 months, in a child growing at normal rates (not sustaining catch-up weight gain), new tissue synthesis is reduced and the amino acids needed are mainly those involved in body maintenance. Arguably, this profile may not be applicable to recovering malnourished children of the same age. During the catch-up growth phase, these children may use a much larger proportion of proteins consumed for new tissue synthesis than do well-nourished children. The availability of sulphur amino acids (cysteine and methionine) may also have an indirect effect on growth, since sulphur is needed for cartilage synthesis during catch-up growth in length. Peanut paste has a lower sulphur amino acid content than dried skimmed milk; the effect on linear growth is unknown.

Milk proteins seem to have a specific hormonal effect and to promote the production of insulin-like growth factor 1 (IGF-1), with a possible effect on linear growth likely due to the casein fraction of milk. This effect has never been tested in malnourished children. Dairy products have high calcium and phosphorus contents, which may also explain their specific effect on growth. Phosphorus is needed for muscle growth and phosphorus deficiency is associated with bone growth retardation in animals, in contrast with calcium, which is associated with decreased bone mineral density, without a clear effect on linear growth. An insufficient intake of phosphorus could possibly be corrected by adding phosphorus salts to the fortification formula of reduced dairy foods or to digest phytates using phytase during food production, which would make the phosphorus more available. Both approaches are used successfully in animal nutrition to promote growth with minimal amounts of dairy products. They have not been tested in foods for malnourished children. There is potential for adding acid resistant phytase to water free RUTF to improve the absorption of iron but this has never been tested.

In contrast to dairy products, plant-based foods often contain high levels of anti-nutrients, which may decrease protein digestibility and mineral absorption. A higher content of anti-nutrients may also explain why attempts to replace dairy products with plant-based sources of protein have given mixed results. Roasting and extrusion cooking4 are the most commonly used techniques to destroy anti-nutrients. However, excessive heat can lead to undesirable chemical reactions with proteins, which limit its application. Lysine, the main limiting amino acid of cereals and groundnuts, has two amino groups and is particularly reactive, which leads to a decrease of protein quality in case of excessive heating.5

Mature dry legumes may contain up to 30 different soluble carbohydrates. Among those, the raffinose family of oligosaccharides are not digested by the small intestine but by the intestinal flora in the colon, hence large quantities may induce flatulence and abdominal discomfort and may explain the poor tolerance of early milk-free, legume-based RUTFs and limitations of legume-based alternative RUTFs.  Flatulence factors can be reduced by as much as 47% to 60% by extrusion cooking or by 70% to 80% by germination, and most efficiently through use of enzymes. These techniques6are not currently used when preparing foods for malnourished children; either lipid-based nutrient supplements or more traditional blended flours.

Conclusions

The authors conclude that although millions of children are treated every year with RUTF, there hasn’t been a single evaluation of the vitamin and mineral status of children at the end of treatment. Furthermore, clinical trials are needed to compare different levels of fortification and their effect on growth and other functional outcomes. Very little is known currently about the effect of RUTF on correction of stunting, which is frequently present in children with SAM. The possibility should be explored of better correcting stunting by treating children with SAM with improved RUTFs containing higher levels of sulphur

amino acids, phosphorus, or zinc. This can also provide clues on how to improve the diet to prevent stunting from occurring in the first place, with relevance for improvement of the diets of children between 6 and 23 months of age.

RUTF has not been optimised, and research to improve it should continue. This research is relevant for the development of foods for moderately malnourished children, as it can provide clues on how to optimise these foods as well. The following aspects should be especially investigated:

  • Determine the amounts of RUTF and of local foods children are typically consuming during treatment and adjust nutrient density accordingly.
  • Assess the feasibility of different processing steps to improve nutritional quality of the food, especially by the use of appropriate enzymes.
  • Measure non-phytate phosphorus in proposed foods and compare the efficacy of different formulations with different levels of non-phytate phosphorus.
  • Determine the vitamin and mineral status of children with MAM after treatment and revise the formulation if needed.

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Footnotes

1Briend A et al (2015. Developing food supplements for moderately malnourished children: Lessons learned from ready-to-use therapeutic foods. Food and Nutrition Bulletin, vol 36, no 1, ppS53-S58, 2015 Supplement. 

2Estimates based on prevalence data which underestimate the number of children suffering from MAM or SAM in a year.

3Absorption of iron takes place in the upper part of the gut, where iron in RUTF may well still be within the fat matrix.

4Extrusion cooking associates mechanical shearing with heating above 100°C for a few minutes in a humid environment and is the most effective method of removing antinutrients.

5The Maillard reaction involves the reaction of an amino group of a protein with carbohydrates.

6They require an aqueous environment during the production process,

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Developing food supplements for moderately malnourished children: lessons learned from RUTF. Field Exchange 50, August 2015. p25. www.ennonline.net/fex/50/rutfmoderatemalnutrition

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