Informal workshop on bioavailability of micronutrients in RUTF

Summary of workshop report¹

Ready to use therapeutic foods (RUTFs) and ready to use supplementary foods (RUSFs) are two types of ready to use food (RUF) or more specifically, examples of lipid-based nutrient supplements (LNS). They are critical in the community-based treatment of severe and moderate acute malnutrition (SAM & MAM) and are currently largely used in feeding programmes. Since 2008, therapeutic feeding programmes worldwide have employed 8000 tons of RUTFs, with a trend of demand rapidly increasing.

Important aspects regarding the bioavailability of micronutrients in these products are not fully known and need more research. RUTFs and RUSFs require a specific micronutrient profile to enable rehabilitation of acutely malnourished children, however the absorption of the micronutrients from such products is not clearly understood. Most available evidence on bioavailability of micronutrients is based on supplementation interventions, which differ from RUTF interventions in two aspects. First, supplementation studies are based on drops or tablets, which are non food matrixes. Secondly, studies are conducted using non SAM (or non-MAM) subjects, however absorption and metabolic systems of the malnourished are generally compromised. Furthermore, no evidence is available on the effect of enhancers or inhibiting factors (i.e. anti-nutritional factors) on the bioavailability of the micronutrients from these kinds of products, which contain relatively high levels of phytate. Bioavailability studies are costly and undertaking research in the settings where SAM occurs is often challenging. Nevertheless, generating evidence on these aspects is important as it may lead to improvements of the impact of these therapeutic products, as well as to a better understanding of micronutrient absorption mechanisms in acutely malnourished children.

In January 2010, an informal workshop was organised by Valid International and the UCL Centre for International Health and Development (CIHD) focused solely on the questions related to the bioavailability of micronutrients from RUTF in SAM children. University and private sector researchers, together with nutrition practitioners interested in the rehabilitation from malnutrition, met in London, UK for a half-day of brainstorming activities about the bioavailability of micronutrients when using energy-dense food matrixes (currently called RUTF, RUSF or LNS). During the workshop, ideas were exchanged on how to measure and increase micronutrients bioavailability in RUTF, to treat SAM in children. The main questions raised, basis of discussions and suggestions/ inputs for possible follow-up research ideas are presented below.

Research questions 1: Which changes could be made to the formulation of RUTF to improve bioavailability of micronutrients?

RUTF is composed of pre-processed food-based ingredients, mixed with a chemical premix of vitamins and minerals. More cereal and pulsebased formulations, as alternatives to peanut-based ones, are expected in the near future. The chemical forms of the vitamins and minerals in available premixes differ. Understanding the bioavailability of micronutrients in RUTF requires collecting evidence on food-based ingredients, as well as the specific chemical forms and dosages of added vitamins and minerals.

A number of activities and research questions were identified:

• Test different food-based ingredients of the RUTF with lower contents of antinutritional factors.
• Update food composition databases related to micronutrients, which are currently often incomplete (e.g. too few micronutrients listed, methods for analysis not specified, chemical forms not declared).
• Identify chemical forms and doses of vitamins and minerals which are sufficiently bioavailable in children with SAM. Key aspects to consider are: i) cost of different chemical forms, ii) encapsulation vs. non-encapsulation, iii) minimum, safe, efficacious dosage when using more bio-available forms (e.g. for iron: use of EDTA; use of small particle size iron (Lohmann), nano form - under development by Azko-Nobel company, or micronized form (SunActiveT).

Question 2: What are the physiological-related factors influencing the bioavailability of micronutrients in SAM subjects?

It is not clear how SAM affects the ability to absorb and utilise micronutrients available from RUTF. Current knowledge on the metabolism of absorption and utilisation of micronutrients among both healthy children and children with micronutrient deficiencies may not apply to children with SAM. Phytic acid is among the main anti-nutritional factors influencing the bioavailability of a few micronutrients in RUTF (e.g. iron, zinc). A new form of phytase enzyme has been successfully tested in healthy adults.

Activities and research questions identified:

• Test RUTF with added phytase: (i) address ethical issues (and regulatory issues) in conducting research on phytase in children with SAM, (ii) select phytase-liquid vs. powder form (developed by DSM), (iii) consider stability/activity of the enzyme in the specific matrix of RUTFs, (iv) address the specific gastric environment in SAM (i.e. higher pH) which might impede the phytase activity. Research on phytase could potentially generate interest in using other kinds of digestion-activated enzymes, such as amylase and tannase.
• Identify maximum tolerable dosages of micronutrients before they become hazardous (e.g. free iron left in the gut when using iron sulphate).

Question 3: Which micronutrients should the research focus on?

The rehabilitation from SAM is achieved only if ALL the micronutrients required are not only present and bio-available, but also, for some of them, when combined according to pre-determined ratios between them. However, the complexity and the cost of measuring the bioavailability of micronutrients limit the choice for research to a few nutrients.

Given this, the group agreed to focus the research on the micronutrients which are required to be in specific ratios with others, since these coincide also with the most crucial ones: Ca, Cu, Fe, K, Mn, Mg, Ph, Se, Zn, vitamin E (and vitamin A eventually).

Study designs and research context

The workshop participants had experience in measuring bioavailability on a limited number of micronutrients (namely iron, zinc, vitamin A and iodine). Participants proposed a few study designs outlined below, which need to be expanded and reviewed by bioavailability experts. For example, it was noted that stable isotopic studies on iron can be realistically undertaken under field settings (e.g. refugee camps) as cold chain transport is not critical (therefore no need for liquid nitrogen), and sophisticated lab equipment can be used elsewhere for blood sample processing and analysis. On the other hand, the participants did not know about the challenges related to studying other types of micronutrients bioavailability (e.g. isotope balance).

Two trial designs were proposed:

Phase 1 study in healthy young children (crossover, bioavailability study) to test (a) impact of phytase on bioavailability of micronutrients and/or (b) to compare the bioavailability of micronutrients from different food formulations of RUTF. Points for consideration were:

• The use of stable isotopic studies.
• The need to ensure to feed RUTF in advance of any trial to the child, so that child gets used to its taste.
• Question as to whether such a trial could be conducted in children with SAM, given the challenges of rapidly changing health status and regurgitation.
• How to best integrate isotopic labels into RUTFs.

Phase 2 study in SAM children to test efficacy of best formulation(s) identified in phase 1 measuring micronutrient status and recovery from SAM.

Next steps

Participants expressed interest in taking these research topics forward and shared possible ideas and funding sources to do this.

For more information, contact: Filippo Dubari email: filippo@validinternational.org or Mélody Tondeur, email: m.tondeur@ich.ucl.ac.uk

¹Dibari. F and Tondeur. M (2010). What is the bioavailability of micronutrients form RUTFs in children affected by SAM. Brainstorming workshop Report. 18th January 2010.