Soya, maize and sorghum ready-to-use therapeutic foods are more effective in correcting anaemia and iron deficiency than the standard ready-to-use therapeutic food: randomized controlled trial.

BACKGROUND: The prevalence of anaemia and iron deficiency (ID) among children with severe acute malnutrition (SAM) and their correction during nutritional rehabilitation are not well documented. This study assessed anaemia and ID prevalence and their predictors at start of SAM treatment, and the efficacy of their treatment and effect on gut health of two novel Ready-To-Use Therapeutic foods (RUTF) prepared from soybean, maize and sorghum (SMS) with (MSMS-RUTF) or without added milk (FSMS-RUTF) compared to those of the standard formulation prepared from peanut and milk (PM-RUTF). METHODS: This was a 3-arms parallel groups, simple randomised, controlled non-inferiority trial in 6-59 months old Central Malawian children with SAM. Anaemia was defined using altitude- and ethnicity-adjusted haemoglobin. Iron status was defined using soluble transferrin receptor (sTfR) and body iron stores (BIS). We used Pearson's chi-square test, t-test for paired or unpaired data, Kruskal-Wallis test for between-arm differences as appropriate and logistic regression to identify independent predictors of anaemia or iron deficiency anaemia (IDA). RESULTS: The sample size was 389. At admission, the prevalence [%(95%CI)] of anaemia was 48.9(41.4-56.5)% while that of ID and IDA were 55.7(48.6-62.5)% and 34.3(28.2-41.0)% when using sTfR criterion and 29.1(24.4-34.4)% and 28.9(23.7-34.9)% when using BIS criterion, respectively. At discharge, nutrition rehabilitation with SMS-RUTF was associated with the lowest prevalence of anaemia [12.0(6.9-20.3)% for FSMS-RUTF, 18.2(11.9-26.8)% for MSMS-RUTF and 24.5(15.8-35.9)% for PM-RUTF; p = 0.023] and IDA [7.9(3.4-17.3)% for FSMS-RUTF, 10.9(4.8-22.6)% for MSMS-RUTF and 20.5(10.7-35.5)% for PM-RUTF; p = 0.028]. SMS-RUTF was also associated with the highest increase in BIS [Change in BIS (95%CI)] among the iron deplete at admission [6.2 (3.7; 8.6), 3.2 (0.8; 5.6), 2.2 (0.2; 4.3) for the same study arms; Anova p = 0.045]. Compared to P-RUTF, FSMS-RUTF had the highest adjusted recovery rate [OR (95%CI = 0.3 (0.2-0.5) with p < 0.001 for FSMS-RUTF and 0.6 (0.3-1.0) with p = 0.068 for MSMS-RUTF]. No effect of iron content on risk of iron overload or gut inflammation was observed. CONCLUSIONS: Anaemia and ID are common among children with SAM. FSMS-RUTF is more efficacious in treating anaemia and correcting BIS among this group than PM-RUTF. TRIAL REGISTRATION: This study was registered on 15 April 2015 ( PACTR201505001101224 ).

Balancing omega-6 and omega-3 fatty acids in ready-to-use therapeutic foods (RUTF).

Ready-to-use therapeutic foods (RUTFs) are a key component of a life-saving treatment for young children who present with uncomplicated severe acute malnutrition in resource limited settings. Increasing recognition of the role of balanced dietary omega-6 and omega-3 polyunsaturated fatty acids (PUFA) in neurocognitive and immune development led two independent groups to evaluate RUTFs. Jones et al. (BMC Med 13:93, 2015), in a study in BMC Medicine, and Hsieh et al. (J Pediatr Gastroenterol Nutr 2015), in a study in the Journal of Pediatric Gastroenterology and Nutrition, reformulated RUTFs with altered PUFA content and looked at the effects on circulating omega-3 docosahexaenoic acid (DHA) status as a measure of overall omega-3 status. Supplemental oral administration of omega-3 DHA or reduction of RUTF omega-6 linoleic acid using high oleic peanuts improved DHA status, whereas increasing omega-3 alpha-linolenic acid in RUTF did not. The results of these two small studies are consistent with well-established effects in animal studies and highlight the need for basic and operational research to improve fat composition in support of omega-3-specific development in young children as RUTF use expands.

Ready-to-use therapeutic food with elevated n-3 polyunsaturated fatty acid content, with or without fish oil, to treat severe acute malnutrition: a randomized controlled trial.

BACKGROUND: Ready-to-use therapeutic foods (RUTF) are lipid-based pastes widely used in the treatment of acute malnutrition. Current specifications for RUTF permit a high n-6 polyunsaturated fatty acid (PUFA) content and low n-3 PUFA, with no stipulated requirements for preformed long-chain n-3 PUFA. The objective of this study was to develop an RUTF with elevated short-chain n-3 PUFA and measure its impact, with and without fish oil supplementation, on children's PUFA status during treatment of severe acute malnutrition. METHODS: This randomized controlled trial in children with severe acute malnutrition in rural Kenya included 60 children aged 6 to 50 months who were randomized to receive i) RUTF with standard composition; ii) RUTF with elevated short chain n-3 PUFA; or iii) RUTF with elevated short chain n-3 PUFA plus fish oil capsules. Participants were followed-up for 3 months. The primary outcome was erythrocyte PUFA composition. RESULTS: Erythrocyte docosahexaenoic acid (DHA) content declined from baseline in the two arms not receiving fish oil. Erythrocyte long-chain n-3 PUFA content following treatment was significantly higher for participants in the arm receiving fish oil than for those in the arms receiving RUTF with elevated short chain n-3 PUFA or standard RUTF alone: 3 months after enrollment, DHA content was 6.3% (interquartile range 6.0-7.3), 4.5% (3.9-4.9), and 3.9% (2.4-5.7) of total erythrocyte fatty acids (P <0.001), respectively, while eicosapentaenoic acid (EPA) content was 2.0% (1.5-2.6), 0.7% (0.6-0.8), and 0.4% (0.3-0.5) (P <0.001). RUTF with elevated short chain n-3 PUFA and fish oil capsules were acceptable to participants and carers, and there were no significant differences in safety outcomes. CONCLUSIONS: PUFA requirements of children with SAM are not met by current formulations of RUTF, or by an RUTF with elevated short-chain n-3 PUFA without additional preformed long-chain n-3 PUFA. Clinical and growth implications of revised formulations need to be addressed in large clinical trials. TRIAL REGISTRATION: Clinicaltrials.gov NCT01593969. Registered 4 May 2012.

Developing food supplements for moderately malnourished children: lessons learned from ready-to-use therapeutic foods.

Ready-to-use therapeutic foods (RUTFs) are solid foods that were developed by changing the formulation of the existing liquid diet, F-100, recommended by the World Health Organization (WHO) for the rapid catch-up phase of the treatment of children suffering from severe acute malnutrition (SAM). The resulting products proved highly effective in promoting weight gain in both severely and moderately wasted children and adults, including those infected with HIV. The formulation of the existing RUTFs, however, has never been optimized to maximize linear growth, vitamin and mineral status, and functional outcomes. The high milk content of RUTFs makes it an expensive product, and using lower quantities of milk seems desirable. However, the formulation of alternative, less expensive but more effective versions of RUTF faces difficult challenges, as there are uncertainties regarding the effect in terms of protein quality, antinutrient content, and flatulence factors that will result from the replacement of current dairy ingredients by less expensive protein-rich ingredients. The formulation of alternative RUTFs will require further research on these aspects, followed by efficacy studies comparing the future RUTFs to the existing formulations.

Ready-to-use foods for management of moderate acute malnutrition: considerations for scaling up production and use in programs.

Ready-to-use foods are one of the available strategies for the treatment of moderate acute malnutrition (MAM), but challenges remain in the use of these products in programs at scale. This paper focuses on two challenges: the need for cheaper formulations using locally available ingredients that are processed in a safe, reliable, and financially sustainable local production facility; and the effective use of these products in large-scale community-based programs. Linear programming tools can be used successfully to design local compositions that are in line with international guidelines, low in cost, and acceptable, and the efficacy of these local formulations in the treatment of MAM was recently demonstrated in Malawi. The production of local formulations for programs at scale relies on the existence of a reliable and efficient local production facility. Technical assistance may be required in the development of sustainable business models at an early stage in the process, taking into account the stringent product quality and safety criteria and the required investments. The use of ready-to-use products, as of any food supplement, in programs at scale will be affected by the practice of household sharing and diversion of these products for other uses. Additional measures can be considered to account for sharing. These products designed for the treatment and prevention of MAM are to be used in community-based programs and should therefore be used in conjunction with other interventions and designed so that they do not replace the intake of other foods and breastmilk. Remaining challenges and implications for the (operations) research agenda are discussed.

Amino acid-enriched plant-based RUTF treatment was not inferior to peanut-milk RUTF treatment in restoring plasma amino acid levels among patients with oedematous or non-oedematous malnutrition.

Ready-to-use therapeutic food (RUTF) with adequate quality protein is used to treat children with oedematous and non-oedematous severe acute malnutrition (SAM). The plasma amino acid (AA) profile reflects the protein nutritional status; hence, its assessment during SAM treatment is useful in evaluating AA delivery from RUTFs. The objective was to evaluate the plasma AAs during the treatment of oedematous and non-oedematous SAM in community-based management of acute malnutrition (CMAM) using amino acid-enriched plant-based RUTFs with 10% milk (MSMS-RUTF) or without milk (FSMS-RUTF) compared to peanut milk RUTF (PM-RUTF). Plasma AA was measured in a non-blinded, 3-arm, parallel-group, simple randomized controlled trial conducted in Malawi. The RUTFs used for SAM were FSMS-RUTF, MSMS-RUTF or PM-RUTF. A non-inferiority hypothesis was tested to compare plasma AA levels from patients treated with FSMS-RUTF or MSMS-RUTF with those from patients treated with PM-RUTF at discharge. For both types of SAM, FSMS-RUTF and MSMS-RUTF treatments were non-inferior to the PM-RUTF treatment in restoration of the EAA and cystine except that for FSMS-RUTF, methionine and tryptophan partially satisfied the non-inferiority criteria in the oedematous group. Amino-acid-enriched milk-free plant-source-protein RUTF has the potential to restore all the EAA, but it is possible that enrichment with amino acids may require more methionine and tryptophan for oedematous children.

Amino-acid-enriched cereals ready-to-use therapeutic foods (RUTF) are as effective as milk-based RUTF in recovering essential amino acid during the treatment of severe acute malnutrition in children: An individually randomized control trial in Malawi.

BACKGROUND: Ready-to-use therapeutic food (RUTF) is used to treat children suffering from severe acute malnutrition (SAM). Standard RUTF uses milk as the primary protein source, which makes the product expensive, and given the high worldwide SAM burden, having a less expensive effective alternative is a public health priority. OBJECTIVE: The objective of this study was to evaluate whether newly developed amino acid-enriched milk-free RUTF (FSMS-RUTF) or amino acid-enriched low-milk RUTF (MSMS-RUTF) treatment could replenish plasma amino acids to levels comparable to those following standard peanut-milk RUTF (PM-RUTF) treatment and to improve understanding of the effects of treatment on anthropometric measurements. A secondary analysis was performed to test the noninferiority hypothesis of plasma essential amino acid (EAA) levels. METHODS: Plasma EAA levels were measured in a nonblinded, 3-arm, parallel-group simple randomized controlled trial conducted in Malawi to examine the efficacy of FSMS-RUTF, MSMS-RUTF and PM-RUTF in the treatment of SAM in 2 groups of children aged 6-23 and 24-59 months (mo). Sample size calculations were performed based on the previous our study. A noninferiority margin was set at -25% of the PM-RUTF arm at discharge. RESULTS: The relative values of the differences (95% CI) in plasma EAA levels between PM-RUTF treatment and FSMS-RUTF and MSMS-RUTF treatments at discharge were -7.9% (-18.6, 2.8) and 9.8% (0.2, 19.5), respectively, in children aged 6-23 mo, while in those aged 24-59 mo, the difference values were 17.8% (1.6, 34.1) and 13.6% (-2.8, 29.9), respectively. CONCLUSION: At discharge, the plasma EAA concentrations in 6-59-mo-old SAM children treated with FSMS-RUTF and MSMS-RUTF were not less than those of children treated with PM-RUTF. These findings indicate that treatment with either of the 3 RUTFs was associated with adequate protein synthesis and that all the formulations provided sufficient functional metabolites of plasma amino acids to support nutritional recovery from SAM.

Soya, maize, and sorghum-based ready-to-use therapeutic food with amino acid is as efficacious as the standard milk and peanut paste-based formulation for the treatment of severe acute malnutrition in children: a noninferiority individually randomized controlled efficacy clinical trial in Malawi.

Background: Development of more cost-effective ready-to-use therapeutic food (RUTF) is a global public health priority. To date, previous lower-cost recipes have been less effective than the standard peanut and milk (PM)-based RUTF, particularly in children aged <24 mo.Objective: We aimed to compare the efficacy of the PM-RUTF to a milk-free soya, maize, and sorghum (FSMS)-RUTF enriched with crystalline amino acids without cow milk powder and a milk, soya, maize, and sorghum (MSMS)-RUTF containing 9.3% skim cow milk powder.Design: This nonblinded, 3-arm, parallel-group, simple randomized controlled trial enrolled Malawian children with severe acute malnutrition.Results: In intention-to-treat analyses, FSMS-RUTF showed noninferiority for recovery rates in children aged 24-59 mo (Δ: -1.9%; 95% CI: -9.5%, 5.6%) and 6-23 mo (Δ: -0.2%; 95% CI: -7.5%, 7.1%) compared with PM-RUTF. MSMS-RUTF also showed noninferiority for recovery rates in children aged 24-59 mo (Δ: 0.0%; 95% CI: -7.3%, 7.4%) and 6-23 mo (Δ: 0.6%; 95% CI: -4.3%, 5.5%). Noninferiority in recovery rates was also observed in per-protocol analyses. For length of stay in the program (time to cure), both FSMS-RUTF in children aged 24-59 mo (Δ: 2.8 d; 95% CI: -0.8, 6.5 d) and 6-23 mo (Δ: 3.4 d; 95% CI: -1.2, 8.0 d) and MSMS-RUTF in children aged 24-59 mo (Δ: 0.2 d; 95% CI: -3.1, 3.6 d) and 6-23 mo (Δ: 1.2 d; 95% CI: -3.4, 5.8 d) were not inferior to PM-RUTF. FSMS-RUTF was also significantly better than PM-RUTF at increasing hemoglobin and body iron stores in anemic children, with mean hemoglobin increases of 2.1 (95% CI: 1.6, 2.6) and 1.3 (95% CI: 0.9, 1.8) and mean body iron store increases of 2.0 (95% CI: 0.8, 3.3) and 0.1 (95% CI: -1.1, 1.3) for FSMS-RUTF and PM-RUTF, respectively.Conclusions: FSMS-RUTF without milk is efficacious in the treatment of severe acute malnutrition in children aged 6-23 and 24-59 mo. It is also better at correcting iron deficiency anemia than PM-RUTF. This trial was registered at www.pactr.org as PACTR201505001101224.

Cereals and pulse-based ready-to-use therapeutic food as an alternative to the standard milk- and peanut paste-based formulation for treating severe acute malnutrition: a noninferiority, individually randomized controlled efficacy clinical trial.

BACKGROUND: The cost of current standard ready-to-use therapeutic food (RUTF) is among the major obstacles to scaling up community-based management of acute malnutrition (CMAM), an important child survival strategy. Identifying a cheaper alternative is a global public health priority. OBJECTIVE: We sought to compare the efficacy of soya-maize-sorghum RUTF (SMS-RUTF) with that of standard peanut paste-based RUTF (P-RUTF). DESIGN: We used a nonblinded, parallel-group, simple randomized controlled trial along with a day care approach that enrolled 2 groups of children aged 6-23 and 24-59 mo, respectively, with severe acute malnutrition (SAM). RESULTS: Intention-to-treat (ITT) and per-protocol (PP) analyses showed noninferiority of SMS-RUTF compared with P-RUTF for the recovery rate [ITT: Δ = -2.0% (95% CI: -7.6%, 3.6%); PP: -1.9% (95% CI: -5.3%, 1.4%)], weight gain [Δ = -0.7 g · kg(-1)· d(-1)(95% CI: -1.3, 0.0 g · kg(-1)· d(-1))], and length of stay [Δ = 2.0 d (95% CI: -1.7, 5.8 d)] in children ≥24 mo of age. In children ≤23 mo of age, the recovery rate of SMS-RUTF was inferior to that of P-RUTF [ITT: Δ = -20.8% (95% CI: -29.9%, -11.7%); PP: -17.2% (95% CI: -25.6%, -8.7%)]. Treatment with SMS-RUTF resulted in a greater increase in hemoglobin [0.670 g/dL (95% CI: 0.420, 0.921 g/dL);P< 0.001]. Treatment with both RUTFs resulted in the replenishment of all of the amino acids tested except for methionine. There were no differences at discharge between RUTF groups in fat mass [Δ = 0.3 kg (95% CI: -0.6, 1.6 kg);P= 0.341] or fat mass index [Δ = 0.4 kg/m(2)(95% CI: -0.3, 1.1 kg/m(2));P= 0.262]. By contrast, comparisons of fat-free mass indicated lower concentrations than the community controls after treatment with either of the 2 RUTFs [Δ = -1.3 kg (95% CI: -2.4, -0.1 kg) andP= 0.034 for comparison between community controls and the SMS-RUTF group; Δ = -1.8 kg (95% CI: -2.9, -0.6 kg) andP= 0.003 for comparison between community controls and the P-RUTF group]. CONCLUSION: SMS-RUTF can be used to treat SAM in children aged ≥24 mo to reduce the costs of CMAM programs. More research is required to optimize SMS-RUTF for younger children. This trial was registered in the Pan African Clinical Trial Registry as PACTR201303000475166.