Kelsey N. Ryan

Use of Whey Protein Soluble Aggregates for Thermal Stability—A Hypothesis Paper

Forming whey proteins into soluble aggregates is a modification shown to improve or expand the applications in foaming, emulsification, gelation, film-formation, and encapsulation. Whey protein soluble aggregates are defined as aggregates that are intermediates between monomer proteins and an insoluble gel network or precipitate. The conditions under which whey proteins denature and aggregate have been extensively studied and can be used as guiding principles of producing soluble aggregates. These conditions are reviewed for pH, ion type and concentration, cosolutes, and protein concentration, along with heating temperature and duration. Combinations of these conditions can be used to design soluble aggregates with desired physicochemical properties including surface charge, surface hydrophobicity, size, and shape. These properties in turn can be used to obtain target macroscopic properties, such as viscosity, clarity, and stability, of the final product. A proposed approach to designing soluble aggregates with improved thermal stability for beverage applications is presented.

Zinc or Albendazole Attenuates the Progression of Environmental Enteropathy: A Randomized Controlled Trial

BACKGROUND & AIMS Environmental enteropathy (EE) is a subclinical condition among children in the developing world, characterized by T-cell infiltration of the small-bowel mucosa and diffuse villous atrophy. EE leads to macronutrient and micronutrient malabsorption and stunting, with a resultant increased risk for infection and reduced cognitive development. We tested the hypothesis that zinc and albendazole treatments would reduce the severity of EE in rural African children. METHODS In a randomized, double-blind, placebo-controlled trial in rural southern Malawi, asymptomatic children, 1 to 3 years old and at high risk for EE, received either a single dose of albendazole, a 14-day course of 20 mg zinc sulfate, or a placebo. Subjects were given the dual-sugar absorption test, and the ratio of lactulose to mannitol (L:M) in urine was used to determine the severity of EE at baseline and 34 days after completion of the assigned regimen. The primary outcome was the change in the L:M. RESULTS A complete set of urine samples was obtained from 222 of 234 children enrolled and analyzed. The mean baseline L:M was 0.32 ± 0.18 among all children and did not differ among groups (normal L:M range, <0.12). At the end of the study, the L:M ratio had increased more in the placebo group (0.12 ± 0.31) than in the zinc group (0.03 ± 0.20; P < .03) or the albendazole group (0.04 ± 0.22; P < .04). CONCLUSIONS Treatment with zinc or albendazole protects against a significant increase in the L:M ratio, a biomarker for EE, in asymptomatic rural Malawian children. These findings could provide insight into the etiology and pathogenesis of EE. Clinicaltrials.gov Number: NCT01440608.

Multiple Micronutrient Supplementation Transiently Ameliorates Environmental Enteropathy in Malawian Children Aged 12–35 Months in a Randomized Controlled Clinical Trial

BACKGROUND Environmental enteropathy (EE) is subclinical, diffuse villous atrophy characterized by T cell infiltration of the small intestinal mucosa associated with nutrient malabsorption and stunting. EE is assessed by the lactulose:mannitol (L:M) test, whereby nonmetabolized sugars are ingested and quantified in the urine. Multiple micronutrient (MN) deficiency morphologically mimics EE, and ω-3 (n-3) polyunsaturated fatty acids reduce mucosal inflammation in Crohn disease. OBJECTIVE We tested the hypothesis that supplementary MNs, with or without fish oil (FO), would improve L:M in rural Malawian children aged 1-3 y compared with a control (C) group receiving a placebo. METHODS The MNs and FO provided the Recommended Dietary Intake for 26 vitamins, minerals, eicosapentaenoic acid, and docosahexaenoic acid. This was a 3-arm, randomized, double-blind, placebo-controlled clinical trial, with the primary outcomes being the change in L:M (ΔL:M) after 12 and 24 wk of supplementation. Comparisons were made for ΔL:M after 12 and 24 wk within each group by using a Wilcoxon matched pairs signed rank test, because the data are not normally distributed. RESULTS A total of 230 children had specimens adequate for analysis; all had an abnormal baseline L:M, defined as >0.10. After 12 wk, children who received MNs + FO had a ΔL:M [mean (95% CI)] of -0.10 (-0.04, -0.15; P = 0.001), and children receiving only MNs had ΔL:M of -0.12 (-0.03, -0.21; P = 0.002). After 24 wk, children who received MNs + FO had a ΔL:M of -0.09 (-0.03, -0.15; P = 0.001); children receiving only MNs had a ΔL:M of -0.11 (-0.02, -0.20; P = 0.001), and the C group had ΔL:M of -0.07 (0.02, -0.16); P = 0.002). Linear growth was similar in all groups, ∼4.3 cm over 24 wk. CONCLUSION Although the effect was modest, these data suggest MNs can transiently ameliorate EE in rural African children. The trial was registered at clinicaltrials.gov as NCT01593033.

Severe and Moderate Acute Malnutrition Can Be Successfully Managed with an Integrated Protocol in Sierra Leone

BACKGROUND Global acute malnutrition (GAM) is the sum of moderate acute malnutrition (MAM) and severe acute malnutrition (SAM). The use of different foods and protocols for MAM and SAM treatment can be cumbersome in emergency settings. OBJECTIVE Our objective was to determine the recovery and coverage rates for GAM of an integrated protocol with a single food product, ready-to-use therapeutic food (RUTF), compared with standard management. METHODS This was a cluster-randomized controlled trial in Sierra Leone conducted in 10 centers treating GAM in children aged 6-59 mo. The integrated protocol used midupper arm circumference (MUAC) as the criterion for admission and discharge, with a MUAC <12.5 cm defining malnutrition. The protocol included a decreasing ration of RUTF and health maintenance messages delivered by peers. Standard therapy treated MAM with a fortified blended flour and SAM with RUTF and used weight-for-height to determine admission to the treatment program. Coverage rates were the number of children who received treatment/number of children in the community eligible for treatment. RESULTS Most of the children receiving integrated management had MAM (774 of 1100; 70%), whereas among those receiving standard management, SAM predominated (537 of 857; 63%; P = 0.0001). Coverage was 71% in the communities served by integrated management and 55% in the communities served by standard care (P = 0.0005). GAM recovery in the integrated management protocol was 910 of 1100 (83%) children and was 682 of 857 (79%) children in the standard therapy protocol. CONCLUSION Integrated management of GAM in children is an acceptable alternative to standard management and provides greater community coverage. This trial was registered at clinicaltrials.gov as NCT01785680.

Including whey protein and whey permeate in ready-to-use supplementary food improves recovery rates in children with moderate acute malnutrition: a randomized, double-blind clinical trial

BACKGROUND The utility of dairy ingredients in the supplementary foods used in the treatment of childhood moderate acute malnutrition (MAM) remains unsettled. OBJECTIVE We evaluated the effectiveness of a peanut-based ready-to-use supplementary food (RUSF) with soy protein compared with a novel RUSF containing dairy ingredients in the form of whey permeate and whey protein concentrate in the treatment of children with MAM. DESIGN We conducted a randomized, double-blind clinical effectiveness trial involving rural Malawian and Mozambican children 6-59 mo of age with MAM treated with either soy RUSF or a novel whey RUSF treatment of ~75 kcal · kg(-1) · d(-1) for up to 12 wk. RESULTS The proportion of children that recovered from MAM was significantly higher in the group that received whey RUSF (960 of 1144; 83.9%) than in the group that received soy RUSF (874 of 1086; 80.5%; P < 0.04; risk difference 3.4%, 95% CI: 0.3%, 6.6%). Children who consumed whey RUSF also demonstrated better growth markers, with a higher mean midupper arm circumference (MUAC) at the time of discharge (P < 0.009), greater MUAC gain during the course of treatment (P < 0.003), higher mean weight-for-height z score at discharge (P < 0.008), and greater weight gain (P < 0.05). No significant differences were identified in length gain or time to recovery between the 2 groups. CONCLUSION This study highlights the importance of milk protein in the treatment of MAM, because the use of a novel whey RUSF resulted in higher recovery rates and improved growth than did soy RUSF, although the whey RUSF supplement provided less total protein and energy than the soy RUSF. This study was registered at clinicaltrials.gov as NCT01790048.

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.

Extending supplementary feeding for children younger than 5 years with moderate acute malnutrition leads to lower relapse rates.

Objectives: Children with moderate acute malnutrition (MAM) have a high rate of relapse and death in the year following recovery. In this pilot study, we evaluate the long-term benefits of an extended course of nutritional therapy for children with MAM. Methods: Rural Malawian children 6 to 59 months old with MAM, defined as a weight-for-height z score (WHZ) between −2 and −3, were provided supplementary feeding for a fixed duration of 12 weeks. The children were then studied for 12 months to assess long-term nutritional status, and compared with children initially treated only until they first reached WHZ > −2. Results: Compared with children treated until they reached WHZ > −2, children treated for 12 weeks were more likely to remain well nourished (71% vs 63%, P = 0.0015) and maintain more normal anthropometric indices during 12 months of follow-up; there was also a trend towards lower rates of severe acute malnutrition (7% vs 10%, P = 0.067) and death (2% vs 4%, P = 0.082). Regression modeling showed that mid-upper arm circumference and WHZ at the end of supplementary feeding were the most important factors in predicting which children remained well nourished (P < 0.001 for each). Conclusions: The duration of supplementary feeding for children with MAM may not be as important as their anthropometry in terms of remaining well nourished after initial recovery. The presently accepted recovery criteria of WHZ of −2 may be insufficient for ensuring long-term nutritional health; consideration should be given to setting higher recovery criteria.

A comprehensive linear programming tool to optimize formulations of ready-to-use therapeutic foods: an application to Ethiopia

BACKGROUND Ready-to-use therapeutic food (RUTF) is the standard of care for children suffering from noncomplicated severe acute malnutrition (SAM). OBJECTIVE The objective was to develop a comprehensive linear programming (LP) tool to create novel RUTF formulations for Ethiopia. DESIGN A systematic approach that surveyed international and national crop and animal food databases was used to create a global and local candidate ingredient database. The database included information about each ingredient regarding nutrient composition, ingredient category, regional availability, and food safety, processing, and price. An LP tool was then designed to compose novel RUTF formulations. For the example case of Ethiopia, the objective was to minimize the ingredient cost of RUTF; the decision variables were ingredient weights and the extent of use of locally available ingredients, and the constraints were nutritional and product-quality related. RESULTS Of the new RUTF formulations found by the LP tool for Ethiopia, 32 were predicted to be feasible for creating a paste, and these were prepared in the laboratory. Palatable final formulations contained a variety of ingredients, including fish, different dairy powders, and various seeds, grains, and legumes. Nearly all of the macronutrient values calculated by the LP tool differed by <10% from results produced by laboratory analyses, but the LP tool consistently underestimated total energy. CONCLUSIONS The LP tool can be used to develop new RUTF formulations that make more use of locally available ingredients. This tool has the potential to lead to production of a variety of low-cost RUTF formulations that meet international standards and thereby potentially allow more children to be treated for SAM.

Acceptability of locally produced ready-to-use therapeutic foods in Ethiopia, Ghana, Pakistan and India

Abstract Successful treatment of severe acute malnutrition has been achieved with ready‐to‐use therapeutic food (RUTF), but only 15% of children with severe acute malnutrition receive RUTF. The objective of this study was to determine whether new formulations of RUTF produced using locally available ingredients were acceptable to young children in Ethiopia, Ghana, Pakistan and India. The local RUTFs were formulated using a linear programming tool that allows for inclusion of only local ingredients and minimizes cost. The study consisted of 4 two‐arm, crossover, site‐randomized food acceptability trials to test the acceptability of an alternative RUTF formula compared with the standard peanut‐based RUTF containing powdered milk. Fifty children with moderate wasting in each country were enrolled in the 2‐week study. Acceptability was measured by overall consumption, likeability and adverse effects reported by caregivers. Two of the four RUTFs did not include peanut, and all four used alternative dairy proteins rather than milk. The ingredient cost of all of the RUTFs was about 60% of standard RUTF. In Ethiopia, Ghana and India, the local RUTF was tolerated well without increased reports of rash, diarrhoea or vomiting. Children consumed similar amounts of local RUTF and standard RUTF and preferred them similarly as well. In Pakistan, local RUTF was consumed in similar quantities, but mothers perceived that children did not enjoy it as much as standard RUTF. Our results support the further investigation of these local RUTFs in Ethiopia, Ghana and India in equivalency trials and suggest that local RUTFs may be of lower cost.

Resistant starch does not affect zinc homeostasis in rural Malawian children.

OBJECTIVE This study tested the hypothesis that Malawian children at risk for zinc deficiency will have reduced endogenous fecal zinc (EFZ) and increased net absorbed zinc (NAZ) following the addition of high amylose maize resistant starch (RS) to their diet. METHODS This was a small controlled clinical trial to determine the effects of added dietary RS on zinc homeostasis among 17 stunted children, aged 3-5 years consuming a plant-based diet and at risk for perturbed zinc homeostasis. Dual zinc stable isotope studies were performed before and after 28 d of intervention with RS, so that each child served as their own control. The RS was incorporated into fried wheat flour dough and given under direct observation twice daily for 28 d. Changes in zinc homeostatic measures were compared using paired Students t-tests and linear regression analysis. RESULTS Children had a mean height-for-age Z-score of -3.3, and consumed animal source foods ≤twice per month. Their habitual diet contained a phytate:zinc molar ratio of 34:1. Children avidly consumed the RS without complaints. EFZ was 0.8±0.4mg/d (mean±SD) both before and after the intervention. Fractional absorption of zinc was 0.38±0.08 and 0.35±0.06 before and after the RS intervention respectively. NAZ was 1.1±0.5 and 0.6±0.7 before and after the RS intervention. This reduction of NAZ corresponded with diminished dietary zinc intake on the study day following intervention with RS. Regression analysis indicated no change in zinc absorption relative to dietary intake as a result of the RS intervention. CONCLUSION Consumption of RS did not improve zinc homeostasis in rural African children without zinc deficiency. RS was well tolerated in this setting.