Research Gaps in the Use of Dairy Ingredients in Food Aid Products

Abstract

Background:

Nutritional interventions to help prevent stunting, particularly in the first 1000 days from conception to 2 years of a child’s life, are a major focus of numerous food aid organizations worldwide. Dairy ingredients can play an important role in enhancing the nutritional value and effectiveness of food products used in food aid.

Objective:

This article addresses gaps in research on malnutrition from both a broad perspective and specific to dairy ingredients.

Methodology:

Narrative review.

Results and Conclusions:

From a broad perspective, there is a need for gaining a consensus by the research community and funders of research on best practices for protocol development, outcomes measured, and reporting of study outcomes. Identification of biomarkers and rapid screening methods and consistent application of their use would expedite future research. A better understanding of nutritional requirements for malnourished populations, including the effects of energy deficits and disease on those requirements, is needed. More specific to dairy ingredients, a key research question is: Does dairy protein or the package of nutrients provided by dairy ingredients have a unique impact on growth, and if so, how? Also, data on the optimal levels of dairy ingredients based on the effective cost of treatment are needed, particularly in the treatment and prevention of moderate acute malnutrition and during pregnancy.

Introduction

Hunger exists in the world today at unacceptable levels. Roughly 800 million people do not have enough food to lead productive lives with 1 of 6 children underweight, 1 of 4 stunted, and poor nutrition a cause of nearly half the deaths of children younger than 5 years. ¹ The prevention of stunting in children during the first 1000 days, the period from conception to 2 years of age, is currently a major focus for many organizations. Other papers presented in this supplement provide both a historical perspective and the latest findings regarding the role of dairy protein and other dairy nutrients in food aid. This article identifies research gaps and suggests way that may help improve knowledge in treating malnutrition in general and also via the use of dairy ingredients.

Information Needs From a Broad Perspective

Better Study Design and Reporting

There is a need for gaining a consensus by the research community and funders of research on best practices for protocol development, outcomes measured, and reporting of study outcomes. A discussion of research gaps in any field, including the use of dairy ingredients in food aid products, begins first with the development of the specific questions to be answered by a study. This is followed by the design of the research study to answer those questions and finally ends with a communication program to disseminate the results to various audiences. But realities of research interfere with implementing this approach perfectly. Many researchers conduct studies in a hospital or research facility in a sanitary and controlled setting. This is often not possible in malnutrition studies where research is often conducted in challenging field conditions and where the primary goal is to get nutrition to a hungry malnourished population, often children. Nevertheless, there are always ways to improve the rigor of studies conducted in this area and communication of their results.

In looking at research gaps from a broad perspective, the first challenge is trying to compare published studies in malnutrition. For example, as part of this supplement, Dr Ghosh referenced a review paper by Imdad and Bhutta. Their objective was to review research on the effect of balanced protein/energy supplementation during pregnancy on birth outcomes in order to get estimates of effectiveness of an intervention. Their initial search identified 4123 titles, but after screening of the titles and abstracts and eliminating studies that did not meet their criteria and those with various deficiencies, there were 11 studies found to include in the review to examine balanced protein energy supplementation. ² This issue occurred in several recent meta-analyses where, although there were vast numbers of studies published, only a few studies were suitable for use in the analyses, thus reducing the evidence base to make decisions. ^3,4 In a recent review, Webb concluded that “although every study faces trade-offs in terms of feasibility, cost, desirability, and rigor, poorly conceptualized or badly conducted studies should not be funded, implemented or published. The idea that some data must be better than no data is false when the data collected are otherwise not used or useless and when scarce resources could have been used in other protective ways.” ^5(p.s70) Although research in malnutrition is often challenging, efforts must be directed toward improving the ability to compare studies and to allow them to be better utilized in meta-analyses.

One simple and obvious approach is to seek agreement among researchers and end users of the research data on the identification and use of common end points, as well as agreement as to the appropriate methodology and timing of the collections of those end points. It is also important to provide detailed information in journal publications about appropriate end points, how to measure them, and how to validate their methodologies. These methods and end points should then be widely adopted across adequately powered, randomized, controlled studies. Similarly, publications need to provide details of the food aid products tested, including descriptions of ingredients, proportions of these ingredients in mixtures, energy, and nutritional composition of the products, amounts offered to participants and amounts actually consumed, and changes in amounts offered/consumed by participants over the course of the study, perhaps corrected per kg body weight. In addition, the effects observed in one study versus another may not be the result of the food aid treatments themselves if the study is conducted at a time of food insecurity in one population but not the other. More complete descriptions of the population groups and conditions under which the study was conducted would allow more meaningful comparisons of studies. In simple terms, the information from a publication should be sufficient to allow replication of the study and provide the context in which it was conducted. Improvements could be obtained if researchers developed protocols and reported research as recommended in the Consolidated Standards of Reporting Trials (CONSORT) 2010 guidelines series for reporting on clinical trials. ⁶

Mechanistic Studies and Biomarker Development

There is a need for the identification of biomarkers and rapid screening methods along with consistent application of their use to expedite future research. Although an obvious end point of food aid studies is weight gain or growth, such data may take a lot of time to collect and may not provide physiological information to understand why a treatment effect was observed or not. Thus, mechanistic research should be considered in this area, and that requires the identification of biomarkers. Fortunately, researchers at the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others are working on identifying and validating biomarkers that would provide early indications of benefit. ⁷ The Biomarkers of Nutrition for Development (BOND) project is designed to provide state-of-the-art information on selection, use, and interpretation of biomarkers, including those for exposure, status, function, and effect of a nutrient. Phase 1 of the project includes the evaluation of biomarkers for six nutrients, including iodine, iron, zinc, folate, vitamin A, and vitamin B12. In addition to biomarker development, use of animal models in malnutrition to help understand mechanisms of how nutrients impact health and outcomes may be beneficial. For example, studies using a pig model could be the way to test the effects of nutrients during pregnancy, fetal growth, and postnatal linear growth.

Nutrient Requirements

A better understanding of nutritional requirements for malnourished populations and the impact of physiological conditions on those requirements is needed. The development of food aid formulations is based in part on best guess nutrient requirements. For example, the World Health Organization has published a technical note that summarizes existing knowledge, presents principles on the dietary management of children with moderate acute malnutrition (MAM), and proposes a nutrient composition profile for supplementary foods for the treatment of children with MAM. ⁸ The nutrient value ranges derived for children with MAM were determined largely by interpolation between recommended intakes for normal healthy children and children with severe acute malnutrition (SAM). As stated by Golden who authored one of the papers upon which the nutrient composition profile is based, “It should be emphasised that there are many uncertainties involved in deriving these first estimates of the nutrient requirements for the moderately malnourished. As new data become available it is anticipated that the proposed nutrient requirements will be incrementally refined and expert opinion will converge.” ⁹

Protein requirements used today largely rely on measurements made on normal healthy individuals. But are these requirements appropriate for malnourished individuals? When considering how to meet the nutritional requirements related to differing physiological states, the question of differentiating between essential and nonessential amino acids has been raised by Dr Manary in this supplement. Dr Manary also showed that there is a strong correlation between protein quality score and rates of weight gain, and although the newly recommended Digestible Indispensable Amino Acid Score (DIAAS) method for protein quality was better than the Protein Digestibility Corrected Amino Acid Score (PDCAAS) method currently used, adjusting for predicted amino acid needs due to malnutrition further improved the DIAAS method. Research by Dr Ghosh indicates that use of total protein versus total utilizable protein (corrected for protein quality) can result in significant underestimations of risk for protein inadequacy in some countries. In addition to protein quality, adjustments for increased demand for protein due to infections and mild to moderate energy deficits should be considered in assessing needs of populations where those conditions still prevail. ¹⁰

The capability exists to determine nutrient needs of malnourished individuals and the impact physiological stresses and infection have on these requirements. However, to do so, more studies based on nutrient composition and less on product comparisons need to be designed and conducted, and information on protein and other nutrient requirements from malnourished individuals in the real world must be obtained. With further development of the DIAAS method, techniques for obtaining digestibility measurements in healthy and malnourished animal models or humans should be pursued.

Information Needs Specific to Dairy Ingredients

Effect on Linear Growth

A key dairy research question is: Does dairy protein per se or the package of nutrients provided by dairy ingredients have a unique impact on growth, and if so, how? Numerous reports and recommendations support the use of animal protein sources in food aid products. ^{11 –15} Dairy ingredients present several benefits. Whole milk powder, dry skim milk powder, milk protein concentrates (MPCs), and whey protein ingredients are all high-quality proteins that are rich in essential, branched chain and also sulfur-containing amino acids that are important for growth. The branched chain amino acids, particularly leucine, play an important role in enhancing and maintaining muscle mass and promoting lean body growth. Although their protein quality is a major advantage, they also provide lactose, minerals, and bioactive compounds, so dairy ingredients can be viewed as a package of nutrients for growth and the prevention of stunting. ¹⁶

However, the question of whether dairy ingredients have a unique effect on the promotion of linear growth, as suggested by some, remains unclear. ^17,18 Stunting (short for age) related to malnutrition at various stages of life is a serious problem, resulting in reduced cognitive function and poorer quality of life, so understanding if and how dairy ingredients affect linear growth is a critical research objective.

There are hypotheses as to how dairy proteins impact growth. For example, dairy affects the production of insulin-like growth factor 1 (IGF-1) in the body, and it has been shown that this increase is associated with the protein, casein, found in dairy ingredients. ^{18 –20} It has also been shown that whey stimulates blood insulin levels. ¹⁹ Both IGF-1 and insulin are important for growth and fetal development. Also, the essential amino acid, arginine, may help placental development, and sulfur amino acids provided by dairy ingredients may help growth plate development. ^9,21 So, amino acids and high-quality protein certainly play a role in fetal development and growth of children.

Lactose is abundant in milk and is known to increase mineral absorption. ^22,23 In addition, lactose and oligosaccharides produced from lactose may also have prebiotic effects to promote growth of beneficial bacteria in the intestine. Recent studies have raised the hypothesis that intestinal microbes may impact health and nutrition in malnourished individuals. ²⁴ So, an interesting question is: Does lactose itself enhance growth? Results from animal research suggest lactose does enhance growth. ^{25 –28} Whether this is due to increased palatability (ie, increased feed intake) or a direct effect on growth along with or independent of protein is unclear. Both of these questions need further research. Studies using whey permeate as a source of lactose and minerals produced positive effects on growth in young pigs, and studies using whey permeate as a source of minerals and lactose in ready-to-use therapeutic foods are currently being initiated (Grenov, personal communication).

Optimal Dairy Ingredient Levels for Reducing “Cost of Treatment”

An issue with the use of dairy ingredients is their cost compared to other ingredients. Optimal levels of dairy ingredients based on the “effective cost of treatment” are needed, particularly in the treatment and prevention of MAM and during pregnancy. This information will enhance linear formulation capability. Dairy products’ versatility derives not only from their own nutritional content but also their ability to compensate for the inadequacies of other ingredients—making them ideal for producing formulations using linear programming. For example, there are multiple ingredient sources of dairy protein, including whole and skim milk powder and MPC that contain both casein and whey protein, and whey ingredients that do not contain casein. Studies have shown that the inclusion of milk powder can enhance the effectiveness of supplemental diets for the treatment of childhood malnutrition. ^{29 –31} A recent study has found that use of whey and skim milk powder was equally effective in the treatment of SAM. ³² Versatility is also important when considering lactose intolerance. Milk protein concentrates have the lactose removed during processing, but the dairy proteins remain in the same ratio as in the original milk. Thus, the use of MPC to produce low lactose products for food aid supplements is a possibility but has not been tested. Milk and whey permeates contain lactose and high levels of minerals.

Typically, costs of ingredients and nutrients are considered when formulating food aid products. A more meaningful approach would be to determine the effective cost of treatment. Although some ingredient or nutrient itself might be more expensive than alternatives, the shorter time period on treatment and/or the nutritional advantages realized using that ingredient or nutrient may far offset the costs associated with the more expensive ingredient or nutrient alone. This is an example of where it might make sense to add another consideration into the system of formulating new products. The linear programming tool described in the paper by Weber and Callaghan in this supplement deals with costs of foods and ingredients, acceptability by the target populations, and several other factors. But perhaps animal modeling could be added to the product testing process too. As different formulations are developed, they could be tested in a malnourished animal model, looking at physiological end points, mechanisms of action, and benefits. Additionally, an internal standard control group could be used in these animal studies, for example, feeding the F-100 formula used in the treatment of SAM to allow side-by-side comparisons within and across studies in a cost-effective manner. As these data are compiled, they will enable better predictions of the effect of changing ingredients and make the linear programming tool more effective in determining the optimal levels of different nutrients and ingredients.

Conclusions

Nutritional research in malnourished populations is very challenging to conduct, but also challenging is the comparison of data from studies that have been conducted. From a broad perspective, development of best practices in study design, outcome measurements, and reporting of outcomes are needed to enhance the ability to compare studies and build the evidence base from which to make recommendations. Additionally, a better understanding of the nutritional requirements of malnourished individuals that includes the impact of energy deficits and disease on these requirements is needed. Development of biomarkers may help expedite research and allow a better understanding of physiological roles for nutrients in malnutrition and its treatment. From a dairy ingredient-specific standpoint, milk itself and dairy products in general are excellent sources of nutrients for the treatment of malnutrition not only in children but also in pregnant and lactating mothers across the lifespan. However, more information is needed on how dairy ingredients affect growth physiology in these groups, when malnourished. Understanding optimal levels of intake, the optimal form(s) of dairy ingredients or nutrients, and the optimal ratio of ingredients to reduce the effective cost of treatment are today’s challenges.