One approach that has been studied by several research groups is the blanket provision of “medium-quantity” LNS (e.g., ∼50 g/d) to children at high risk of malnutrition. In this issue of PLOS Medicine, Lieven Huybregts and colleagues describe the results of a cluster-randomized pragmatic trial conducted in Chad to evaluate this strategy in the context of a food distribution program [9]. In this case, the product (Plumpy'Doz, 46 g/d) was added to a package of monthly household food rations for a period of 4 months and targeted to children 6–36 months of age (n = 1038). This intervention did not significantly reduce the incidence of the primary outcome, wasting, which is perhaps not surprising given that the control group also received the household ration, designed to cover 86% of daily energy requirements. However, the intervention group exhibited greater growth in height, lower prevalence of anemia, and less morbidity (29% reduction in incidence of diarrhea, 23% reduction in incidence of fever) than the control group. Because the quantity of food (energy provided) was presumably not limiting in either group, this speaks to the importance of dietary quality for infants and young children.

Three other trials have investigated the blanket provision of a similar quantity of LNS to that used in Chad [10]–[12]. In all three studies, two from Malawi and one from the Democratic Republic of Congo (DRC), infants were enrolled at 6 months of age and were randomized to the intervention group(s) that received LNS or to a control group that received another type of food supplement intended to provide an equivalent amount of energy. These studies have produced mixed results for weight and height gain, and it seems likely that some of this variation may be explained by differences across the trials in the foods provided to both the control and intervention groups. For example, control groups received food that was fortified with micronutrients (both Malawi studies) [10],[12] or enriched with fish powder (DRC) [11], which contrasts with the situation in Chad where the control group received unfortified staple foods. Furthermore, in the first Malawi study [10] (as in Chad), the LNS included dried skim milk powder as a key ingredient, whereas in the second Malawi study [11] the LNS did not include any milk and in the DRC [12] the amount of milk was about one-fifth of the amount in the LNS used in the other two studies. Other research has suggested that milk products may increase child growth by stimulating growth factors such as IGF-I [13],[14]. The phytate content of the products also differed, which can affect the absorption of key nutrients such as iron and zinc.

These studies illustrate that conclusions regarding the efficacy of various types of LNS may depend on the target group (age range), baseline prevalence and type of undernutrition, study design (e.g., type of control group; duration of intervention), and ration size and composition of the products being evaluated. Large variability across these dimensions in the small number of studies conducted to date makes it impossible to generalize.

There is clearly a need for additional research to understand the potential growth-promoting effect of certain ingredients in LNS (e.g., milk powder, essential fatty acids). The new study by Huybregts et al. [9] is an important contribution to the evidence base. Meanwhile, programmatic experience with the blanket provision of both “medium-quantity” and “small-quantity” LNS is growing, and in some cases is providing further evidence regarding effectiveness for prevention of wasting and stunting [15]. While that evidence is not as robust as the results of randomized controlled trials, careful attention to study design and data analysis should yield interpretable findings that are immediately relevant to real-world settings. Programmatic studies are also essential for understanding optimal ration size for the target age group and how best to integrate the appropriate use of high-quality fortified products with the other essential components for improving infant and young child nutrition, such as promotion of continued breastfeeding, dietary diversity, responsive feeding practices, and attention to hygiene and sanitation [5],[6]. Finally, high-quality programmatic studies can help provide urgently needed information on the cost and comparative cost-effectiveness of different integrated strategies for filling nutrient gaps and promoting healthy growth.