ReviewStunting is a recognized problem: Evidence for the potential benefits of ω-3 long-chain polyunsaturated fatty acids
Introduction
Stunting, defined as height-for-age z-score <–2 according to the World Health Organization's (WHO) growth standards remains a major nutritional problem worldwide, especially in middle- and low-income countries, including Indonesia. Stunting occurs in one-third of children <5 y of age and causes 14% of childhood deaths in developing countries [1]. According to the Indonesian national basic health research data [2], the national prevalence of stunting in Indonesia was 37.2%, which was divided into 18% of stunting (z-score <–2 to ≥–3) and 19.2% of severe stunting (z-score <–3). This number increased from the previous national survey in 2010 and 2007, which were 35.6% and 36.8%, respectively. Following the survey, an annual nutritional status monitoring has been conducted under the coordination of the Ministry of Health of Indonesia and found that in 2015, prevalence of stunting in children <5 y of age was 29% [3], which slightly decreased in 2016 of 27.5% [4], but increased in 2017 of 29.5% [5]. More importantly, the prevalence of stunting is not decreasing.
A number of nutritional feeding programs to treat stunting are basically addressing the problem of malnutrition, such as using biofortification, prebiotic foods, and remedial formula such as ready-to-use therapeutic foods (RUTFs) that meet the WHO standard, and formulas known as F-75 and F-100 as well as modified dried skim cotton oil (modisco). The last two formulas are common in the treatment of malnutrition in Indonesia. RUTFs are energy-dense, micronutrient-enhanced pastes with a homogenous mix of lipid-rich foods that can be given directly to the patient without cooking. The nutritional profile of the RUTF is similar to the WHO-recommended therapeutic milk formula used for inpatient therapeutic feeding programs. Currently, the availability of RUTF is supported by UNICEF as a part of a community-based management for acute malnourished children globally [6]. The F-75 is designed to promote recovery of normal metabolic function and nutrition electrolytic balance. Hence, it is initially admitted to inpatients with no adequate appetite or those who have a major medical complication. Rapid weight gain is precarious in this stage, as patients do not gain weight. Once the acute condition is stabilized, it is advised to change the diet to F-100, which enables the patient to recover weight and lean body tissue loss [7].
Children with malnutrition not only need diets containing energy and nutrients to recover their weight, but they also require nutrients that support optimal functional development of tissues, including the central nervous system. A study by Danaei, et al. concluded that the leading risk worldwide for stunting is fetal growth restriction, which is defined as small for gestational age (10.8 million cases of stunting out of 44.1 million) [1]. Hence, sufficient dietary intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) are essential to support normal brain development, especially in the critical periods during pregnancy, lactation, and childhood.
The ω-3 LCPUFAs are involved in various neuronal processes, ranging from regulation of gene transcription to effects on cellular signaling processes [8], and protection against the pathogenesis of retinal diseases [9]. Nutrient deficiency during the brain growth spurt, which is between the last trimester of gestation and the first 2 y of childhood can damage brain function [10].
In the RUTF, as well as the F-75/F-100 and modisco, which are being used to date, the ω-3 LCPUFA composition is limited (Supplementary Tables 1–3). In general, intervention studies that used the F-75/F-100 as well as modisco and RUTF showed an improvement of weight; however, limited data were reported on height. The efficacy of RUTF has been evaluated in a number of studies for treatment of malnourished children, including those in Nigeria [11], Malawi [12], and India [13], and concluded that RUTF significantly improved the weight gain of the children. A study in Indonesia using quasiexperimental pre–post-test with a control group design in outpatient malnourished children ages 6 to 59 mo showed that a 5-wk intervention with F-75/F-100 increased the weight of the children by 507 g compared with the control group, which only gained 80 g [14]. Another study that used a randomized blinded pre–post-test with a control group design of inpatient malnourished children ages 1 to 3 y reported that after a 6-mo intervention, the weight gain in the intervention group, which received modisco with elemental milk formula containing medium chain triacylglycerol (TG) and polymer carbohydrate, was significantly higher (1527 g) than the control group given modisco with regular milk formula (726 g) [15]. Moreover, the data showed that the improvement of weight for height in the intervention group is significantly higher (z-score from –3.59 to –1.57) than in control group (z-score from –3.99 to –2.98) [15].
The effect of LCPUFA substitution for children with malnutrition has been reported in studies by Jones et al. [16] and Hsieh, et al. [17]. The Jones et al. study reported on malnourished children who received high-oleic RUTF made with peanut oil from a high-oleic acid peanut cultivar, hence the ratio of linoleic acid (LA) to α-linolenic acid (ALA) was 1:1. The children had a significantly better weight-for-height (WFH) when they recovered from malnutrition than children who were fed standard RUFT that contained 53 times more LA than ALA, although still marginally below average WFH [16]. The levels of ω-3 eicosapentaenoic acid (EPA) and ω-6 docosapentaenoic acid (DPA) decreased from 3.2% to 2.4% [16]. This indicates that the standard RUTF did not support circulating docosahexaenoic acid (DHA) levels. In contrast, the children with high-oleic RUTF showed increased EPA and DPA and the decreasing of DHA levels during recovery period was protected. Additionally, high-oleic RUTF also induced a reduction in arachidonic acid (AA) levels, indicating that less LA was transformed to AA or that AA was displaced from plasma phospholipids by the increased levels of ω-3 LCPUFAs [16]. The study by Hsieh, et al. showed that DHA levels in red blood cell (RBC) membranes significantly decreased after a 4-wk intervention by standard RUTF (from 5.2 to ∼4%) [17]. In the children receiving fish oil, DHA levels in RBC membranes increased over time to ∼6% to 8%. Only supplementation with fish oil increased EPA levels, whereas flax oil RUTF did not change the overall ratio of ω-6 to ω-3 compared with baseline. This ratio increased with standard RUTF but decreased with the fish oil supplementation compared with the flax oil RUTF [17]. Here, we review the potential benefits of ω-3 LCPUFAs for optimizing growth and development of stunted children.
We reviewed the following:
- [1]
ω-3 LCPUFA metabolism to highlight the importance of ω-3 LCPUFAs and not rely on the conversion of ALA to ω-3 LCPUFA;
- [2]
The health benefits of ω-3 LCPUFAs (and not ALA) during pregnancy, lactation, and throughout child growth and development;
- [3]
The recommended intakes and compare them to actual intakes to highlight the importance of increasing intake of ω-3 LCPUFA;
- [4]
How the recommended intakes can be met through various ω-3 LCPUFA-enriched foods; and
- [5]
The rationale for the inclusion of ω-3 LCPUFA in RUTF, which may prevent stunting.
Section snippets
ω-3 LCPUFA metabolism
Plants are able to synthesize LA (18:2 ω-6) and ALA (C18:3 ω-3); however, because humans cannot, they need to obtain these PUFAs from their diet. Therefore, they are considered essential fatty acids (EFAs) [18]. The metabolism of these EFAs to the LCPUFAs including AA (20:4 ω-6) in the ω-6 pathway and EPA (20:5 ω-3), DPA (22:5 ω-3) and DHA (22:6 ω-3) from the ω-3 pathway, has been well described [19], [20] and is shown in Figure 1. Δ-6 desaturase is the enzyme in the first step of the pathway
The role of ω-3 LCPUFAs on neurologic development
DHA is a crucial element in the nervous system, which is responsible for development of the sensory, perceptual, cognitive, and motor neural system during the brain growth spurt [9], [32]. It is the most fluidizing compound in the cell membrane [33], which is fundamental for growing membranes [34]. The retina, functionally an extension of the brain, is highly enriched with DHA, especially the retinal photoreceptor outer segment disk membranes [35]. The need for DHA in very early pregnancy has
Foods enriched with ω-3 LCPUFAs
In countries with traditionally low fish consumption as well as for certain individuals or communities for whom consumption of fish is not be suitable or convenient, ω-3–enriched foods could play an important role in meeting the recommendations for ω-3 LCPUFA. Lacto-ovo-vegetarians (LOVs) may obtain a limited amount of ω-3 LCPUFAs from eggs, milk, and dairy products, whereas vegans must rely on in vivo biosynthesis of these fatty acids from ALA, which depend on the ratio of ALA and LA from the
Inclusion of ω-3 LCPUFAs in RUTF rationale
In this study, we reviewed evidence that humans are able to synthesize ω-3 LCPUFAs from ALA, albeit limited, especially to DHA. Therefore, rather than relying on the conversion of ALA to ω-3 LCPUFAs including DHA, it is better to consume preformed ω-3 LCPUFAs. We have provided evidence that ω-3 LCPUFA are vital
- •
For neurologic development, especially DHA;
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From birth to old age, especially DHA;
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For cognitive development, especially DHA; and
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To prevent chronic disease in children.
However, ur current
Conclusions
The ω-3 LCPUFA must be obtained from preformed ω-3 LCPUFA (not from the conversion from ALA to DHA), which are provided in fish. However, numerous barriers to consume fish lead to a failure to meet the reference values for fish consumption. A low dose of food enriched with ω-3 LCPUFA can be used as a long-term strategy to achieve the health benefits of ω-3 LCPUFA for optimal health, including for stunted children. Due to the remedial formula to treat stunted children currently lacking on ω-3
Acknowledgment
We are grateful to the Ministry of Research, Technology and Higher Education of the Republic of Indonesia for World Class Professor Program, contract number 123.40/D2.3/KP/2018.
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SR conceptualized the study and drafted the manuscript. BJM co-authored the manuscript and was involved in drafting and finalizing the manuscript. Both authors contributed to the manuscript, read, and approved the final manuscript.