Association Between Intakes of Protein, Calcium and Milk With Gene Expression and Linear Growth of School Aged Children
Condition: Nutritional Stunting; Nutritional Anemia; Nutritional Deficiency; Nutrigenetic; Nutrigenomic; Linear Programming; Food Based Recommendation
MeSH terms: Malnutrition
Study type: Interventional

Summary: 
      Protein is one type of nutrients known as the cause of stunting in developing countries since
      the mid-1970s (1) but then less attention on protein intake with the assumption that protein
      intake is sufficient. Compilation of published and non-published dietary intake research
      among Indonesian children aged 3-12 years (2), 0-18 years old (3) and 1-3 years old (3) found
      that protein intake among Indonesian children was sufficient (4). This finding is also
      confirmed by some other studies in 6 low-income countries and lead to the conclusion that
      growth restriction is not due to protein deficiency (5). Since then, micronutrient received
      main attention for the past 4 decades (1) to improve the health and survival of young
      children in developing countries. Issues on the need to re-examined protein recently emerge
      after the paper of Semba (1,6) regarding the low circulating amino acid among stunted
      children. It was hypothesized that the correlation between the low level of circulating amino
      acid with linear growth was through the mechanism of rapamycin complex C1 (mTORC1) and
      general control nonderepressible 2 (GCN2) pathway that contributes in the synthesis of
      sphingolipids and glycerophospholipids (6). However, the mechanism on how amino acid link to
      linear growth remains unclear.

      Fortification among Asian children revealed that only milk as food vehicles reported a
      significant effect on linear growth (2). It is likely that the effect on linear growth is
      influenced not only on micronutrient content of the fortified foods but also on protein and
      amino acid profiles of milk as the food vehicle.
    

Detailed description: 
      Background:

      The understanding of stunting has shifted from attention to protein and micronutrients in
      60-80s to amino acids and calcium in the past two decades. Amino acids are suspected to be
      nutrients that determine to stunting because recent studies have shown that growth can be
      carried out by the information pathway through the mTOR pathway (the mechanistic target of
      rapamycin). mTOR is a serine/threonine protein kinase from the PI3K family related kinases
      which are the main subunits of 2 complex proteins, namely mTORC1 and mTORC2. The mTORC1
      protein includes 5 main parts for cell growth, nutrition, growth factors, oxygen, energy, and
      stress. The mTORC2 protein is used in the cytoskeletal organization and cell survival. The
      activated mTORC1 protein initiates anabolic processes such as synthetic proteins, lipids, and
      nucleotides and inhibits catabolic processes such as autophagy. mTORC1 consists of three core
      proteins: mTOR, Raptor (regulatory protein associated with mTOR) and mLST8 (deadly mammals
      with Sec13 protein 8).

      Activation of the mTORC1 pathway as a controller of growth and metabolism is in accordance
      with the adequacy of intracellular essential amino acids. Deficiency of leucine, isoleucine,
      and valine determines mTOR downregulation. Inadequate intake of essential amino acids will
      repress protein and lipid synthesis as well as cell growth that will affect bone and chondral
      palate growth, skeletal muscle growth, nervous system myelinization, immune function and the
      size of the organ formed (Saxton & Sabatini, 2017). Research by Semba, et.al (2016) shows
      that in stunting children's serum, the levels of the nine essential amino acids are very low.
      Given that the body does not form essential amino acids directly, the intake of amino acids
      from food becomes very important (Nuss & Tanumihardjo, 2011). Essential amino acids are
      mostly contained in animal protein, but consumption in developing countries is still limited.
      Consumption of animal food sources is associated with a lower risk of stunting.

      Study of the mTORC1 pathway that has been done in vitro studies and experimental animals. In
      humans, the evidence of amino acid signaling through the mTORC1 pathway by using metabolomic
      aspects and proteomic and transcriptomic characteristics is still unknown. Analysis of genes
      related to MTORC1 pathway may answer this question

      The scope of services:

        1. To assess intakes of energy, macronutrients (protein, fat, carbohydrate), calcium and
           other micronutrients related to growth (zinc, iron, magnesium)

        2. To assess linear growth

        3. To assess gene expression of the mTORC1 pathway in school-age children in Malang, East
           Java.

      The objective of research:

        1. To assess energy and nutrient intake (especially for protein and calcium)

        2. To assess the expression of mTOR gene

        3. To assess the linear growth (height)

        4. To assess the association between intake of protein, calcium, milk with gene expression
           of mTOR and linear growth of children who received food-based intervention with or
           without milk with comparable calcium and protein intakes
    

Intervention name(s): Milk supplementation; Food Based Recommendation (FBR) nutrition education
Intervention type(s): Dietary Supplement; Other
Intervention description(s): Fresh milk from local farmer. No artificial sweetener and preservatives. Brandless.; Food Based Recommendation is result of OPTIFOOD WHO that analysed local food to optimize nutritional status according to problem nutrient.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Primary purpose: Treatment