Nutritional Deficiency Clinical Trial
Official title:
Association Between Intakes of Protein, Calcium, and Milk With Gene Expression and Linear Growth of School Aged Children in Malang
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.
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
;
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