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International Journal of Science and Healthcare Research
Vol.4; Issue: 3; July-Sept. 2019
Website: www.ijshr.com
Review Article ISSN: 2455-7587
Interplay With Dietary Components - Diet Therapy to Treat the Metabolic
Disorders
Dimpee Verma1, Jyotsna Verma2
1
Lady Irwin College, Delhi University, Delhi, India
2Sir Ganga Ram Hospital, New Delhi- 110060
Corresponding Author: Dimpee Verma
ABSTRACT
Keywords: metabolic disorders, impact of
Our daily life interactions between genetic and nutrients, nutrition, genetic makeup, polygenic
environmental factors including over nutrition diet, nutrigenetics
have promoted the pathogenesis of polygenic
diet related diseases. These complex interactions INTRODUCTION
between genetics and nutrition are investigated Diet related lifestyle, particularly
by nutrigenetics which is relevant to metabolic over nutrition and sedentary behavior has
health and disease. Diet including dietary drastically promoted today's talk of the town
chemicals can be a serious risk factor for a of what is known as Polygenic Diet-Related
number of diseases, affect health by altering [1]
gene structure and expression. This alteration Diseases. These diseases are caused due to
causes metabolic disorders (MDs) from which some genes that determine our responses to
round the world 20-25% population is suffering. the food we eat, the supplements we take
The Indian scenario includes detection and cure and how these foods interact with our genes
for certain MDs based on the diet modification. to affect our health. Common variations
Pure MDs like obesity, insulin resistance etc. are found throughout the human genome
generally arise because of poor nutritional explain individual differences in response to
habits, thus creating a harmful environment in the dietary intake.
body due to the diseases. Sometimes, MDs can
also lead to genetic basis e.g. hyperlipidemias in Nutrigenomics and Nutrigenetics
which children and apparently healthy adults are Nutrigenomics, the integration of
also predisposed to coronary artery diseases. In genomic science with nutrition, is the study
some cases, genetic factors (like unique HLA of the effects of food and food constituents
haplotype) can predispose to either Type 1 [2]
diabetes or Celiac disease. At the extreme end of on gene expression. It is a research
the spectrum, there are inherited MDs which focusing on identifying and understanding
themselves lead to disease. In phenylketonuria molecular level interaction between
(PKU)-restricting amino acids (AA) with dietary nutrients and other dietary bio-actives with
protein supplements, Maple syrup urine disease genome. Nutrigenomics aims to enhance
(MSUD)- thiamine with reduced branched AA, rational means to optimize nutrition with
tyrosinemia 2- reduced phenylalanine and respect to the subject's genotype. It is
tyrosine, homocystinuria- reduced methionine associated with the idea of personalized
but high cystine, galactosemia-reduced milk and
milk products are recommended. The above nutrition based on one’s genetic profile. It
conditions need specific dietary modifications studies the effect of nutrients on genome,
based on the genetic factors involved as well as proteome, metabolome and explains the
the knowledge of nutritional requirements and relationship between the specific nutrients
nutritional status. Thus, personalized nutrition and nutrient-regimes (diet) on the human
[2,3]
based on the genetic makeup is essential to health. Nutrigenomics is highly
create wonders in both prevention and treatment personalized because it looks at the
of metabolic disorders.
International Journal of Science and Healthcare Research (www.ijshr.com) 114
Vol.4; Issue: 3; July-September 2019
Dimpee Verma et al. Interplay With Dietary Components – Diet Therapy to Treat the Metabolic Disorders
biomarkers within each individual. disorder would occur that causes the body to
Researchers suggest that current technology have either too much or too little of the
can be used to build an ideal diet/intake of essential substances needed to stay healthy.
certain nutrients or a 'nutriome' that ensures Metabolic disorders can occur in different
[4]
proper functioning of all pathways involved conditions i.e.
[2]
in genome maintenance. Missing enzyme or vitamin that is
Nutrigenetics, on the other hand, necessary to complete metabolic cycle.
researches into the effect of a single gene or Abnormal chemical reactions that hinder
single food compound relationships. With metabolic processes.
the modern genetic data, we now know that External or foreign substances that cause
dietary bio-actives affect health by altering a disease in the liver, pancreas,
gene expression and structure and also, that endocrine glands or other organs
dietary practices can be more closely involved in metabolism.
personalized to individual genetic profiles. Nutritional deficiencies
Nutrigenetics aims to identify how genetic Thousands of these metabolic disorders are
variation affects the response to nutrients. caused due to single gene mutations e.g.
This knowledge can be applied to optimize Sickle cell anemia, cystic fibrosis, maple
the health and prevent/ treat diseases. The syrup urine disease (MSUD), Gaucher
ultimate aim is to offer people, the disease, hemochromatosis etc. Around the
personalized nutrition based on their genetic world, 20-25% population is suffering from
makeup. metabolic disorders. Among this, metabolic
Both of these branches require an disorders affect 40% of the people over the
understanding of nutrition, genetics, [5]
biochemistry and range of 'omic' age of 60 years. The Indian scenario
technologies to investigate the complex includes the detection and cure for certain
interaction between genetic and metabolic disorders based on the diet
environmental factors relevant to metabolic modifications.
[1]
health and disease. Effect of nutrients on the body
Common dietary chemicals act on
How do metabolic disorders occur? human genome directly/indirectly alter gene
[6]
It is an old fact that “diet affects expression. Some naturally occurring
health”. Nutrients and foods usually interact chemicals in food are ligands for
with genes in a benign manner but transcription and directly alter the gene
sometimes, this interaction can have fatal expression (Figure 1). Cell signaling is an
outcomes. There is an increasing important component of regulation of gene
recognition that nutrients have the capacity expression and metabolism, banking on both
to directly regulate the metabolic processes, internal as well as external signals to ensure
via impacting the expression of enzymes, [2]
receptors, hormones and other proteins. For the maintenance of homeostasis.
example- different nutrients and food bio- Individual nutrients can each be considered
actives have an effect on neurotransmitters as signals, which regulate the transcription
like dopamine and serotonin; both influence factors that modify the gene expression.
the mood and behavior. Due to naturally occurring mutations in
The food that we eat consists of human genome, humans differ in their
carbohydrates, proteins and fats that DNAs. These mutations are called
undergo a chemical process to transform it variations/ polymorphisms of DNA. The
into the fuel that keeps one alive. This most common polymorphisms are “Single
chemical process is called metabolism. If Nucleotide Polymorphisms” or SNPs. These
this breakdown of nutrients does not occur SNPs influence the way, individuals absorb,
transport, store or metabolize the
or metabolism process fails, the metabolic [6]
nutrients. If there is an intake of some
International Journal of Science and Healthcare Research (www.ijshr.com) 115
Vol.4; Issue: 3; July-September 2019
Dimpee Verma et al. Interplay With Dietary Components – Diet Therapy to Treat the Metabolic Disorders
nutrients that are not in accordance to one's transcription/ translation of genes and post-
genetic profile, it will affect the genes as translational and conformational changes in
well as DNA and simultaneous change in protein, as well as in their location. These
the transcription process will be there. As a molecular events are the basic mechanisms
result, undesired proteins will be formed controlling cell growth, proliferation and
that would ultimately, lead to the production ultimately lead to “Metabolism”.
of altered metabolites. Those would not be It is reported that gene, protein and
accepted by the body, would cause gene metabolite signatures are linked with
alteration and thus, the disease. specific nutrient or dietary protocols that are
Other dietary chemicals alter signal systematically organized to serve as
transduction pathway and chromatin molecular biomarkers for the early detection
structure to indirectly, affect gene of diseases in response to the nutrient
[7] [8,9]
expression. Ligands (dietary chemicals- induced changes in the body. The effort
nutrients) are the first messengers that, by is to identify these 'dietary signatures' or
binding in a receptor, give rise to changes pattern of effects ranging from effects at the
that ultimately, lead to “signaling cascade”. cellular level to the entire body systems.
Series of biochemical reactions, that are The desired outcome from this research is to
initiated by stimulus acting on a receptor place the genetic factors for the chronic
that is transduced to the cell interior via diseases and conditions, whether it is a
messengers and ultimately to effector certain gene itself or an epigenetic marker
molecules, resulting in a cell response to the and how foods influence it.[2]
initial stimulus (Figure 2). At molecular
level, such responses include changes in the
Food Nutrients
Cell signaling
Transcription
Ntu ics
regi nom mRNA
Mutations/ ten ige Translation
SNPs sci Nutr Regulate
Proteins
Metabolites
Gene structure/
Expression
Figure1. Cyclic representation of direct impact of nutrients on genome
Nutritional Therapy determine one's metabolic responses to the
Common variations are found food supplements he/she takes. That is why;
throughout the human genome, explain the some people who consume high fat diet,
individual differences in response to the have no cholesterol problems; while others,
[10]
dietary intake. Some individuals respond even on taking a small amount of fat, show
differently than others to exactly the same their cholesterol level at the peak. People
nutrients. This is because of the genes that drink coffee but for some, it becomes lethal.
International Journal of Science and Healthcare Research (www.ijshr.com) 116
Vol.4; Issue: 3; July-September 2019
Dimpee Verma et al. Interplay With Dietary Components – Diet Therapy to Treat the Metabolic Disorders
CYP1A2 is a gene that breaks caffeine in Ligands(Nutrients)
the liver. Some people’s system breaks it Ingestion
faster and gets rid of the caffeine, preserves Attach to receptor proteins
healthy antioxidants and protects heart. But Chemical reactions
other’s system breaks it at a slower rate, Receptor activation transduceligands to
thereby, increasing the risk of heart attack. Induce changes cell interior
Therefore, when people grow up with some Signaling Cascade Effector molecules
metabolic disorders, nutritional therapy/ Causes changes
dietary modification is the first option to Transcription/ Translation Result in cell response
cure them. Diet can be a risk factor as well of genes
as treating weapon for a number of
metabolic disorders. (Table 1) Affect metabolism
Figure 2. Flow chart to show the signal transduction pathway
in response to nutrients
Table 1: Diseases, their cause and dietary plan to cure them
DISEASE CAUSE DIETARY GUIDELINES
Phenylketonuria Phenylalanine hydroxylase is responsible for breakdown of Limiting the supplementation of amino
Phenylalanine. Deficiency of this enzyme does not convert acids but dietary protein supplements
phenylalanine to tyrosine. should be given.
Maple Syrup Urine Body's inability to use 3 branched chain amino acids (BCAAs) - Thiamine should be given with limiting
Disorder (MSUD) Leucine, Isoleucine and Valine. BCAAs and their by-products the supplementation of BCAAs.
(ketoacids) level increases and causes brain damage and alteration in Fruits & vegetables are mostly permitted
mental state. without measurements except in few
diseases like classical MSUD.
Type 2 Tyrosinemia Deficiency of the enzyme tyrosine amino transferase (TAT) which is Diet with reduced phenylalanine and
required for the multi-step process of breaking down of ‘tyrosine’ tyrosine content should be given.
occurs due to the mutations in TAT gene.
Galactosemia Deficiency of enzyme galactose-1-phosphate uridyl transferase that Exclude galactose/lactose from the diet
enables to metabolise galactose with the substitution of casein
hydrolysate containing formula or infant
soy formulas
Gaucher Disease Inability of the body to breakdown a particular kind of fat that No such dietary guidelines. Only enzyme
accumulates in liver, spleen & bone marrow replacement therapy (ERT) is available.
Glucose/ Galactose Defect in the transportation of glucose and galactose across the Remove lactose, sucrose and glucose
mal-absorption stomach lining which leads to severe diarrhoea and dehydration from the diet
Hyperthyroidism Increased secretion of thyroid gland hormone with a consequent High calorie (4000-5000 kcal), high
increase in metabolic rate protein (100-125g) diet including snacks
in between meals, multi-vitamin mineral
supplements, avoid caffeine rich foods
Hypothyroidism Condition of decreased production of thyroid hormone called High dietary fiber should be given to
MYXEDEMA. This condition is characterized by a decreased rate of prevent constipation, a calorie restricted
energy metabolism 30-40% below normal diet is prescribed
Homocystinuria Mutations occur in the gene cystathionine beta-synthase (CBS gene). Increased cystine with lowered
This gene holds instructions for making an enzyme that uses vitamin methionine diet is preferred.
B-6 to metabolize the amino acids (homocystine and serine). Due to
these mutations in the gene, building up of homocystine & other toxins
in the blood that damage the nervous system.
METHODS FOR ANALYSIS gene’s biological functional impact on
Analysis of blood or a cheek swab DNA is trait/ disease, i.e. focusing on allelic
done to study the necessary genotype. variation in specific biologically
1. A common way to assess the genetic relevant regions of the genome as
data is called 'Candidate Gene certain mutations will directly impact
Approach'. This study focuses on the functions of the genes and lead to
association between genetic variation phenotype/ disease state being
[11]
with pre-specified genes of interest and investigated.
phenotypes/ disease states. When examining functionality between
Candidate genes are often selected for genes in pathways, the gene product are
study based on ‘priori’ knowledge of described in 3 different ways (biological
International Journal of Science and Healthcare Research (www.ijshr.com) 117
Vol.4; Issue: 3; July-September 2019
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