Cholesterol: Genetic, Clinical and Natural Implications

Abstract

Cholesterol is a lipid that has multiple functions. It is of great importance for cell membrane structure and function in vertebrates. Metabolites of cholesterol viz. bile salts, steroid hormones and oxysterols, fulfill important biological functions. Hypercholesterolemia is an important risk factor for cardiovascular diseases. It is caused by an imbalance between cholesterol secretions into the blood and its uptake. This article is totally based on literature survey. The authors clearly explained the types of cholesterol, their functions and actions. They explored the cholesterol at molecular level by considering genes that regulate it. A number of diseases related to cholesterol were also highlighted. Plants products which can reduce the level of cholesterol were also explored. Moreover drugs that reduce cholesterol were also focused upon and the plant products which can act as their alternative were explained. Control of cholesterol through gene expression was also discussed. The aim of writing this article is to create awareness among the readers worldwide regarding the impact of cholesterol on their health. Moreover this article will help to select food items that can reduce the level of cholesterol and thus safeguard health.

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Research Journal of Pharmaceutical, Biological and Chemical
Sciences
Cholesterol: Genetic, Clinical and Natural Implications
Tanwi Priya1, Shashank Maurya2, Kishwar Hayat Khan3*
1, 2 School of Biosciences and Technology, VIT University, Vellore-632014, Tamil Nadu, India.
3. Assistant Professor (Senior), Medical Biotechnology Division, School of Biosciences and Technology, VIT
University, Vellore-632014, Tamil Nadu, India.
ABSTRACT
Cholesterol is a lipid that has multiple functions. It is of great importance for cell membrane structure
and function in vertebrates. Metabolites of cholesterol viz. bile salts, steroid hormones and oxysterols, fulfill
important biological functions. Hypercholesterolemia is an important risk factor for cardiovascular diseases. It
is caused by an imbalance between cholesterol secretions into the blood and its uptake. This article is totally
based on literature survey. The authors clearly explained the types of cholesterol, their functions and actions.
They explored the cholesterol at molecular level by considering genes that regulate it. A number of diseases
related to cholesterol were also highlighted. Plants products which can reduce the level of cholesterol were
also explored. Moreover drugs that reduce cholesterol were also focused upon and the plant products which
can act as their alternative were explained. Control of cholesterol through gene expression was also discussed.
The aim of writing this article is to create awareness among the readers worldwide regarding the impact of
cholesterol on their health. Moreover this article will help to select food items that can reduce the level of
cholesterol and thus safeguard health.
Keywords: Cholesterol, Genes related to cholesterol, Diseases, Drugs, Natural foods
* Corresponding author

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INTRODUCTION
Lipids are water-insoluble cellular components of diverse structure. Fatty acids are
carboxylic acids. It possesses hydrocarbon chains ranging from 4 to 36 carbons long. They
are also called as hydrocarbon derivatives. In some fatty acids, this chain is un-branched and
fully saturated (contains no double bonds); in others the chain contains one or more double
bonds, group. Cholesterol, the major sterol in animals, is both a structural component of
membranes and precursor to a wide variety of steroids. Cholesterol is one of the lipids. It is
an essential component of the cellular membranes determining the fluidity and biophysical
properties by lowering the permeability and increasing the compactness. The distribution of
this lipid in the membrane is not uniform but it is enriched in micro-domains, the so-called
rafts [1]. Cholesterol is required for embryonic and fetal development [2]. Cholesterol is also
a source of bioactive molecules such as steroid hormones, vitamin D and bile acids, which in
turn can regulate cellular metabolism and both intracellular and extracellular
communication. It is also important for signal transduction [3]. It forms a vital part of the
membranes of the spinal cord, nervous system, peripheral nerves and the brain. It is the
main constituent of myelin sheath that functions as an insulation layer. Cholesterol is also a
forerunner of important hormones such as testosterone, estradiol.
Cholesterol homeostasis is a matter of vital importance in animal physiology, and
perturbations in its normal levels have been associated with diseases such as
atherosclerosis, diabetes and Alzheimer’s disease *4+. Disorders in lipid (e.g., cholesterol and
triglycerides) and lipoprotein metabolism are major established independent risk factors in
the development and progression of atherosclerotic CHD.
Cholesterol is essential but excess of it leads to deposition in the blood arteries and
constricts them leading to blockage and ultimately heart stroke. The deposition of
cholesterol in blood arteries leading to the formation of plaque and obstructing blood flow
has been explained in the figure 1.
Fig1: Blood flow in human. A. The blood flows is continuous in normal circumstances. B. The flow of blood
gets obstructed due to plaque formation in the artery.
The main factors responsible for high cholesterol levels are hereditary factors, stress,
smoking, obesity and dietary cholesterol. Cardiovascular diseases (CVDs) are the major
killers of people globally and around 30 per cent of the total deaths worldwide is due to
CVDs [5]. The total number of deaths is projected to reach 23.3 million by 2030 [6]. As per

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the data given by WHO, 42 per cent of the total deaths in Egypt is due to CVD. It contributes
38 per cent in case of USA and 28 per cent in India.
This review article is totally based on literature survey. The authors did the literature
survey based on modern methods. They took the help of various search engines like science
direct, PubMed and Google scholar. Books and journals were also used in the survey. The
literatures of the past five years were focused. Others important literatures of the past were
also considered. Literatures that have been used in making this article are not restricted to a
particular geographical area but were taken from across the globe.
As the corresponding author of this article has the knowledge of biochemistry,
molecular biology and biotechnology he tried to explore the cholesterol in a very systematic
manner. This review article will summarize current knowledge about the cholesterol. The
authors focused on the physical and chemical nature of the cholesterol. They also focused
on the biosynthesis of cholesterol. All the types of cholesterol were deeply studied. There
functions were highlighted and their impacts on human health were explored.
Communicable diseases represent a worldwide problem as reported by the
corresponding author of this article [7]. Moreover the corresponding author along with the
other authors also reported that the infectious disease is the cause of morbidity and
mortality worldwide [8]. The corresponding author alone has reported his finding on
typhoid which comes under infectious diseases [9-13]. In this article the authors described
about the cholesterol in case of infectious diseases such as typhoid. Moreover the
corresponding author of this article reported about the various technologies related to gene
transfer in animals and also in plants [14-17]. In this article he along with the other authors
explored the genes in concerned with cholesterol. A numbers of genes were described that
regulates cholesterol. In addition to this the corresponding author also reported plant
product to be used against typhoid [18-22]. In this article the authors did an exhaustive
survey and presented a number of plants product that have potential to decrease the level
of cholesterol in blood. Moreover the authors also surveyed the drugs used to decrease the
cholesterol. The interesting thing about this article is that the authors have tried to replace
the drugs used to decrease cholesterol with plants products. This article reviews recent
major efforts towards understanding the importance of cholesterol in day to day life and
also to safeguard one self against the demerits of cholesterol. The main aim of writing this
article is to create awareness in the mind of people globally regarding the impact of
cholesterol on human health so that to reduce the risk of life. The genes related to
cholesterol were also explored so to make the study easy for the biotechnologists.
Moreover this article also focuses on how to lead a good life with minimal dependence on
the drugs.
Physical and chemical nature
Cholesterol is also known by few other names such as Cholesterin, Cholesteryl
alcohol, Cholestrin, Cordulan, Dusoline, Dusoran, Provitamin D and Cholesterine.
It is an amphipathic sterol present in higher animals. It’s a waxy lipid and distributed in body
tissues. Cholesterol can be toxic in the form of polar lipid [3]. Its molecular formula is
C27H46O and molecular weight is 386.65354. The IUPAC name of cholesterol is

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(3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]
2,3,4,7,8,9,11,12,14,15,16, 17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol. The melting
point of cholesterol is 140°C and its specific gravity ranges from 1.06 to 1.07. Cholesterol is
minimally soluble in water but insoluble in blood. It is solubilized by its combination with
either phospholipids or bile acids. The major part of total cholesterol present is synthesized
by the liver and other tissues and a small amount is absorbed in the diet from animal
derived foods. It’s stored in the cell in the form of cholesterol esters. It’s a source of
biologically active molecules such as steroid hormones (cortisol, cortisone, aldosterone and
progesterone), cholecalciferol (vitamin D) and bile acids [3].
Biosynthesis of Cholesterol
The liver and intestines are the sites where the cholesterol can be synthesized. The
biosynthesis in liver and intestines contribute to ten and fifteen per cent, respectively, of
the amount produced per day. The synthesis takes place in the cytoplasm and microsomes
from the acetate group of acetyl-CoA. The acetyl CoA is derived from oxidation reaction in
the mitochondria and then carried to the cytoplasm. The cofactor NADPH is involved in all
the reactions of cholesterol biosynthesis. The formation of HMG-CoA ultimately leads to
the conversion of Acetyl-CoA to mevalonate. The whole process is summarized in the Fig2.
Fig2. Biosynthesis of Cholesterol: Acetyl CoA leads to the formation of HMG CoA which gets converted into
mevalonate which in turn forms Isopentenyl pyrophosphate (IPP) accompanied by loss of CO2. IPP molecules
get converted into squalene which in turn forms cholesterol.
Types of Cholesterol
Cholesterol travels within the body by forming a complex with some proteins which
are termed as lipoproteins. A lipoprotein is an association of protein and lipids and it exists
in combination with proteins in order to allow fats to move across the cell. The protein
component plays a part in emulsification of fat molecules. Some examples of lipoproteins
include enzymes, transporters, structural proteins, antigens, toxins and adhesins. Depending
on the ratio of fat to protein content, lipoproteins can be classified as low density
lipoprotein (LDL) which is known as bad cholesterol, high density lipoprotein (HDL) termed

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as good cholesterol and very low density lipoprotein (VLDL) which is similar to LDL and
triglycerides .
Low Density Lipoproteins
Low density lipoproteins (LDL) or Bad cholesterol, as they are widely known, are
lipoproteins which transport cholesterol from liver and intestine to the cells and tissues of
the body through bloodstream. They play a vital role in the transfer of cholesterol and
metabolism. The density of these particles lies in the range 1.019-1.063 g/ml [23]. A protein
known as apolipoprotein B-100 that contains 4536 amino acid residues is present in each
LDL particle. The diameter of each LDL particle is around 22 nm and the hydrophobhic core
consists of linoleate and esterified cholesterol molecules. A copy of apolipoprotein B-100
and phospholipids are present in the surface monolayer. The major components which
constitute LDL molecule are represented in Table 1.
Table 1. Components of LDL
Other than these listed components, some other constituents such as
phosphatidylinositol, -tocopherol, carotenoids, oxycarotenoids and ubiquinol-10 are also
present in minute amounts. There are some subtype patterns of LDL among which those
having size in the range 19.00 to 20.50 nm are categorized as Pattern B and those with sizes
of 20.6 to 22 nm were kept under the category of Pattern A. The concentration of LDL with
their effects is listed in the table 2.
Table 2. Reference chart for LDL levels
S.No
Components
Composition
Reference
1.
Phosphatidylcholine
450 molecules/ LDL particle
[23]
2.
Sphingomyelin(SM)
185 molecules/LDL particle
[23]
3.
Lysophosphatidylcholine (lyso-PC)
80 molecules/LDL particle
[23]
4.
Phosphatidylethanolamine (PE)
10 molecules/LDL particle
[23]
5.
Diacylglycerol (DAG)
7 molecules/LDL particle
[23]
6.
Ceramide (CER)
2 molecules/LDL particle
[23]
7.
α-tocopherol
6 molecules/LDL particle
[23]
S.No
Concentration
(mg/dL)
Inference
1.
25 to less than 50
Optimal level which are observed in healthy young children prior to the onset
of atherosclerotic plaque in the artery walls of the heart
2.
<70
Nearly optimal level which is observed in condition of advanced symptomatic
cardiovascular disease
3.
<100
Sub-optimal level which corresponds to lower rates of symptomatic
cardiovascular disease
4.
100-130
Higher chances of developing symptomatic cardiovascular diseases.
5.
130-160
It relates with much higher chances of symptomatic cardiovascular disease.
6.
160-200
Alarming level corresponding to almost certain symptomatic cardiovascular
disease event.
7.
>200
Highest risk of developing symptomatic cardiovascular disease.

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High Density Lipoprotein
High density lipoprotein or HDL as it is commonly known is the good cholesterol
which carries cholesterol from the cells and tissues to the liver and thus it reduces
cholesterol in the blood. These are also known as alpha-lipoproteins or heavy lipoproteins
because of their small size and high density. They increase in size by the uptake of
cholesterol while circulating through bloodstream. This uptake is known as reverse
cholesterol transport which has been depicted in fig3.
Fig3. Lipoprotein Particle Metabolism: The dietary fat gets metabolized after it enters intestine and then liver
brings about the subsequent steps of the metabolism. The process is mediated by receptors for HDL, LDL and
chylomicron remnants.
This transport leads to retrieval of cholesterol from other tissues of the body and
return it to liver for excretion as bile or in the feces. It has been reported that HDL has a
genetic basis too and thus its role in the prevention of heart diseases is also guided by the
genetic makeup of an individual [24]. Some other factors include the size of HDL particles
and other proteins in the blood. Another important fact is that even though HDL levels
correlate with good cardiovascular health but specifically increasing its levels may not lead
to a better cardiovascular health [25]. The recommended levels of HDL have been
represented in table3.
Table 3. The recommended levels of HDL
S.No
HDL Level
(mg/dL)
Inference
Reference
1.
Less than 40 for men
Less than 50 for women
High risk of heart diseases
[26]
2.
40-59
Normal HDL levels
[26]
Very Low Density Lipoprotein
Very low density lipoprotein or VLDL is a type of lipoprotein with the highest amount
of triglycerides and it is categorized as a type of bad cholesterol because it eventually gets
converted into LDL and causes buildup of cholesterol on the walls of arteries [27]. VLDL

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plays a role in transport of triglycerides from the liver to the peripheral tissues for storage.
Most of the plasma triglyceride is carried by VLDL and thus the levels of VLDL triglycerides
and plasma triglycerides are almost the same. VLDL contains apolipoprotein B-100,
apolipoprotein C1, apolipoprotein E, cholesterol, cholesteryl esters and triglycerides when it
is released from the liver and then it picks up apo C-II and apoE from HDL to become mature
VLDL.The normal range for VLDL cholesterol is 2-30 mg/dL and higher levels are associated
with stroke and heart diseases.
Triglycerides
Triglycerides are a type of fat present in the body. A triglyceride molecule is basically
an ester which constitutes a glycerol molecule bound to three fatty acids. The excess
calories which lie unused by the body get converted to triglycerides and then these are
stored in the fat cells. Thus triglycerides are the chemical form in which food remains within
the body. Then at later stages hormones release these triglycerides for energy between the
meals. As per the guidelines given by American Hearts Association (AHA), triglyceride levels
should be maintained at a level of less than 150 mg/dL. Increased levels are associated with
occurrence of coronary heart diseases [28].
Genes associated with cholesterol disorders
Gene is a segment of nucleic acid that encodes a functional protein or RNA and is the
unit of inheritance as described by the corresponding author [16-17]. Recombinant DNA
technology has brought about a complete revolution in the way living organisms are utilized.
This is achieved by transferring new DNA sequences into animals or by removing or altering
DNA sequence in the genome as reported by the corresponding author [16]. He also
reported in his article about gene transfer technologies. In this article the authors explained
the aspects of cholesterol at molecular level. The authors have done an exhaustive survey
and tried to explore a number of genes in concerned with cholesterol.
Cholesterol is delivered to the cells of the body through bloodstream. A mutation in LDLR
gene will result into familial hypercholeresterolaemia which is characterized by non-
absorption of LDL cholesterol and its circulation in blood. The other genes responsible for
hypercholesterolemia are APOB, LDLRAP1 and PCSK1 [29]. The advancements made in
genotyping technology have unveiled the genetic mechanisms behind cardiovascular
diseases and several candidate genes have been identified which are involved in these
disorders. Even though there are environmental factors too which influence the outbreak of
cardiovascular disorders but the majority of such diseases are because of mutation in the
genes [29-30].
LDLR
LDLR is one of the vital genes required for cholesterol regulation. Some other roles of
this gene are cholesterol homeostasis, lipid metabolism, lipid transport, VLDL receptor
activity, lipoprotein binding and transmembrane signaling receptor activity. The proximal
region of the 3’ UTR of LDL receptor mRNA possess vital regulatory sequences which are
involved in controlling the messenger stability and they mediate berberine induced increase
in LDLR mRNA half-life [31]. Hypercholesterolemia is an autosomal dominant disorder

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caused by a mutation in LDLR. The LDL-R synthesis dysfunction of familial
hypercholesterolemia patients leads to arterial stenosis and calcification. LDL gets attached
to the receptor sites on the targeted cells and get absorbed. The production of these
receptors is controlled by LDLR gene present on chromosome 19 at position 13.2 in human
beings. This gene family includes cell surface proteins involved in receptor-mediated
endocytosis of specific ligands [32]. The gene brings about combination with LDL particle
and its excretion outside the cell by endocytosis. The LDL particle is taken up by the cell and
it reaches lysosomes.
APOB
APOB gene is located on chromosome 2 between positions 24 and 23.
Apolipoprotein is the main protein constituent of chylomicrons, LDL and VLDL. It acts as a
recognition signal which brings about the cellular binding and internalization of the LDL
particles by apoB/E receptor. The gene APOB codes for the main apolipoprotein of LDLs and
it has two isoforms viz. ApoB-48 which is synthesized in the gut and the second one apoB-
100 is synthesized in the liver. The N-terminal sequence is common in both the isoforms.
ApoB-48 is shorter in length and it is produced after the RNA editing of apoB-100 at residue
2180, which results in a stop codon and early termination of translation. ApoB-48 shares
48% similarity with the sequence of apoB-100. A mutation in this gene is responsible for
hypercholesterolemia and other diseases that affect plasma cholesterol and apoB levels.
The major polymorphisms include insertion and deletion polymorphism within the coding
region of the signal peptide of apoB and it is associated with the risk of coronary heart
diseases and myocardial infarction. [33]. High levels of apoB can lead to plaques that are
responsible for atherosclerosis. There is one apoB-100 per LDL particle thus LDL can be
quantified using apoB-100 concentration.
PCSK9
The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene is located on
chromosome 1 at position 32.3 in human beings and it encodes a polyprotein convertase
NARC1 which belongs to the proteinase K subfamily of the secretory subtilase family. This
protein is synthesized in the form of a soluble zymogen which encounters autocatalytic
intramolecular processing in the ER. It is basically a serine protease that decreases the levels
of both hepatic and extrahepatic LDL and VLDL receptors [34]. Overexpression of this gene
has been linked to decreased levels of LDL receptors (LDLR) because of degradation of the
mature receptors [35]. Mutations in this gene are associated with a third form of autosomal
dominant hypercholesterolemia. Geneticists are evaluating the methodology to maintain
the LDL levels by inhibiting PCSK9 gene [36]. The hepatic expression of LDLR protein
increases due to inactivation of PCSK9 gene and it accelerates clearance of circulating LDL
and it results into reduced plasma cholesterol [37].
LDLRAP1
LDLRAP1 is located on the short arm of chromosome 1 in case of human beings. This
gene is involved in the production of a cytosolic protein which removes cholesterol from
bloodstream. This protein has a phosphotyrosine binding domain which interacts with

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cytoplasmic tail of the LDL receptor. It is required for both internalization of the LDL-LDLR
complex as well as effective binding of LDL to the receptor. In the absence of LDLRAP1
protein LDL receptors fail to effectively remove LDL particles from bloodstream and thus
these LDL particles remain in the blood. Thus, a mutation in LDLRAP1 gene will lead to
increased levels of LDL in blood which will get deposited in the coronary arteries. This
ultimately leads to the clinical condition known as atherosclerosis. Mutation in this gene
results into an extremely rare inherited hypercholesterolemia known as autosomal recessive
hypercholesterolemia (ARH) [38].
APOA1
The gene APOA1 is located on chromosome 11 between positions 24 and 23 and it is
involved in the synthesis of apolipopretein A-I which is a component of HDL. This
apolipoprotein joins with the cell membrane and facilitates the movement of cholesterol
and phospholipid from within the cell to outside. HDL is formed when these substances
combine with apoA-I outside the cell. APOA1 protein induces cholesterol efflux and it is a
cofactor for LCAT (lecithin cholesterolacyltransferase) which forms majority of the plasma
cholesteryl esters[38]. ApoA-I brings about cholesterol esterification which converts
cholesterol to a form that can get integrated into HDL and get transported through the
bloodstream. Mutation in this gene results into an altered APOA1 protein and causes an
inherited condition known as familial HDL deficiency in which HDL levels are low in the
blood and thus elevated chances of cardiovascular disorders.
ABCA1
The ATP-binding-cassette-transporter-A1 gene is located on chromosome 9 at
position 31.1 and it is responsible for the synthesis of proteins which transport molecules
across the cell membrane. It acts as a cholesterol efflux pump in the cellular lipid removal
pathway [39]. Alterations in ABCA1 gene results into a medical condition termed as familial
HDL deficiency which is associated with high risk of cardiovascular diseases before the age
of 50 years. If the altered gene is present in two copies then it gives rise to tangier disease
which is characterized by buildup of cholesterol in the body tissues leading to impaired cell
function. The level of HDL may fall to zero in the patients in some cases.
APOE
The apolipoprotein E gene is located on chromosome 19 at position 13.2 and it codes
for apolipoprotein E which complexes with lipids and form lipoproteins. It is vital for the
normal catabolism of triglyceride rich lipoprotein components. A mutation in this gene
impairs chylomicron and VLDL clearance and thus results into type III hyperlipoproteinemia
which is characterized by high levels of plasma cholesterol and triglycerides[40].
LCAT
The lecithin-cholesterol acyltransferase (LCAT) gene is located on chromosome 16 at
the position 22.1 and it encodes the lecithin-cholesterol acyltransferase which is an
extracellular cholesterol esterifying enzyme responsible for cholesterol transport. This

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enzyme is synthesized primarily in the liver and plays a central role in extracellular
metabolism of plasma lipoproteins. It converts cholesterol and lecithins
(phosphatidylcholines) to lysophosphatidylcholines and cholesteryl esters on the surface of
LDLs and HDLs. LCAT also plays a crucial role in reverse cholesterol transport and thus lack
of LCAT activity will result into accumulation of free cholesterol in the body tissues [41]. This
gene works alongside ABCA1 and APOE and bring about maturation of glial derived nascent
lipoproteins. Alterations in LCAT cause Norum Disease which is characterized by improper
esterification of plasma cholesterol. The genes and also their roles are summarized in table
4.
Table 4. Genes Associated with Cholesterol Disorders
S.No
Gene
Role
Associated Disorders
Reference
1.
LDLR
Cholesterol homeostasis &
transport
Hypercholesterolemia
[31]
2.
APOB
Synthesis of apolipoprotein B
Familial Hypercholesterolemia,
atherosclerosis
[33]
3.
PCSK9
Regulation of cholesterol in
bloodstream
Familial Hypercholesterolemia
[34]
4.
LDLRAP1
Removal of cholesterol from
bloodstream
Hypercholesterolemia
[38]
5.
APOA1
Synthesis of a component of HDL
Familial HDL deficiency
[38]
6.
ABCA1
Acts as a cholesterol efflux pump
Tangier disease
[39]
7.
APOE
Catabolism of triglyceride rich
lipoprotein components
Hyperlipoproteinemia type III
[42]
8.
LCAT
Extracellular metabolism of
plasma lipoproteins
Norum disease
[41]
Diseases and cholesterol
Salmonella typhi is the causative agent of enteric fever. A severe and protracted
hypertriglyceridaemia, decrease in HDL-cholesterol levels and increase in LDL-cholesterol
levels in patients with enteric fever at the peak of fever has been reported [43]. Levels of
triacylglycerides and cholesterol esters were rapidly elevated while di- and
monoacylglycerides appeared in heart muscle after intraperitoneal administration of
typhoid endotoxin into mice [44]. Content of total lipids was markedly increased in mice
myocardium after intraperitoneal administration of typhoid endotoxins. Concentrations of
triacylglycerols, free fatty acids, esterified and free cholesterol were mainly altered as
reported by the other researchers [44].
Dengu fever is an infectious disease caused by virus. Genetic and pharmacological
modulation of cholesterol biosynthesis can regulate dengue virus replication [45]. Lipid
profile changes in case of dengue infection. Lowest cholesterol, VLDL levels are the highest
in Dengue Shock Syndrome and [46]. Changes in the plasma lipid profile as a potential
predictor of clinical outcome in dengue hemorrhagic fever has been reported [47].
HIV is an infectious disease. Lipid abnormalities are common in treatment-naïve HIV-
infected patients even in the absence of major host-related risk factors for dyslipidemia.

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HIV-infected patients should, therefore, be routinely screened for lipid disorders before
commencement of anti-retroviral therapy [48]. Cholesterol involvement in the pathogenesis
of neurodegenerative diseases have also been studied by the researchers [49]. Coronary
heart disease is a world-wide health care problem. Cholesterol is a major risk factor for the
development of coronary heart disease [50]. The authors considered a number of diseases
and surveyed the level of cholesterol and summarized it in the table 5
Table 5: Alteration in lipid profile in diseased condition.
S.No.
Diseases
Change in lipid profile
References
1
Cancer
Redued LDL
Reduced HDL
[51-53 ]
2
Severe Dengue
Redued LDL
Reduced HDL
[47]
3
Severe Malaria
Raised LDL
Raised HDL
Reduced triglycerides
[54]
4
Typhoid
Raised LDL
Reduced HDL
Reduced triglycerides
[55]
5
Post-polio
Raised LDL
Raised HDL
Raised triglycerides
[56]
6
Alzheimer’s Disease
Raised LDL
Raised HDL
Raised triglycerides
[57]
7
Advanced Tuberculosis
Reduced LDL
Reduced HDL
[58]
8
Hepatitis C
Lower LDL
Lower HDL
[59]
9
Measles
Lower LDL
Lower HDL
[60]
10
Autism
Abnormally low LDL
Abnormally low HDL
[61]
11
Influenza A
HDL loses its anti-inflammatory
properties
[62]
Impact of food on cholesterol
After the advent of medical science, drugs are available for almost all the disorders
and cardiovascular disorders are not an exception. But the common fact which still
withholds is that prevention is better than cure and in this context modifying one’s food
habits is one of the simpler ways to counter the problem of cholesterol. Nature has
provided us numerous options for this purpose and we just need to adopt those food items
in our lifestyle in order to have a healthy living. Several food crops have shown cholesterol
lowering potential; for e.g. lime treated maize husk supplements reduce plasma LDL levels
in hypercholesterolemia people [63-64]. Oats is a wonder food item and it is highly efficient
in reducing cholesterol levels, its mechanism of action has been depicted in fig.4.

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Fig4. Mechanism of cholesterol reduction by Oats. A. Polyphenols present in oats causes reduction in total
number of adhesion molecules on the endothelial surface. B. Oats reduce chances of LDL entrapment in the
vascular wall. C. Oats prevent LDL oxidation and scavenge reactive oxygen species D. Oats preserve the
production of NO and thus inhibit endothelial dysfunction.
The corresponding author of this article Khan reported that the medicinal plants are
the backbone of traditional medicine [65]. He explored and reported plants products against
diseases [18-22]. Khan also reported that the majorities of the diseases occurs mainly due to
the imbalance between prooxidant and antioxidant homeostatic phenomenon in the body
[11]. The authors explored the plants and its products to be consumed to reduce
cholesterol. Several other such natural cholesterol controlling agents have been
represented in Table 6. Moreover the day to day use of cereals and their relation with
regards to cholesterol has been listed in the table 7. In addition to this saturated fatty acids
contents of animal food is listed in table 8.
Table 6. Food items capable of maintaining cholesterol levels
S.No.
Food Item
Impact on Cholesterol
Components Responsible
Reference
1
Pomegranate
(Punica granatum)
Inhibits CuSO4-induced LDL
oxidation,Reduced Cholesterol
accumulation, Inhibits macrophage foam
cell formation,
Attenuation of atherosclerosis,
Scavenge superoxide anion, hydroxyl and
peroxyl radicals
Antioxidants such as flavonoids
(anthocyanins), polyphenols
(Tannins, Proathocyanidins)
[66-68]
2
Sweet Orange (Citrus
sinensis)
Increases HDL level.
lowers LDL and triglycerides.
Prevents LDL oxidation
Increases ACTH,
corticosterone,aldosterone.
Decreases erythrocyte and platelet
aggregation.
Flavonoids (hesperidin, naringin),
inositol, ascorbic acid
[69-71]
3
Amla (Emblica
officinalis)
exerts the inhibitory effect of hepatic
HMG CoA reductase enzyme activity.
Corrects dyslipidaemia. Reduction in
LDL,VLDL and triglycerides alongwith a
significant increase in HDL. Induces aortic
plaque regression.
Tannins(emblicanin A and B,
punigluconin, pedunculagin),
Flavonoid (rutin)
[72-74 ]

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July-September 2013 RJPBCS Volume 4 Issue 3 Page No. 1356
4
Garlic (Allium sativum)
Suppresses LDL oxidation. Raises HDL.
Reduces VLDL. Inhibits hepatic
cholesterol synthesis.
Reduces aortic plaques. Antithrombotic,
antilipidemic, hemodynamic,
Inhibits Vascular calcification
S-ethylcysteine,
g-glutamyl-S-allylcysteine,
g-glutamyl-S-methylcysteine
g-glutamyl-S-propylcysteine,
Allicin(Mimics statins), saponins
[75-79]
5
Onion (Allium cepa)
Reduces blood triglycerols. Limits hepatic
cholesterol biosynthesis.
Excrete cholesterol through
gastrointestinal tract.
Allicins
[78]
6
Watermelon (Citrullus
lanatus)
Vasodilator, improves endothelial
dysfunction,decreases lipid peroxidation
in liver,
Attenuation of hypercholesterolemia-
induced atherosclerosis
Citrulline
[80-82]
7
Almonds (Prunus
amygdalus)
Scavenge free radicals. Inhibit copper
induced oxidation of LDL. Increase HDL
Fiber, flavonoids,
[83]
8
Apple (Malus
domestica)
Enhanced fecal excretion of bile acids,
hepatic degradation of cholesterol
Inhibits ApoB synthesis,
Decreased cholesterol
Esterification
Polyphenols, Pectin, Flavonoid
(Procyanidins)
[84-86]
9
Cranberry (Vaccinium
macrocarpon)
Inhibit LDL oxidation. Increases reverse
cholesterol transport. Decreased risk of
atherosclerosis.
Flavonoids (anthocyanins,
quercetin, myricetin),
hydroxycinnamic acids, polyphenols
(proanthocyanidins)
[87-90]
10
Mulberry (Morus alba
L.)
Inhibits LDL oxidation. Scavenge free
radicals. Promotes HDL uptake in liver.
Inhibits hepatic lipogenesis. Increases
LDL-receptor activity
Flavonoids (anthocyanins, rutin,
Phenols, Flavonols (morin,
quercetin and myricetin),a-linolenic
acid,unsaturated fatty acid (linoleic
acid)
[91-93 ]
11
Grape(Vitis vinifera)
Inhibits LDL oxidation ,enhanced reverse
cholesterol transport,reduced
intestinal cholesterol absorption,
Increased faecal excretion of lipids and
cholesterol, inhibits platelet aggregation,
reduced secretion of ApoB containing
lipoproteins
Flavanols (proanthocyanidin,
Polyphenol (tannins), Flavonois
(naringenin)
[94-97]
12
Banana (Musa
sapienturn)
Hypocholesterolaemic effect
Soluble and insoluble fibers,
flavonoids
[98-99]
13
Tomato (Solanum
lycopersicum)
Reduces dietary cholesterol absorption.
Decreases serum lipid peroxidation and
LDL oxidation
Tomatine (a-tomatine and
dehydrotomatine), lycopene.
[100-102]
14
Arjun (Terminalia
arjuna)
Anti-oxidant, anti-ischemic
Polyphenols (gallic acid, ellagic acid),
flavonols (catechin, gallocatechin,
epigallocatechin)
[103-104]

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Table7: Cereals for controlling cholesterol
Table8. Saturated fatty Acid Content of Edible oils from plant sources
Table 9: Saturated fatty acid content of animal foods
S.No.
Type of Oil
Percentage of saturated fatty acids
Reference
1
Cod liver oil
19 %
[115]
2
Channel catfish oil
26 %
[115]
3
Mackerel
35 %
[115]
4
Whale
19 %
[115]
5
Cow milk fat
62 %
[115]
6
Chicken fat
33 %
[115]
7
Egg yolk
53 %
[115]
8
Beef liver
39
[115]
9
Beef tallow
48 %
[115]
10
Lard
36 %
[115]
S.No.
Cereal
Impact
Reference
1.
Wheat
(Triticum spp.)
Reduces LDL levels without affecting
glucose and insulin metabolism
[105-106]
2.
Brown Rice (Oryza sativa)
enhanced the fecal excretion of
neutral sterols
[107]
3.
Barley (Hordeum vulgare)
Decreased hepatic cholesterogenesis
[108]
4.
Jowar (Sorghum sp)
Inhibit HMG CoA Reductase.
Increases HDL
[64]
5.
Oats (Avena sativa)
Lowers HDL. Carries cholesterol out
of the body. Reduction in waistline,
atheroprotective
[109-110]
6.
Rye ( Secale cereale)
Prevents LDL oxidation
[111]
7.
Buckwheat ( Fagopyrum
esculentum)
Increase in HDL levels
[112]
8.
Quinoa (Chenopodium
quinoa)
Reduces LDL
[113]
S.No.
Type of oil
Percentage of saturated fatty acids
Reference
1
Mustard oil
0.06 %
[114]
2
Corn Oil
13 %
[114]
3
Coconut Oil
88 %
[114]
4
Soybean oil
15 %
[114]
5
Cottonseed oil
26 %
[114]
6
Palm oil
48%
[114]
7
Olive oil
14 %
[114]
8
Peanut oil
19 %
[114]
9
Sunflower seed oil
10 %
[114]
10
English Wallnut oil
11 %
[114]
11
Safflower oil
9 %
[114]
12
Linseed oil
13 %
[114]

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July-September 2013 RJPBCS Volume 4 Issue 3 Page No. 1358
Drugs and their alternative natural products to reduce cholesterol
The genetic cause of high cholesterol can be treated by drug therapy. Currently,
there are drugs in the pharmaceutical market for this purpose. These drugs acts by binding
with the cholesterol present in the intestines and thus preventing it from being absorbed. In
other words, these drugs act as scavenger and thus the body begins to utilize more
cholesterol to produce bile and ultimately leading to a fall in blood cholesterol levels. It has
been reported that wood cellulose lowers cholesterol by about 33 per cent and
Hydroxypropyl-methylcellulose (HPMC) lowers it by around 50 per cent [116]. Even though
these drugs are capable of maintaining the blood cholesterol levels but there are some
better alternatives which can be used as an alternative to these drugs. Statins decrease
cholesterol levels by increasing the uptake of LDL, by blocking synthesis of hepatic
cholesterol and activating hepatic production of apoA-I. These drugs can be replaced by
whole grains, nuts, fatty fish, pure sugarcane and amla [117]. Similarly Niaspan acts by
decreasing the fractional catabolic rate of apoA-I without affecting the rate of synthesis and
it can be replaced by peanuts, fish and bran [117]. Similarly Gemfibrozil and fenofibrate
which induce production of the primary HDL apolipoproteins, apoA-I and apoA-II can be
replaced by oats, bran and apple [118]. These drugs also promote positive regulation of
lipoprotein lipase activity and thus blocking fatty acid and triglyceride synthesis ultimately
leading to a fall in the levels of VLDL and triglycerides. Raisins and grapes can replace the
drugs Cholestyramine and Colestipol which act by blocking bile acid synthesis by binding
with them and thus inhibiting hepatic reapportion [119]. Another drug Ezetimibe works by
blocking the intestinal brush border transporter involved in cholesterol transport and this
drug can be replaced by soy protein [120].
Control of cholesterol through gene expression
A newly designated method is to engineer protein expression in order to express LDL
receptors. In this method, engineered versions of the LDL receptor were constructed by site-
directed mutagenesis of the receptor cDNA and then transfected into fibroblast like COS
cells derived from monkey kidney tissue. These cell lines were produced by killing CV-1 cells
by SV40 virus which is capable of producing a large T antigen but it has minor defect in the
process of genomic replication. Cells were then assayed for their potential to bind with
various ligands such as VLDL and LDL after rectifying the variations in cell surface expression
levels. Deleting specific cysteine rich repeated elements within the receptor reduces LDL
binding. This leads to a better understanding of the critical regions of the protein required
for LDL binding. These studies have the promise to treat familial hypercholesterolemia in
future [121].
CONCLUSION
In this article the authors explored the cholesterol and made it easy to understand to
the readers. All types of cholesterol were discussed separately and their impacts on human
health were discussed. The authors also explained the biosynthesis of cholesterol in the
body. A lot of genes were explored by the authors and their functions were summarized.
The authors also listed a number of drugs used to reduce cholesterol and a number of
natural foods used for the same purposes. It is now the duty of the fellow researchers to

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July-September 2013 RJPBCS Volume 4 Issue 3 Page No. 1359
come forward and explore the other genes that take part in cholesterol regulation.
Moreover they should also try to discover safer drugs that can bring down the cholesterol to
normal level. Medicinal plants and natural food should be explored to reduce the
cholesterol. Much attention is required to reduce the cholesterol as it is related to
cardiovascular disease. The lowering of cholesterol will definitely reduce the rate of
blockage, stroke and death rate.
ACKNOWLEDGEMENTS
The authors and the corresponding author Dr. K.H.Khan, Assistant Professor (senior)
wishes to thank VIT University, Vellore-14, Tamil Nadu, India for providing the facility for
writing this manuscript.
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