Cholesterol is a sterol (a combination steroid and alcohol) and
a lipid found in the cell membranes of all body tissues,
and transported in the blood plasma of all animals.
Lesser amounts of cholesterol are also found in plant
name originates from the Greek chole- (bile)
and stereos (solid), and the chemical suffix -ol for an alcohol, as researchers first identified
cholesterol in solid form in gallstones in 1784.
cholesterol is not dietary in origin; it is synthesized
internally. Cholesterol is present in higher concentrations
in tissues which either produce more or have more
densely-packed membranes, for example, the liver,
spinal cord and brain, and also in atheromata. Cholesterol
plays a central role in many biochemical processes,
but is best known for the association of cardiovascular
disease with various lipoprotein cholesterol transport
patterns and high levels of cholesterol in the blood.
doctors talk to their patients about the health concerns
of cholesterol, they are often referring to "bad cholesterol",
or low-density lipoprotein (LDL). "Good cholesterol"
is high-density lipoprotein (HDL); this denotes the
way cholesterol is bound in lipoproteins, the natural
carrier molecules of the body.
is required to build and maintain cell membranes;
it makes the membrane's fluidity - degree of viscosity
- stable over wider temperature intervals (the hydroxyl
group on cholesterol interacts with the phosphate
head of the membrane, and the bulky steroid and the
hydrocarbon chain is embedded in the membrane). Some
research indicates that cholesterol may act as an
antioxidant. Cholesterol also aids in the manufacture
of bile (which helps digest fats), and is also important
for the metabolism of fat-soluble vitamins, including
vitamins A, D, E and K. It is the major precursor
for the synthesis of vitamin D and of the various
steroid hormones (which include cortisol and aldosterone
in the adrenal glands, and the sex hormones progesterone,
the various estrogens, testosterone, and derivatives
cholesterol has also been implicated in cell signalling
processes, where it has been suggested that it forms
lipid rafts in the plasma membrane. It also reduces
the permeability of the plasma membrane to hydrogen
ions (protons) and sodium ions.Cholesterol
is essential for the structure and function of invaginated
caveolae and clathrin-coated pits, including the caveolae-dependent
endocytosis and clathrin-dependent endocytosis. The
role of cholesterol in caveolae-dependent and clathrin-dependent
endocytosis can be investigated by using methyl beta
cyclodextrin (MÎ²CD) to remove cholesterol from the
is minimally soluble in water; it cannot dissolve
and travel in the water-based bloodstream. Instead,
it is transported in the bloodstream by lipoproteins
- protein "molecular-suitcases" that are water-soluble
and carry cholesterol and triglycerides internally.
The apolipoproteins forming the surface of the given
lipoprotein particle determine from what cells cholesterol
will be removed and to where it will be supplied.
largest lipoproteins, which primarily transport fats
from the intestinal mucosa to the liver, are called
chylomicrons. They carry mostly fats in the form of
triglycerides and cholesterol. In the liver, chylomicron
particles release triglycerides and some cholesterol,
and are converted into low-density lipoprotein (LDL)
particles, which carry triglycerides and cholesterol
on to other body cells. In healthy individuals the
LDL particles are large and relatively few in number.
In contrast, large numbers of small dense LDL (sdLDL)
particles are strongly associated with promoting atheromatous
disease within the arteries. For this reason, LDL
is referred to as "bad cholesterol".
1987 report of National Cholesterol Education Program,
Adult Treatment Panels suggest the total blood cholesterol
level should be: <200 mg/dl normal blood cholesterol,
200-239 mg/dl borderline-high, >240 mg/dl high
lipoprotein (HDL) particles transport cholesterol
back to the liver for excretion, but vary considerably
in their effectiveness for doing this. Having large
numbers of large HDL particles correlates with better
health outcomes, and hence it is commonly called "good
cholesterol". In contrast, having small amounts of
large HDL particles is independently associated with
atheromatous disease progression within the arteries.
conditions with elevated concentrations of oxidized
L.D.L. particles, especially small LDL particles,
cholesterol promotes atheroma formation in the walls
of arteries, a condition known as atherosclerosis,
which is the principal cause of coronary heart disease
and other forms of cardiovascular disease. In contrast,
HDL particles (especially large HDL) have been the
only identified mechanism by which cholesterol can
be removed from atheroma. Increased concentrations
of HDL correlate with lower rates of atheroma progressions
and even regression.
the lipoprotein fractions, LDL, IDL and VLDL are regarded
as atherogenic (prone to cause atherosclerosis).
Levels of these fractions, rather than the total cholesterol
level, correlate with the extent and progress of atherosclerosis.
Conversely, the total cholesterol can be within normal
limits, yet be made up primarily of small LDL and
small HDL particles, under which conditions atheroma
growth rates would still be high. In contrast, however,
if LDL particle number is low (mostly large particles)
and a large percentage of the HDL particles are large,
then atheroma growth rates are usually low, even negative,
for any given total cholesterol concentration.
effects are further complicated by the relative concentration
of asymmetric dimethylarginine (ADMA) in the endothelium,
since ADMA down-regulates production of nitric oxide,
a relaxant of the endothelium. Thus, high levels of
ADMA, associated with high oxidized levels of LDL
pose a heightened risk factor for cardiovascular disease.
human trials utilizing HMG-CoA reductase inhibitors
or statins, have repeatedly confirmed that
changing lipoprotein transport patterns from unhealthy
to healthier patterns significantly lower cardiovascular
disease event rates, even for people with cholesterol
values currently considered low for adults; however, no statistically significant mortality benefit
has been derived to date by lowering cholesterol using
medications in asymptomatic people, i.e., no
heart disease, no history of heart attack, etc.
of the better-designed recent randomized human outcome
trials studying patients with coronary artery disease
or its risk equivalents include the Heart Protection
Study (HPS), the PROVE-IT trial, and the TNT trial.
In addition, there are trials that have looked at
the effect of lowering LDL as well as raising HDL
and atheroma burden using intravascular ultrasound.
Small trials have shown prevention of progression
of coronary artery disease and possibly a slight reduction
in atheroma burden with successful treatment of an
abnormal lipid profile. The American Heart Association
provides a set of guidelines for total (fasting) blood
cholesterol levels and risk for heart disease:
||Desirable level corresponding to lower risk
for heart disease
||Borderline high risk
as today's testing methods determine LDL ("bad") and
HDL ("good") cholesterol separately, this simplistic
view has become somewhat outdated. The desirable LDL
level is considered to be less than 100 mg/dL (2.6
mmol/L), although a newer target of <70 mg/dL can
be considered in higher risk individuals based on
some of the above-mentioned trials. A ratio of total
cholesterol to HDL another useful measureâ€” of far
less than 5:1 is thought to be healthier. Of note,
typical LDL values for children before fatty streaks
begin to develop is 35 mg/dL.
should be aware that most testing methods for LDL
do not actually measure LDL in their blood, much less
particle size. For cost reasons, LDL values have long
been estimated using the Friedewald formula: [total
cholesterol] âˆ’ [total HDL] âˆ’ 20% of the triglyceride
value = estimated LDL. The basis of this is that Total
cholesterol is defined as the sum of HDL, LDL, and
VLDL. Ordinarily just the Total, HDL, and Triglycerides
are actually measured. The VLDL is estimated as one-fifth
of the Triglycerides. It is important to fast for
at least 8-12 hours before the blood test because
the triglyceride level varies significantly with food
clinical evidence has strongly supported the greater
predictive value of more-sophisticated testing that
directly measures both LDL and HDL particle concentrations
and size, as opposed to the more usual estimates/measures
of the total cholesterol carried within LDL particles
or the total HDL concentration.
low levels of cholesterol are termed hypocholesterolemia.
Research into the causes of this state is relatively
limited, and while some studies suggest a link with
depression, cancer and cerebral hemorrhage it is unclear
whether the low cholesterol levels are a cause for
these conditions or an epiphenomenon.
dietary cholesterol sources are animal food products.
Examples are egg yolk (~1234 mg/g), beef products
(~381 mg/g), shrimp products (176 - 256 mg/g) .
Plant products (eg. flax seed, peanut), also contain
cholesterol-like compounds, phytosterols, which are
suggested to help lower serum cholesterol. 
sources (including textbooks) incorrectly assert that
there is no cholesterol in plants. This misperception
is made worse in the United States, where Food and
Drug Administration rules allow for cholesterol quantities
less than 2 mg/serving to be ignored in labelling.
While plant sources contain much less cholesterol
(Behrman and Gopalan suggest 50mg/kg of total lipids,
as opposed to 5g/kg in animals), they still contain
LL. Another cholesterol hypothesis: cholesterol
as antioxidant. Free Radic Biol Med 1991;11:47-61. PMID
TH. Do sterols reduce proton and sodium leaks through
lipid bilayers? Prog Lipid Res 2001:40:299â€“324. PMID
- a b Anderson RG. Joe Goldstein and Mike Brown: from
cholesterol homeostasis to new paradigms in membrane
biology. Trends Cell Biol 2003:13:534-9. PMID
- Ockene IS, Chiriboga DE, Stanek EJ 3rd, Harmatz
MG, Nicolosi R, Saperia G, Well AD, Freedson P,
Merriam PA, Reed G, Ma Y, Matthews CE, Hebert JR. Seasonal variation in serum cholesterol levels:
treatment implications and possible mechanisms. Arch Intern Med 2004;164:863-70. PMID
- "About cholesterol" - American Heart Association
- Ostlund RE, Racette, SB, and Stenson WF (2003). "Inhibition
of cholesterol absorption by phytosterol-replete
wheat germ compared with phytosterol-depleted wheat
germ". Am J Clin Nutr 77 (6): 1385-1589.
EJ, Gopalan Venkat. Cholesterol and plants. J
Chem Educ 2005;82:1791-1793. PDF