CHOLESTEROL, WHAT IS IT, HOW TO LOWER YOUR CHOLESTEROL
Cholesterol is a steroid lipid, found in
the cell membranes of all body tissues, and transported in the blood plasma of
all animals. Most cholesterol is not dietary in origin, it is synthesized
internally. It is present in higher concentrations in tissues which either
produce more or have more densely packed membranes; for example the liver,
spinal cord, brain and atheroma. 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 in the blood.
History of the name
The name originates from the Greek chole- (bile) and stereos (solid), as
researchers first identified cholesterol in solid form in gallstones.
Trans Fats
Physiology
Synthesis and intake
Cholesterol is primarily synthesized from acetyl
CoA through the HMG-CoA reductase pathway in many cells/tissues. About 20–25% of
total daily production (~1 g/day) occurs in the liver, other sites of higher
synthesis rates include the intestines, adrenal glands and reproductive organs.
For a person of about 150 pounds (68 kg), typical total body content is about 35
g, typical daily internal production is about 1 g and typical daily dietary
intake is 200 to 300 mg. Of the 1,200 to 1,300 mg input to the intestines (via
bile production and food intake), about 50% is typically reabsorbed into the
bloodstream.
Properties
Cholesterol 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" which are water soluble and carry
cholesterol and fats internally. The proteins forming the surface of the given
lipoprotein particle determine from what cells cholesterol will be removed and
to where it will be supplied.
The largest lipoproteins, which primarily transport fats from the intestinal
mucosa to the liver are called chylomicrons. They carry mostly triglyceride fats
and cholesterol (both from food and especially internal cholesterol secreted by
the liver into the bile). In the liver, chylomicron particles give up
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. Conversely, large numbers of small LDL particles are
strongly associated with promoting atheromatous disease within the arteries.
(Lack of information on LDL particle number and size is one of the major
problems of conventional lipid tests.)
High density 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. Conversely, having small amounts of large HDL particles is strongly
associated with atheromatous disease progression within the arteries. (Note that
the concentration of total HDL does not indicate the actual number of functional
large HDL particles, another of the major problems of conventional lipid tests.)
The cholesterol molecules present in LDL cholesterol and HDL cholesterol are
identical. The difference between the two cholesterol derives from the carrier
protein molecules; the lipoprotein component.
Regulation
Biosynthesis of cholesterol is directly regulated by the cholesterol levels
present, though the homeostatic mechanisms involved are only partly understood.
A higher intake in food leads to a net decrease in endogenous production and
vice versa. The main regulatory mechanism is the sensing of intracellular
cholesterol in the endoplasmic reticulum by the protein SREBP (Sterol Regulatory
Element Binding Protein 1 and 2). In the presence of cholesterol, SREBP is bound
to two other proteins: SCAP (SREBP-cleavage activating protein) and Insig-1.
When cholesterol levels fall, Insig-1 dissociates from the SREBP-SCAP complex,
allowing the complex to migrate to the Golgi apparatus, where SREBP is cleaved
by S1P and S2P (site 1/2 protease), two enzymes that are activated by SCAP when
cholesterol levels are low. The cleaved SREBP then migrates to the nucleus and
acts as a transcription factor to bind to the "Sterol Regulatory Element" of a
number of genes to stimulate their transcription. Amongst the genes transcribed
are the LDL receptor and HMG-CoA reductase. The former scavenges circulating LDL
from the bloodstream, while HMG-CoA reductase leads to an increase of endogenous
production of cholesterol.
More Books about Lowering Cholesterol
A large part of this mechanism was clarified by Dr Michael S. Brown and Dr
Joseph L. Goldstein in the 1970s. They received the Nobel Prize in Physiology or
Medicine for their work in 1985.
The average amount of blood cholesterol varies with age, typically rising
gradually until one is about 60 years old. A study by Ockrene et al. showed that
there are seasonal variations in cholesterol levels in humans, more on average
in winter.
Function
Cholesterol is an important component of the membranes of cells, providing
stability; it makes the membrane's fluidity stable over a bigger temperature
interval. 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. It is the major precursor for the synthesis of vitamin D, of the
various steroid hormones, including cortisol, cortisone, and aldosterone in the
adrenal glands, and of the sex hormones progesterone, estrogen, and
testosterone. The presence of cholesterol has a direct effect on the fluidity of
the membrane. Further recent research shows that cholesterol has an important
role for the brain synapses as well as in the immune system, including
protecting against cancer.
Excretion
Cholesterol is excreted from the liver in bile and reabsorbed from the
intestines. Under certain circumstances, when more concentrated, as in the
gallbladder, it crystallises and is the major constituent of most gallstones,
although lecitin and bilirubin gallstones also occur less frequently.
Role in atheromatous disease
See also the main article hypercholesterolemia
In conditions with elevated concentrations of LDL particles, especially small
LDL particles, cholesterol promotes atheroma plaque deposits in the walls of
arteries, a condition known as atherosclerosis, which is a major contributor to
coronary heart disease and other forms of cardiovascular disease. (Conversely,
HDL particles have been the only identified mechanism by which cholesterol can
be removed from atheroma. Increased concentrations of large HDL particles, not
total HDL particles, correlate with lower rates of atheroma progressions, even
regression.)
There is a world-wide trend that lower total cholesterol levels tend to
correlate with lower atherosclerosis event rates. However, the primary
association of atherosclerosis with cholesterol has always been specifically
with cholesterol transport patterns, not total cholesterol per se. For example,
total cholesterol can be low, yet made up primarily of small LDL and small HDL
particles and atheroma growth rates are high. Conversely, if LDL particle number
is low (mostly large particles) and a large percentage of the HDL particles are
large (HDL is actively reverse transporting cholesterol), then atheroma growth
rates are usually low, even negative, for any given total cholesterol
concentration.
Multiple human trials utilizing HMG-coA reductase inhibitors or "statins", have
repeatly 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.
Some of the better recent randomized human outcome trials studying patients with
coronary artery disease or it's 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:
The source of this article is
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