Understanding Cholesterol: The Good, the Bad, and the Necessary
1: Understanding Cholesterol: The Good, the Bad,
and the Necessary
Excerpted from The Harvard Medical School Guide
to Lowering Your Cholesterol
By Mason W. Freeman, M.D. with Christine Junge
Reprinted by permission of the McGraw-Hill Companies; © Copyright
2005 by President and Fellows of Harvard College.
All Rights Reserved.
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High cholesterol is a serious health problem
that affects about fifty million Americans. It's
a major risk factor for cardiovascular disease
(CVD), which half of all men and a third of all
women will get at some time in their lives. I'll
spend the majority of this book on the two things
my patients ask about most: how cholesterol and
heart disease are connected and what they can
do to optimize their cholesterol levels. But
I want to take a few pages early on to clarify
that cholesterol in and of itself isn't bad.
While too much cholesterol can be harmful, just
the right amount of it does a lot of important
work in the body. But like carbohydrates in recent
years, cholesterol has gotten such a bad rap
that most people don't know the good it does.
Cholesterol performs three main functions:
- It helps make the outer coating of cells.
- It makes up the bile acids that work to digest
food in the intestine.
- It allows the body to make Vitamin D and
hormones, like estrogen in women and testosterone
Without cholesterol, none of these functions
would take place, and without these functions,
human beings wouldn't exist.
What Is Cholesterol?
Cholesterol is a fat, or lipid. It is also a
sterol, from which steroid hormones are made.
If you held cholesterol in your hand, you would
see a waxy substance that resembles the very
fine scrapings of a whitish-yellow candle. Cholesterol
flows through your body via your bloodstream,
but this is not a simple process. Because lipids
are oil-based and blood is water-based, they
don't mix. If cholesterol were simply dumped
into your bloodstream, it would congeal into
unusable globs. To get around this problem, the
body packages cholesterol and other fats into
minuscule protein-covered particles called lipoproteins
(lipid + protein) that do mix easily with blood.
The proteins used are known as apolipoproteins.
The fat in these particles is made up of cholesterol
and triglycerides and a third material I won't
discuss much, phospholipid, which helps make
the whole particle stick together. Triglycerides
are a particular type of fat that have three
fatty acids attached to an alcohol called glycerol—hence
the name. They compose about 90 percent of the
fat in the food you eat. The body needs triglycerides
for energy, but as with cholesterol, too much
is bad for the arteries and the heart.
A Lipoprotein by Any Other Name
The two main types of lipoproteins important
in a discussion on heart disease are low-density
lipoproteins (LDL) and high-density lipoproteins
(HDL). Though the names sound the same, these
two particles are as different as night and day.
The differences stem from their densities, which
are a reflection of the ratio of protein to lipid;
particles with more fat and less protein have
a lower density than their high-protein, low-fat
counterparts. There are countless other lipoproteins,
some of which I'll discuss in later chapters,
but in order to get a basic understanding of
how cholesterol affects your body and how the
food you eat affects your cholesterol levels,
LDL and HDL are the ones to start with.
What Are the
Different Types of Fats?
Most people are vaguely familiar with
the terms saturated and unsaturated fat.
But what do they really mean? All fats
have a similar chemical structure: a chain
of carbon atoms bonded to hydrogen atoms.
What differs is the length and shape of
their carbon atoms and the number of hydrogen
atoms. These slight structural differences
create crucial differences in how the body
reacts to them. I'll go into more detail
about diet and cholesterol in Chapter 6,
but for now, here's a primer:
- Saturated fat. The
word saturated here refers to the number
of hydrogen atoms these fats have. The
chain of carbon atoms that makes up these
fats holds as many hydrogen atoms as
possible, so they're saturated. Saturated
fats are unhealthy.
- Unsaturated fat. These
have fewer hydrogen atoms and are healthy
for you. There are two different kinds
of unsaturated fats: polyunsaturated
and monounsaturated. Polyunsaturated
fats, like omega-3 fats and omega-6 fats,
have four or more carbons that are not
saturated with hydrogens. Monounsaturated
fats have just one pair of carbon molecules
that are not saturated with hydrogens.
Low-Density Lipoproteins (LDL)
In most people, 60 to 70 percent of cholesterol
is carried in LDL particles. LDL particles act
as ferries, taking cholesterol to the parts of
the body that need it at any given time. Unfortunately,
if you have too much LDL in the bloodstream,
it deposits the cholesterol into the arteries,
which can cause blockages and lead to heart attacks.
That's why people refer to LDL as the "bad" cholesterol.
The good news is that the amount of LDL in your
blood-stream is related to the amount of saturated
fat and cholesterol you eat. So, most people
can decrease their LDL if they follow a reduced-fat
diet. When you get a fasting cholesterol test,
your doctor should test for the level of LDL
High-Density Lipoproteins (HDL)
HDL is basically the opposite of LDL. Instead
of having a lot of fat, HDL has a lot of protein.
Instead of ferrying cholesterol around the body,
HDL acts as a vacuum cleaner sucking up as much
excess cholesterol as it can (see Figure 1.1).
It picks up extra cholesterol from the cells
and tissues and takes it back to the liver, which
takes the cholesterol out of the particle and
either uses it to make bile or recycles it. This
action is thought to explain why high levels
of HDL are associated with low risk for heart
disease. HDL also contains antioxidant molecules
that may prevent LDL from being changed into
a lipoprotein that is even more likely to cause
heart disease. Lifestyle changes affect HDL levels—exercise
can increase them, while obesity and smoking
lower them. As for diet, in general, the high-fat
diets that raise LDL also raise HDL, while low-fat
diets lower both. However, by carefully choosing
the right foods, you can eat a diet that lowers
LDL without lowering HDL, as I'll discuss in
You Mean My Body Makes Cholesterol?
Cholesterol is so important to the body that
it makes it itself—Mother Nature doesn't
leave it up to humans to get whatever they need
from diet alone. So even if you ate a completely
cholesterol-free diet, your body would make the
approximately 1,000 mg it needs to function properly.
Your body has the ability to regulate the amount
of cholesterol in the blood, producing more when
your diet doesn't provide adequate amounts. The
regulation of cholesterol synthesis is an elegant
process that is tightly controlled.
1.1 HDL to the Rescue
High cholesterol levels result in atherosclerosis,
a narrowing or hardening of the arteries
that can cause heart disease, stroke, and
other major health problems. Fortunately,
the body uses its own "good" cholesterol
to clear out the "bad" cholesterol
before it becomes harmful.
The system works much as your thermostat and
furnace work to regulate the temperature in your
home. The thermostat in this case is a protein
that can sense the cholesterol content of a cell.
When it senses a low level of cellular cholesterol,
the protein signals the genes of the cell (the
furnace in this analogy) to produce the proteins
that make cholesterol. The cell makes more cholesterol,
and it also makes more proteins on the cell surface
that can capture the circulating LDL particles,
thereby retrieving cholesterol by bringing it
in from the blood. It is this regulation that
permits the commonly used cholesterol-lowering
drugs to work so effectively, which I will describe
in more detail in Chapter 8.
Almost all of the cells of the body can make
the cholesterol they need. The liver, however,
is an especially efficient cholesterol factory,
efficient enough that it can afford to export
much of what it makes. The liver packages much
of its cholesterol into lipoproteins that can
be delivered to cells throughout the body, providing
a supplement to what each cell can make on its
own. This supplement is especially important
to the areas of the body that utilize a lot of
cholesterol—like the testes in men and
the ovaries in women, where the sex hormones
In an attempt to make the public health message
about keeping your cholesterol at a healthy level
easy to understand, educators often don't emphasize
the point that all humans make substantial quantities
of cholesterol. But it's important that you understand
this because it clears up confusion a lot of
my patients voice. When I tell a patient that
she has high cholesterol, she may say, "How
could that be? I hardly eat any foods with cholesterol.
My body must somehow make cholesterol—that's
what's wrong!" So I have to explain that
making cholesterol isn't something that she uniquely
and unluckily does—all humans do it, and
we wouldn't survive otherwise.
Your blood cholesterol level is determined by
the sum of how much cholesterol your body makes
and how much you take in from food, minus how
much your body uses up or excretes. High cholesterol
can result from a problem in any of the variables
in that equation—your body may produce
more cholesterol than it needs due to a genetic
predisposition, you may be getting too much from
your diet, or you may not excrete cholesterol
in your bile efficiently. The fact that Americans
have higher blood cholesterol levels than citizens
of the Far East or Africa could be due to differences
in genetic factors, but most evidence suggests
that our higher cholesterol levels are largely
a product of our high-fat, high-cholesterol diet.
Your body does need food to fuel the cholesterol
production process, but it can be virtually any
kind of food, even the cholesterol-free kind.
As long as the food contains carbon—which
carbohydrates, fats, and proteins all do—it
provides the body with the building blocks to
make its own cholesterol. Cholesterol is made
out of the carbon that is recycled from the food
you eat. Saturated fats, however, raise blood
cholesterol levels more than other types of food,
which is why people watching their cholesterol
are told to avoid them. This is true even if
saturated fat (which doesn't have any cholesterol
in itself but is often found in foods with high
cholesterol) is eaten in a cholesterol-free food.
Why saturated fat does this is still something
of a biological mystery.
Family History Lessons: Familial Hypercholesterolemia
There are a variety of genetic disorders that
affect how the body makes lipids. In terms of
heart disease risk, the most detrimental lipid
disorders increase LDL levels and decrease HDL
levels. The majority of these disorders are caused
by a few problematic genes combined with environmental
factors such as obesity or a diet high in saturated
fat. As far as treatment goes, it doesn't matter
if your high cholesterol is caused by problematic
genes or not. Medication and lifestyle changes
are still prescribed based on your HDL and LDL
levels. However, the discovery of these genetic
problems has greatly increased researchers' understanding
of lipoproteins and cholesterol.
A family history of heart troubles can increase
anyone's risk for heart disease, but for people
with a gene mutation that causes extremely high
cholesterol levels—and at an early age—it
nearly guarantees it.
Kelly's father died of a heart attack at twenty-eight,
before she was born. A police officer, he collapsed
while trying to break up a fight. An autopsy
showed that three of his coronary arteries were
nearly 80 percent blocked—an unusual circumstance
in such a young man. Kelly's mom is a nurse,
and despite the reluctance of her doctors, she
had Kelly's cholesterol tested when Kelly was
one year old. The sobering result: Kelly's cholesterol
The pediatricians hadn't dealt with such a high
cholesterol level in a child so young, and so
they referred Kelly to a specialist. Early treatment
consisted of a low-fat, low-cholesterol diet. "It
wasn't nearly as bad as people might think," says
Kelly. "My mom modified recipes, even for
baking, and I would eat 'treats' occasionally,
like pizza or cake at a birthday party. I was
also very active, playing soccer, softball, taking
dance classes, and swimming a lot in the summer.
My mom really encouraged this, too."
While Kelly's mother had special motivation
to be so vigilant, it's a good lesson for all
parents. "In some ways, it was good to have
to adopt a healthy lifestyle so early," she
says. "It would be very hard to suddenly
have to start eating a certain diet and develop
the exercise habit."
In elementary school, Kelly started taking the
cholesterol-lowering medication Questran, which
had to be mixed into a beverage. Kelly recalls, "It
tasted horrible and I usually took it during
school, so it made me feel 'different' from other
kids." Her mom decided against trying niacin,
which is used to lower cholesterol, because of
the side effects, but as a teenager Kelly did
take the herbal supplement Cholestin, which helped
somewhat. I first saw Kelly when she was eighteen
years old, and our initial step was to try one
of the statins. This step produced a dramatic
improvement in her cholesterol—better results
than we achieved with other drugs. I recently
switched Kelly to the statin Lipitor, starting
at a lower dose and working up to 80 mg/day.
She took time off from her medications when pregnant
and breastfeeding, but overall she has had no
side effects and is looking forward to continued
Kelly has familial hypercholesterolemia, specifically
Frederickson type IIa. This condition is usually
due to a mutation in the LDL receptor, although
there are at least two other genetic mutations
that could cause the same picture. Kelly's LDL
is quite high, but her HDL is in a very healthy
range, and she's never had a problem with high
triglycerides. Her daughter, who is seven, shows
no signs of cholesterol problems, but her two-year-old
son's cholesterol is about 260, with a relatively
low HDL level.
Kelly, like her mom, is a nurse and knows what
she needs to do to protect her health and that
of her children. But she is quick to point out
that she leads a healthy lifestyle not only to
keep her cholesterol in check. She also wants
to stay healthy and live a long life for her
kids and husband. And she wants to set a good
example along the way. "It can be difficult
sometimes. Things get hectic with a job and raising
a family. Occasionally when things get crazy,
I think how easy it would be to pick up dinner
at a fast-food joint. And once in a while, I
do, but fast food isn't part of our lifestyle."
Although she doesn't "worry" about
it, Kelly knows that heart disease is still the
leading cause of death for women. That knowledge
almost seems inescapable based on news reports
and even the ads for cholesterol-lowering drugs.
Still, she says that she feels good about taking
all the necessary steps to protect her heart
health. "I tell my daughter that there's
nothing wrong with my heart but that I have to
see a specialist regularly to check up on it
to keep it healthy." Her mom—and stepdad—continue
to play an active role in looking after Kelly's
heart health and that of her children.
The loss of Kelly's dad is tragic. Fortunately,
her mom put two and two together and helped set
Kelly on a healthy path that is likely to steer
her away from heart problems and makes it less
likely that one terrible family "tradition" will
be carried forward.
The Other Source: Diet
For most people—especially those with
high cholesterol—the liver and other cells
aren't the body's only sources of cholesterol.
Our society's typical high-fat diet also packs
a powerful cholesterol punch. How can cholesterol
from a hamburger and French fries eventually
make its way to your heart's arteries? As you
eat food with cholesterol, your intestines go
through a complex process of breaking down fat
molecules and building them into new molecules
that the body can use (see Figure 1.2).
Intestinal enzymes rapidly dismantle the long,
complex fat molecules into their component fatty
acids, reassemble them into new triglyceride
molecules, and package these new triglycerides—along
with a small amount of cholesterol—into
chylomicrons, a lipoprotein that has a very,
very low density. The amount of triglyceride-rich
particles in the blood increases for several
hours after a meal as the intestines release
a barrage of chylomicrons filled with triglycerides.
1.2 How Food Becomes Cholesterol
At the same time, dietary carbohydrates and
proteins that are absorbed from the intestines
pass to the liver, which converts them to triglyceride
molecules, packages them with apolipoproteins
and cholesterol, and releases the resulting very
low-density lipoproteins (VLDL) into the bloodstream.
As chylomicrons and VLDL course around the body,
they temporarily stick to the walls of blood
vessels in muscles that need energy or in fatty
tissue that stores energy. Enzymes come along
and remove most of their load of triglyceride
molecules, which are then transported inside
the muscle or fat cells. As triglyceride is drained
from the chylomicron or VLDL particles, their
protective protein coats are rearranged and reconfigured,
essentially giving them a new address label that
can be read by the liver or other tissues that
take up lipoproteins.
Both chylomicrons and VLDL become more and more
dense as they give up their low-density fatty
cargo. Eventually, all that remains is the packaging
material—the protein and cholesterol—and
a fraction of the original triglyceride. Chylomicron
remnants don't linger in the circulation—the
liver filters them from the system and recycles
Many of the triglyceride-depleted VLDL remnants,
though, keep circulating and undergo further
modification of their lipid and protein content.
Eventually these particles are converted to LDL.
Virtually all cells in the body can take up and
use LDL for their individual needs. But because
there are usually more LDL particles in circulation
at any one time than your body can use, it's
your liver's job to clear the excess from the
blood and use it to make more bile acids or new
lipoproteins. If the liver can't keep up with
the supply of LDL, these particles can come to
rest in the wrong places, typically in the lining
of blood vessels. In extreme cases, they may
settle in the skin and tendons, where they form
HDL is made by the liver and intestines and
has two main jobs. HDL particles give chylomicrons
and VLDL the proteins that signal the liver
to trap them and extract their fat. They also
sponge up excess cholesterol from the linings
of blood vessels and else-where and carry it
off to the liver for disposal.
People who can't package lipoproteins effectively
in the liver because of a genetic mutation still
carry out the majority of the body's functions
quite well, although they do tend to have problems
absorbing vitamins A, D, E, and K and often have
blood cell and neurological problems as a result.
Those vitamins are fat-soluble, meaning they
are carried in the fat particles that make up
lipoproteins, so if the body can't package these
molecules, it can't absorb the vitamins.
Why You Need to Know
When patients come to me because they have high
cholesterol, I'm always amazed at how interested
they are not only in the "how-they-can-get-better" part
but also in why they have a problem. I think
the knowledge of the two goes hand in hand. Knowing
how cholesterol is made in the body and how cholesterol
is absorbed from food is the foundation for understanding
how the right eating plan and, when necessary,
cholesterol-lowering drugs, are effective.