CHAPTER 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:

  1. It helps make the outer coating of cells.
  2. It makes up the bile acids that work to digest food in the intestine.
  3. It allows the body to make Vitamin D and hormones, like estrogen in women and testosterone in men.

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 cholesterol.

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 Chapter 6.

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.

FIGURE 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 are created.

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 was 350.

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 good results.

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.

FIGURE 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 their components.

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 yellow deposits.

HDL is made by the liver and intestines and has two main jobs. HDL particles give chylomicrons and VLDL the proteins that sig-nal 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. Know-ing 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.