How LDL Cholesterol Becomes Atherosclerotic Plaque

Here’s an interesting article about how high levels of LDL cholesterol end up causing atherosclerosis.

The body uses cholesterol for various purposes, and it has a system for transporting cholesterol in the bloodstream. Like fat, cholesterol doesn’t dissolve in water. To transport fat and cholesterol via the bloodstream, the body puts them in packages called lipoproteins. As the name suggests, a lipoprotein contains fatty substances (lipids) as well as some protein.

Not only do fatty substances like cholesterol fail to dissolve in water, they float on top of it. That’s because they are less dense than water. They are also less dense than protein. The lipoprotein particles that are largest and contain the most fat also have the lowest density. The “bad” cholesterol that people talk about is low-density lipoprotein (LDL). These are lipoprotein particles that carry fat and cholesterol from the liver to the rest of the body. LDL is like a wheelbarrow full of fat and cholesterol traveling from the liver to the rest of the body. In contrast, high-density lipoprotein (HDL) picks up the cholesterol from the tissues and carries it back to the liver. HDL is like a mostly empty wheelbarrow picking up fat and cholesterol and taking it back to the liver.

The article explains that cholesterol is always entering and leaving the intimal layer of the arterial wall. The cholesterol is brought in by LDL and is taken away by HDL. If the cholesterol is brought in faster than it leaves, it builds up to form a deposit called an atheroma. The more LDL there is in the bloodstream, the faster the LDL particles enter the wall of the arteries. The cholesterol is likely to build up into an atheroma if there isn’t enough HDL to carry the cholesterol back out fast enough or if the LDL undergoes some chemical change within the wall of the artery before it can be removed. Here’s an article that explains the kinds of chemical changes that can occur to the LDL while its inside the arterial wall.

Why does cholesterol build up in the intima of the arterial wall but not in other kinds of tissue? It’s because the concentration of LDL is far higher in the arterial intima than in any other tissue. The probable reason for this high LDL concentration is the fact that the arterial intima is not drained by lymph vessels. LDL particles are small enough to leak through the gaps between the endothelial cells that pave the inner surface of the artery. Then, they can diffuse throughout the loose structure of the arterial intima. However, they are too big to leak through the pores in the carbohydrate-and-protein meshwork of the medial layer. Thus, they cannot make their way through to the lymphatic system, which is highly efficient at carrying lipoproteins back to the bloodstream.
Photo by Oregon State University

Humans Are Starch Eaters

Here’s an interesting talk by Nathaniel Dominy, PhD, an Associate Professor of Anthropology at Dartmouth University. He explains the central role of diet in the amazing worldwide success of the human species. If you can’t find enough to eat, you can’t do any of the other things that you would need to do to help you and your children survive.

He makes several important points. One is that human beings are behaviorally “plastic.” He uses the term “plastic” in the scientific sense, meaning that something can take any shape. Our behavior is “plastic” because it can easily be reshaped. As he pointed out, human beings can adapt to many different climates because we have learned to make and wear clothes. We can also learn to eat lots of different foods.

One type of food that is available everywhere except the Artic is starchy foods. All of the energy in our diet comes from sunlight, which green plants use to make glucose out of carbon dioxide and water. Plants then store a lot of this glucose in the form of starch, often in their roots or tubers and in their seeds. Unfortunately, starch is hard to digest. To digest it, we use amylase, an enzyme that converts the starch back to glucose.

Dominy suspects that our ancestors’ ability to recognize and use tuber-forming plants opened up a food source unknown to other primates. “It’s kind of a gold mine. All you have to do is dig it up.

Dominy points out that, when compared with other primates, human beings have extra copies of the gene for the starch-digesting enzyme amylase. As a result, we have a lot more amylase in our saliva than gorillas or chimpanzees do. People from societies that depend heavily on starchy diets have several more extra copies of the amylase gene and therefore produce a lot more amylase in their saliva. In other words, they have become genetically more efficient at digesting starches. This kind of change can be seen in genetically related populations that have been adapting to different diets for only a few thousand years.

Although humans can and do eat practically anything (we are behaviorally plastic), that doesn’t mean that we are well adapted to a meat-based diet. As he puts it, “Anatomically, we’re not adapted to meat at all…. We simply don’t have the adaptations that you would need to chew meat efficiently. Anyone can look at the teeth of their dog or cat and see what your teeth should look like if you’re going to eat meat. Our teeth don’t match.” Dominy concludes, “The fundamental component of the human diet is a mix of plant foods, with a large amount of starch coming from tubers and seeds.”

In this context, I’d point out that the adaptations to a meaty diet go far beyond the shape of the teeth. Even though dogs often eat a fatty, meaty diet, they generally don’t get high cholesterol or atherosclerosis unless they also have a thyroid disorder that upsets their cholesterol metabolism. In contrast, human beings that eat a fatty, meaty diet are much more susceptible than dogs are to high cholesterol and atherosclerosis. That explains why atherosclerosis is the leading cause of death in the United States but practically nonexistent in societies where people eat a low-fat, plant-based diet.

How Low Should Your Cholesterol Levels Be?

Ideally, your total cholesterol should be below 150 mg/dL. According to William Castelli, who was the medical director of the Framingham Heart Study for many years, people with a total cholesterol value of less than 150 mg/dL simply don’t get heart attacks. And once someone’s total cholesterol is that low, the ratio between the “good” and “bad” cholesterol simply doesn’t matter.

The total cholesterol value is the single most important clue to a person’s risk of heart attack. Once the cholesterol levels in the blood rise to, say, the mid-160s, then the ratio of good versus bad cholesterol (HDL versus LDL) really starts to matter.

William Castelli once explained, “Four out of five people on this earth can’t get their cholesterol over 150; they don’t get heart attacks. One out of five people can’t get their cholesterol down to 150. They do get heart attacks. And almost all of them live in affluent countries.” The “four out of five people” Castelli meant live in societies that eat a low-fat, high-fiber, largely plant-based diet. That kind of diet keeps blood cholesterol levels naturally low.

He Should Have Won the Nobel Prize!

In 1913, a Russian pathologist named Nikolai Anitschkow figured out the cause of atherosclerosis, which is the underlying cause of nearly all heart attacks and most strokes. He even published his findings in the major international medical journals of his day. He should have won the Nobel Prize. If people had recognized the importance of his work, millions of premature deaths could have been avoided.

By the late 19th century, pathologists knew that people who had died of heart attacks and strokes tended to have a lot of softy, fatty material stuck to the inner walls of their arteries. This material eventually hardens with the buildup of scar tissue and calcium deposits. The presence of this material is called atherosclerosis, which means hardening of the arteries. The material itself is called plaque.

In its early stages, atherosclerotic plaque looks and feels like cheesecake. In 1910, a German chemist named Adolf Windaus showed that like real cheesecake, atherosclerotic plaque is rich in cholesterol. Because of his work on the chemistry of sterols, Windaus won the Nobel Prize in chemistry in 1928.

As soon as Windaus published his findings about the cholesterol in plaque, Nikolai Anitschkow started an important series of experiments at the Military Medical Academy in St. Petersburg. Anitschkow dissolved some purified cholesterol in sunflower oil and fed it to some rabbits. Control rabbits got some sunflower oil without added cholesterol. The rabbits that got cholesterol in their sunflower oil got atherosclerotic plaque, but the control rabbits did not. To the naked eye and under a microscope, the plaque from rabbit arteries looked a lot like the plaque from human arteries.

Anitschkow and his coworkers discovered a lot of important things about atherosclerosis in those early experiments. As cholesterol researcher Jon Gofman argued,

If the full significance of his findings had been appreciated at the time, we might have saved more than 30 years in the long struggle to settle the ‘cholesterol controversy’ and Anitschkow might have won a Nobel Prize. Instead, his findings were largely rejected or at least not followed up. Serious research on the role of cholesterol in human atherosclerosis did not really get underway until the 1940s.

Why were Anitschkow’s findings ignored? Because they couldn’t be repeated in dogs. As a result, many scientists assumed that the findings wouldn’t apply to human beings, either. That’s an idiotic assumption, because atherosclerosis is rare in dogs, which are natural carnivores. Anitschkow guessed correctly that dogs and other carnivores are good at excreting excess cholesterol. Human beings and rabbits are not. Tragically, no one listened, probably because they’d rather eat meat than rabbit food.

My Cholesterol Is Too Low for the Heart Attack Risk Calculator!

I tried to use the National Cholesterol Education Program’s Risk Assessment Tool for Estimating Your 10-Year Risk of Having a Heart Attack. I entered my data on the form, and I got back an error message, telling me to enter a total cholesterol value of 130 or greater! According to the calculator, even if my cholesterol went up to 130 mg/dL, I’d still have less than a 1% chance of having a heart attack within the next 10 years.

(Note: here’s a live version of the tool, which does not give an error message:

If I ran the National Cholesterol Education Program, I’d really educate people about cholesterol. I’d tell them the simple truth: that when you keep your total cholesterol at less than 150 mg/dL, coronary artery disease ceases to exist. Nearly everyone can easily achieve that goal by eating a low-fat (<10% of calories), plant-based diet.

Instead, the NCEP tells people that a total cholesterol level of  up to 200 mg/dL is “desirable.” Lots of people with this “desirable” cholesterol level are dying of heart attacks, which is why many people, including many doctors, are confused.Photo by winnifredxoxo

Weight and Cholesterol: When Average Is Abnormal

I just discovered that I’m normal, which means that I’m way below average. I’m 5 foot 5 inches tall and weigh about 125 pounds. That gives me a body mass index of 20.8, which is normal. Yet it also means that I’m skinnier than about 95% of the American women my age. To become officially overweight, I’d have to gain at least 25 pounds. To be as fat as the average American, I’d have to gain a total of 40 pounds. To qualify as obese, I’d have to gain a total of 50 pounds.

If you live in the United States, you have probably noticed that most of the people around you weigh more than they should. That’s because you probably know, more or less instinctively, what healthy people are supposed to look like. Unfortunately, we can’t automatically recognize that some of our other measurements, such as our total cholesterol values, are also wildly abnormal. That’s because nobody has an instinctive feel for what healthy blood values are supposed to be. It’s tempting to evaluate them by comparing them to the average values for our population, but how can we tell if the average value in our population is normal or abnormal?

The U.S. federal government’s “Healthy People 2010” guidelines regarded total cholesterol of 240 mg/dL as “high” and a level of 200 mg/dL as “desirable.” Yet people are still at risk for heart disease as long as their total cholesterol is above 150 mg/dL. The last time my blood was tested, my total cholesterol was 120 mg/dL. According to statistics from the Centers from Diseases Control and Prevention, my total cholesterol level is unusually low. More than 95% of the Americans in my age-group have a total cholesterol value that’s way higher than mine. Yet I suspect that my cholesterol levels, like my weight, are normal and healthy. It’s the average person who’s dangerously abnormal.

The numbers are staggering. People whose cholesterol level is “high” by American standards (over 240 mg/dL) have more than twice as much cholesterol in their blood as I have. The average American has a total cholesterol level of about 200 mg/dL. This means that even the average person has far more cholesterol in his or her blood than I do. No wonder their arteries are getting clogged!

My blood cholesterol level may seem amazingly low, but it’s about average for someone in rural China. In the late 1990s, the China-Cornell-Oxford Project found that the average total cholesterol level in rural Chinese people was 127 mg/dL. As a result, heart attacks were rare in China. Overall, American men were 17 times as likely as Chinese men to get a heart attack. American women were about 6 times as likely as Chinese women to get heart attacks.

In some areas of rural China, coronary artery disease was practically nonexistent. A population of a few hundred thousand people could go for a couple of years without anyone under age 65 dying of a coronary. Not one person. The study didn’t analyze the causes of death among the elderly, but there probably weren’t many coronaries among people over 65, either.

Why were cholesterol values and rates of coronary artery disease so low in China? The study showed that diet makes the difference. Overall, the Chinese were eating only about a tenth as much animal protein and three times as much fiber as Americans were eating. The less animal protein people ate, the lower their cholesterol values were, and the less likely they were to die of heart disease and various cancers. There didn’t seem to be any “safe” level of intake of animal protein. Eating even a small amount of animal protein produced a small but measurable increase in risk. On the other hand, the more vegetables people ate, the safer they were.

My cholesterol values look like those of someone from rural China because I eat no animal protein but lots of rice and other grains and vegetables and beans and fruit. Anyone who thinks that this kind of diet is boring or unsatisfying has simply never had dinner at my house.

I know from reading the scientific literature on nutrition that people in the United States could dramatically improve their health and increase their life expectancy by shifting from the standard American diet, with its heavy emphasis on animal protein and its heavy load of fat, to a diet based on unrefined plant foods. This simple correction in the diet would enable people to drop to a normal weight without counting calories or limiting their portions. It would practically eliminate heart disease and greatly reduce the risk of other diseases. So why doesn’t our government tell us about this?

Worse yet, our government is still urging people to eat animal protein. Although the Healthy People 2020 goals supposedly “reflect strong science,” their dietary advice flies in the face of what we learned from the China-Cornell-Oxford study. In particular, the Web site says the following: “Americans with a healthful diet consume a variety of nutrient-dense foods within and across the food groups, especially whole grains, fruits, vegetables, low-fat or fat-free milk or milk products, and lean meats and other protein sources.” Since we know from the China-Cornell-Oxford study that eating animal protein is the major contributing cause of our major cause of death, and that there’s no safe level of intake of such foods, why in the name of good common sense is our government saying that a diet that includes these foods is healthful?

What’s Next, an Atherosclerosis Acceptance Movement?

The Hidden Danger of the “Fat Acceptance” Movement

You know the old saying, “If something is too good to be true….” Well, the “fat acceptance” movement is telling people something that sounds too good to be true. They are insisting that people can be “healthy at any size” and sometimes even that being overweight is healthier than being slim. They’re wrong, and the smarter and more educated people among the “fat acceptance” movement should know better. They “cherry pick” misleading findings from a few studies and ignore a vast scientific literature on the effects of diet on health. Such behavior is sickening, and the advice they give is dangerous.

Here’s the simple truth: excess body fat is only one of the possible bad effects of eating the wrong kind of food. Eating too much fat and too much animal protein can send you to an early grave even if you are thin and exercise a lot. The classic example is Jim Fixx, author of The Complete Book of Running, a 1977 bestseller that launched the running boom. Fixx had claimed that his grueling exercise regimen, which had enabled him to lose 60 pounds, allowed him to eat as much as he wanted of whatever he wanted. When I read that in his book, I thought, “But what about cholesterol?” So I was saddened, but not surprised, when Fixx dropped dead at age 52 of a heart attack while running. To my disgust, the media reacted to his death by asking whether running was good or bad for you, ignoring the obvious dietary angle to the story.

The simple truth is that eating the wrong kind of food can kill you, even if it doesn’t make you fat. Another simple truth is that you can’t outrun cholesterol. As a member of the high-IQ club Mensa, Fixx should have been smart enough to figure that out before it was too late. Unfortunately, he believed what he wanted to believe, and ate whatever he wanted to eat, and in the end it killed him.

As I mentioned, obesity is only one of the bad effects that is likely to result from eating the standard American diet–not just the heavily processed “junk food” that everyone knows is bad for you, but the meat and dairy products and eggs and fish that the US Department of Agriculture has been encouraging us to eat.

Collectively, the bad effects of eating the standard American diet are called “Western diseases.” This is because medical doctors who had been trained in Europe and the United States were stunned to find that these health problems, which were common back home, were rare to nonexistent in Asia and Africa. Besides overweight and obesity, they include heart disease, diabetes, various cancers, arthritis, varicose veins, multiple sclerosis, etc. etc. etc. Western diseases were (and still are) the major causes of death and disability in the United States and Europe because people there eat too much animal protein and too much fat. These diseases were rare in Asia and Africa because the populations were eating a low-fat, largely plant-based diet. A monumental study of nutritional epidemiology in China ( showed in detail how closely the consumption of animal protein and fat were linked to many of these diseases. The less animal-based food and fat people ate, the healthier they could be.

The good news is that if you eat the diet that will protect you against the other “Western diseases,” your weight problem will solve itself. People who eat a low-fat (<10% of calories) diet based on unrefined plant foods rapidly become heart-attack-proof (total cholesterol, <150 mg/dL) and can prevent and even reverse many of the other Western diseases. It’s hard to stay fat when you are eating a truly healthy diet. When overweight Americans switch to a low-fat, purely plant-based diet, they lose weight easily without having to count calories or limit their portions. They can eat to their hearts’ content and still stay slim. The “fat acceptance” advocates overlook that obvious fact.

The “fat acceptance” advocates are right that thin does not equal healthy. But they are wrong when they say that you can be healthy at any size. Rather than wasting their time trying to make people feel better about being fat, they should work toward educating people about a truly healthy diet, which will enable people to improve their own health and maintain a desirable weight without feeling hungry. The activists should also use their political clout to improve the nutrition curriculum at medical schools, which has been shown repeatedly over the past 40 years to be inadequate.

On one point, I do agree with the fat acceptance advocates. I think that people should be treated with respect regardless of their size and state of health. However, I feel that overweight people deserve to be told the truth about how their weight affects their health and about how their food choices affect both their health and their weight.

How Low Should Total Cholesterol Be?

Below 150 mg/dL, According to Dr. Caldwell Esselstyn

“Based on the groundbreaking results of his 20-year nutritional study—the longest study of its kind ever conducted—this book explains, with irrefutable scientific evidence, how we can end the heart disease epidemic in this country forever by changing what we eat. Here, Dr. Esselstyn convincingly argues that a plant-based, oil-free diet can not only prevent and stop the progression of heart disease, but also reverse its effects.”

Heart attack is virtually nonexistent in populations whose heavily plant-based diet keeps the average person’s total cholesterol below 150 mg/dL.